ace |IMKSAP Medical Knowledge Self-Assessment Program” Infectious Disease 25 AMARA 9 Category 1 Credits™ available until American College of Physicians December 31,2021 aading beer ein npn iroAttention MKSAP 18 Complete subscribers: If you are receiving the MKSAP 18 print books as part af your MKSAP 18, Complete subscription, remember that you will receive regular content updates in your online account through MKSAP 18 Digital's New Info Updates. New Info Updates will fheuson practice: changing updates, includ Ing new guidelines. You wil also receive four sets of MKSAP 18 Extension Questions (formerly MKSAP Update Questions) that will alow you to earn, CME credits and MOC points through January 202, Not a MKSAP 18 Complete subscriber? IF you wish to add MICSAP 18 Digital to your peint subscription at any time, upgrade to MKSAP 18 Complete for the most value-packed, cost-eifieient combination of NKSAP products, Please callour ACP Member and Customer Service Department, and they will help you arrange easy access to MKSAP 18 Complete. As part of MKSAP 18 Complete, you will receive MKSAP 18 Digital, Including regular content updates through New Info Updates, and fou sets of MESAPI8 Extension Questions (formerly MKSAP Update Questions) that ‘will allow you to earn CME credits and MOC pomts through 2024. You will also recelve MKSAP 18 Flashcards, Virtual Dx. and Board Basics (print and book) at no extra charge. ACP Member and Customer Service 800-ACP-1915 Outside the US. call 215-351-2600 (Monday to Friday. 9 am pm ET) Disclaimer Regarding Direct Purchases from Online Retailers ‘CME and/or MOG for NKSAP 18 fs available only if you purchase the pro sgfam directly trom ACP. CME ereditsamd MOC points cannot beawarded to these purchasers who have purchased the program from non authorized sellers, such as Amazon, eBay, or any other such online retaileracp| MKSAP & Infectious DiseaseWelcome to the Infectious Disease Section of MKSAP 18! {In these pages, you Will nd updated formation on central nervous system Infecttons, skin and soft tissue infections, ‘community-acquired pneumonia. tick-borne diseases, urinary tract infections, Mycobacterium tuberculosis and nontuber~ ccalous mycobacterial infections, sexually transmitted infections, bioterrorism, travel medicine, infectious gastrointestinal wdromes, ransplant-assoclated infections, HIV and AIDS, lcalth care-assoclated Infections, and other clinical challenges. All of these topics are uniqutely focused on the needs of generalists and subspecialists outside of infectious disease. ‘Tac core content of MKSAP 18 has been developed as in previous editions all essential information that is newly researched and written in TI topic areas of internal medicine —created by dozens of leading generalisss and subspecialis's and guided by certification and recertification requirements, emerging knowledge in the field, and user feedback, NKSAP 18 also contains 1200 all-new peer-reviewed, psychometrically validated, mulliple-choice questions (MCQy) for self assessment and study, including 108 in Infectious Disease. MKSAP 18 continues to include High Value Care (HVC) recommendations, based on the concept arbalancing clinical benefit with ensts and harms, with associated MCQs illastraring these principles and HVC Key Points called out in the (ex. Internists practicing in dhe hospilal setting can easily find comprehensive Hospitalist focused content and MCQs, specially designated in blue and with the (0 symb. Ifyou purchased MKSAP 18 Complete, you also have access to MKSAP 18 Digital, with additional tools allowing you to ‘customize your learning experience, MKSAP Digital includes regular text updates with new, practice-changing information, 200) new self-assessment questions, and enhanced custom-quiz options. MKSAP Complete alsa includes more than 1200 ‘electronic, adaptive learning, enhanced flasheards for quick review of important concepts, as well asan updated and enhanced version of Virtual Dx, MKSAP's image-based self-assessment tool. As before, MKSAP 18 Digital is optimized for use (on your mobile devices, with iOS- and Android-based apps allowing you to syne between sour apps and online account and submit for CME credits and MOC points online. Please visit us at the MKSAP Resource Site [mksan.aeponiline.org) to find out how we can help you stu and MOC points, and stay upto date, arn CME credit (On behalf of the many internists who have offered theit time and expertise to create the content for MRSAP 18 and the editorial staff who work to bring this material to yau in the best possible way, we are honored that you have chosen to ‘use MKSAP 18 and appreciate any feedback about the program you may have. Please feel ree to send any comments 10 mksap_editors@aeponline org, Sincerely Patrick C. Alguire, MD, FACP. Falior in Chief Senior Vice President Emeritus ‘Medical Education Division American College of PhystclansInfectious Disease Committee Patricia D. Brown, MD, FACP, Section Editor* Professor of Medicine ‘Wayne State University School of Medicine Assodate Chief of Staff for Medicine John D. Dingell VA Medical Center Detroit, Michigan Karen C Bloch, MD, MPH, FACP! Associate Professor Department of Medicine and Health Policy Division of Infectious Diseases Vanderbilt University Medical Center Dashvill, Tennessee Larry M. Bush, MD, FACP? Affiliated Professor of Biomedical Sciences Charles E. Schunidt College of Meateine Florida Atlantic University Boca Raton, Florida Adfillted Assoctate Professor of Medicine Unversity of Miami-Miller School of Medicine FFK Medical Center alm Beach County, Florida {Loulse M. Dembry, MD, MS, MBA, FACP® Professor of Medicine Infectious Diseases and Kpidemiology “ale University School of Meuicine New Haven, Connecticut Michael Frank, MD, FACP! Professor of Medicine hief, Division of Infectious Diseases ice Chair for Education Department of Medicine Medical Callege of Wisconsin Milwaukee, Wisconsin Rocirigo Hasbun, MD, MPH* Profescar af Medisine Department of Infectious Diseases UT Health-MeGovern Medical School Houston, Texas Fred A. Loper, MD, MACP* Richard Vial Professor Vice Chair for Education Department of Medicine {Louisiana State University Health Sciences Center New Orleans, Louisiana Jose A. Vazquez, MD, PACP? Chief. Division of Infectious Diseases Professor, Department of Medicine Medical College of Georgia at Augusta University Augusta, Georgi Editor-in-Chief Patriek C. Alguire, MD, EACP? Senor Vice President Emeritus, Medical Education American College of Physicians Philadelphia, Pennsyhania Deputy Editor Davoren Chick, MD, FACP* Senior Vice President, Medkcal Education American College of Physicians Philadelphia, Pennsyvanis Infectious Disease Reviewers Susan C. Bleasdale, MD, ACP? Reata C.Casanas, DO, FACP? Manjit S. Dhillon, MBBS, EXCP! Dimitri M. Drekonja, MD, FACP! Lisa A. Grobskopt, Mtn! Muhanumad Umar Khan, MBBS, EACP* Felicia M. Lewis, MD, FACP* Maricar E Malinis, MD, EACP2 Zavi Min, MD, FACE George Samuel, MD! Hospital Medicine Infectious Disease Reviewers J. Hoon Beang, MD, FACP? Jeana Benwill, MD! Infectious Disease ACP Editorial Staff Linnea Donnarumuna?, Staff Roltor Margaret Wells', Director, Self-Assessment and Fiducational Programs Becky Krumm’, Managing Fditor, Self Assessm¢ Educational Programs and ACP Principal Staff Davoren Chick, MD FACE Senior Vice President. Medical EducationPatrick C. Alguire, MD, FACP* Senior Vice President Emeritus, Medical Education Sean Mckinney" Vice President, Medical Education Margaret Wells! Director, Self-Assessment and Educational Programs Becky Krummt Managing Fiitor Valerie Dangovetsky* Administrator Ellen Mefonald, PhD" Senior Staff Faitor Megan Zhorowshi Senior Staff Editor adkle Twomey" Senior Staff iditor Randy Hendrickson! Production Administrator/tditor Julia Nawrocki! Digital Content Associate /Hditor Linnea Donnarumma' Stal] Editor Chuck Feng suajf ator Joysa Winter* Staff Flitor Kimberly Kerns! Audmain'straive Coordinator Disclosure of Relationships with any entity producing, ‘marketing, reselling. or distributing health care goods or services consumed by, or used on, patients. Patrick C. Alguire, MD, FACP Royalties UpToDate Hoon Baang, MD, FACP Stock Options’Holdings Sarepta Therapenties Susan C. Bleasdale, MD, FACP Reseurch Grants/Contracts Rempex Pharmaceuticals, Theravance Biopharma Consultantship MedMined, Ine Larey M. Bush, MD, FAC. Homoraria Merck Manual Beata C. Casanas, DO, FACP Speakers Bureau Pfizer, Allergan Davoren Chick, MD, FAC Rowalties Wollers Kluwer Publishing, Consukariship EBSCO Health's DynaMed Plus, Other: Owner and sole proprietor of Coding 101 LIC: research consultant (spouse) for Vedanta Biosciences Ine Louise M. Dembry, MD, MS, MBA Roarel Member Seciely for Llealtheare fpidemiology of America ‘Stocks Options/Hloldings Advzneed Technical Sunport/Ready och Rodrigo Hasbun, MD, MPH Speakers Bureau Pfizer. Medicine's Company, Biofire Diagnostics, Merck Consultanship BioMerieus Fred A. Lopez, MD, MACP Royalties UpTobatc Maricar F. Malinis, MD, FXCP Other: primary investigator for clinical trials for Chimerix, Astellas Pharma US Ing, and Oxiord Immunotec ‘ose A. Vazquez, MD, BACP Research Grants/Contraets Astellas Pharma US Ine Speukers Bureau AllerganAcknowledgments ‘The American Collage of Physician (ACP) gratefully acknowledges the special contributions tothe develop ment and production of the ith ection ofthe Medical Knowledge Self Assessment Program’ (MKSAP" 18) made by the following people: Graphic Design Barry Moshinski (Dinecion Graphic Services), Michael Ripa (Graphics Tecnica Administrator. and Jenner Groner (Graphic Designer Proctuction Systems: Dan Tloffimann (Director, Information Technology), Scott Hur (Manager, Cntere Sysiems), Net! Kohl (Genior Architet), and Chris Faticrson (Senior Archie) MESAP 18 Digital: Under the direetion of Steven Spadt (Senior Viee President, Technology), the digital version of MKSAP 18 was developed within the ACP’s Digital Products and Services Department, led by Brian Sweigard (Diteetor, Digital Products and Services). Other members ofthe team, incuuded Dan Barron (Senior Web Application Developer Architect), Chris Forrest (Senior Software Developer/Liesign Lead), Kathleen Hoover (Senior Web Developer, Kara Regis (Manager, User interface Design and Development) Brad Lord (Senior Web Application Developer), ard John DicKnight (Senior Wed Developer). The College also wishes to acknowledge that many other petsons, (y0 numerous to mention, have contributed to the production of this program. Without their dedicated efforts, this program would not have been possible MKSAP Resource Site (mksap.acponline.org) ‘The MKSAP Resource Site (mksap.aeponline.ong) is 4 con lunually updated site that provides links to MKSAP 18 online answer sheets for print subseribers: access to MKSAP 18, Digital: Beard Basics e book access instructions; informa tuon cn antinuing Medical Fdacation (CME), Maintenance of Certification (MOC), and international Continuing Professional Development (CPD) and MOG errata; and ‘other new information. International MOC/CPD For information and instructions on submission of inter natlonal MOCICFD, please yo to the MKSAP Resource Site (mksapacponline org) Continuing Medical Education The American College of Physicians is accredited by the Acereditation Council for Continuing Medical Fauestion (ACCME) o provide continning medical education for physicians ss cesignates this endur SAP 18, for a maximum of 275 AMA PRA (Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of thelr participation inthe activity Up t0 25 ANA PRA Category 1 Credits! are available from, December al, 2018, to December 31, 2021, for the MKSAP 18, infectious Disease section. Learning Objectives The learning objectives of MKSAP 6 are + Close gaps hetween actual cate in your pructice and preferred standards of care, based on best evidence +» Diagnose disease states that are Tess common and sometimes overlooked andl confusing » Improve management of comorbid cunditions that can complicate patient care + Determine when to refer patients for surgery or care by subspevitises Pass the ABIM Certification Examination Pass the ABIM Maintenance of Certification Examination Target Audience + General internists and primary care physicians + Subspecislists wino need to remain wp to date in internal medicine + Residents preparing for the certifying examination in internal medicine + Plysiclans preparing for mannenance of eerification in ‘internal medicine (recertification) ABIM Maintenance of Certification (Check the MKSAP Resouve Site (rnksap.aepontine.org) for the latest information on how MKSAP tests ean be used fo apply to the Ameriean Board of Internal Medicine (ARIM) for Maintenance of Certification (MOC) points allowing completion of the CME activity Successful completion of the CME activity, witieh includes participation in the evaluation component, enables the pa ejpant to earn up to 275 medical knowledge MOC ports the ABIM'S MOC program. Itisthe CME activity provider's esponsibility o submit participant completion information 1O ACCME for the purpose of granting MOC ered Earn Instantaneous CME Credits or MOC Points Online Print subscribers can enter their answers online to eam instantaneous CME credits