—TABLE OF CONTENTS— ABBREVIATIONS.................................................................................................................................................. 2 TABLE 1A Clinical Approach to Initial Choice of Antimicrobial Therapy ........................................................ 4 TABLE 2 Recommended Antimicrobial Agents Against Selected Bacteria .............................................. 62 TABLE 3 Suggested Duration of Antibiotic Therapy in Immunocompetent Patients.................................. 65 TABLE 4 Comparison of Antibacterial Spectra ............................................................................................ 66 TABLE 5 Treatment Options for Selected Highly Resistant Bacteria....................................................... 72 TABLE 6 Suggested Management of Suspected or Culture-Positive Community-Associated Methicillin-Resistant S. Aureus (CA-MRSA) Infections ........................................................ 74 TABLE 7 Methods for Drug Desensitization.............................................................................................. 76 TABLE 8 Risk Categories of Antimicrobics in Pregnancy........................................................................ 77 TABLE 9A Selected Pharmacologic Features of Antimicrobial Agents ...................................................... 78 9B Pharmacodynamics of Antibacterials...................................................................................... 83 TABLE 10A Selected Antibacterial Agents—Adverse Reactions—Overview................................................ 84 10B Antimicrobial Agents Associated with Photosensitivity .............................................................. 88 10C Antibiotic Dosage and Side-Effects ......................................................................................... 89 10D Aminoglycoside Once-Daily and Multiple Daily Dosing Regimens..................................... 97 TABLE 11A Treatment of Fungal Infections—Antimicrobial Agents of Choice ........................................... 98 11B Antifungal Drugs: Dosage, Adverse Effects, Comments ......................................................... 112 11C At A Glance Summary of Suggested Antifungal Drugs Against Treatable Pathogenic Fungi .................................................................................................... 115 TABLE 12A Treatment of Mycobacterial Infections .................................................................................... 116 12B Dosage and Adverse Effects of Antimycobacterial Drugs ......................................................... 126 TABLE 13A Treatment of Parasitic Infections ............................................................................................. 129 13B Dosage and Selected Adverse Effects of Antiparasitic Drugs ................................................... 139 13C Parasites that Cause Eosinophilia (Eosinophilia In Travelers)............................................. 142 TABLE 14A Antiviral Therapy (Non-HIV)...................................................................................................... 143 14B Antiviral Drugs (Non-HIV) ......................................................................................................... 155 14C At A Glance Summary of Suggested Antiviral Agents Against Treatable Pathogenic Viruses .................................................................................. 160 14D Antiretroviral Therapy in Treatment-Naïve Adults (HIV/AIDS) ............................................. 161 14E Antiretroviral Drugs and Adverse Effects (HIV/AIDS)............................................................... 171 TABLE 15A Antimicrobial Prophylaxis for Selected Bacterial Infections.................................................... 174 15B Surgical Antibiotic Prophylaxis .............................................................................................. 175 15C Antimicrobial Prophylaxis for the Prevention of Bacterial Endocarditis in Patients with Underlying Cardiac Conditions ................................................................................................... 