Adult Infectious Disease Bulletpoints Handbook
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Robert M. Gullberg, M.D., FACP
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Adult Infectious Disease Bulletpoints Handbook - Robert M. Gullberg
Holmes
Antibiotics
How Antibiotics Work
Aminoglycosides- inhibit 30S ribosome. Gentamicin/Tobramycin - 6 mg/kg daily dosing. Watch for nephrotoxicity; especially in elderly females, and ototoxicity. Amikacin- MAI, MDRTB, and pediatric use.
Antifungals- Azoles- Fluconazole (diflucan) 150-400 mg po/IV daily. Ltraconazole (Sporanox)-200 mg bid po. Voriconazole (Vfend)-200-300 mg po bid. Also 4 mg/kg IV q 12 hrs. Posaconazole- 100 mg/day po. Watch for liver toxicity, fluid retention with itraconazole, and drug-to-drug interactions. Echinocandins- Caspofungin 50 mg/day IV. Micafungin 100 mg/day IV. Poor urine concentration. No orals available Polyenes- Amphotericin B-1-1.5 mg/kg IV daily. Watch for bone marrow toxicity, high LFTs, nephrotoxicity, phlebitis, rigors. Lipophilic Ampho B- 5 mg/kg IV daily- less toxicity than non-lipid formulation. Terbinafine (Lamisil)- 250 mg/day po daily for up to 3 months for onychomycosis.
Anti-Influenza- neuraminidase inhibitors are DOC, 70-90% effective. Oseltamivir (Tamiflu- 75 mg BID for 5 days) and zanamavir (Relenza, can’t use in pts. with lung disease) are effective for prophylaxis and for flu if given less than 48 hours after symptoms. Peramivir coming out in future.
Aztreonam- a monobactam beta-lactam. Well tolerated. Narrow spectrum- gram negative aerobic rods. IV use only. Poorly absorbed and not used orally. Generally not nephrotoxic. Used in intraabdominal, pulmonary, and GU infections.
Cephalosporins- minimal cross-over reaction with penicillins (<5%) unless anaphylactic to penicillins. 1st generation- Oral- cefadroxil 500 -1000 mg daily, cephalexin 250-500 mg QlD. IV- cefazolin 1-2 gms q 8 hrs. Covers alpha, beta-strep (not enterococcus), MSSA and Tribe 1 gram negative rods. 2nd generation- Oral- cefuroxime 750 mg BID, IV- 750 mg IV q 8 hrs.- covers what 1st generation cephalosporins cover plus Haemophilus influenza, Pasteurella multocida. Cefoxitin 1 gm q 6 hrs. Cefotetan 1 grm q 12 hrs- cover anaerobes below diaphragm (Bacteroides fragilis) plus Tribe 1 gram negative rods-E.coli, Klebsiella, Proteus. 3rd generation-ceftriaxone 1-2 gms q12- 24 hrs- long half life. Use in orthopedic infections-septic joints, osteomyelitis, and bacterial meningitis. Cefotaxime- used in peds.Ceftazidime- good for pseudomonas. 4th generation-IV cefepime 1-2 gms q 8-12 hrs. Covers MSSA, alpha and beta-strep, Tribe 1 and Tribe 2 (like pseudomonas, serratia) gram negative rods. 5th generation-ceftaroline-covers MRSA, MSSA, alpha and beta- strep and CAP organisms. Side effects- similar to PCNs. Cefotetan- bleeding, ceftriaxone- increase in LFTs, and diarrhea.
Clindamycin- inhibits 50S ribosome. 150-300 mg po TID-QID. (600 mg IV q8) Covers anaerobes above diaphragm and back up
pneumococcal, Staph drug. Side effects- C.difficile diarrhea, neutropenia, increased LFTs.
Colistin(colistmethate; polymyxin E)- a bactericial drug that binds to lipolysaccharides in the outer cell membrane of Gram-negative bacteria (esp Acinetobacter and Pseudomonas) allowing disruption and leakage of cell contents. It causes reversible nephrotoxicity and neurotoxicity. It can cause vertigo, weakness, and paresthesias. Inhalation dose is 50-75 mg in NS via neb 2-3x/day. IV dose- 1.5-5 mg/kg/day, pending on CrCl. It is not active against Proteus, but kills KPC (Klebsiella pneumonia carbapenamase) organisms.
Coumadin Interaction- Major- sulfa, tetracycline, macrolides, quinolones, metronidazole. Minor-penicillins, cephalosporins, penams, clindamycin, aminoglycosides.
Daptomycin- good Staph aureus (MSSA or MRSA) drug, also enterococci and strep. Causes cell death by depolarizing the cell membrane. Used from MRSA and MSSA, especially bacteremia and right sided endocarditis. Surfactant breaks down med ineffective in lungs. Monitor CPK, if 5-10 X greater, consider discontinuing med. Use 6-10 mg/kg/day. Only IV.
Extended beta-Lactamase Penicillins- Oral- amoxicillin-clavulanate (Augmentin) 500-875 mg bid. IV- piperacillin-tazobactam (Zosyn) 3.375 gms q6 hrs, or ticarcillin-clavulanate (Timentin), ampicillin-sulbactam (Unasyn). Broad spectrum- cover anaerobes, aerobic gram – rods, enterococcus, strep and MSSA. Amox-clav.- watch for diarrhea. Piperacillin tazobactam/Ticarcillin clavulanate-. Watch for thrombocytopenia. Clavulanate, tazobactam, sulbactam are suicide
inhibitors.
Linezolid- blocks protein synthesis at the ribosomal level. Very expensive. 100% bioavailable. IV and oral concentrations equivalent. Watch for bone marrow toxicity (especially low platelets), serotonin syndrome (it is an MAO inhibitor) if given with SSRIs; neuropathy, GI side effects. Very good for VRE, MRSA. 2014- Sivextro (Tedizolid)- use 200 mg daily rather than BID and less BM dysfunction.
Macrolides- block 50S ribosome. E-mycin- 333 mg tid. (not used as much because of GI effects) Extended macrolides- Clarithromycin- 250- 500 mg po bid- metallic taste, or Azithromycin- 500 mg bid x day 1, then daily for 4 days (T ½ life of over 60 hours). Watch drug-drug interactions; liver metabolism. Good for resp tract pathogens and MAI.
Metronidazole- nitroimidazole class. Acts by deactivating enzymes by forming thio-ether bonds with cysteine by being reduced to nitroso intermediates. Best anti-anaerobic antibiotic below diaphragm. Poor lung penetration. Also, good for certain protozoa- E. histolytica, trichomonas, giardia. Good for C. difficile diarrhea and rosacea, bacterial vaginosis. Adverse effects- bad taste, disulfiram reaction with ETOH, CNS changes or neuropathy, GI side effects. Dosing- 500 mg tid/qid po/iv.
Nucleoside inhibitors- for herpes simplex virus and HZV. Acyclovir- (prodrug famciclovir); pencyclovir (prodrug valacyclovir), Famvir, Valtrex.
Penams- Imipenam 500 mg q 6 hrs, Merapenam-1 gm q 8 hrs. Ertapenam- 1 gm q 24 hrs. Broad spectrum; especially gram negative aerobes/anaerobes, MSSA and alpha and beta- strep. No MRSA or enterococcal coverage.