o MOC points. You can submit yourarswers using online answer sheets that are provided at mksap acoonline org. wherea record of your MKSAP 18 credits will be aallable, To earn CME credits or to apply for MOC points younced to answer allof the questions ina test and eam a score of at least 50% correct (number of comectanswers divided by the total number of questions), Please ‘note that ifyou are applying for MOC points, you must also enter your birth date and ABIM candidate number, ‘Take either of the fol wing approaches: 1. Use the printed answer sheet at the back ofthis book to record your answers. Go to mksap.acponline.org, access ‘Ute appropriate online ansiver sheet, transcribe your ‘ansivers, and submit your test for instantaneous CME credits or MOC points. There is no additional fe for this 2. Go to inksapacponllinorg, access Uie appropriate online: answer sheet, cirectly enter your answers, and submit ‘your tes for instantaneons CME credits or MOC points, ‘There is no adlitional fe fbr this service Earn CME Credits or MOC Points by Mail or Fax Pay a $20 processing fee per answer sheet and submit the printed answer sheet at the back ofthis book by ‘mall or {x 28 instructed on the answer sheet. Make sure you calculate your score and enter your birth date and ABIM candidate number, and fax the answer sheet to 215-351-2799 or mail the answer sheet 'o Member an Cascomer Service. American College of Physicizins, 190 N. Independence Mall West, Philadelphia, PA 19196-1572, using the courtesy envelope provided in your MKSAP 18: slipcase, You will need your 10 digit order number and 8-digit ACP ID number, which are printed on your pack ing slip. Please allow 4 to 6 weeks for your score report to be emailed back to you, Be sure to include your email address for a response Ifyou do not havea 10 digit order number and @ digit ACP 1D number, or Ifyou neal help creating a user-name and password fo access the MKSAP 18 onlineanswer sheets, go to mksap.acponline.org or email custserv@acponline.org, Disclosure Policy Iis the policy of the American College of Physicians (ACP) to ensure balance, independence, objectivity, and scientific rigor in all ofits echicational activities. To this ‘end, and consistent with the policies of the ACP and the Accreditation Couneil for Continuing Medical Education (ACCME), contributors to all ACP continuing medical ‘education activities are required to diselose all relevant Ahanctal relationships with any entity producing. mar keting, re-selling. of distributing health care goods or ser vices consumed by, oF used on, patients. Contributors are required to use generic names in the discussion of ther peutic options and are required to identify any unap proved, off label, or investigative use af commercial prod ucts or devices. Where 2 trade name Is used, all available trade names for the same product type are also included. I trade-name products manufactured by companies with whom contribistors have relationships are discussed, con tributors are asked to provide evidence-based eltatlons in support ofthe discussion, The information is reviewed. by the committee responsible for producing this text. If necessary, adjustments to topics or contributors’ roles In content development are made to balance the discussion. Further, all readers of this text are asked to evaluate the: content for evidence of commercial bias and send any rel evant comments to mksap_editors@acpontine.org so that Future decisions about content and contributors can be ‘made in light of this information, Resolution of Conflicts To resolve all conflicts of Interestand influences of vested interests, ACP’s content planners used best evi dence and updated clinical care guidelines in developing content, when such evidence and guidelines were avait able. All content underwent review by peer reviewers not on the committee {0 ensure that the material was balanced and unblased. Contributors’ disclosure infor ‘mation can be found with the list of contributors’ names and those of ACP principal staff listed in the beginning, of this book, Hospital-Based Medicine Forthe canvenience of suseribers wi provide care in hospital settings, content that is specific to the hospital setting has beet highlighted in blue. Hapa eons ED) highlight where the hospital-only comtent begins, continues over more than one page. and ends High Value Care Key Points ey Points in the text that relate o High Value Care concepts (ahatis, concepts that aiseuss balancing clinical benefit with costs and harms) are designated by the HVC icon HVC] Educational Disclaimer ‘The editors and publisher of MRSAP 18 recognize that the development of new material offers many opportu- nities for error. Despite our best efforts, some errors may persist in print. Drug dosage schedules are, we believe, accurate and in accordance with current standards. Readers are advised, however, (o ensure that the recom- mended dosages in MKSAP 18 coner with the infor mation provided ia the product information material This s especially important in cases of new, infrequently used, or highly toxic drugs. Application of the informa ton in MKSAP 18 remains the professional responsibility, of the practitioner,The primary purpose of MKSAP 18 is educational Information presented, as well as publications, technol ‘gies, products, and/or services discussed, is intended to inform subscribers about the knowledge, techniques, and ‘experiences of the contributors. A diversity of professional ‘opinion exists, and the views of the contributors are their ‘own and not those of the ACP. Inclusion of any material in the program does not constitute endorsement or recom mendation ty the ACP. The ACP does not warrant the safety, reliability, accuracy, completeness, or usefulness of and dis- 50y orthore wth aktered cellars enmity ampicillin iors | covemgp ali W cafrinsne dreoloterine plusiV I moxifonacn insead of cephalospara NM vimetheprin suliamethowsssie hatesd of amprelin| Allergies to lactams Hosptakacquired bacterial W vancomycin plus ether V meningitis cotazdime,colepme, or mecopene'n Neurosurgical procedurse | Wencomycin plus ther V cefosidine,celepmne,cr | meropenem redhces morbidity and mortality in adults with pneumoceecal ‘meninytis and reduces the risk of neurologic sequclacin bacte tal meningitis in developed countries it should be gen «on comitanily with the first dose of antibiotic therapy: RRP INSamiatareste a ES *+ For diaghonis of hactesial meninglus, dhe cerebrospinal Mute Gram stain resltispesitve In 60% 10 90% of infections; latex aggatination esting for arterial antigens snot ree ‘ommended because low senstnity and specifiy Intravenous antibiotic therapy and dexamethasone should be started @s soon as possible when bacterial ‘meningitis s suspectec Selection of initial empiric ant bioties is based on age. local epidemiologic patterns of pneumococcal resistance, and the necessity for ampseil lin coverage for Lsterta monocytogenes, Adjunctive dexamethasone seduces morbidity and mor tality in adults with pneumococcal meningitis and reduces the risk of neurologic sequelie in bacterial ‘meningitis in developed countries.Central Nervous System Infectior Subacute and Chronic Meningitis, Subacute and chronie meningitis are defined by symptom duration between 5 and 30 days and more than 36 days, respectively. The most common infectious causes. are Mycobacterium tubereulesis and fang Tuberculous Meningitis: Mycobacterial tuberculesis meningitis classically presents as, basilar meningitis with cranial ncuropathies (particulary of era nial nerve), mental status changes. and the sendrome of nap propriate seeretion of anticuretic hormone. A history of tuber culosis exposure, an abnormal chest radiograph, 2 positwe tuberculin skin tes! result, and a positive interferon 7 release assay result are suggestive but can be absent, CSP examination, shows. lymphocytic pleocytosis (leukocyte eountof 100 500/41 100 50010). clevated protein evel, and hypeghcorrhachia. CSF acid. fst bacilli smenris insensitive, and culture results are Positive In only 38% to 88% OF patlents. Culture sensitivity Increases when lumbar punctures are performed serially for at least 3 days. Nuclet acid aruplifeation testing should be per formed when possible, espectally when the aeid-L! bacl stain result s negativeand suspicion & high, because it might increase diagnostic yield. Antituberculous therapy should be adminis tered for | year, and adjunctive glucocorticatds shoald be given. initially because oftheir assocation with improved outcomes. Fungal Meningitis Fungal pathogens, including Cryptococcus neoformans, Coccldloides immitis, Hisioplesma capsulatum, and endemic smyeoses, are a significant cause of subacute or chronie menin= agitis syndromes. Fungal meningitis is diseussed in the Fungal Infections chapter: Neurobrucellosis Neurobrucellosis cccurs in 4% £0 18 of patients wath bruce- losis, which is endemic to countries in the Mediterranean, Middle Fas, and Central America. It may present with menin itis, meningoencephaiitis,eranial neuropathies, myelopathy. radiculopathy; or strake or as 2 brain abscess. The diagnosis is made by a positive cullaze or serologic test result for brucel losis in the CSF or blood. Treatment consists of combination antimicrobial therapy (such as ceftriaxone, fampin, and doxy: ‘ycline) for atleast 6 months. Parasitic Meningit Acute primary amebie meningaencephallds caused by Naeger, Balamuthia, and Acanthamoeba species isi fatal infection that lnicaly resembles bacterial meningitis. Preshwater exposure is a key historical cle, Examination of a fesh SF sample can reveal motile trophovoltes, hut the Centers for Disease Control ‘and Presenton shold perform confirmatory testing by PCR Treatment shoud Include mitefosin: Helminth infections causing eosinophilic: meningitis inchide Angiastrongylus cantonensis, Raylisasearis procyonis. ‘Teentasoltum (neuroeysticercosts), Schisiosomaspecies schis osomiasis), and Gnathosioma, Neurceysticereesis is endemic inMexico, South Ameriea,and Asia. It most commonly presents with setzares or hydrocephalus, and CT sean of the head shows, ‘multiple cysts orcalified lesions. Noninfectious Causes MedicationssuchasNSAIDS, antibities,and intravenous immune lobalin can oceasiomally cans aseptic meningitis. Meningeal Iinovement of leukemia, lymphoma, and metasatic carcinoma cean ako present as aseptic meningtis, with the CSE cytology showsing atypical or irmmatore cells and severe hypelyeorrhnchi (10 my/dl-[0.6 mmol/L). Systemic lnpuserythematosas Behiet disease (recurrent cral and genital uleers with iidocyelts), Vogt Koyanagi ada syndireme (uwworeninggencenaits sarcoidosis can all present with asepric meningitis. Finally, chemical meningitis can be seen ater intrathecal injections, new resuugeal procedies, or spinal anesthesia, ‘+ Tubercalous meningitis classically presents as basilar ‘meningitis with crantal neuropatiies, menial status ‘changes, and the syndrome of inappropriate secretion, ofantidturesie hormene; i should be treated with antituberculous therapy for 1 year along with initial adjunctive glucocorticoids. neu Freshwater exposure is a key historical ciue in suspected cate primary amebie meningoencephalts. ‘Medications such 2s NSAIDS, antibiotics, and intrave- ‘nous immune globulin can occasionally cause aseptic meningits. Health Care-Associated Meningitis and Ventriculitis Health care associated meningitis and venteiculitis, of noo, ‘comial meningitis, canoccur after head trauma or aneurosur- gical procedure (craniotomy, lumbar puncture) or secondary to.2 device infection (for example, CSF shunt or drain, intra ‘thecal pamp, deep brain stimulatos)..Normal or abnormal CSF cell count, glucose level, and protein level do not reliably con: firm or rule out infection in these patients, Staphylococcus species and entere gram-negative becteria are the mest com: mon causes, but up (0 SO% of infections can have negative ‘aalture eaults, The use of -D-gluean and galaetomannan CSF assays may ald in the diagnosis of health care related fungal \entriculitis and meningitis. Empirie antimicrobial therapy i cautlined ia Table 2 and should be accompanied by device moval if present (Gi oc So # Staphylacoceusspecies and enteric gram-negative bacieria are the most common causes of health care associated meningitis and ventriculitis, but up to 50% of infections ean have negative cultare resus.Focal Central Nervous System Infections Brain Abscesses Brain abscesses can occur tn immunocompetent or immuno: suppressed persons and are most commonly seen in men. Predisposing conditions in immunocompetent patients can be ssc in Table 3, Brain abscesses are most commonly caused by sznacrobes, aerobic and microaerophilie streptococci, and Enterobacteriacene. Initial erupirie therapy is gnided by the kely predisposing condition and is outlined in Table 4. Aspiration of the brain absexss for culture is preferred for efinitive diagnosis: surgical or stereotactic drainage should be Condition Incidence Contguousioc ofinfectionsuchassinuitis 50% | (Frontal lobe) ard otis mecka (emporal lobe oF leerebolirn) Hematogenous sometimes th mutiple 25% abscesses odontogene resultng from vricans reprococti, endocarditis injection drug use) Cryptogenic most lively