179 15D Management of Exposure to HIV-1 and Hepatitis B and C................................................... 180 15E Prevention of Opportunistic Infection in Human Stem Cell Transplantation (HSCT) or Solid Organ Transplantation (SOT) for Adults with Normal Renal Function ........................... 183 TABLE 16 Pediatric Dosages of Selected Antibacterial Agents ................................................................ 185 TABLE 17A Dosages of Antimicrobial Drugs in Adult Patients with Renal Impairment............................... 186 17B No Dosage Adjustment with Renal Insufficiency by Category................................................. 194 TABLE 18 Antimicrobials and Hepatic Disease: Dosage Adjustment ....................................................... 194 TABLE 19 Treatment of CAPD Peritonitis in Adults ................................................................................... 194 TABLE 20A Recommended Childhood and Adolescent Immunization Schedule in The United States .... 195 20B Adult Immunization In The United States ................................................................................. 196 20C Anti-Tetanus Prophylaxis, Wound Classification, Immunization ................................................ 198 20D Rabies Post-Exposure Prophylaxis........................................................................................ 199 TABLE 21 Selected Directory of Resources............................................................................................. 200 TABLE 22A Anti-Infective Drug-Drug Interactions....................................................................................... 201 22B Drug-Drug Interactions Between Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIS) and Protease Inhibitors ......................................................................................... 208 TABLE 23 List of Generic and Common Trade Names ............................................................................. 209 INDEX OF MAJOR ENTITIES .......................................................................................................................... 211 1 2 ABBREVIATIONS 3TC = lamivudine CXR = chest x-ray IDSA = Infectious Diseases Society of America AB,% = percent absorbed d4T = stavudine IDV = indinavir ABC = abacavir Dapto = daptomycin IFN = interferon ABCD = amphotericin B colloidal dispersion DBPCT = double-blind placebo-controlled trial IMP = imipenem-cilastatin ABLC = ampho B lipid complex dc = discontinue INH = isoniazid ACIP = Advisory Committee on Immunization Practices ddC = zalcitabine Inv = investigational AD = after dialysis ddI = didanosine IP = intraperitoneal ADF = adefovir DIC = disseminated intravascular coagulation IT = intrathecal AG = aminoglycoside div. = divided Itra = itraconazole AIDS = Acquired Immune Deficiency Syndrome DLV = delavirdine IVDU = intravenous drug user AM-CL = amoxicillin-clavulanate Dori = doripenem IVIG = intravenous immune globulin AM-CL-ER = amoxicillin-clavulanate extended release DOT = directly observed therapy Keto = ketoconazole AMK = amikacin DOT group = B. distasonis, B. ovatus, B. thetaiotaomicron LAB = liposomal ampho B Amox = amoxicillin Doxy = doxycycline LCM = lymphocytic choriomeningitis virus AMP = ampicillin DRSP = drug-resistant S. pneumoniae LCR = ligase chain reaction Ampho B = amphotericin B DS = double strength Levo = levofloxacin AM-SB = ampicillin-sulbactam EBV = Epstein-Barr virus LP/R = lopinavir/ ritonavir AP = atovaquone proguanil EES = erythromycin ethyl succinate M. Tbc = Mycobacterium tuberculosis AP Pen = antipseudomonal penicillins EFZ = efavirenz Macrolides = azithro, clarithro, dirithro, erythro, roxithro APAG = antipseudomonal aminoglycoside (tobra, gent, amikacin) ENT = entecavir mcg = microgram ARDS = acute respiratory distress syndrome ERTA = ertapenem MER = meropenem ARF = acute rheumatic fever Erythro = erythromycin Metro = metronidazole ASA = aspirin ESBLs = extended spectrum β-lactamases mg = milligram ATS = American Thoracic Society ESR = erythrocyte