_— ae Se ee Inhibiting the Growth of | of” Pathogens In Vivo... using Antimicrobial ~~. -~ A gents Sone is susceptible or resistant to various antimicrobial agents. TS aN Introduction Tetracyolnes Drug Resistance Characteristics of an Ideal Aamcgycosties| “Superbugs" Antimicrobial Agent paecree, How Bacteria Become uoroquinolones Resistant to Drugs How Antimicrobial Agents Work Multidrug Therapy B-Lactamases Antibacterial Agents Synergism versus Antagonism sone Strategies In the Wa ‘Some Major Categorios of ‘Antimycobacterial Agents Drug Resistance Arteactrl Agents Antifungal Agents Empiric Therapy Cephalosparins Antiparasitic Agents Undesirable Effects of Carbapenems eee Antimicrobial Agents Giycopeptides : Concluding Remarks -— ETS After studying this chapter, you should be able to: * Identity the characteristics of an ideal antimicrobial agent * Identify the four most common mechanisms by which i microbial agents * Compare and contrast chemotherapeutic agents, bacteria become resistant to antimicrobial agents antimicrobial amen on ‘anunlodes os to thole . Stat went tthe Lo MRSA," *MRSE;" “CRE, “VRE, intended purpose - * Siato the five most common mechanisms o acon ot * ata tha wens frlactam ring, f-lactam antibiotics, «_iiimicrobial agents an a eee Ditlerentiate berween bactericidal and bacteriostatic + Name threo major groups of bacterial enzym destroy the f-lactam ring ents . + Sine the dit tween narrow-spectrum and + Stato six actions that linans andor patients ca ed-apactunn colina take to help in the war against drug resistance ‘Spectrum antimicrobial agents ‘e Scanned with CamScannerINTRODUCTION Chapter 8 contained information regarding the control of icrobal growth in vitro. Another aspectof controlling growth of microorganisms involves the use of rugs to test {and, hopefully, to cure) infectious diseases; in other words, using drugs to control the growth of pathogens in vivo. ‘Although we most often hear the term chemotherapy used in conjunction with eancer (ie., cancer chemotherapy), chemotherapy actually refers to the (Acremotnereneu- ) See of any chemical (or drug) to tic agent is any treat any disease or condition. | Srugusedto treat | The chemicals (or drugs) used Seas | co treat diseases are referred to as chemotherapeutic agents. By definition, a chemotherapeutic agent is any drug used to treat ‘any condition or disease, oe For thousands of years, people have been discovering and using herbs and chemicals to cure infectious diseases, Native witch doctors in Central and South America long ago discovered that the herb, ipecac, aided in the treatment HISTORICAL NOTE (G2.,, The Father of Chemotherapy 2 The true beginning of modem ‘chemo- as ‘therapy came in the late 1800s when Paul Ehrlich, a German chemist, began his search for chemicals (referred to as “magic bullets”) that would destroy bac- teria, yet would not damage normal body cells. By 1909, he had tested more than 600 chemicals, without success, Finally, in that year, he discovered an arsenic compound that Proved effective in treating syphilis, Because this was the 606th compound Ehrlich had tried, he called it “Compound 606." The: ‘technical name for Compound 606 is arsphenamine, and the trade name was Sal- varsan. Until the availability of penicillin in the early 1940s, Salvarean and a related compound—Neo- salvarsan—were used to treat syphilis. Ehrlich also found that rosaniline was useful for treating African trypanosomiasis, entery, and that a quinine extract of cinchon, is otedie in eesting malaria. During the ‘naan centuries, the alchemists of Europe searched for ways cure smallpox, syphilis, and many other diseases that yas rampant during that period of history. Unfors many of the mercury and arsenic chemical thar sc? used frequently caused more damage to the patienr the thogen. 7 ie cheotherapeutic agents used to treating, diseases are collectively referred to as antimicrobial agegst ‘Thus, an antimicrobial agent is any ical (or drug) used to treat { The chemothea. ) Srinteclons disease, either by | Pout agents neg | inhibiting or by killing pathogens | ects | in vivo. Drugs used to treat bacte- Fal diseases are ealed antibacterial agents, whereas he mse to a fungal diseases are called antifun, cpus Droge aed to teat poral dea ea ‘antiprotozoal agents, and those used to treat viral dseass are called antiviral agents. Some antimicrobial agents are antibiotics. By definition, an anti bioticis a substance produced by: microorganism that is effective in Killing or inhibiting the growth of other microorganisms. Although all antibiotics are antimicrobial tively retered to as antimicrobial agents An antibiotic isa ‘substance produced by a microorganism | that is effective in killing oF inhibiting the growth of other usually those that live in soil. The antibiotics produced soil organisms give them a selective advantage in the: for the available nutrients in the soil. aa mn Penicillin and cephalosporins are commis rd examples of antibiotics produced by ceoet aos | moulds; bacitracin, erythromycin, al Chloramphenicol are examples of antibiotics produced by bacteria, : Although originally produced by microorganisms, et antibiotics are now synthesized or manufactured in set maceutical laboratories. Also, many antibiotics have used to treat bac” | rial diseases. Sa ot aneticaly, an antimicrobial agent is any chemical HEC inhibits the growth of microbes, Hoeven, ne this book, the term is used in refercnee oo drugs thet are treat infectious diseases, Scanned with CamScannerSTUDY AID clarifying Drug Terminology “f é magne that all RA chemotherapeutic agents ‘gre contained within one very targe wooden box. Within that large box are many ‘smaller boxes. Each of the smaller boxes contains rugs to treat one particular category of diseases, For example, one of the smaller boxes contains drugs to treat cancer; these are called cancer chemothera- ic agents. Another of the smaller boxes contains Grugs to treat hypertension (high blood pressure). ‘Another of the smaller boxes contains drugs to treat infectious diseases; these are called antimicrobial agents. Now imagine that the box containing antimi- crobial agents contains even smaller boxes. One of these very small boxes contains drugs to treat bac- terial diseases; these are called antibacterial agents. ‘Another of these very small boxes contains drugs to treat fungal diseases; these are called antifungal agents. Other very small boxes contain drugs to treat, protozoal diseases (antiprotozoal agents) and drugs to treat viral infections (antiviral agents). To appro- priately treat a particular disease, a clinician® must select a drug from the appropriate box. To treat a fun- gal