odontogeric} 19% | Neurosurcery oc nenetating head trauma 10% ntral Nervous System Infections performed if tne abscess is large (2.5 em), Antibiot therapy should be given for 4 (08 weeks with follow up emanial imag. ing to ensure resolution of the infection, Immunossppressed patients (those with HIV or AIDS, patients undergoing solid organ or bone marrow trangplemia tlon) are al risk for development of brain abscesses from sev eral oppoctuntstic mfections. See HIV/AIDS and Infeetions in Transplant Recipients for further discussion. + Drainabscesses in immunocompetent paltents are ‘treated empirically based on the likely predisposing fac tor with surgical or sereatactic drainage of abscesses greater than 2.5 em. Cranial Abscess (Cranial epidural and subdural abscesses can arise from under Iyingostcomyelitis complicating paranaeal sinusitis (Pott pully fumor) of otitis media or after neurosurgical procedures oF head trauma, Rarely they may arises a complication of bac terial meningitis. Cranial epidural abscesses are usually slow growing, presenting with subacute t chronic symptoms of headache, localized bone pain, and focal neurologie sign. In contrast, subdural empyema isa mpidly progressive infection Predisposing Condition Usual Causative Agents Empiric Antimierobial Therapy Ottis media ar mastoicits Streptococci (aerobic ar anaerobic), Metronidazole plus third-generation | Bucteroidesspecies, Pevotells species, cephalosporin’ i} Enterobacteriacsae’ Sinaetie Streptococs Bactersides species, Metronidazole pls «third-generation Enterobarteriscene, Saphylococeus aureus, cephalespora> Mhaemephiles species Dental sepsis Mixed Fusobacterium, Prevotlla and Bacteroides species; streptococci S.oureus stieprococe, Enterebacteraceae, Coowridiom species Ponevating trsume or aker newosurgery Lung abscess, empyema, bronchi Nocarcia spaces Endocerdis Hematogenousspread frem pelvic. ita abdominal ox gynecolaci infections Inmunecompromises patents, Hiv.infected patients acter Species Fuscbacterium, Actinomyces, Racteroides, ‘and Prevotolla spaces: steptococd: S.aureus, sueprococel Enteric gramnegativebactoria, anaerobic Listeria species, tungal organisms (Cryptococausneotormansy.o parasiicor os protozoal organisms (oxoplasmn gor Asporgilus, Cocodloides, anc Nocarcia Ponicilin plus metronidazole | | Vancorryen us a third-generation ephalesporn Pesiclin rue matronidazsle placa sulfonamide! | Vancomycin plus gentamicin Metronidasole plus third-genérstion cephalosporins Metronidazole plus thite-guneration halosporin’***; antifungal or amtiparastc agent “etme tain cued by reins Sap yaa Vue ceasidne or calepie finicton case by Prudomants runes asc Maropotem an supa aneamyen ea aa barons a wtitaphyacees lacmoxciinCentral Nervous System Infections ‘with high mortality that represents'a neurosurgical emergency. ‘The CSF formula in both parsmeningeal infections shows newt tophilie pleaeytoss and a very high protein level, frequently ‘with negative Gram stain and culture results. Pathogen ident Fieation is best achieved by ealtare of theahscess obtained dir ing sangjealceainage. © Incranialepidural and suhelural abscess, pathogen -entifization fs best achieved ky culture of the abscess objained during surgical drainage. Spinal Epidural Abscess Spinal epidural abscess most commonly results from hemratoa ‘enous dissemination, with S. aureus accounting for approxi mately 50% of infections; streplocaceus and gram-negative bacillisuchas Escherichia coliarealsoimplicated, Predisposing factors fur bacteremia include endocarditis, injection drug use, Jong: term) intravenous catheters (hemodialysis catheters, cen ‘al Hines), and urinary tract infection. Spinal epidural abscess ‘ean abo occur after neurosutgieal procedures (spinal fasion, ‘epidural catheter placement) or paraspinal mjection. Patients usually develop localized pain atthe site of infection that later radiates down the spine. MEI i theimaging modality of chotce to identify location and extent of the abscess. All patients Should undergo 4 haseline laboratory evaluation, including, ‘exythrocyte sedimentation rate and C reactive protein. Blood caltures should be obtained before starting. antibiotics. ‘Although the duration of antibiotic therapy lacks robust sup ‘porting data and must be determined on a case-by case bess atleast 6 weeks of efective antimicrobial terapy is reasonebie, Surgical drainage i indicated in patients with neurologic sympioms or signs (ower extremity weakness, numbness, bladder and bowel dysfunction), Follow-up MRI is not ma cated unless the patient has persistent elevation of inflamma tory markers, lack of clinical response, or new neurologic symptoms or signs. Tubercalosis (Port disease) and brucelioxs should be considered in patients with negative culture results and appropriate travel history and risk factors. EL ‘= MRI is the imaging modality of choice t identify Ioca. tion and extent of a spinal epidural abseess, and blood Ccaltures should be obtained before staring amibiotic therapy. Encephalitis Encephalitis is Inflammation of the brain parenchyma Possible encephalitis is defined by the presence of one major {ateted consciousness formore than 24 hoats) and bw minor (fever, new onset seize, new onset focal neanslogic fil Ings, CSE pleocylosis, and abnormal MR orelectrocucephal raphie findings! cetera fom the Intemational Fncephalitis Consortium, probable or confined encephalts teqires one 6 major and at least three minor erliela, The causative agent is ‘unknown in 37% t070% of infections, depending on whether ‘viral PCR is used and autoimmune causesare investigated. The ‘most common Known causes are viral (hexpes simplex virus Iypes | and 6, varicella-zoster virus, and West Nile virus) and autoimmune diseases. Viral Encephalitis Herpes Simplex Encephalitis, HSV-1 is the most common cause of sporadic encephalitis in the United States. requiring prompt identification and treat ment with intravenous acyelovie. Factors associated with an adverse outcome include older age, abnormal Glasgow coma scale. and delay in starting antiviral therapy. HSY-1 encephalt lis presents with fever, seizures, altered mental status. and focal neurologe derieas with unilateral temporal lobe edema, hemorrhage, or enhancement on imaging, Bilateral temporal lobe findings in the insula or cingulate are less commonly seen. The CSF formula usually shows lymphocytic pleoeytoss, anclevated protein level, anda normal glucose level. The diag, nosis is confirmed by HSV PCR of the CSE (08% sensitivity 94% specificity). However, false-negative results have been reportedif HSV is suspected. a repent PCR should he obtained within 1 week while continuing acyelovie therapy. Therapy uration for HSV encephalitis should be M4 10 21 days. lectrocnceohalography can be helpful in identifying the Joral dysfunction and specific area of the brain involved and in deieeting subclinical seizure activity. Human herpesvirus 6 can cause severe encephalitis in transplant reefpients, Cytomegalovirus can cause encephalitis, with perwentricular enhancement on imaging in immano suppressed patients (hose with AIDS or ater transplantation) Dingnesis isby PCR of the CSE for eytomegalovinas. and treat ‘ment is parenteral ganciclovi, Cytomegalovirus and Epstein Barr virus can cause meningoencephalits in young. immuno ‘competent patients presenting with infectious menonucleasis syndromes, agree of ce Varicella-Zoster Virus Encephalitis, Vorieella zoster virus (VZV) is a commonly umderdiagnnsed. treatable cause of encephalitis in adulis. VZV ean present with vvasculopathy with a stroke, encephalitis, meningitis, raticw lopathy, or nyelitis, Patients can present without a vesicular ish, 9 a PCR of the CSF of a serum-to-CSF anti VZV IgG ‘shemle be ordered in all patients with encephalitis. Ireatment ‘with intravenous acyclovir for 10 to 1¢ days is recommended, Arboviruses Arboviral CNS infections in the United States are most com ‘monly seen in summer or fall and! include West Nile (WNV), Easier and Western equine encephalitis, St Louis encepha tis, Powsassan. and La Crosse viruses. WNV is the most com ‘ion cause of epidemic viral encephalitis in the United States. WAY can cause meningtis, encephalitis, acute accid paraly sis (Similar (© polionivelitis), neuropathy, and retinopathy.Older patients. andl those who have undergone trarsplantation rare immunosuppressed have a higher risk of death. WNV affects the thalamus and the basal gunglia patients present ‘with facial or atm tremors, parkinsonism, and myoclonts, Hypadense lesions orenhancements may be seen in the thal ims, basil ganglia, and midbrain on MRI of the brain. Diagnosis is confirmed by a positive WNY feM tn the CSF or Serum: treatment is suppoctive. IV encephalitsis the ease oF HIV-associated dementia in later stagss of the untreated illness; IL Gun abo present as CUS encephalitis, consisting of perivascular inflammation resulting frum infiltration of CDs” lymphocytes, which may oceur as part of an immune reconstituiion syndrome, in some easesassociated with viral escape (low levels of detectable HIV RNA in CSP). ED ‘+ Herpes simplex virus 11s the most common ease of sporadic encephalitis in the United States, presenting ‘with fever, seizures, altered mental status, and focal neurologe defieits; prompt dentitication and treatment ‘with intravenous acyclovir improves outcomes. Varicella zoster virus (V2¥) isa treatable form ot encephalitis and may present without vesicular rash, so polymerase chain reaction of the cerebrospinal Maid (CSP) ora serum. to CSF antt-VZ¥ igG should be ‘ondered in all patients with encephalitis. West Nile virus isthe most commun eause of epidemic Viral encephalitis in the United Slates Autoimmune Encephalitis Auioimmune neurologic diseuses can manifestas encephalitis, ‘cerebelils, dystonta, status epilepticus, cranial neuropathies, and myoclonus. Anti N-methyl D aspartate recepiorenceph slits is most common; i was intially described a8. paminee plastic syndrome:afecting young women with ovarian terato ‘mas, but it can be associated with other tumors (sex com seromal (umors, small cell hung cancer) or occur without a ‘tumor. Young women (<35 years) often present after viral Hike lulness with behavioral changes, headaches, and fever followed by altered mental status, scares, abnormal movements, and autonomic Instabiliy. Treaument includes intravenows gluco comticoids, intravenous immune globulin, tumor removal (if present), and, in some cases, plasmapheresis and ritaximeb. Prion Diseases of the Central Nervous System Prions cause rare but refentlessly progressive and rapidly fatal neurodegeneralive disezses characterized by dementia and ataxia. The cause of diseases an abnormally folded prion pro {cin, In humans, prion diseases ovcur by three mechanisins sporadic (spontaneous), familial (genetic), and acquired Prion Diseases of the Central Nervous System (infectious or ransmissbe). In patients of any age presenting ‘with otherwise unexplained mpidly progressive dementia and ataxia, diagnosis ofa prion dissase should be considered (TableS): the infectious forms aze now Tare (Table 6), Prion diseases have no known therapy Sporadic Creutzfeldt-Jakob Disease Spontaneous (sporadic) disease & the most common form of Creutzeldt Jakob disease (CID), with an incidence of per Inillion worldwide. No environmental risk factors are known, Clinical manifestations include rapidly prupressive dementia, Usually ower 4106 months, Ataxia, myoclonus, and pyramidal and extrapyramidal signs may be observed. Loss of vision is, not uncommon, and patients become comatose before dying, | Rapid cogeitive decline Two ofthe following signs or symptoms: Myoclorus Pyromidalextrapyramical dysanction Visualessfunction Cerebellar dysfunction Akinesie vin Focal coal grt example neglect aphasaaclula, | Sal | Typical EEG sndfor MR Otherinvestications should not suegestanalternative diagnosis European MRI-CJD Consortium Criteria (20097 Progressive dermentla | One of the folowing signs or symptoms: | Myoclonas | FyramiclVextrapyramidal symptoms Akinetic matiem AND Either ‘Wool EEG Hlevated CSF protein 14.3: (with total diseave duration: yeas) oR | Typical rl Foutine investigations should nat sugges an atomainve hagnesis [0 Geuatac ine dna Foch Ri Visualicerebeliar csfunction |Skin and Soft Tissue Infections eee Disease Classification Acquired Idiopathiconly {not ‘enaronnnenta) Sporadi fatal frill ncomoia | Sporadic oD | seopabidtamminstle Yaiet Drom | Kru innerted Fail CD | oss | owen “The diagnosis can be made by clinical history and MRI; cer ebrospinal fluid analysis positive for either total Taa or 14.33 protein may also be useful Transmissible Prion Diseases Variant CD (CID) is the human form of bovine spongiform encephalopathy. It generally affects younger persons (age 15-50 years), frequently presenting with rapidly progressive neuropsychiatric manifestations (depression, withdrawal) and peripheral neuropathy, followed by cerebellar ataxia, invotun tary movements, and cognitive deciine over a 22 month, period, Beecause ¥CID can be transmitted throug blood prod. ucts and tissue, iis a serious public health concern world ‘wide, Probable yCID is diagnosed by typical MRI findings (hockey stick sign” in the posterior thalamus) and tonsil