sedimentation rate Mino = minocycline ATV = atazanavir ESRD = endstage renal disease Moxi = moxifloxacin AUC = area under the curve ETB = ethambutol MQ = mefloquine Azithro = azithromycin Flu = fluconazole MSSA/MRSA = methicillin-sensitive/resistant S. aureus bid = twice a day Flucyt = flucytosine NB = name brand BL/BLI = beta-lactam/beta-lactamase inhibitor FOS-APV = fosamprenavir NF = nitrofurantoin BW = body weight FQ = fluoroquinolone (CIP, Oflox, Lome, Peflox, Levo, NAI = not FDA-approved indication C&S = culture & sensitivity Gati, Moxi, Gemi) NFR = nelfinavir CAPD = continuous ambulatory peritoneal dialysis FTC = emtricitabine NNRTI = non-nucleoside reverse transcriptase inhibitor CARB = carbapenems (DORI, ERTA, IMP, MER) G = generic NRTI = nucleoside reverse transcriptase inhibitor CDC = Centers for Disease Control GAS = Group A Strep NSAIDs = non-steroidal Cefpodox = cefpodoxime proxetil Gati = gatifloxacin NUS = not available in the U.S. Ceftaz = ceftazidime GC = gonorrhea NVP = nevirapine Ceph= cephalosporin Gemi = gemifloxacin O Ceph 1,2,3 = oral cephalosporins—see Table 10C CFB = ceftobiprole Gent = gentamicin Oflox = ofloxacin CFP = cefepime gm = gram P Ceph 1,2,3,4 = parenteral cephalosporins—see Table 10C Chloro = chloramphenicol GNB = gram-negative bacilli P Ceph 3 AP = parenteral cephalosporins with antipseudomonal CIP = ciprofloxacin; CIP-ER = CIP extended release Griseo = griseofulvin activity—see Table 10C Clarithro = clarithromycin; ER = extended release HEMO = hemodialysis PCR = polymerase chain reaction Clav = clavulanate HHV = human herpesvirus PEP = post-exposure prophylaxis Clinda = clindamycin HIV = human immunodeficiency virus PI = protease inhibitor CLO = clofazimine HLR = high-level resistance PIP = piperacillin Clot = clotrimazole H/O = history of PIP-TZ = piperacillin-tazobactam CMV = cytomegalovirus HSCT = hematopoietic stem cell transplant po = per os (by mouth) CQ = chloroquine phosphate HSV = herpes simplex virus PQ = primaquine CrCl = creatinine clearance IA = injectable agent/anti-inflammatory drugs PRCT = Prospective randomized controlled trials CRRT = continuous renal replacement therapy ICAAC = International Conference on Antimicrobial PTLD = post-transplant lymphoproliferative disease CSD = cat-scratch disease Agents & Chemotherapy Pts = patients CSF = cerebrospinal fluid 3 ABBREVIATIONS (2) SA = Staph. aureus Tetra = tetracycline Pyri = pyrimethamine SD = serum drug level after single dose Ticar = ticarcillin PZA = pyrazinamide Sens = sensitive (susceptible) tid = 3 times a day qid = 4 times a day SM = streptomycin TMP-SMX = trimethoprim-sulfamethoxazole QS = quinine sulfate SQV = saquinavir TNF = tumor necrosis factor Quinu-dalfo = Q-D = quinupristin-dalfopristin Tobra = tobramycin SS = steady state serum level R = resistant TPV = tipranavir STD = sexually transmitted disease RFB = rifabutin TST = tuberculin skin test subcut = subcutaneous RFP = rifapentine UTI = urinary tract infection Sulb = sulbactam Rick = Rickettsia Vanco = vancomycin Tazo = tazobactam RIF = rifampin VISA = vancomycin intermediately resistant S. aureus TBc = tuberculosis RSV = respiratory syncytial virus VL = viral load TC-CL = ticarcillin-clavulanate RTI = respiratory tract infection Vori = voriconazole TDF = tenofovir RTV = ritonavir VZV = varicella-zoster virus TEE = transesophageal echocardiography rx = treatment WHO = World Health Organization Teico = teicoplanin S = potential synergy in combination with penicillin, ZDV = zidovudine Telithro = telithromycin AMP, vanco, teico ABBREVIATIONS OF JOURNAL TITLES AAC: Antimicrobial Agents & Chemotherapy COID: Current Opinion in Infectious Disease JAC: Journal of Antimicrobial Chemotherapy Adv PID: Advances in Pediatric Infectious Diseases Curr Med Res Opin: Current Medical Research and Opinion JACC: Journal of American College of Cardiology AHJ: American Heart Journal Derm Ther: Dermatologic Therapy JAIDS: JAIDS Journal of Acquired Immune Deficiency Syndromes AIDS Res Hum Retrovir: AIDS Research & Human Retroviruses Dermatol Clin: Dermatologic Clinics JAMA: Journal of the American Medical Association AJG: American Journal of