infection, for example, the clinician must select a drug from the box containing antifungal agents. chemically modified to kill a wider variety of pathogens or reduce side effects; these modified antibiotics are called semisynehetic antibiotics. Semisynthetic antibiotics include semisynthetic penicillins, such as ampicillin and nafcillin, Antibiotics are primarily antibacterial agents and are thus used to treat bacterial diseases. CHARACTERISTICS OF AN IDEAL ANTIMICROBIAL AGENT ‘The ideal antimicrobial agent should: * Kill or inhibit the growth of pathogens * Cause no damage to the host * Cause no allergic reaction in the host + Be stable when stored in solid or liquid form + Remain in specific tissues in the body long enough to be effective i r Killthe pathogens before they mutate and become resistant roit this book to refer toa “The term clinician is used throughout th oe ed xo physician or other health care professions! ‘make diagnoses and prescribe medications. HISTORICAL NOTE The First Antibiotics In 1926, Alexander Fleming (Fig. 9-1), a Scottish bacteriolo- Gist, accidentally discovered the first antibiotic when he noticed that the growth of contaminant © Penicitiium notatum mould colonies on his culture plates ‘was inhibiting the growth of _ 2 [ae - iz 2 — ah} Figure 9-1. Alexander Fleming. (Provided by Calbuon at the English Wikibooks project) Staphylococcus bacteria (Fig. 9-2). Fleming gave the name “penicillin” to the inhibitory substance being produced by the mould. He found that broth cultures fof the mould were not toxic to laboratory animals and that they destroyed staphylococci and other bacteria He speculated that pericilin might be useful in treat- ing infectious diseases caused by these organisms ‘As was stated by Kenneth B. Raper in 1978, "Con- tamination of his Staphylococcus plate by a mould was an accident; but Fleming's recognition of a potentially important phenomenon was no accident, for Pasteur’s observation that ‘chance favors the pre~ pared mind’ was never more apt than with Fleming and penicilin."© During World War Il, two blochemists, Sir How- ard Walter Florey and Ernst Boris Chain, purified pPenicilin and demonstrated its effectiveness in the froatment of various bacterial infections. By 1942, R. The discovery of Scanned with CamScanner452 Section IV * Controling the Growth of Microbes oe The acover of pnkinby Alexander A. Colonies of Staphylococcus aureus (a bacte- Fear growing welin tne ea the pate 8. Colonies ‘re pooty developed in this area ofthe plate because of an ‘antbost (pencil Being produced by the colony of Pen ‘cium notatum (a mould) shown at (C) (This photograph ‘riginaly appeared n the Bish Jounal of Experimental Pa- thoiogy 9 1929) (From Winn WC dr et al. Koneman’s Color Atlas and Textbook of Diagnostic Mirobiology. 6th ed, Phila- eipha, PA: JB Lippincott, 2008) the U.S. drug industry was able to produce sufficient Peniciln for human use, and the search for other an- tibiotics began. (Earlier—in 1935—a chemist named Gerhard Domagk discovered that the red dye, Pron- tosil, was effective against streptococcal infections in ‘mice. Further research demonstrated that Prontosil was degraded or broken down in the body into sul- fanilamide, and that sulfanilamide [a sulfa drug] was the effective agent. Although sulfanilamide is an an- timicrobial agent, it is not an antibiotic because it is (ot produced by a microorganism.) In 1944, Selman yaksman and his colleagues isolated streptomycin ‘uberculosis drug) and subsequently investigators— Ehrich, Fleming ‘man, and Domagk—w various times, Unfortunately, most antimicrobj effects, produce allergic aa agents have some side of resistant mutant pathogens,” Pe™it development HOW ANTIMICROBIAL AGENTS Wop, able, an antimicrobial agent muy Tbe che pathogen without damaging the wi, infected person). To accomplish this, the agen me 2 metabolic process OF STUCTUFEPostessedy en" put not possessed by the host. ‘The five most common mechanisms ofseioy microbial agents are as follows: = «= Inhibition of cell wall synthesis “ents eaaes— « Inhibition of nucleic acid synthesis (cithey mt RNA synthesis) _ : Nay « Inhibition of protein synthesis ‘«* Inhibition of enzyme activity ANTIBACTERIAL AGENTS Sulfonamide drugs inhibit production of folic sci. tamin) in those bacteria that require, P-aminobenasie x3, (PABA) to synthesize folic acid. Because the molecule is similar in shape to the PABA molecule be, teria attempt to metabolize sulfonamide to produs ks acid (Fig. 9-3). However, the enzymes that conver Padi to folic acid cannot produce folic acid from the sulfonamide mole- cule. Without folic acid, bacteria cannot produce certain essential proteins and finally die. Sulfa drugs, therefore, are called competiti inhibitors, that is, they inhibit growth of microorganisms by competing with an eat Tequired to produce an essential metabolite. Sulh dupe vastatic, meaning that they inhibit growth ofbice) (as opposed to a bactericidal agent, which kills baci! Cells of humans and animals do not synthesize foi from PABA; they get folic acid from the food ts Consequently, they are unaffected by sulfa drugs. most Gram-positive bacteria, including st and staphylococci, penicillin interferes with ter and cross-linking of peptidoglycan, a component oft cell walls. Thus, by inhibiting cell wall synthesis oA destroys the bacteria. Why doesn’t penicillin 0 a human cells? Because human cells do not haves ‘There are other antimicrobial agents that bt, action; they inhibit a specific step that is es Bacteriostaic dose inhibit growth of bacteria, whereas bactericidal agers kill bacteria. ilar > . Spelling Tip 7) 4 {ote that the word bacteriostatic 4 tains an “g." . bacterician oe, Whereas the word ir does not. Scanned with CamScannerChapter 9 = Inhibiting the Growth of Pathogens In Vivo using Antimicrobial Agents ‘ ens Nie Sulfaniamide Figure 9-3. The effect of sulfonamide drugs (see text for 153 the microorganism’ metabolism and, thereby, cause its destruction. Antibiotics such as vancomycin, which destroys only Gram-pos- itive bacteria, and colistin and nalidixic acid, which destroy only Gram-negative bacteria, are referred to as narrow-spectrum «antibiotics, Those that destroy both Gram-positive and Gram-negative bacteria are called broad-spectrum antibiotics. Examples of broad-spectrum antibiotics are ceftriaxone, levofloxacin, and tetracycline, Tables 9-1 and 9-2 conn information about some of the antimicrobial drugs most frequent! used to treat bacterial infections. ee Antimicrobial agents work well against bacterial patho- gens because the bacteria (being prokaryotic) have different cellular structures and metabolic pathways that can be disrupted or