biopyy to detect scrapie assoctated prion protein tn a patent witha compatible clinical presentation (ce Table 5). latrogente CID is exccedingly mre, but transmission has been documented with contaminated cadaverte prtultary- derived hnman growth hormone and gonadotropin, dura mater, stereotactic electroencephalogeaphy needles, neurosur- sical instraments, corneal transplants, medical instruments, implanted electroencephalography electrodes, and blood, transfusions Familial Prion Disease ‘Many mtations have been associated with the prion pro gene. Allare autosomally dominant. These inclade the gradu ally proxsessive Gerstmann Striussler Scheinker syndrome andl the rapidly progressive fatal familial insemna a a + Prion disease should he inchaded in the differential diag ‘nosis ofa patient of any age presenting with otherwise unexplained rapidly progressive dementia and ataxia. + Spontancous CreatzfekdL-Jakob disease is the most com. ‘mon form of prion disease and has no known risk RIOT. Skin and Soft Tissue Infections Introduction ‘Skin infections usually result from epidermal compromise that allows skin colonizerssuch as Staphylococcus aureus and Stieprococeus pyogenes to become pathogenic. Predisposing, conditions include vascalar disease, Immunodeficiency, net ropathy, previous cellulitis, obesity, skin trauma, tinea pedis, and lymphedema, Infectionscan be characterized by anatomic, involvement and presence or absence of pus. Nonparulent spreading skin infections include erysipelas, ceulitis, and necrotizing sol isee infection; purulent skin infections refer to absceses (Figure 2), furuncles, and carbuncles. Paralent skin infections are generally caused by staphytococd. inctud- ing. methicillin resistant Staphylococcus aureus (MRSX): rnonpuruient skin infections ate usually caused by 8 hemolytic streptococci. Table 7 inclucles other skin Fathogens and their ‘associated risk factors for less common causes of skin infec tion, Complications of infections include systemic infamma, tory response (as in severe cellulitis) or systemic toxin release {as in tose shoek syndome) Erysipelas and Cellulitis Hiysipelay refers to infeetion of the epidermis, upper dermis, and superficial lymphatics. Usually involving the face or lower ‘extremities, this infection is brighily erythematous with dis tinct elevated borders and associated fever, ymphangitis, and regional Iymphaclenopathy see MKSAP 18 Dermatology). Callatitis refers to infection involving the deeper dermis and subcutaneous fat tissue, Inflammatory’ signs of infection are similar to erysipelas, ut the area of involvement ts less weil, demarcated Although thediagnosis of erysipelas ur cellulitis is usally established clinically, appreximately one Unird of patients are FIGURE 2. Acutancous atscss draining purser ae ssw; its ‘used by malin isan Spiyecocus owes bate. a Mineeremonas hydrophila Vinnie wlnifcus, Vibrio. porshaemoltics Ensipelothricdhusiopathiae Contact mith rechanter ake, roam rivore (including brackish water ‘Contact with leeches ‘Contact with alt waterorbractish water ‘Contac: with drippings from raw zesfood Consumption of undercooked shellish (panicdany oysters) Liver cithosis or chronic Iver disease ‘Contac: with saltwater inarine We(can also Infect frestmoter Fah) Posteurelle mubocida Contac: pilmatly wit eats and ogs Ceprocvtophaga canimosses Contact primarily with doge Bacitusardtvac ‘Contact with infected animals or animal ‘products. May be the esut of bicterorism Francisllatulawnsis Contact withorbite om nfected animal (partculary cateachropod bites (pariculaly tees) ‘Burkhoera mall: Contact with tissues or boul fuids of infected mules orhorses Cloetichom perkingens Surgary or other significant rourna Mycobacterium marinum Contactwith fresh water orsalkwiter, inelacing fish tanks and swimming pools Mycobacteriam fortum Expenure to freshwater footbatha/pedicuresat nal zalena partcdatly alter ar shoving: sugery ‘Skin and Soft Tissue Infections ‘Comment Callas nonspecific clnicalapppeerance: ‘miner tourna to skin usuelly lead to Inoculation ‘oforganiem Callus through dee: noculatoninw skin | ligation leads to bacteremia with secandary sk infection Hallmarkshemorhage buloeimaeaot | cellulitis lesion) CCelluits usualy involves the hand or arm, especially nthose Handling fish, shellish of ‘ctasienaly,poutryor meat contaminated with becterum Causes eryineloid dicease ellis occurs as aresut of eat scratch or bite Callie ancicepse ae present, patculerlyin patente with hypospllentan Evemnaious pruritic lesion with central eschor: spore-forming organism Ulzoroglandler syndrome choracteiced by Ulcerative lesion with centraleschar and localzed sander hymohadenyaathy, constitutional symptoms often present Pustules with suppurative localzed lymph nodes or eeratve rule tite o NNecrotiing infection, oten teferredtoas clestial myonecrosisor ges gangrene Lesion is often tauma zssociated and often involes the upper exterrity papular lesions become uicerative at ste af nocuation: ascendna lymphaticspread can be seen (spototicheid! appearance): systemic toxicity usualy absent | Fuuncls: posopentve woundineaien | ‘misdiagnosed. Clinical mimics include contac! or stasis der rratitis, Iymphecema, erythema nodosum, deep ven fyombosis, thmombophlebiuis, lipadermatoscierosis, eryth romelalgia, rauma-related inflammation, and hypersensitiv MKSAP 18 Dermatology). Blood culture results are positive in approximately 5% of patients with ery sipelas and cellulitis and are not routinely indicated: however: ccultures should be performed for those who ereimmunocom ‘or have unususl previpiating, Ciecunistances, including Immersion injury or animal bites Culture of skin tissue aspirate or biopsy should also he consid cred for these patients. Radiograph maging snot helpnl foe the diagnosis of erysipelas or cellulitis but may be helpful when a deeper necrotizing infection is suspected, For immunocompetent patients with cellulitis orerysip elas who have no systemicsigns or symptoms (mild infection), ity renetions (se promised, exhibit sever: ses empiric onl therapy directed against streplacocet is recom rmencled as outlined in Table & (see MKSAP 18 Dermatoigy. Treatment duration for uncemplicated infection can be as short as days but should be extended as necessiry until the infection improves. In patien 5 with systemic signs (moderate {infection), ineravencus treatment is recoramencded (see Fable 8). Treating predisposing factors (aich as tinea pedis. edema, and primary skin disorders) may decrease the risk for recur rent infection. Propaylactie anubinties such as penicilin or erythromyein can be considered In patients with more than three episodes of celllitis anmaally Patients who are immupocompromised, who have ss temic inflammatory response syndrome and hypotension, oF who have evidence of deeper necrotizing infection such as bullae and desyuamation (severe infection) should receive urgent uation for debridement. Initial ermpirie al € 9‘Skin and Soft Tissue Infections In Sn Treatment Enipolasorcelllitis Mic: Ox peniclin, amoxclie, caphalesn, diclexacilin,cincamycin Moderate: Intravenous penicilin ceftriaxone, cefazolin, lindemcin Severe: Surgical azzeszmentfor possible necrotizing component and empiric inravenous vancomycin pls Piperscilin-tazobactem, injrencin,cr merspenem Necrotizing fasitis Plymic-obial infection: Surgical sscessment/dexidement and combination theeapy such as vancomycin plus piperaollintazeboctam 0: migenem er meropenem Supeococcus pyogenes or Cesium perkingens: Surgical assessmertidebridementand pencilin plas | 389 °C (120°) Syitelicblood praceura <90 mm Hg Difuse maculaecash with subsequerk desquamatr, espacial ise cant Involvomontofthroe or more of the following organ syst Gestrontestinal (nates, vor, ciarhoa) Musculor severe myalgia or ivefoldor greeter increase sehurn Gens rua level. Mucous membrane hyperemia ofthe vagina, conjuncivae, | | orphan) | Kidney (blood wea rivogen orserum creatine evelat | leastiwicethe upper imiof narmal) | Livor(biieubin, aspaate aminotransferase, or alanine aminotraniferace concentration twice the upper init of normal Blood (plarelat count <1 00,0001 [100107 | Central nervous ystern(ciserientation without foal paula tare) Negative results on serolagietestng fer RockyMountain =| spotied fever lepiosoioss, and meas; negative cerebrospinal fg cultures lororganisms other tan Staphylococcus aureus sho deh Pa chloe 508 eros vies | Definite case | tocleion of GABHS frome tere site (bloud,cerebroypnel Mid, operative wound) | | Probable case Isolation of GABHS fom a nonsterile ste(Jhrout, vagina skin lesion) | Hypotension (stoic prossure-<#0 mm Ha) “The presence cf 22 of the following findings: Kidnay{acata kidney irjury ile) Liver (elevated aminotransferase concentrations) Shin erythematous mactacrash, soft issue necrosis) Blood (coagulopathy, incucing thrombecyopeniaard disseminated intravascular cougulation) Pulmonary (ocite respiratory cstess syndeome) 13Community-Acquired Pneumonia [Ee 2a atte an injcton drag se Streptococcal 1855 associaied with skin an soft ussue infection, particularly NE Bacteremia anil mortality rales are higher with streptococcal than staphylococesl surgical debridement. Antibioties for streptococcal ISS consist of penicilin plusclincamyein, the atter added to eradicate the Aigh inoculum of bacteria present and to suppress toxin pro duction. IF methieilin- susceptible aureus isthe cause, na cillin and clindamycin are recommended: for MRSA. vancomycin plus clindamycin or linezolid monotherapy is preferred. More studies are needed fo establish the exact role of intravenous immune giobalin in this setting. and i is not recommended in the most revent guidelines by the Infectious, Diseases Society of Amertca. ‘+ Source control fortoxie shack syndrome typically requires surgical debridement Streptococcal texie shock syndrame is treatel with penicilin and clindamycin, Infection with methicillin-suscepéible Staphylecoceus ‘aureus is treated with nafeillin and clindamyeins line- zolid monotherapy or vancornyein plus clindamycin is, preferred forinfection with methicillin resistant S.qureus. TSS. Source control typically requires Community-Acquired Pneumonia 1 Epidemiology Communiy acquired peuronia (CAP) is aKaling cane of Infection and hoyptalzaton tn the United States, asoclated ‘wih more than $10 alin array n helt ere expend tans. The spectram of lies due to CAP ranges from lasses, ts aporolmacly 0% of patie cman in th amtulaory sutra iretons, katesornosptaiation Increase with advanced az: the incidence of hospitalization farCAParnongadults 80 years or clderis 25 times higher thn inadats younger han 0 yar, The definition of CAP has recently expanded 10 inclade sora ati prv our angiciacs tag eat cae ssacited paceronta (HAP) Ti chang ws tae Deane the mlcrobiclogy and iretment of patients wath CAP long ere alts GF who Were tepid ta te eee Frith eet aiersabaan nay from var oCeomarniy well patients with sniar comorbidities Praca elim enor ilibote aed implica none, eaing W « aces theuse of unnecessarily brad antibites, ierentaing CAP iin tre cept -scquied ppeamond BIA retin os cally canta fae Health Ghe-Aavoclate nfretions fo HAP dseusiom P classification simplifies treatment and hes 14 Microbiology CAP fs usually caused by infection with a viral or bacterial pathogen: fungal or mycobacterial infections occur much less frequenth The probabilty of infection witha speetic oganism ‘aries hase! on age, comorbldtes, seasonality, and geagraphy. Epldemtologicisk actors or conditions associated with speciic pathogens sre Fisted in Table 1. Hecause causative organisms have variable virulence, severity of tines, whicl influences site ofeare, is use to guide empiric antibatie therapy (Table 12). Streptococeus pneumoniae, previously considered the leading cause of CAP, aecounts for only 8% to s%OF Hospital ied cases in recent stcies. Ths decreas in incidence a east partially results from the siecess of vaccination strates Comerses ratesof CAP causcelby Siaphyloccccts aueeusand Enlerobacteriacene are rising, even among patients without identifiable health care exposure. The CDC EPIC trial a recent rmallicenter study that performed prospective microbiotogte snc! molecular testing on patients hospitalized with CAR more frequently ident bacterial pathogen in CAP infections requiting hosplalzation (Pgure 4), 5. pneumoniae was the most common bacteriat use. although rhinovirus (%) and influence vines (6) were higher in incidence. The significance of vizal detection i CAP is unclear; an antecedent mild respiratory viral infection may increase the risk fora secondary bacterial jfeetion. This phe nomenon is well documented for postinflucnza CAP caused by S. aureus, S. pneumoniae, ant Streptococcus pyogenes: Despite extensive laboratory investigation, no aasatieeorgan ism was identified in 62% of patients in the CDC EPIC tr Atypical pneumonia refers to CAP caused by organisms not cuhivatsble on standart bacterial media, ielding vinases and fastidious bacterizsuch as Legfonellaspecies, Mycoplasina 114 Sngle or multiple viruses rather than a Legion pocurophia Stptylacenee Pree re erahucrsone Mycoplasma me foro! — mycobacteda Srepacoccis oe — = Vins ls bacteria Es FIGURE 4. The that oops ocertages