Gastroenterology Dig Dis Sci: Digestive Diseases and Sciences JAVMA: Journal of the Veterinary Medicine Association AJM: American Journal of Medicine DMID: Diagnostic Microbiology and Infectious Disease JCI: Journal of Clinical Investigation AJRCCM: American Journal of Respiratory Critical Care Medicine EID: Emerging Infectious Diseases JCM: Journal of Clinical Microbiology AJTMH: American Journal of Tropical Medicine & Hygiene EJCMID: European Journal of Clin. Micro. & Infectious Diseases JIC: Journal of Infection and Chemotherapy Aliment Pharmacol Ther: Alimentary Pharmacology & Therapeutics Eur J Neurol: European Journal of Neurology JID: Journal of Infectious Diseases Am J Hlth Pharm: American Journal of Health-System Pharmacy Exp Mol Path: Experimental & Molecular Pathology JNS: Journal of Neurosurgery Amer J Transpl: American Journal of Transplantation Exp Rev Anti Infect Ther: Expert Review of Anti-Infective Therapy JTMH: Journal of Tropical Medicine and Hygiene AnEM: Annals of Emergency Medicine Gastro: Gastroenterology Ln: Lancet AnIM: Annals of Internal Medicine Hpt: Hepatology LnID: Lancet Infectious Disease AnPharmacother: Annals of Pharmacotherapy ICHE: Infection Control and Hospital Epidemiology Mayo Clin Proc: Mayo Clinic Proceedings AnSurg: Annals of Surgery IDC No. Amer: Infectious Disease Clinics of North America Med Lett: Medical Letter Antivir Ther: Antiviral Therapy IDCP: Infectious Diseases in Clinical Practice Med Mycol: Medical Mycology ArDerm: Archives of Dermatology IJAA: International Journal of Antimicrobial Agents MMWR: Morbidity & Mortality Weekly Report ArIM: Archives of Internal Medicine Inf Med: Infections in Medicine NEJM: New England Journal of Medicine ARRD: American Review of Respiratory Disease J AIDS & HR: Journal of AIDS and Human Retrovirology Neph Dial Transpl: Nephrology Dialysis Transplantation BMJ: British Medical Journal J All Clin Immun: Journal of Allergy and Clinical Immunology Ped Ann: Pediatric Annals BMTr: Bone Marrow Transplantation J Am Ger Soc: Journal of the American Geriatrics Society Peds: Pediatrics Brit J Derm: British Journal of Dermatology J Chemother: Journal of Chemotherapy Pharmacother: Pharmacotherapy Can JID: Canadian Journal of Infectious Diseases J Clin Micro: Journal of Clinical Microbiology PIDJ: Pediatric Infectious Disease Journal Canad Med J: Canadian Medical Journal J Clin Virol: Journal of Clinical Virology QJM: Quarterly Journal of Medicine CCM: Critical Care Medicine J Derm Treat: Journal of Dermatological Treatment Scand J Inf Dis: Scandinavian Journal of Infectious Diseases CCTID: Current Clinical Topics in Infectious Disease J Hpt: Journal of Hepatology Sem Resp Inf: Seminars in Respiratory Infections CDBSR: Cochrane Database of Systematic Reviews J Inf: Journal of Infection SGO: Surgery Gynecology and Obstetrics CID: Clinical Infectious Diseases J Med Micro: Journal of Medical Microbiology SMJ: Southern Medical Journal Clin Micro Inf: Clinical Microbiology and Infection J Micro Immunol Inf: Journal of Microbiology, Immunology, Surg Neurol: Surgical Neurology CMN: Clinical Microbiology Newsletter & Infection Transpl Inf Dis: Transplant Infectious Diseases Clin Micro Rev: Clinical Microbiology Reviews J Ped: Journal of Pediatrics Transpl: Transplantation CMAJ: Canadian Medical Association Journal J Viral Hep: Journal of Viral Hepatitis TRSM: Transactions of the Royal Society of Medicine 4 TABLE 1A – CLINICAL APPROACH TO INITIAL CHOICE OF ANTIMICROBIAL THERAPY* Treatment based on presumed site or type of infection. In selected instances, treatment and prophylaxis based on identification of pathogens. Regimens should be reevaluated based on pathogen isolated, antimicrobial susceptibility determination, and individual host characteristics. (Abbreviations on page 2) ANATOMIC SITE/DIAGNOSIS/ ETIOLOGIES SUGGESTED REGIMENS* ADJUNCT DIAGNOSTIC OR THERAPEUTIC MEASURES MODIFYING CIRCUMSTANCES (usual) § AND COMMENTS PRIMARY ALTERNATIVE ABDOMEN: See Peritoneum, page 43; Gallbladder, page 15; and Pelvic Inflammatory Disease, page 23 BONE: Osteomyelitis. Microbiologic diagnosis is essential. If blood culture negative, need culture of