destroyed by drugs that do not damage the eukaryotic host's cells. As mentioned earlier, bactericidal agents kill bacteria, whereas bacteriostatic agents stop them Narrow-spectrum antibiotics kill ether Gram-positive or Gram-negative bacteria, whereas broad- antibiotics kill both Gram positives and Gram negatives. Class/Category Description/Source Examples of Antibacterial Agents within the Class or Category Penicilins* Naturally occurring penicilins; produced bby moulds in the genus Peniciium ‘Semisynthetic penicillins: broad spectrum aminopenicilins ‘Semisynthetic penicillins: ‘penicillinase-resistant ponicilins Penicillin plus -lactamase inhibitor Derivatives of fermentation products ‘of the mould, Cephalosporium acre- ‘monium (now called Acremonivm strictum) Cephalosporin plus f-lactamase Inhibitor Monobactam? Carbapenems* Synthetic drug ive Imipenem is a semisynthetic orivati ‘of thienamycin, produced by Step tomyces 8PP- Benzylpenicillin (penicilin G), phenoxymethy! peniciin (penicitin V) Amoxicilin, ampicilin Cloxacilin, dicloxacilin, methicilin, nafciin, oxacilin, “Amoxiitin-clavuanic acid (Augmentin), ampicitin-sutbactam (Un- ayn, piperacilin-tazobactam (2syr) Broad-spectrum (third-generation) cefdinir, cetditoren, cettizoxime, ceftriaxone; tit ‘cephalosporins are less lended-spectrum (tourth-generation) cephalosporins: cefepime; Extend generation cephalosporins have increased activity against Gram-negative bacteria ;ctam (active against To pscudomonas),ceftazidime-avibactam (active against ‘carbapener-resistant Ent ‘Aztreonam Ertapenom, imipenem, meropenem, doripener (continued) erm Scanned with CamScanner454 Section V + Controlling the Growth of Microbes Ctass/Category Description/Source sie Aminocyclitol Produced by Streptomyces spectaD rocouring antibiotics oF sori ‘Aminoglycosides _ Naturaly occuring ori romano nara entootcscenved HOM . ithotic antibic Fitenyeine ‘compounds produced by Strepto- ‘myces mediterrane! Fiuoroquinolones Synthetic drugs thromycin is produced by Strepto- amet spain, ‘erythraeus; the others are ‘natural analogs of erythromycin or ‘semisynthetic antibiotics Tetracyciines: ‘Tetracycline is produced by Strep- tomyces rimosus; the others are semisynthetic antibiotics Gyeyleycine —_Third-generationtetracyctine Lncosamides _Lincomnycin was initially isolated from Streptomyces lincolnensis; clinda- mycin is a semisynthetic antibiotic Giycopeptide Produced by Streptomyces orientalis ‘Streptogramin Produced by Streptomyces spp. Oxazolidinone ‘Synthetic drug Upopentide Produced by Streptomyces reseospanus ‘Suifonamides ‘Synthetic drugs derived from sutfanamide TP ‘Synthetic drug Polypeptides Originally derived from Baactius pobmyxa ‘Original isolated from Bacilus l- ‘cheniformis (formerly named Bacil- lus subtits) Chloramphenicol Originally produced by Streptomyces vonazuelae Nivoimidazoles Synthetic drug Nitrofurantoin Synthetic drug Fostomycin _Crignaly produced by Sreptomyces spp. or Category ‘Spectinomycin, trospectinomycin ‘Amikacin, gentamicin, kanamycin, neomycin, netiimicin, pparomomycin, sisomicin, streptomycin, tobramycin, Rifampin (rtampicin),rifabutin, rifaximin Ciprofloxacin, gatifloxacin, gemifloxacin, levofloxacin, ‘moxifloxacin ‘ometinas -aitomyein, clathromycin, erythromycin Doxycycline, minocycline, tetracyctine Tigecycline (broad activity against Gram-positive and “Gram-negative bacteria But not against Pseudomonas) Clindamycin Vancomycin Quinupristin-daitopristin Linezolid, tedizolid Daptomyein ‘Sulfadiazine, sulfasalazine, sulfamethoxazole (SMX), suffisoxazoe, ‘rimethoprim-sulfamethoxazole (TMP-SMX oF co-rimoxazoe, trisulfapyrimidine (triple sulfa) Used alone or in combination with SMX Polymyxins: polymyxin B, polymyxin E (colistin) Bacitracin ‘Broad activity but rarely used because of the potential for serous side effects Metronidazole, tinidazole Used only for treatment of lower urinary tract infections Used only for treatment of lower urinary tract infections “-Lactam antibiotics (ie. antibiotics that contain a lactam rng). Information Source: Yao JOG, | from growing and dividing, Bacteriostatic agents should be used only in patients whose host defense mechanisms (see a roperly (i.e. only i Patients whose bodies are capable of killing the pathosen is stopped). Bacteriostatic agents immunosuppressed or leukopenic (patients having an abnormally low number of ‘white blood cells) because the host defense mechanisms of Chapters 15 and 16) are functioning pi ‘once its m lication is should not be used in patients ‘such patients would be unable to eliminate the nongrowi bacteria. Some of the mechanisms by which antibacterist agents kill or inhibit bacteria are presented in Table 9.2. Vireualy all ofthe antibacterial agents currently available ithe ill bacteria or inhibi ther growth: Reeeschene ns attempting to develop antibaceral agents that target bacterial Moatring RC J Anibacteral agents. in: Murray PR, etal, ede. Manual of Cincal Microbiology. Sth ed. Westing virulence factors, rather than targeting the pathogens be selves. Bacterial virulence factors ine eis sul such as toxins and teen Some Major Categories of Antibacterial Aget!s Penicillins bet Penicillins are referred to as B-lactam drugs becats¢ molecular strocure includes 2 oareaded ring so known asa lactam rng (shown in Fig. 9-4) Beis interfere with the synthesis of bacterial cll wallssn4 5° ‘maximum effect on bacteria that are atively dividing 02 are bactericidal drugs. Penicillin G and penicilia Scanned with CamScannerChapter 9 + Inhibit ting the Growth of Pathogens In Vivo using Antimicrobial Agents Eee z 155 ode of Action ce : : of cell wall ‘Spectrum of Activity Bactericidal or Bacteriostatic inition ‘aztreonam, Gram-negative bact ‘synthesis (also. - ‘Bactericidal Bacitracin (also disrupts cell Broad spectr membranes) po! nt ‘Bactericidal Gerbapanem Broad: Cophalosporins Broed spectrum Bactericidal Carbapenems Broad spectrum Bactericidal Fostomycin Broad spectrum Bactericidal Penicilins and semisynthetic Broad Bactericidal penicillins m Bactericidal encore Gram-positive bacteria innibition of protein Aminoglycosides Primarily Gram-negative bacter coaen synthesis ‘and 8, aureus; not etecive ‘against anaerobes, Chloramphenicol Broad spectrum eateinodats ee ‘Most Gram-positive bacteria and Bacteriostatic or bactericidal, some Gram-negative bacteria; ‘depending upon drug concen- highly active against anaerobes _tratio : crieemnmictm — veiateentitero’ eaten Unezolid Gimtnasmre cocorey becteria ean ‘higher concentrations Mupirocin Broad spectrum Bacteriostatic ‘Streptogramins Primarily Gram-positive bacteria, Bactericidal Tetracyctines Broas-epectum and sme acel-Bacteostate Inhibition of nucleic