ot gathogensdeecedamong spitaae patents ith conmunty cquiedgrearona inthe COCEPE Sud se mt pipsCommunity-Acqui sk Factor Heswyaicchol use corp Structural ling dicoaco fhronchisessie, ‘Common Pathogens Sreptococeus pneumoniae, oralflars(arpiraion) Klebsial preumanize Haemophilus nfuuenzae, S, preamorise, Moraxall catarrhals, Legionella preumophils, Peeudomoras aeruginosa P asraginosa, Burthaiclericepocis, Stonotoshomonas maltophila, Staphylococcus aureus Spticfbreie| Aspiction (scizures, neurclogie ‘mparmer, loss of conseiourness) Age 65 years Postural ness Ramat oxposwe ra anaorches, Ecorobacreinceoe Influoras.inus,S proviroriae, thinovirus S aureus, Sreptoceceus pyogenes, S.proumoniae Bids Chorcophit sta Hcoplra canal, Cooticoeusreomas ose sea ero ones oe Peterlee ire snetrdomesicned hot bine uch specs Soo = SS Rodent droppings Hantavirus | — Facet sine | Heb exoare Lagi poms est yc ast parts —— Fe red tes Fisopleae caputum Boson: demas Sune eee Gosidies a Se ee id ot wes Pe clapmiaivgmetiones — Wiretarna paiRiouawes tiachin Seer) ‘pneumoniae, and Chlamydophila pneumoniae. Respiratory irae account for ncarly al ial pneumonia infections, but Jess common pathogens inclice varicella-zoster virus or Hantavirus Legionelia pneumophila isa roengized cause of AP requiring hosptlalizaon or CU admission, Legjonetosis ‘associated with waler exposure, inluding hot tubs and air ecncitioning units: however. infection may oceur without an @bvious source. A bivory of travel has been reported in spproximately 10% of Lgionela cases eporie tothe CDC CAP cause by araerobic bacteria uncommon, & primar 2 seen with sspaten, and i caused by microserophic oo pharyngeal ora. Rsk factors for aspiration pneumonia inchade Secreased consciousness (aeahol or iid! substance use, se sere, soke), poor dentition gastmcsophageareix, an so sang, Zoonotic cases of CAP include Coxiella bumeté and Fancivella rularensis Mycobacterial or fungal causes of CAP sould be considered tn patients with framuocompromising ‘editions, epidemiologic risk facors for infection (such as ecarcerajion, certain hobises oF occupations, and pertinent seenal or foreign tre, or aabacute presertationsanin thre ‘eno do no respond to conventional antibactena treatment. EI «© The definition of community-acgaited paeamonia (CAP) has recently expanded to inchide some patients previously categorized as having health care associaled pneumonia beans: the microbiology and treatment of patients with CAP in Jong-term care Bellies or who ‘were hospitalized in the preceding 3 months do not dif fer substantially from that of community dwelling patients with similar comorbidities, ‘+ Streptococcus pneumoniae sccunts for onky 5% tb 15% ofcommunity acquired pneumonia (CAP) infections requiring hospitalization, whereas rates of CAP caused. by Staphylocaceus aureusand Enterobacteriaceae are rising, even among patients without identifiable health care exposure. ‘+ The significance of viral detection in community acquired pneumonia is unclear; bowever, an antecedent mild respiratory viral infection may increase the risk for a secondary bacterial infection. 15Healthy patientwthout antbictic. inpreceding3 months Stoptoceccus prewmoniae Mycoplasma oR Chlornycophile Macrlide Doxyeycine Respiratory viruses Healthy patient from region with | 225% nacolde resciance anong 5. pneumoniae Comorbicities' or antbioticuse in Seme as above Same at inpations,nor.iCU Respiratery quinolene oR Batam plusa macrolide Racpirstory quinolone Blactom plus a macrolide | eal a | ‘Oralanaerodes enema se eateries my Sey eae & Paar lf penicillin allergic, a respiratory ee Magee decrees oe | Any Risk factorfor CA-MRSA (see text) Standard therapy PLUS | CAMRSA conmanin ocainedmebici-estnStnhyomcus aves | tpn wit wcrsin Foe Maral A ed 5, rent Bae J, Carp GD, Dean NC. Deel St vancomycin oR linesotal iM J Miser M Nader MS ores, [1] Diagnostic Evaluation CAP should be suspected and chest imaging performed in any fall presente gail er amouled rah ugh, een OF chest pin, Symptons may be sublle or absent In older ats or murstpnresed patina. ana ica shou feather freed for purrs mdicgaphie worn these populations Foseroanteror and late chest raiogra phy isrecommended, In adiition to confirming the diagnosis, tepagc patarca’ may jrowtle dhaaea pase 16 pathogens (fable 13) and guide clinteal decisions regarding, appropriate ste of eare. When plain radiographs are normal bbut suspicion for CAP remains high, chest radiography may be repeated after 24 hours: for patents at high risk (febrile neu. ropenia, risk for anthna, or acute respinatory distress sym drome requiring Inervention) wich normal ridiographs, chest CT should be pursued. Routine laboratory studies are indicated to ascertain the severity of infection, determine the optanal sie of eare, and, ensure appropriate antimicrobial dosing, HIV testing, shouldyt ea aetna Rightlowerlobe Oral anacrobes (spiration) | pneumonia Lingabstess/ Oralanacrabes Staphylococcus aureus, cesiaylesion _Klebsiellapneumoniae, Nocardia ‘Aatinomyces, Phodocccws, ‘ycobactera, encemic fungi ieentital ‘Avypical pathogens(Leaionella, sefitate Mycoplasma, Chlamycophiia) viruses | Flewalefusorw — Otalanserobes anginosus-constelats enpyems (g}uP seeprococd)§ aureus S-preumonive be performed if indicated: 4 positive result expands the spec ‘ram of potentially causative organisms, Procalciionin lee, iF ‘sealable as 2 point of care test, is insufficiently sensitive or specific to independently diagnosis CAP or a microbiologic cause but may support s diagnosis along with other clinical “Snddings Mapid testing for mfluenza virus may assist in ident Sing patients who woukl benefit from oseltamivir and who sequire droplet precautions at hospital admission, but a past five fest result does not exclude 2 concomitant bacterial pathogen. Diagnostiestudiesto identify a causative onpinism are not ‘outinely indicated in outpatients with CAP but should be considered in non ICU hespitalized patients when this informa Son would change therapy crallow treatment de escalation. All patients with CAP who require admission 10 the ICU should fendergo diagnostic evaluation In an attempt to confirm a seicrobial cause. Interpretation of sputum Gram stain and ccoure is hampered by the pesenve of oropharyngeal eolont zation, ani growth may reflect nonpathogenic organisms, & eed quality sputum culture obiained before antibiotie initia, ‘jon fs suggestive or dlagnostie i up 10 80% af eases of pret. -mococeal pneumonia sensitivity decreases afer antibiotic herapy. Sputum Gram stain and culture are appropriate for patients admitied to the ICL, patients who did noc respond 19 patient antibiotic therapy, patients with cavitary Tang Scions, and patients with underlying stractural lung disease. Jn these cases, consideration for mycobacterial or fungal eases may be newessary, flood enlture results are positive in 20% to 25% ofpatients Jeth pneumococeal pneumonia; ever culture resultsare pos ithe in patients with oher bacterial causes. Pneumocoxcal frinary antigen testing is more than 70% sensitive, and results are nol affected by artibioticauminisiration, Legionetea uri rary antigen test results are positive In most patients with L pneumophila serotype | infection. However, the test does 10; tee! other strains: and resulls can remain positive for prolonged periods after infection, Rapid antigen testing fer Community-Acquired Pneumonia influcrza virus on nasal swabs offers the adeantage of point ff care diagnosis but 'S less sensitive tan polymerase Chala reaction based techniques. Respiratory viral panel results using niicleie acid amplification are positive in up to patients hospitalized with GAP: however, a positive result may reflec viral coinfection or antecedent predisposing infection rather than current clinical liness. Although these panelsare Jess helpful in guiding, ‘bie Uhetaps a positive respiratory viral panel might have sig nificant infection control implications among patients admit led othe hospital Additional testing Is indicated only in setect patients ‘asedlon epidemiologic risk factors (see Table 1), clinical find Ings, or radiographic patterns (sce"Teble 13). Fungal an acl fas hucilli stains of sputum or fungal antigen testing can be performed. Serology for Coxiella burnett, Francisella tular of cisions about discontinuing antibi ensis, Legionella, Mycoplasma, anid. Chlamggtophila, wsing acute and convalescent sera, ean document seroconversion or 2 far inerease ia titers Patients with pleural effusions of unknown cause o those thicker than 1 cm should undergo thoracentesis to exclude concomitant empyema requiring drainage (ee MKSAP 18 Pulmonary and Critical Care Medicine) Bronchoscopy with transbronchial biopsy should be consid ered in patients with an unrevealing noninvasive evaluation who do not respond te empiric dherapy. ED SORA + Diagnostic studies to identify a eusative organism are HVC ‘not roatinely indicated in outpatients with community acquired pneumonia (CAP) but should be considered in ‘non ICU hospitalized patients when this information ‘would change management; diagnostic studies should bee performed in ail patients admitted to the CU with car ‘For patients with pneumococcal pneumonta, a good ‘quality sputum culture obtained before antibiotic initia tion is suggestive or diagnostic in up to 80% of cases; blood culture results are positive in 20% to 25% of cases; pneumococcal urinary antigen testing is more than 70% sensitive, and results are not affected by antibiotic administration. ‘= Legionella urinary antigen test results are posit ‘most patients with £. pneumophila serotype 1 infection, butit doesnot detect other strains, and results can remain positive for prolonged periods after infection. Management Site of Care oO Ambulatory management is adequate for many patients with CAP. Multiple clinical prediction models are available to tden- tify patients who would most benefit from hospital or ICL admission (Table 14), bat complexity and lack of consensus limit their use. Although prediction rules may ald in 7PsP >S0yeers | Comortidties Malignancy Congestive heartfaiure | Carebrovasculardizease Kidrey disease iva caso Heartrate2!25/min Respiration rato 230/erin Temperature <35°C (99 For BAO NC(I04°F} 5090 men Hg Vital signs Physical examination Atered mentation | acme tae Radiographic findings site of care decisions, scores should not supersede clinical judgment “The Pneumonia Severity Index (PSD) isa validated predic tor of all cause mortality at 50 days. The initial assescment determines the presence of 1 variables assoctated with adverse ‘outcomes (ee Table 14) Patients with mo risk factors (severity isk class J can Iypieally be managed as outpatients, Those ‘with at least one risk factor are strattied using. second scor ing system into a risk classification between IT and V based on ‘4 more complex point system that includes residence in ruursiig home, abnormal Iahoratory test resulis, anid radio graphic findings. ‘Tae CURB 65 (Conti Jood Urea nitrogen [EUNI, spiratory rate, ilood pressure, and age 265 years) score Is asimplified, albeit slightly less predictive, tool for identity ing patients at low risk. Thirty day mortality among palients with 2 CURB 65 score of © oF 1 was Tess than 3%, 8 ambulatory treatment is appropriate for most patients ‘with scores les than 2. The modified CRB 65 omits BUN measurement and supports ambulatory elinteal assess ment: patients with aseore of Lor more warrant considera tion for hospitalization 18 Respiration rate 10min ‘SEP <90 mm Hy or DBP dmmbg, Confusion BUN=20 mg/el (7.1 nmol) 1331p Sowey trotoaonam peren;potents signed cent ye mona en cttw at IDSAJATS Criteria: Rospiatin rate>30/min | Temperature <6 C96.8°F) Hypotension requiring aggressive fluid wesveetation Cenfusionor disorientation BUNS20 mg/dL (27.1 mmol) Levkogrecoure 286 | 4. Other manifestations inetcing {facial paleyonal wostmont he samo for oul localized cizoase 1428-4 | Latedisseminated 26m0 Recurertlerge int Tworterserologictesting Intl rheummatologic treatment: same athrits: neurologic asforenlylocaiaed but 30 prem oaetes! Recurentanhats akerintil pewopathy treatment W cafiiaxone excepnalopathyt or ermatolociesyrptoms Neurologic isase: Mcefriaxonex 28d GGerodermatits donee rophicans) "A it BD ce dy, 9 rb > eral remo pen EM ears mara nes FO=y eh = oor wes da FIGURE 6. Eythems rigans leon ast otek aden sssociated with multiple concurrent PM lesions at sites distant rom the original tick attachment. Infection of cardiac tissue results in Injury to the con. dvetion system and atrioventricular (AV) nodal block. Progression to complete heart Hock cant oceur rapidly despite antibiotic ieatment, so hespitalization is dicated for close monitoring of patients with severe cardiac involve iments symptomatic patients with dizziness, eyncope, or dyspnea asymplomatic patients with first-degree AY block, 22 and a PR interval of 300 milliseconds or greater: and Patients with a higher degree AV block. Permanent pace ‘maker placement is not necessary because the heatt block, is reversible Infection of neurologie tissue occurs in approximately Ly of untreated pattenis. Aseptic meningitis, facial palsy (unilateral or bilateral), and radiculopathy may be present in caloskeletal. or eardiae findings. Lumbar puncture is indicated when cesitral ne-wous system infection (such as neurnborreliosis) is suspected cere bbrospinal faid lymphocyte pleoeyiosis supporis the diagnosis (see Central Nervous System Infection). ‘When EM leslonsare present, laboratory confirmation is unnecessary: In the absence of diagnostic skin findings. serologie diagnosis should be parsued through a two tiered. approach (Figure 7); the initial enzyme-linked immuno: sorbent assay (ELISA) is highly sensitive bat lacks specific ity and mus! be confirmed by a Wester blot test. The C ELISA test detects antibody against a highly conserved bacterial epitope and may be more sensitive than tradi onal whole cell sonicate ELISA, especially lor the inolation o associated with shin, tousTick-Borne Diseases Pouible Lyme dneove — t (Wistar of ek ees Consular ahomotve dings Snendomicares?” |,” | ewluntionicnegat andcinealeurpicion ‘erin, consider two testing Yes rf Nonspecife symptoms low dineal spon Enthema migrars No EM highclncl capcom | Wokethersexing Twotiored serologic testing rogues stn tapy Terone test — Elkorira I Negative 1 Poste or aquivecaresuk ‘moveto te’ two tes) q ‘Contr aerate diagnos OR ignsaympioms 290 ys, Syraptoms 330 cays ght IgG Western Got ‘Symptoms = 857196 "were act ey, No [ Frater ifen ans | Le Spropiate fr clinea ste oR |S 25/10bands postive SS 1gG:55/10 bans De ad r pottve vet evi dress FIGURE 7. Seog tosing rye dseae EU —enyre led ismurosrbotsesy EM ~ erphenamigens; IF anmuroforstentanib say Age wt pion Said Caren use pa oat gt fe re il sme OU? European strains &. garini anel B, alzelll, bul, because of ‘nsafficient specificity, confirmatory Western blot testing is sill required. IgM antibody is detectable before 1gG antibody tn ely Jnfection; however, IgG antibody should be detectablealter 39 Gays of symptoms. Because klated IgM positivity is Mkely t0 bea false positive after the first month ofsymptomns testing fr JM is not recommended after this Lime period. Antibodies may reniain for years despite reatment, therefore, serial titers are not useful Late Disseminated Disease Approximately 60% of untreated patients with Lyme disease develop a moncarticular or oligcarticular inflammatory srthriisasa late complication, The knee and other langejoints ace Uhproportionally affected, fven without antibiotte reat ‘ent, inflammation typically resolves over weeks to months 2n have a relapsing remitting patiem. In approsimatel Lo’ of untreated patients, artis persists (see MKSAP 18 Rheumatology). Late neurologic or skin findings (acroxletma lis chronica attophicans and borselial Iymphocytoma) are ‘nue in the United Siatesbut more frequent in European infee ms. Diagnosis Is made with the two tier semlogic tes. Treatment requires prolonged ora] antibioies; parenteral ther apy is used when oral therapy ts unsaecessnul(see"1able 16). Post-Lyme Disease Syndrome Post-Lyme disease syndrome has been reported in approxi mately 10% of patients after treatment of EM (Table 17) Although often erroneously called “chronic Lyme disease.” studes hve found no microbiologe evidenee of chrunte or latent infection after appropriate treatment. Symptoms, Include fatigue, arthralgia, myalgia and impairment ofmem ory or cognition that can last for years after treatment of the acute infection. Clinical tials have shown no benefit of pro longed antibiotic treatment for post Lyme disease syndrome. 23| Diagnosis ofLyme disease based on CDC case citeria EM or positive serclogictirding) Resoluton or sabilzation ofthe objactive manifestation: of Lyme danase efter andard teestment Onset of t east one ofthe following within monthsofLyme dicease diagnosis, with perdstencelor atleasté monthsater antibioictrsatment thats of suficient severity to resultin ecraazad level of functioning | 1 Fatigue 2. Widespread musculoskeletal pain 3.Cognitveimpairment | Exclusion Criteria An untiested vekchorne coinfection uch as babesiosis) | | Ongoing symptom: atrivuiable vo Lyme disease such 25 antibione-retractary Lyme arts) “Symotome of fatigue er musculoskeletal psins or a diagnos of fibromyalgis or chronic fatigue syndrome predazing te onect ‘ollyme cizeace An alternative disgnosis accounting forthe syinpterns Slate cal nse tam ie dare, ‘Minn gundose arapaneas sndbawesn cnc rer gt Evuluation for coinfection with another tick borne pathogen or for a noninfectious cause is indicated: when ao alemattve diagnosis is found, treatment issymptonrate, PS «The causative spinochete of Lyme disease may be trans- ‘mitted when an infected Ixodes scapular tick attaches, for at least 36 hours. ‘© Early localized Lyme disease usually presents within 4 weeks of infetion and is characterized by erythema ‘nigrans (EM) at tesite of ick attachment; patients ‘with EM anda compatible exposure history do not require confirmatory laboratory testing and should recehe oral antibiotic therapy, + Easy disseminated Lyme disease can alfect the cardio ‘vascular and newologle systems: the diagnosis should be confirmed through an enzyme-linked immunosor- ent assay followed hy confirmatory Western biot testing |with presumptive treatment depending on disease severity, + Post Lyme disease syndrome (iatigue, arthralgia, ‘myalgia, and impairment of memory or cognition) can {ast for years, even after treatment ofthe acute infec tions there is no ole for prolonged antibiotis for this condition. 24 Babesiosis Babesiosis is caused by the intraerythroeytie protozoan Babesia micvori, which is spread by the black legged deer tick. Because of the common yector, babesiosis occurs in areas Of Lyme endeniciy (see Figure 5), most frequently during sum: ‘mer months. In Rurope, babesios's is eaused by several differ cent Babesia specics and is spread by the 1. ricinus tick ‘Transfusion of infected blood products and rare congenital transmission also allows for year-round infection, which may ecur outside endemic regions. (Clinical findings range from asymplomatic presentations approximately 20%) to fatal disease (10%). Risk factors for severe disease include age older than 50 years, immunocom promise, or aspkenia. Symptoms begin within | month alter tick bite and within 6 months after transfusion of infected blood products. Symptoms are nonspecific and include fever (69°), fatigue (82%), chills (67%), headache (47%), myalgia (42%), and cough (28's), Physical examination may reveal jaundice, hepatomegaly, and splenomegaly, which rarely pro gresies (0 splenic rupture. The hallmark of habestosts 1s hemolysis, with anemia almost invariably present. With severe discase, thromboeytopenia, elevated liver erzyme levels, and, acute kidney injury are possible. Rabesios's is diagnosed by visualization of the causative oxganism on thin bloed smears, manifesting as intraeryth, rocylie ring forms simllar to these seen in malaria tetrads resembling a Maltese cross (Figure 8). With low. level patasitemia, multiple smears may need (0 be exam ned, and the sensitivity of microscopy is low. Therefure, polymerase chain reaction or serology should be pursed if smear findings are negative but clinical suspicion of babe siosis is nigh Treatment depends on disease severity (Table 18). Alter trvatment, patients should be monitored closely for relapse: it relapse occurs, prolonged therapy extending more than 2 ‘weeks aller clearance of parasitemia is necessary for cure, Fn OGO'W 0-502 RSS S5ee985 Bap trerensced POLES S259, 3°02 F Se SoPoBeg OSS, Cada ONS OAM ‘Sowing irtrsryhrcy grass, Occasional, merazates re angen tetas resembling» MalesecrssRegimen Asymetomatic <3 months of faasitamia Asymptomatic 28 months of Meriter forclearance:na sreatmont indicated ‘Acovaquone plus perestemia sutheomyets| Milde moderate dens» Atovacuione plus datheemycio| Severe disease requiring ICU Cindamycin plus quinine Severe dizease with 10% parsitoia,hemoclonin love 10 g/dL (1009/), DG Wallis Uclewy Exchange vanshison faire [DS= acm epiaay dane jpn, + Babesiosis, an Infection caused by an intmaerythrocytic protozoan, presenis with clinical findings ranging trom asymptomatic infection to fatal disease: symptoms are usually nonspecific, but hemolytic anemia isa hallmark: ofdisease. Clindamycin plus quinine and, * Diagnosis of habesiosis by visualization ofthe organism: ‘on blood smear, serology, or polymerase chain reacticn, *+ Treatment of babesiosis depends on disease severity; atbvaquone plus azitromyeln are most appropriate for mild disease, whereas clindamycin plus quinine remains the regimen of choice for severe disease. Southern Tick-Associated Rash Illness Southern tick- associated rash illness (STARI) presents with EM ‘sions identical to those sen in Lymedsease but without etn 2 progression or complications. STARI is associated with Amblyomma americanum, also known es the Lone Star tick, sn occurs in the southeastern, south central, and easier {United States. No infectious causehas been confirmed Therefore, agnosis is based on clinial and geographic features. Becutse START and early-stage Lyme disease may be clinically initin sisal, teatment with doxvevelin is recommended. *+ Southern tick associated rash illness may be clinically Indistinguishable trom early-stage Lyme disease, and thas treatment with doxyeyeline is recommended Human Monocytic Ehrlichio: and Granulocytic Anaplasmosis Human monocytic ehrlichiosis (HME) and human gronlo ete anaplasmosis (HGA) ae clinica similar illnesses spread Tick-Borne Diseases by different tick vectors and caused by distinct bacterial path (gens. ME iscoused by Enichia chaffeensis, which s trans- mitted by the Lone Star tick. andl poets most coramonly in the southeastern and south central United States. HGA is ‘caused by Anaplasmia phagocytophilum, which is transmit. ted by Ixodes ticks, and occurs in areas of Lyme endernicity (ee Figuce 5) These syndromes typically begin with a nonspecitic febrile illness 1 to 2 weeks after a tick bite (Table 19). Rash is uncommon in contrast to Rocky Mountain spotted lever, Laboratory study abnormalities, ncuding leukopenia, throm: bbecytopenia, and increased serum aminotransferase levels, are nonspecific The organisms causing HME and HGA replicate inside ewkocytes and cause hallmark basophilic inclusion bodies called morulae (Figure 9). Serologic findings often are negative in acute illness: (esting of a convalescent specimen 2 4 weeks alter onset of symptoms is usually confirmatory Polymerase chain reaction of whole blood at the time of acute illness may be diagnostic, particularly if performed before therapy. Doxyeyeline is the recommended treatment for both HIME and BGA. Because delay in treatment is associated with increased mortality emplile therapy shoul be started even tn the absence of confirmatory testing, + Human monocytic ehelichiosis and human granulocytic snaplasmsts cause a nonspecific febrile illness begin ning | to2 weeksaftera tick bite. Acute Serologic incings are often negative in both human monoeytic ehrliehios's and human granulocytic ansplasmosis; polymerase chain reaction of whole lopd at the ume of acute ness may be disgnostc. + Doxyeyeline is recommended far both human mono yc ehrlichiosis and human granulocytic anaplasmo- sis:empiric therapy should be started without awaiting recalls of eonlicmatory testing. Rocky Mountain Spotted Fever Rocky Mountain pote fever (RMSE) is caused by Rilatsa rickets and transite by malupe ick veetors thas been repocted throughout the continental Unite tte bat ours tnost frequemly in the “RAISE bel” extending from North Garcia to Oklahoma Clinically, RMSF presente with nonspecine symptoms similarto tho of HME and HOA Cable 1) but can pores toasepilcmenlngoencepal Te ballnark stu Iga msc tar eraption around te ake or wrist, with cna spread nd progetian pee eee wena se Youn ot pleat BS oct o ot of plexes the faces generally spare. Purpura flminans may occur and ‘emul i los of digs or linbe: although skin Redings we tlimately noted in greater tn. 904% ofpatcns with RSF, the earliest macular rash eecursa median of3 day afer onset re 10). Lesions 25Tick-Borne Diseases | veaor Lore Starck Bladk-leaged deer ick Geography Southeastem,mid-Atantic and Noheastern and upper Mcuest soul centval Urited States United States Confection Notreporeed: potentalor Lyme slsease,babesiosis, | coinfection wah STAR! cr Powassanvius, Borel | Heantand virus because of imiyarnotot | comman vector Incubstionperied S18 days 5.14 diye | meseming ssa Smoome Curannoue signe Fever headache, myaigas navses, vomiting, dlathea. corjunctval injestion Nonepecfc rach in 30% of adel with mocian ensot Scdaye ater fever FFaver,neadache, rryaigias chills ach are (<10%), ‘American dog uc, brown Gog tick, Rocky Mlouniain wood tick Thrcughoutthe United Statost None | 21Ddaye Fever bodice ch nag] naveta abconipatpan | proeghobe, weplcrenkonis Macslopapular eruptionin 90% al patient, progresting to potechi mith rwolwrnont af plneand soles odemay onext Iredian of 8 days sforfaver aboratorystudy ——_Laukopenia thrombocytopenia, _Leukopaniathrembocytoparia, Thrombocytopenia inéreased sbnommalties incressed serum aminovransterase increased sorumaminovarstersse serum arinotiansierase levels, lovels,rslcanemia levels midaremia formal or shghtlymereasee leukocyte count, hyponatremia Disgross Metubsinmonccries (0%), Morulioln