Rifampin Gram-positive and some Gram-neg- Bactericidal acid synthesis ‘ative bacteria (.g., Neisseria meningitidis) Broad spectrum Bactericidal Destruction of DNA Effective against anaerobes Bactericidal Disruption of cell Gram-negative bacteria, Bactericidal Gram-positive bacteria Bactericidal Inhibition of enzyme Primary Gram-positive bacteria and Bacterlostatic activity ‘some bacteria Gram-positive and many Gram-neg- Bacteriostatic ative bacteria «oc agai bot Gran postive and Gram-negative bacteria, but spectrum may var wth te nvidua antinierbil aoe, referred to.as natural penicillins because they are produced and can be purified directly from cultures of Penicillium moulds. Natural penicillins are effective against some Gram-positive bacteria (especially Streptococcus spp.), some anaerobic bacteria, and some spirochetes. A few Gram- negative bacteria (e.g., Neisteria meningitidis and some strains of Haemophilus influenzae) remain susceptible to natural penicillins. By modifying side chains on the peni- cillin molecule, the pharmaceutical industry has extended the antibacterial activity of the antibiotic to include other Gram-negative bacteria. “The symbol ~p"is the Greek letter “beta.” The complete Greek alphabet can be found in Appendix D. Gephalosporins “The cephalosporins ae also B-lactam antibiotics and; like penicillin, are produced by moulds. Also, like penicillins, Eephalosporins interfere with cell wall synthesis and are bac- tecicidal The cephalosporins are classified as first-generation, Second-generation, third-generation, fourth-generation, and fifty generation cephalosporins. The first-generation gents are active primarily against Gram-positive bacter Second-generation. ns have increased activity ‘eumple of a fourth-generation cephalosporin with activity Sgainst both Gram positives and Gram negatives including Praeruginea. Cefaroline isa ffth-generation cephalosporin Scanned with CamScanner456 Section IV * Controlling the Growth of Microbes ‘alosporin, and that has expanded activity a cocci including methicillin. (MRSA) and methicilin-resistant Se Its s. N CHA of” Si ‘COOH Cophalosporin i a , of” se Figure 9-4. Sites of f-lactamase attack on penicilin, ceph- carbapenem molecules (see text for detalls). ‘epidermidis activity against aerobic Gram-negative bacteria cephalosporins, igainst aerobic Gram-positive resistant Staphylococcus aureus mimics that of the third-generation Carbapent ems, including imipenem and Sorinmoyprtlncatae acy inhibit cell lude B-lactam 'wall synthesis and ring (Fig. 9-4). Carbapenems have excellent activity against d spectrum of bacteria, including m, : Genpatre Pecan sai Go ep and most anaerobes. Carbapenems have been consi “antibiotics of last resort” because of their actvgy Gram-negative bacteria that have developed reins many different antimicrobial agents. Unforumately, ease are beginning to develop resistance to the carba, If Klebsiella or Enterobacter spp. become resisant at carbapenems, they are referred to as carbapenem.n- Enterobacteriaceae (CRE). Because these organise’ also resistant to many other antibiotics, thereisa ging * cffort by the Centers for Disease Control and (CDC) to imi their spread in healthcare Flies hgg® Glycopeptides : Giycopeptides, including vancomycin, also target yy bacterial cell wall. They have excellent activity spun’ most aerobic and anaerobic Gram-positive bacteria be have no activity against most Gram-negative bien, ‘Unfortunately, these popular drugs have several Bacteria, especially enterococci, are becoming resistant, these drugs, and they have a number of toxic side efuae ‘When enterococci become resistant to vancomyrin thy are referred to as vancomycin-resistant enterococci (VRE} Tetracyclines ‘TTetracyclines are broad-spectrum drugs that exer the cffect by targeting bacterial ribosomes and thereby hal protein synthesis. They are bacteriostatic. Tetragyins are effective against a wide variety of bacteria, indig chlamydias, mycoplasmas, rickettsias, Vibrio cblene, i spirochetes, such as Borrelia spp. and Treponema paliden. ‘Aminoglycosides — Aminoglycosides are bactericidal broad-spectrum also inhibit bacterial protein synthesis. The major fictor at limits their use is their toxicity. Aminoglycosides ae eftctt against a wide variety of aerobic Gram-negative baci, butare ineffective against anaerobes. They are used tut infections with members of the family Enterobacterisco* (€-g., Escherichia coli and Enterobacter, Kiebiells, Pros SO ‘atia, and Yersinia spp.), as well as P. acruginasa and V. chlo Macrolides ; Macrolids inhibit protein synthesis. They ae come iostatic at lower doses and bactericidal at higher 02 ‘The macrolides include erythromycin, clarithromys™ and azithromycin, They are effective against ch 7 mycoplasmas, 7: pallidum, H. influenzae, and Legion Fluoroquinolones ow Fluoroquinolones are bactericidal drugs that inhitit! synthesis, The most commonly used Suoroqui™ oro Ciprofloxacin, is often effective against member family Enterobacteriaceae and P aeraginess. Le, and moxifloxacin are broad-spectrum agents win ‘gainst both Gram-positive and Gram-negative Scanned with CamScannerChapter 9 + Inhibit Inhibiting the Growth of Pathogens in Vivo using Antimicrobial Agents 4 87 Figure 9-5. Risk of carbapenem-resistant Infections. (Provided by the CDC) Multidrug Therapy Insome cases, a single antimicrobial agentis not sufficient todestroy all the pathogens that develop during the course ofa disease; thus, two or more drugs may be used simul- taneously to Kill all the pathogens and to prevent resistant mutant pathogens from emerging. In tuberculosis, for example, in which multidrug-resistant (MDR) strains of Myabecerizo tubercuasis are frequently encountered, four drugs—isoniazid, rifampin, pyrazinamide, and ethambu- tol-are routinely prescribed, and as many 2s 12 drugs may be required for especially resistant strains (see Table 9-3 for antimycobacterial agents). Synergism versus Antagonism ‘The use of two antimicrobial agents to treat an infectious disease sometimes = a degree of pathogen killing that is far greater than that achi by When the use of two antimicrobial agents, to treat an infectious disease produces a degree of pathogen killing that is far either drug alone. This is known geste than that as synergism. Synergism i ae ieved by either | thing! Many urinary, respirt™y drug alone, the phe- TB ectnal infections respond nomenon is known particularly well ‘to acombination as synergism, Prtrimethoprim and sulfamethos: : Sole, a combination referred t0 a5 | Cotrimoxazole; brand names include Bactrim and Sept™- ~ drugs produces an extent of pathogen killing that is tess than that achieved by either drug