nautaphile(-50®,, Aruto and corvalorcont seaoand convalercent sexte and corwaloocent rahogies, bigpey of cin wth torologioe whole blood PCR oralogies, whole blood PCR tmmurohictochomical analysis Treatment Doxycycline Dosyeycine Doxjeyeline | Forty 3% <8 5%-10% Siati-Scahorntc wauctelwhibess Bacal serie FIGURE 9. Merle ow} opsetng ws brophilcincsion bodes leaky of apaiert whee of fever and thus muy not be found at the first ctinical presentation, nnmunohistochemical analysis of skin biopsy sarnples may be diagnostic As with HIME and HGA, acute serology is aot 26 FVGURE 10. Peetialans purr skin upen in apatens wt lnestge Foxly Mount spate ee, re ge esse ids: dass Ud Se MAR NOS ak sensitive, although (esting convalescent serum may provile a retrospective diagnosis. Dosyeyeiine should be given empirically when MSF 1s clnially suspected because treatment delay 1s aseciated with more severe disease and inereased mortality+ Rocky Mountain spotted fewer (EMSP) presents simile ‘o both human monocytic eilichiosi ant human _anulocylicanaplasnosis: the major dillereniaing feature of RMSF f the presenceofa rash but the rash ‘may not appear until $ days after onst of fees, + Doxweveline shonll be given empirieally when Rocky ‘Mountain spotted fever is clinically suspected. Urinary Tract Infections Epidemiology and Microbiology Community acquimed urinary trict infections (UTIs) account fe approximately § million ambulatory visits and 1 million Baspltalizations each year in dhe United States, making them, fone of the most commen infections for which an antibiotic is prescribed in clinical practice, Another 1 million nesceomal [ls are diagnosed anally, primarily indwelling urinary catheter-associated UTs, acoounting for an estimated 40% of ll Dealth care associuted infections (see Heakh Care: Associated Jnfections). Approximately haf ofall women expertenee & UTI Dy age 30 years: sexual activity is a mjor risk factor Approximately 5% of otherwise healthy women who experience 42 OTT are at greater risk of developing fuuwre infeviluns. Other [Ut risk factors include structural and functional abnormalities, ‘se of spermicidal agenis snd diaphragms, pregeancy diahetes srelitus, obesity, urethral catheserization (or other urinary rick estrumentation), immunosuppression, and genetic factors UTis are classified based on anatomic location as lower {o)stis), upper (pyclonepiarts, perineplaricabsees), oF pros fatits. The term uncomplicated UTI refers to infections in sonpregiant women without structural or neurologic abnor snalities or comorbidities. UTIs in men, pregnant women, ad persons with foreign bodies (for example, indwelling cathe fers, caleuld, Kidney disease, immunocompromise, obstrue fon, urinary etention from neurvlogic disorders health care -sssociated infections, or recent antibicticuse are considered to be complicated. Advanced age in the presence of other major ‘comorbidities or with significant frallty may be considered ‘complicating factor in UTI, although agealone does not define complicated versus uncomplicaied infection. Designating an Saxiectlon as complicated influences the choice and duration of ‘antimicrobial herapyand exient of investigation. Nevertheless, {Se potential for uncomplicated (Tis to evolve into clinically severe disease should not be underestimated, nor should the ‘argency'or seriousness of complicated Us be overstated ‘Most infections oceur by the ascending toate. In 95% of these cases. UTIs are caused by a single bacterial species, mainly gram negative aerooie bacilli originating from the Jbewel, Uropathogente Escherichia colt accounts for 75% to 95% of UTIs in women. Less common urinary pathogens mmelude other members of the Enterobscteriaceae famiy, Urinary Tract Infections streptococe (in particular Strepiococeus egllaetiae), enten ‘coca, and staphylococet (most often Staphylococcus sapto phuticus). UTls occurring in hospitals and long term care facilities frequently Involve a more varied group of organisms (sac as Enterobacter, Providencia, Morganelia, Clirobacter, Serratia, and Pseudomonas). Isolation of Staphylococcus ‘aureus fiom the urine may be related to instrumentation bit should suggest the possiblity of 2 hematogenous infection fiom asource outside the urinary tract. ED + The term uncomplicated urinary iractinicetion refers loinéeelions in nonpregnant women without stmactural or neurilogie abnormalities or comorbidities, * Designatingan infection as complicated influences the choice and duration of antimicrobial therapy and extent of investigation, Urinary tmet infections in men, pregnant women, and Persons with foreign bodies, Kidney disease. immuno ‘compromise, obstruction, urinary retention ffom new robbie disorders, health eare-associated infections, ar recent snibiotic use are considered to be complicated. Diagnosis In persons with symptoms of UT, diagnosis in the outpatient setting Isbased on a combination of clinical features, deer ing ifthe presumed infectious process isin the lower or upper urinary tract, and the findings of significant pyturia (210 leutho- eytes/i) and bacteriuria (hocteria In the urine). Pyura can be detected by urine dipstick, which relies on the presence of leu kocyte esterase, Although the sensitivity and specificity of dip. atic testing are high fabout 75% and 85%, respectively), pyuria ‘may resuit from urinary trict disordersother than infection. The presence of leukoeytecasts supportsa diggnosis of pyelonephet tis, Microscopic oF grons hematuria may be present with a UTT ‘but may also be encountered with nephrolithiasfsand tumors. positive nitrite test result signifies the presence of gram negative bacteria capable of converting nitrates ino nitrites but nega tive in UTI caused by nonconverting organisms (Enteracaxcus, Staphylococeus, or Sireplocoecusspecies) Quantitative cultures of @ midsiream, clean yokd urine: sample are the most accurate way to demonstrate bacteriuria in patients with suspected! LTT. Because the microbiology is predictable and treatment courses are short, culture is not recommended in women with uncomplicated cystitis, Urine cultures are indicated in pyelonephritis, complicated eystitis, and recurrent UTIs; additionally, they are recommended in patients with histories of multiple antibiotic allergies and in those in whom the presence ofa resistant organism is Sus pected (such as recent antibiotic treatment, health care associated infection, previous muticrag resistant UTI). The growth of 10° colony-forming units (CFU)/mL. of urine is considered significant bacteriuria; however, lower CFU counts Support a diagnosis in those with UTI symptoms. 27Urinary Tract Infections: ED, inte atasimasinestuies are not ete er dag hhosis or treatment of UTs. [maging may be indicated when the diggnosis is unclear, when a structural abnormality or complication is suspected, or in patients with severe iliness, Immunocompromise, oc lack of response to appropriate ther apy, Ultrasonography can detect obstruction, whereas. non contrast helical CT i eonmnmended for visualizing kidney stones, Although less sensitive than CF, kidney ullrasoncgr phys less expensive, requires less radiation exposure, and can be used in pregnant women or ifCT is unavailable, Contrast. (CTurography)is recommended when intiarersal ‘or perinephrie abscess is suspected. RODS RMR + Quantitative cultures ofa midsteeam, dean void urine ‘sample are the most accurate way to demonstrate bacte- siucia in patients with suspected urinary tract infection. HVE + Urine cule is not recommended tn: women with uncomplicated cystitis but is indicated in pyelonepinr fis, complicated eystitis, recurrent urinary tract infee ‘dons, patien's with multipte anuibiotteallergies, and in patients in whom a resistant organism is suspected. enhance! Management [EZ] Avmptomatic Bacteriaria ‘Asymptomatic bacteriuria isdefined as the presence ofat least 10° CFU/ml. of @ uropathogen from two consecutive voided, Urine speeimens in women or one specimen in men, oF more than 102 CFU/ml. of one bacterial spectes from a catheterized, "urine specimen in women oF men, in all eases without local or systemic signs orsymptoms of active infection, The prevalence oF asymplomatie bacteriuria is as low as 1% 10 5% in healthy Premenopausal women (2% 10% in pregnant women) and nearly 100% In patients with Tong: term indwelling urinary catheters, ‘The presence of pyuria accompanying asymptomatic bac terluria IS net an Indication for antimicrobial treatment. Although bacteriuria increases the risk of symptomatic UTI, treatment of asymptomatic bacteriuria neither decreases the frequency of symmpiontaite infections nor improves ether out comes. Inappropriate treatment of asymptomatic bacteriuria major driver of antimicrobial rsistance, particularly in health care facltes. Treatment of asymptomatic bacteriuria Is, how ever, indicated in pregnant women and in patients scheduled (0 undergo an invasive procedure involving the urinary tract HVC + Inappropriate treatment of asympiomatic bacteriuria is ‘a majordriver of antimicrobial resistance. partiealzely in health care facilites, + Treatment of asymplomatie bacteriuria is ireicated in pregnant women and in patients scheduled to undergo an invasive procedure involving the urinary tract. 28 Cystitic Recommended first tine antibiotte regimens lor uncompli cated cystitis (urinary frequency and urgeney, dysiria, and suprapubic discomfort) should consider the increased rateof antimicrobial resistance of F. coll the effieaey and advan ‘ages of short course therapies, and the potential adverse clfcets (of the ceology and on patients) Preferred agents include nitrofurantoin (5 days}, trimethoprim sulfamethox: azole (3 days), and fesfornycin (1 dose, but expensive and Tess elMfeacious) In geographic areas where trimethoprim sulfamethoxa, ‘le: resistin: exceeds 20%, an akemative agent should be selected. The FDS recently indiealed that thuoreqainotones should be reserved for ather serious bacterial infections: haw ever: fluoroquinolones (3 days)and B lactam agents Gincluding. amoxicillin clavulanate, ceflinie, cofactor. and cefpodaximic prosetil, each 3.7 days) are considered acceptable alternative second ine therapies. i Lactams are not preferred if other Fecommended agents are available because they are less effec live in eradicating infection. During pregnancy, the safest, antibioties are amoxicillin clavulanate, cephalosporins, and pitrofurantoin, Tetreyelines and fuoroquinolanes are con ‘ruindicated, and trimethoprim suamethoxazoleean oniy be used suely during the second trimeser. Extenled-spectram, B lactamase producing sirains of Enterobacteriacene causing cystitis have mcreased in frequency; especially in patients with, recent antimterubial or health care: facility exposure, Because Of the greater risk of resistant and polymicrobial infections, urine culnure and susceptibility testing are indicated 41 all, patienis with complicated cystitis. Fluoroquinotenes are the preferred choige pending results, although fosfoycin and lerofurantoin are reasonable options, The recommended treatment duration fs 7 10 10 days rather than a 3 day, short course rggimen but fe much less well defined. Other than in pregnant women, et of eure Is noL iraicated im those report ing resolution of ssmptonss. ED + Preferred agents for uncomplicated cystitis include nitrofurantoin (5 days), irimethoprim-sulfamethoxa- ‘ole © days), and fesfornyetn (I day, but least preferred) Auoroquinolones should not be used as first-line ther apy in gysits. Acute Pyelonephritis oO Lower urinary tract symptoms (Irequency, urgency, and dysun ria) offen precede the onset of fever, els, flank pain, anel at ‘mes nausea and vornting, which characterize acute pyelore pris, Infection can usually be managed in the outpatient setting with oral antibiotics. Hospitalization is advised for patients with hemodynamt: instability, cbstructive disease, Diegnancy, complicating comorbulities, known pathogen resistance requiring parenteral antibiotic therapy, inability to {clenate oral medications, or lick of reliable home supervision and clinical follow up.Every patient equines a urine culture with susceptibility {esting obtained delore initiation of empiric therapy. Fuoroquinolones (ciprofloxacin for 7 days or levoflovacin for Sdoysfor uncomplicated infections, 10 H4daysincomplicated infections) are the only oral agents recommended for empiric ‘catpatient treatment, but an initial dose ofa long. seting par enteral antibiotic (such as ceftriaxone, I'g, or a once daly aminoplveuside) should replace Muoroquineliones when lecal resistance rates exceed 10%, When a fuoroqninolone is con traindicsted, trimethoprim sulfamethosavinle twice dally for 1H aays may be used after the pathogen fs proven to desuseep ‘ble: trimethoprim sulfamethoxazole should be avoided as {ital empiric therpy because of the high level of 1 col resistance to this antibiotic in the community, Depending on therisk of antinierubyal resistance and on secent antibiotic use, inpatient parenteral antimicrobial ‘options incudea fuoraquinolone, extendect-speecrum cepha losporins (cefrfaxone or cefepime) or penicillin (piperaeilin tazcbactam), oF a earbapenem (meropenem, imipenem, or erapenem), Agaln, fuoroquinolones are avolded for