alone, the phenom- ‘enon is known as antagonism. tagonism. The extent of pathogen Lalling is less than that achieved by either drug alone. Antagonism isa bad thing! ANTIMYCOBACTERIAL AGENTS “The mycobacteria, such as M,ruberculsis, are prokaryoris organisms, but because of their slow growth rate and igh lipid content in eher cell walls, chey ofa Toney iierent antibiotics for treatment. Table 9-3 lists some of ie fa and the agents used to treat ‘mycobacterial infections. As ‘mentioned earlier, multidrug ayrapy is often necessary to eliminate the organisms ANTIFUNGAL AGENTS to use antimicrobial drugs against ‘because they are eukaryotic ibe more toxic to the patient. ris much more: difficult fungal and p! pat fang sche drugs end Scanned with CamScannerSection IV * Controlling the Growth of Microbes 158 <= Drugs’ used to treat Organisms fee ‘Mycobacterium tuberculosis Ritampin, isoniazid, pyrazinamide, re) Drug-resistant Mtb lad RIE + Rucroauinclone, amikacin, capreomyein ‘Mycobacterium avium-Mycobacterium intraceliulare Claritiromycin, ethambutol, abun : . complex Crarthromycin, amikacin, imipenem, cofoxt Mycobacterium abscessus Clarteromycn, a ‘ 0 ts Clarithromycin, rifabutin ‘Mycobacterium haemophitum Cusitromyc, al “a ‘Mycobacterium kansasi a ethamby Mycobacterium leprae Dapsone, rifampin «Tis Information ls provided solely to scqualnt readers of this book with the names of some entimycobacterial agents and should net be cox ‘88 advice regarding recommended therapy. ‘Most antifungal agents work in one of the following three ways: + By binding with cell membrane sterols (e.g., nystatin and amphotericin B) + By interfering with sterol synthesis (e.g., azoles such as fluconazole, clotrimazole, and miconazole; echinocandins such as micafungin and caspofungin) * By blocking mitosis or nucleic acid synthesis (e.g. griseofulvin ‘Antifungal and anti- parasitic drugs tend to be more toxic to the patient because, like the infected and 5-lucytosine human, they are eu- i : Examples of antifungal agents Karyotec organisms.) are given in Table 9-4. ANTIPARASITIC AGENTS Antiparasitic drugs are usually quite toxic to the host and work by (a) interfering with DNA and RNA synthesis (e.g., chloroquine, pentamidine, and quinacrine) or (b) interfering. Aspergillosis, blast with metabolism (eg, metronidazole; brand name Fig Table 9-5 lists several antiparasitic drugs and the dae they are used to treat. ANTIVIRAL AGENTS Antiviral agents are the newest weapons in antimicrbid methodology. Until the 1960s, there were no drugs frie treatment of viral diseases. Antiviral agents are paricals difficult to develop and use because viruses are within host cells, but, as can be seen in Table 9-6, quit few drugs have been found to be effective in ceria vn! infections. ‘The first antiviral agent effective against human mz nodeficiency virus (HIV) (the causative agent of aoqe! immune deficiency syndrome or acquired immunode ciency syndrome [AIDS])—zidovudine (also knowa 8 azidothymidine)—was introduced in 1987. A variety additional drugs for the treatment of HIV infection wet introduced subsequently. Certain of these antiviral = Fungal Disease(s) That the Drug Is Used to Treat tomycosis, invasive candidiasis, cocci tococcosis, KS cla iasis, coccidioidomycosis, enpt Icormycosis, paracoccidioidomycosis, systemic sporotichoss Scanned with CamScannerChapter 9 « primary amebic meningoencephaliis penne ‘trypanosomiasis (with or without CNS i (Senpernris i ie OS chore papesiosis a, comer Set tn a siasis (cutaneous) Leishmaniasis (mucocutaneous) Leishmaniasis (visceral) Malaria (non-chloroquine resistant) Matava (chloroquine resistant) Toxoplasmosis: Nematode infection (ascariasis, trichuriasis) ‘rematode infection (schistosomiasis) Cestode infection (tapeworms) Inhibit ting the Growth of Pathogens tn Vivo Using Antimicrobial Agents 159 Drug(s) Used to Treat* Amphoteracin 8 Paromemyein, metronidazole, tniazole Pentamidine, suramin, etoriine Benznidazole, nifurtimox ‘Atovaguone, azithromycin Te , motronigazole Nitazoxanigo ‘Trimethoprim-sultamethoxazole Jodequinol, paromomycin, metronidazole Tinidazole, nitazoxanide, metronidazole, paromomycin Paromomycin, mittefosine Pentavalent antimony, liposomal amphotericin B Uposomal amphotericin B, mitefosine Chloroquine Malarone, doxycyctine, mefloquine Pyrimethamine, spiramycin, sulfadiazine, folinic acid ‘Albendazole, mebendazole «This nfermabon s provided solely to acquaint the reader withthe namea of some antiparasiis agents And Should no Be CONSIST a BOGE regarding recommended therapy. (NS, contral nervous system, are administered simultaneously, in combinations referred to as “cocktails.” Unfortunately, such cocktails are quite expensive, have significant side effects, and some strains of HIV have become resistant to some of the drugs. Recently, combinations of agents have been incorporated into single pills taken once daily that simplify treatment of HIV. DRUG RESISTANCE “Superbug: ‘These days, it is quite common to hear about drug-resistant bacteria, or “superbugs,” as they have been labeled by (rote 9-6 Miuewag fs Virus/Viral Infection(s) Antiviral Agents” Herpes simplex infections Infivenza virus types A and B (Osettamivir, peramt Hepatitis B virus Hepatitis C virus Human cytomegalovirus Varicella-Zoster virus HIV; nucteoside/nucleotide analog reverse transcriptase inhibitors HIV: non-nucleoside reverse transcriptase Acyclovir, cidofovir, famciclovir, foscarnet, ganciclovir, penciclovir,triuriine, valacyclovir, valganciclovir Adefovir, entecavir, Daclatasir, dadabuvir, peginterferon a-2a. ribavirin, simeprevir, sofosbuvit idofovis ovi, ‘ Cidotovi,foscamet, cone oacarnt, ganciclowt,valacytow,vaganciciovt | ivir, zanamivir ferferon a-2a, tenofovir Jedipasvir, ombitasvir, partaprevi, pegint valganciclovir lamivudine, stavudine, tenofovir, zalctabine, tn pote Inhibitors ‘Amprenavir, atazanavir, indinavir, lopinavit, nelfinavir, ritonavir, saquinavir HIV: fusion inhibitor Enfuvirtide HV: integrase inhibitor ee © potyomavies (PML) — cael “TNs efomaton a provided aaaly To acquaint ho reader wih te names o t272 amend era. se PA: Lippincott Wears & Wins: 2013 ee Scanned with CamScanner460 Section IV + Controling the Growth of Micro?08 9-6). Although “superbug” can refer to an there resistant to only one antimicrobial agent, the term usualy refers to moltidrug-resistant organisms [DROs) (.., organisms that are resistant to more than oeeniey clas of antimicrobial agent), Infections caused by superbugs are much more difficult to treat. Especially troublesome superbugs are listed in Table 9-7. Ie is important to note that bacteria are not the only microbes eee reat tative deelped rian | recto drugs, Cerin