empiric therapy in severely il patients with complicated pvelonephr tis because of the increasing potential for resissance in E coll aad other aerobic gram-negative bucl, Therapy can be completed with active oral agents when an adequate clinical response has been observed. Patients with bacteremia do not require longer courses of taiment and may be converted to appropriate orl therapy when clinically sable, Imaging studies are only necessary in pation Jonged fever (272 hours) or persivent bacteremia, 8p which complications such as obstruction or pecinephric and intrare fal abscesses must he exelusled, Routine follow up urine eal sures are only Indicated in pregnant women. ED + Every patient with acute pyelonephritis requires a urine culture with susceptibility testing obtained before initi- ation of empiric therapy; follow-up urine cultures are only indicated in pregnant women. * itis prudent to avoid choosing a fluoroquinolone in severely ill patients with complicated pyelonephritis ‘vecause of the increasing potential for resistance Escherichia cols well as other aerobic gram negative Dac swith pro Recurrent Urinary Tract Infections in Women 4a catimated 25% to 30% of patients experience a second epi sede of infection within 6 months of thetr first UTI. Refapsed {infections are those that recur within 2 weeks of completing, antimicrobial therapy (5% 10% of cases) with the same organ. sm (determined by repeat culwie). Relapse suggests infection, ‘with a resistant strain of bacteria, incomplete treatment of an infection of the upper urinary tract, or a structural abnormal 2, Induding renal calcul Retaftetion, che most common ‘ype of recurrent UTI, is generally caused bya bacterial strain Urinary Tract Infections separate from the original infection and presents more than 2 weeksafter cessition of teatment forthe previous infection. Symptomatic relapsed infection requires 9 urine eulture, Assuming the onganism is sensitive, patients are treated for infection ofthe upper urinary tract for 7 to 10 days with the same antibiatie as preseribed for the previous infection or. if bacterial resistance i discovered, an alternative agent. Likewise, the same first line antimicrobial agent can be given, for teinfections, although an aerative antibiotic shomld be used if the rseurrence occurs within 6 months, partiewlady if the original agent was. trimethoprim-sulfamethowvzole, because of the increased chance of resistance, Strategies to prevent infection recurrence include avoid: ance of spermicide contraceptives. urination soon after inter- course. topical vaginal estrogens. ascorbic acid (vitamin © and methenamine salts, Cranberry produets have not been. proven effective m controlled tras. Prophylactic daily antima- crobial agents have been found to reduce the tisk of recur rences by nearly 95%; they ar an option in women who have. had three or more UTis in the previous 12 months, or two oF more in the previes 6 months. and have received no benefit from other prevention elforts, Prophyluctic therapy should be ‘considered in pregnant patients who have required treatment {or qsttis or asymptomatic bacteriuria to prevent recurrence during preynaney. Antibiotic complications and pot ‘emergence of resistance must be considered. Approximately 50% of patients revert to previous recurrence paiterns within, 6 months of prophylasis discontination, Recemmended pro- phylactic anuibiovies include nitofuramoin, trimetioprim- sulfamethoxazole. trimethoprim, cephalexin, of fosiomycin. Fluoroguinolones are very fective but not recommended. Other options include posteotial antimicrobial prophylaxis and self diagnosis with self treatment. + Reinfection is generally caused by a bacterial train sep- arate from the oeiginal infection and presents more ‘than 2 weeks afer cessation of treatment for the previ ‘ous infection. ‘» Prophylacti daily antimicrobial therapy isan option in ‘women who have had three or more urinary tract infec ‘ions in the previous 12 months or two or morein the previous 6 months: other options Include posteottal antimicrobial prophylaxis and self diagnosis with self ‘treatment Acute Bacterial Prostatitis Benign prostatic hyperplasia resuling in urinary obstruction and altered urine flow & the most common reason for the increased incidence of UTIs in men older than 60 yeurs. Other Fisk factors include unprotected senual intercourse, chronic indwelling urinary catheters, and trunsrectal prostate biopsy. appre velop chronle prostatls after actte nection 29om Mycobacterium tuberculosis Infection Presenting sympioms inelude sueen onset of fever pel vie or perineal pain. urinary frequency and dysuria, and Increasing obstructive syrmpioms, Acute bacterial prostatitis, frequently presents as a severe systemic Infection and is the ‘most common cause of acteremis in alder men. Cautions, digital rectal examination of the prostate reveals boggy and ‘ender gland, Urinalysis and culture are required to con the diagnosis, Although pyuria may be present for rea other than infection, its absence strongly indicates no infec lion. Prosuite-specifie antigen test results may be elevated Jecause of inflammation of the gland and should be avoided fn the setting of presumed infection Hospitalized patients and those with severe infection require blood cultures, Gram newative uropathegens account for about 80% of infections, two thirds of which are F cul Proteus, Enterobacter, Serratia, Klebsiella, and sometimes Pseudomonas anil enterocoecal species compose mest of the other pathopens. In men 35 years oF younger, sexually trans mitted Infections, Tucluding Neisserta gonorrhoeae and Chlamydia trachomatis, must be vonsidered, Fluornquinolone anvibioties (eiprofloxaein, levofloxacin) are the preferred oral agents for eating acute bactertal pros tatiis but should not be used If recent genitexuinary insite: ‘mentation was performed, especially transrectal prestate bop Sies, because mos! E coll strains are now Teststant (0 {ucroquinolones. ‘reatment duration Is typically 4 weeks. Hospitalized patients shoald initially ceceivea broad spectra parenteral antibforic, such z-an exiended spectrums penicillin tor cephalosporin, with the possible addition of an aminogly coside. Imaging studies are not recommenced tnless a pros tate abscess suspected clingally: ET * Gram-negative uropathogens account for about 80% of cate prostatitis inicetions: In men 85 years or younger, sexually transmitted infections, including Neiserier gonorrhoeae and Chlamydia trachomatis, must be considered ‘+ Sluoroguinolone antibiotics are the preferred oral agents [or treating acute bacterial prosailtis but should net be used if recent genitourinary instrumentation was performed because most F. coll stains are new resist ant to fluoroquinolones, Mycobacterium tuberculosis Infection Epidemiology Tubereuloss one of theulest and most prevalent inietious diseases inthe wr. remlag ove Of the moet Gratin cones of death ftom an infectious disease wordwile Although rates of Mycobacterium tubercuosts infection remain relatively low in North Amerie 30 third of the work's population isinfected with the bacteria. As (0f2015, appruximately 10 million new cases are reported cach, ‘year throughout the world, and approximately 2 million deaths are documented each sear, including 260,000 in per sons infected with HIV. More than 60% of infections are reported from Southeast Asia, India, China, Mietonesta, Russia, and sub Sahoran Africa. Multtray-resistant tuberem losis (MDRTB) accounts for 3.1% of newinfections and 20% oF elapsed. Infections, Extremely drug resistant tuberculosis ‘now accounts for approximately 10% of al MDR-TR infections, ‘worldwide, In2015, 9557 tuberculosis infections were reported {inthe Untied States (3.0 per 100,000 persons). Most inketions, in the United States occur in foreign. horn persons; however bother persons al high risk include thase with also’olism, Urban poor, homaeless persons, injection drug users, prism inmates, persons living in shelters, HIV positive persons. and older adults Despite great strides worldwide in controling M, tuber Cculasis it remains a major global health goncem, Phe burden, fdisease throughout the world and rapid trivel from country tocuuntry ensures steady stream of active tuberculosis cases, inthe United States ‘+ Most Mycobacterium tuberculosis infections in the United States occur in foreign-born persons; however, ‘other persons at high risk include those with alcohol fam, urban poor, homeless persons, injecilon drug ‘users, prison inmates, persons living in shelters, HIV- positive persons, and olderadals. + Multidrug resistant (uberculosis (MDR-TB) accounts for 3.3% of new infections and 20% of relapsed infections; extremely drug resistant tuberculosis now accounts {or approximately 10% of all MDR 18 infections worldwide. Pathophysiology Humans are the oaly known reserveir for M. tuberculosis. ‘which is most commonly transmitted from person to person by acrosollzed droplets. Although the éroplets dry rapidly, the smallest droplets may remain suspended in the air for several hours. Persons who have visible acid fast bacilli (AFB) on microscopy are the most likely to tans Infection, The most contagious patientsare those with cavitary or laryngeal tuber culosis and those whose sputum contains « high bacterial load. After depesition In the respiratory Vael, tubercular bacilli are ingested by alveolar macrophages that initiate an immunologic cascade eventually raalting i thedevelopment of classic caseating granulomas, Most persons (90%) who become infected with M. tuberculosis remain asymptomatic and develop latent tuberculosis. The Fisk of developing disease after infection {depend primarily on enclogencus factors such as the person's, innate immune sem, nonimmunologic defenses (aheolar macrophages, phagosome formation, phagocytosis) amd thefunction of cell mediated immunity. Specific risk factors for Geveloping, active tuberculosis among infected persons are shown in Table 20. The risk for developing active infection Is approximately 5% in the first 2 years after infection and then Sh for theremainlerof their assuming a0 cause of iam nosuppression is present (see Table 20). ‘+ Most persons who become infecied with [Mycobacterium tubereulosis remain asymptomatic and develop latent tuberewloss + Risk faciors for developing active tuberculosis ‘include immanosuppression, tumor necrosis factor-c.inhibitors. injection drug use, silicos chronic kidney disease, diabetes mellitus, recent infection, and matnuttition, Clinical Manifestations Tuberculosis is classified «s pulmonary, extrapalmonary. oe ‘both; the tau main forms are primary and secondary tubercu bbs, Primary taherculosis occurs scon after the initial infec ‘on, mest frequently in children and immunosuppressed per sons. Often, the lesions heal spontaneously. Secondary or ‘activation tuberculosis results from endogenous reaetivation of a latent infection, Most eases of vetive tuberculosis are 50 yeas Montorhening ana Widney function ext ests Acjustor idreyiny. Cycles Peychonssconvubions,depresion, _Ayidoxine may decrease CNS averse ete. Measure drug headaches dh; draginracions serum levels | Capreomyein Kidney vestodar andausiton tort Montorheariagard Hine funsiontot role Adjuster | hedney iru Etionamide Glupset:hepatotoxtiy May cause nypethyrotsm, Kanamycn and amikacin Leveloxacie, mosiloxaciy Pora-amirosalicyc acid Bedaquiline hypersensitivity Auditory. vestibular and kidney toxicity Not approved by tho FDA for TB treatment Monitor vestibular, | hearing, a licney function Glupset dasnes: hypersensitivity, Notapprovedby the =A for TBreaent Shou not be used dig nencions maiden cleaners Hoy une myeoniRSRA eopslyaea | hepacioney aierenide Masaretee sea oe | Nausea jentpsn headache elevated DAaoproved cralagent fr MOR slonaey TB resent Diners nels hemoptyn teat fr conbsncacn Rerapy sents sree om prolonged GT renal rotowibla, Nove modiansmncfscicn nibs mycobacterial adenosine triphosphate syrthase, Should be given as directv abserved thera. “Doe hen hug mcorsiAaton wth ncn eptsenntha marae rian TE liminate risk for active mycobacterial infection in this until patients are considered! noncontagiouss and the disease is population, ‘cured. In the hospital, this mearss having high Index of spi CECT NNN 828 PFN. Udercuossin high nsk goupsand ntatingimme diate aicborne isolation in negative pressauns roams (airborne + All pavients diagnosed with latent tuberculosis who are being treated with a tumor necrosis factor inhibitor should receive treatment to reduce risk of reactivation and death f1om disseminated aisease, Prevention From the public health perspective, the best way 10 prevent Patients with negative smear results infection olution moors) until the diagnosis can be excluded Recent CDC guidelines recommend criteria to determine that a patient is no longer contagicus ancl .a possible public health threat. Taeseinclude appropriate antimicrobial therapy forat least 2 weeks, clinical improvement of signs and symp- toms. and three negative sputum smears collected at least 8 hours apart, with one being an early morning specimen, re less. contagious, fubereosis ts to diagnose, isolate, and treat infection rapidly although they may still have tberculosis, 35