viruses Gillin | actor, ther types / herpes simplex vis influenza viruses), fungi (both yeasts and moulds), parasitic protozoa, and helminths have also devel- coped resistance to drugs. Parasitic ; protozoa that have become drug resistant include strains (of Plasmodium falcipariem, Tricomonas vaginalis, Leishmania spp., and Giardia intestinalis, of microbes (¢.9.. viruses, fungi, and protozoa) have also become MOR. How Bacteria Become Resistant to Drugs How do bacteria become resistant to antimicrobial agents? Some bacteria are naturally resistant to a particular anti- microbial agent because they lack the specific target site for that drug (e.g., mycoplasmas have no cell walls and are, therefore, resistant to any drugs that interfere with cell wall synthesis). Other bacteria are naturally resistant because the drug is unable to cross the organism's cell wall or cell membrane and thus cannot reach its site of action (e.g., ribosomes). Such resistance is known as Is also possible for bacteria that were once susceptible toa particular drug to become resistant to it; this is called cpuired resotance, Bacteria usually acquire ry sr vjoties and other antimicrobial agents by gg. sntehanisms, each of which is listed in Table 9.g fy described as follows: eg . antibiotics, such as the penicillins ee ‘act to block the synthesis Of the cet Pill by preventing the cross-linking of pepedn srordereo do this, the antibiotic muse ise bag BR to proteins in the cell wall; these protein molea je) called drug-binding sites. A chromosomal mutatig: result in an alteration in the structure of the drug. site, so that the drug is no longer able to bind, ee cannot bind to the cell, it cannot block the crow, '% Of the cell wall, and the organism is, therefore react to the drug. = To enter a bacterial cell, a drug must be able through the cell wall and cell membrane. A, mutation can result in an alteration in the stu of the cell membrane, which, in turn, can permeability of the membrane. If the drug is no’ able to pass through the cell membrane, it cannotrest its target (e.g., a ribosome or the DNA of the cell nd the organism is now resistant to the drug. Often his ‘occurs with mutations to the proteins that make porin channels through which the antibiotic crs the cell membrane. These resistance factors are called porin mutants. * Another way in which bacteria become resistant to1 certain drug is by developing the ability to produce enzyme that destroys or inactivates the drug. Beciwe enzymes are coded for by genes, a bacterial cell would have to acquire a new gene for the cell to be ableto produce an enzyme that it never before produced. The primary way in which bacteria acquire new genes isby conjugation (see Chapter 7). Often, a plasmid contiit- ing such a gene is from one bacterial cel (the donor cell) to another bacterial cell (the rept cell) during conjugation. For example, many bactefit have become resistant to penicillin because they be acquired the gene for penicillinase production duis conjugation. (Penicillinase is described in the follows section.) A plasmid containing multiple genes for 68 resistance is called a resistance factor (R-factor).A reo?" ent cell that receives an R-factor becomes MDR ( it becomes a ). Bacteria can also acquire genes by transduction (whereby bacteriophages 7) bacterial DNA from one bacterial cell to anothe!) Ke transformation (the uptake of naked DNA from jee, aoe and transformation in Chapter 7.) * A fourth way in which baci become esis ping the ability to produce MDR known as MDR transporters or efflux pumps) annidy pump enables the cell to pump drugs out of the before the drugs can damage or kill the cel. The Si encoding these pumps are often located on pl meet bacteria receive during conjugation. Bacteri@ © pas, Scanned with CamScannerresistant voor spp. (VRE) Peonginosa ost cite? -Aenetobacter boumanait ‘Rebsila pneumoniae (KPC or CRE) Mutidrug-resistant M. tuberculosis (40R-TB) Bacteria can acquire re- Stance to antimicrobial i mutation or the ansduction, transforma Having direct contact wath another [perion infection Shanng personal items, such a8 towels of ‘ator, that have touched infected shin * Touching surfaces or tems, sch as vied ‘bandages, contaminated with MRSA What are the signs and symptoms? Mot sph skin elections, nccng MRSA, appear as 1 bump or fected area onthe sin that may be > Reet > Swoon > Paks > Warm the touch > Fuld pacrotierdanage > Accompanied bya fever @ call For more information, pl 1-800-CDC.INFO or visit www.cde.gov/MRSA, Gotan never ton ta COC forte rach wc pe en Pn en sacar baSBine rile isan Effect The drug cannot bind tothe bacterial co the cot The dug cant pss CUD ho cl meta, ‘cannot enter the cell ‘The drug Is destroyed or inactivated by the ¢ My ‘Tho drug is pumped out ofthe cel befor it can, kill the coll ame x What if suspect an MRSA shin infection? Cover the area witha bandage and contact your ‘heattcare profesional. tis expecially important {0 contact your healthcare professional # signe {and symptoms of an MRSA skin infection are ‘ccompanied by a fever. How are MIRSA skin infections treated? “Treatment for MRSA shin infections may incude having a heskincare professional rain the nfecton 206. in some cases, prescrbe an antibiotic Do nat attempt to dein the infection yourself ~ doing 30 could worten or spread itto others. you are Som mamsbicec be sue to ake al of the doen {even if the infection is getong beter, unless your healthcare professional tls you to stop taking t- How cant protect my family from MRSA shin infections? > Know the signs of MRSA skin infections and get treated eerty 2 Keep cuts and scrapes clean and covered Encourage good hygiene such at essing hands regula ® Discounage sharing of persona tema such a8 towels and razon Scanned with CamScannerChapter 9 « | inlbtng the Growth of Pathogens In Vio using, Antimicrobial Agents 1 garage” iscalled the P-lactam ring. Some baceer Toe ee bet destroy the Some bere Weng hee eneymes are Leas Brlactamases. When sport aera rng is destroyed, Bootie no longer works. th a organisa that produces Those resistant to ant- psig the Pinca sing (collectively feed bat ec antibiotics or Plactams), oa etoned earlier, there ae three types of : eneliases ceplonpornases, pone Pere rbapencmases. Peniclnaes the B-lactam ring in pen- ¢eteg thus, an organism that veioes pnicllinae resistant PMpenicillins. Cepbalosporinases to pety the P-lactam ring in eelonporin; hus, an organism Surproduces cephalosporinase is asdineto cephalosporins. Some feeteria produce both types of prlncamases, Some bacteria can tos produce carbapenemate enzymes that can inactivate tillin,cephalosporin, and carbapenem antibiotics. “To combat the effec of P-lactamases, drug companies ave developed special drugs that combine a f-lacuam an- Siblede with a B-lactamase inhibitor (e.g. clavulanic acd, sulboctam, avibactam, or tazobactam). The B-lactam inhib tor reversibly binds to and inactivates the B-lactamase, thus enabling the companion drug to enter the bacterial tell and disrupe cell wal synthesis. Some of these special combination drugs are as follows: + Clavulanic acid (clavulanate) combined with amoxicillin (brand name, Augmentin) + Salbaceam combined with ampicillin (Unasyn) + Avibactam combined with ceftazidime (Avyca2) «Tazobactam combined with piperacillin (Zosyn) * Tizobactam combined with ceftolozane (Xerbaxa) A B-lactam antibiotic is an antibiotic that contains a B-lactam, ting in its molecular structure, Penicilinases, ceph- alosporinases, and carbapenemases are examples of Brlactamases; they destroy the B-lactam antibiotics. SOME STRATEGIES IN THE WAR AGAINST DRUG RESISTANCE + Education is erucial—eduecation of health care profes sionals and, in turn, education of patients. 2 + Patients should never pressure clinicians to prescribe antimicrobial agents. Parents must stop demanding ant biotis every time they have a sick child. The majority © Sore throats and many respiratory infections are CV by viruses, and viruses are unaffected by antibiodcs Because viruses are not killed by antibiotics, patienss and parents should not expect antibiotics when hey of their children have vial infections. Instead of demanoe antibiotics from clinicians, they ‘should be asking hy one is being prescribed. * Ttisimporeant that clinicians Pressured by patients They should esente edocs only when warranted (ieconly when tee suated need for them). Wheres eat, Cees should collect a spec , clinicians Hinata ren rederndbe cd (ce Chapter 13)to determine which sntieioobel aeons lhc bene antimicrobial agents * Clinicians should prescribe an inexpensive, /-spectrum: drug whenever the laboratory results demonstate that De ee Sree, kills the pathogen. According to a ‘some estimates, at least half of current antibiotic use in the United States is inappropri- ate—antibiotics are either not indicated at all or incor- rectly prescribed as the wrong drug, the wrong dosage, mr oe wrong cee showed that antibiotics ‘prescribed in. of acute: jiratory tract visit and of those, 80% were unnecessary according toCDC guidelines.‘ Table 9-9 lists upper respiratory infections that typically do not benefit from antibiotics. Taking antibiotics for these viral infections will not cure the infections, will not keep other individuals from catching the illness, and will not help the patient feel better. * Patients must take their antibiotics in the exact manner in which they are prescribed. Health care professionals should emphasize this to patients and do a better job ‘explaining exactly how medications should be ‘taken. * Te is critical that clinicians prescribe the appropriate amount of antibiotic necessary to cure the infection. ‘Then, unless instructed otherwise, patients must take «all their pills—even after they are feeling berter. Again, this must be explained and emphasized. If treatments are cut short, there is selective Killing of only the most ‘susceptible members of a bacterial population. The more resistant variants are left behind to multiply and cause anew infection. « Patients should always destroy any excess medi should never keep antibiotics in their medicine cabinet. ‘Antimicrobial agents, including antibiotics, should be taken only when prescribed and only under a clinician’ supervision. “Taking antibiotics in that chances of h il some of the beneficial indigenous intestinal micro aminating the competition for food and space, making jt easier for pathogens to gain & sbovic Paradox: Hor the Mine of Anibotcr eee cr Carte Prce. 2nd ed, Cambrtge, MA: Pores Publishing; 2002. ; eng oa " oc al.Anibosc we in acute respiratory inert Seo J gr pene pica fora prison J Fm Pract 2001;50(10) 853-858. Scanned with CamScanner— 164 Section IV + Controfing he Growth of NM — Tati oie 0-2 Meni j by Usually Caused es uaees ba ts infection = a ; ve Ne Ne a ‘Yes A scald Qn otvrvte oath chan ands) YS re ‘Sore throats (other than ore ‘and adults) i te No Soca ce yon med = re ts Fd in the middle ear = ‘Src: Tra Cort for isso Gorivl aed Proven, tanta : ae ice good infection _* Isthe patient pregnant? Seviin deste kaowy : procedi ey suspected LC. car ir fo © Health care professionals must pact ecto 1m erie eatsagnale tie. thermal prevention and control C Frequent and proper handwashing s essential to prevent the transmission of pathogens from one patient to another. Health care professionals should monitor for important pathogens (uch as MRSA) within health care settings ‘and always isolate patients infected with MDR pathogens. In recognition of the urgency to control antibiotic sage in hospitals, the Center for Medicare and Medicaid Services has decreed that all hospitals should establish an ‘Anuibiotic Stewardship Committee. This committee would be tasked with overseeing antibiotic usage and would consist ious Dis ians, hospital pharmacists, and laboratorians from the Clinical Microbiology Laboratory. EMPIRIC THERAPY In some cases, a clinician must initiate therapy before laboratory results are available. This is referred to as em- Piric therapy. In an effort to save the life of a patient, it is sometimes necessary for the clinician to “guess” the most likely pathogen and the drug most likely to be effective. It will be an “educated guess,” based on the clinician's prior ‘experiences with the particular type of infectious disease that the patient has. Before writing a prescription for a ‘certain antimicrobial agent, several factors must be taken into consideration by the clinician; some of these are in the following list: * Ifthe laboratory has reported the identity of the the clinician can refer toa “pocket chare seer EEmost hospitals. This pocket char, which is technically known as an antibiogram, is published by the Clinical ‘Microbiology Laboratory; it usually contains antimiero bial susceptibility test data that have been accumulated luring the past yea. The pocket chart provides important information regarding drugs to which various beeterat Pathogens were susceptible and resistant (Fig, 9-8), “k ch ae alerpicto ‘any antimicrobial agents? Ob- it would be unwise to prescri i epee aege ibe a drug to which * Whatis the age of the patient? Certain dru, ‘waindicated in very young or very old patienes tO bee «Is the patient an inpatient or outpatient? Cernain, fan be administered only intravenously and tease cannot be prescribed for outpatients. Ifthe patient is an inpatient, the clinician mast precy a drug that is available in the hospital pharmacy (ie drug that is listed in the hospital formulary). ‘Whaat is the site of the patient’s infection? If the pate has cystitis (urinary bladder infection), the clinician ag prescribe a drug that concentrates in the urine. Such, drug is rapidly removed from the blood by the kidney, and high concentrations of the drug are achieved inte urinary bladder. To treat a brain abscess, the clinica would select a drug capable of crossing the blood-tnia barrier. ‘What other medications is the patient taking or receiving? ‘Some antimicrobial agents will cross-react with ceraa other drugs, leading to a drug interaction that cou e harmful to the patient. ‘What other medical problems does the patient have? Cera antimicrobial agents are known to have toricside fies (€.g., nephrotoxicity, hepatotoxicity, and ototoxicigy). For Saves inician would not prescribe a nephrotos | ig to a patient who has prior kidney damage. Isthe putea eabopenices ieermsnereeea fs, it would be necessary to use a bactericidal agent tote | the patient's bacterial infection, rather than a bacter Static agent. Recall that bacteriostatic agents sh ped only in patients whose host defense mechanisms ictioning properly (i.e., only in patients whose b are capable oflilingthe pathogen pee is mlepioo™ is stopped). A leukopenic patient has too few white! cals to kill the pathogen, and the immune sytem of immunocompromised patient would be unable to Pathogen. kill the ‘The cost of the various dru gs is also a major consideration. ‘enever possible, clinicians should prescribe less costly, thant Pectrum drugs, rather drugs. Although the patient's weight #7 influence the dos ye of a par ony. itis usualy taken into ; eration when oF | ing which drug! prescribe. ‘expensive, broad-spectrum Scanned with CamScanner166 Section IV + Controlling the Growth of Microbes UNDESIRABLE EFFECTS OF ANTIMICROBIAL AGENTS “The following are some of the many reasons why antimi- crobial agents should not be used indiscriminately: ‘* Whenever an antimicrobial agent is administered to a patient, any organisms within that patient that are suscep tible to the agent will die, but resistant ones will survive. ‘This is referred to as selecting for resistant organisms ig. 9-9). The resistant organisms then multiply, become dominant, and can be transmitted to other people. To prevent the overgrowth of resistant organisms, sometimes several drugs, each with a different mode of action, are administered simultaneously. + The patient may become allergic to the agent. For ex- ample, penicillin G in low doses often sensitizes those who are prone to allergies; when these persons receive a second dose of penicillin at some later date, they may hhave a severe reaction known as anaphylactic shock, or they may break out in hives. * Many antimicrobial agents are toxic to humans, and some are so toxic that they are administered only for serious diseases for which no other agents are available. One such drug is chloramphenicol, which, if given in high doses for a long period, may cause a very severe type of anemia called aplastic anemia. Another is streptomycin, which can damage the auditory nerve and cause deafness. Other drugs are hepatotoxic or nephrotoric, causing liver or kidney damage, respectively. With prolonged use, broad-spectrum antibiotics may destroy the indigenous microbiota of the mouth, intestine, or vagina. The person no longer has the protection of the = indigenous microbiota and thus Prolonged antibiotic] becomes much more: tible to tse can lead to pop- | infections caused by. oe ulation explosions of ‘opportunists or micron! | Secondary invaders. The resultant are resistant to the overgrowth by such organisms antibiotics) bei is referred to as a superinfection, Used. Such over’ | A superinfection can be thought Growths are known | of as a “population explosion” of 85 “superinfections.” | Ofganisms that are usually present only in small numbers. For example, the prolonged use of oral antibiotics ‘ean result in a superinfection of Figure 9-10 ilus- trates the various ways in which an- tibiotic resistance Spreads. CONCLUDING REMARKS In ecent years, microorganisms have developed resistance rt St such a rapid pace that many People, including many raters te space, the resstant organi mutpy ane oacor Prrcominant organisms in the patient's inigonous micot wrote ence process occurs when farm arms tang proces ee gh fed and when anit I» and cutting boards] homes. Bot ofthese topes wor iosusso Crap) scientists, are beginning to fear that science is losing te *#™ against pathogens. Two recent initiatives are worth 108! * In August 2016, the CDC announced the launch of Antimicrobial Resistance Laboratory Neework (RS? rater ene seven regional laboratories to network and! With clinical and public health laboratories to det SUPPort response to resistant organisms human samples. When new resistance threat 0°02 Scanned with CamScannerChapter 9 + Inhibiting the Growth of Pathogens In Vivo using Antimicrobial Agents “RESISTANCE At enincs ery or ANTIBIOTIC RESIS bocteria in their intestines 167 TANCE AIEEE IMPACT sone ess ietonscone.. are 2 Figure 9-10. Examples of how antiblotic resistance spreads. (Provided by the CDC) are detected within health care facilities or at state and local public health labs, the ARLN regional Jabs will pro- vide additional laboratory capacity and testing services to characterize and track resistance to support public health response to these threats. The seven regional laboratories began offering testing in January 2017. * In September of 2016, the United Nations General Assembly brought the issue of antibiotic resistance to the floor of the United Nations and ‘urged members to unite in a worldwide effort to control the inappropriate ‘se of antibiotics and to urge the continued development of new antimicrobial agents. Unfortunately, some strains of pathogens that are Fesistant to all known drugs have arisen; examples include ‘certain strains of M. tuberculsis (the bacterium that causes tuberculosis) and P aeruginasa (the bacterium that causes many different types of infections, including pneumonia, urinary tract infections, and wound infections). To win the ‘war against drug resistance, more prudent use of currently {vailable drugs, the discovery of new drugs,and the devel~ ‘opment of new vaccines will all be necessary. Unfortunately, se omeone once said, “When science builds a better mousetrap, nature builds a better mouse.” To learn more about antibiotic resistance, the book by Dr. Stuart Levy (previously cited) is highly recommended. Fortunately, antimicrobi in Chapters 15 and 16. Scanned with CamScanner