bone. Culture of sinus tract drainage not predictive of bone culture. Review: Ln 364:369, 2004. For comprehensive review of antimicrobial penetration into bone, see Clinical Pharmacokinetics 48:89, 2009. Hematogenous Osteomyelitis Empiric therapy—Collect bone and blood cultures before empiric therapy NAI Newborn (<4 mos.) S. aureus, Gm-neg. bacilli, MRSA possible: Vanco+ MRSA unlikely: (Nafcillin or Table 16 for dose. Severe allergy or toxicity: (Linezolid 10 mg/kg IV/po q8h See Table 16 for dose Group B strep (Ceftaz 2 gm IV q8h or CFP oxacillin) + (Ceftaz or CFP) + aztreonam). Could substitute clindamycin for linezolid. 2 gm IV q12h) NAI Children (>4 mos.)—Adult: S. aureus, Group A strep, MRSA possible: Vanco MRSA unlikely: Nafcillin or Severe allergy or toxicity: Clinda or TMP-SMX or linezolid . Osteo of extremity Gm-neg. bacilli rare oxacillin Adults: ceftaz 2 gm IV q8h, CFP 2 gm IV q12h. Peds dosages in Table 16. See Table 10 for adverse reactions to drugs. Add Ceftaz or CFP if Gm-neg. bacilli on Gram stain (Adult doses below. Peds Doses: Table 16 Adult (>21 yrs) S. aureus most common but MRSA possible: Vanco MRSA unlikely: Nafcillin or Dx: MRI early to look for epidural abscess. Vertebral osteo ± epidural variety other organisms. 1 gm IV q12h; if over oxacillin 2 gm IV q4h Allergy or toxicity: TMP-SMX 8–10 mg/kg per day div. IV q8h or linezolid NAI abscess; other sites Blood & bone cultures 100 kg, 1.5 gm IV q12h 600 mg IV/po q12h (AnIM 138:135, 2003) . See MRSA specific therapy (NEJM 355:2012, 2006) essential. comment. Epidural abscess ref.: ArIM 164:2409, 2004. Specific therapy—Culture and in vitro susceptibility results known MSSA Nafcillin or oxacillin Vanco 1 gm q12h IV; if over Other options if susceptible in vitro and allergy/toxicity issues: 2 gm IV q4h or cefazolin 100 kg, 1.5 gm IV q12h 1) TMP/SMX 8-10 mg/kg/d IV div q8h. Minimal data on treatment of 2 gm IV q8h osteomyelitis; 2) Clinda 600-900 mg IV q8h – have lab check for inducible resistance especially if erythro resistant (CID 40:280,2005); 3) [(Cip 750 mg MRSA—See Table 6, Vanco 1 gm IV q12h Linezolid 600 mg q12h IV/po po bid or levo 750 mg po q24h) + rif 300 mg po bid]; 4) Daptomycin page 74 ± RIF 300 mg po/IV bid 6 mg/kg IV q24h; –clinical failure secondary to resistance reported (J Clin Micro 44:595;2006); 5) Linezolid 600 mg po/IV bid – anecdotal reports of efficacy (J Chemother 17:643,2005), optic & peripheral neuropathy with NUS long-term use (Neurology 64:926, 2005); 6) Fusidic acid 500 mg IV q8h + rif 300 mg po bid. (CID 42:394, 2006). Hemoglobinopathy: Salmonella; other Gm-neg. CIP 400 mg IV q12h Levo 750 mg IV q24h Thalassemia: transfusion and iron chelation risk factors. Sickle cell/thalassemia bacilli Contiguous Osteomyelitis Without Vascular Insufficiency Empiric therapy: Get cultures! Foot bone osteo due to nail P. aeruginosa CIP 750 mg po bid or Levo Ceftaz 2 gm IV q8h or CFP See Skin—Nail puncture, page 52. Need debridement to remove foreign body. through tennis shoe 750 mg po q24h 2 gm IV q12h NAI Long bone, post-internal fixation S. aureus, Gm-neg. bacilli, Vanco 1 gm IV q12h + Linezolid 600 mg IV/po bid Often necessary to remove hardware to allow bone union. May need revascularization. of fracture P. aeruginosa [ceftaz or CFP]. + (ceftaz or CFP). Regimens listed are empiric. Adjust after culture data available. If See Comment See Comment susceptible Gm-neg. bacillus, CIP 750 mg po bid or Levo 750 mg po q24h. For other S. aureus options: See Hem. Osteo. Specific Therapy, page 4). * DOSAGES SUGGESTED are for adults (unless otherwise indicated) with clinically severe (often life-threatening infections. Dosages also assume normal renal function, and not severe hepatic dysfunction. § ALTERNATIVE THERAPY INCLUDES these considerations: allergy, pharmacology/pharmacokinetics, compliance, costs, local resistance profiles. 5 TABLE 1A (2) ANATOMIC SITE/DIAGNOSIS/ ETIOLOGIES SUGGESTED REGIMENS* ADJUNCT DIAGNOSTIC OR THERAPEUTIC MEASURES MODIFYING CIRCUMSTANCES (usual) § AND COMMENTS PRIMARY ALTERNATIVE BONE/Contiguous Osteomyelitis Without Vascular Insufficiency/Empiric therapy (continued) Osteonecrosis of the jaw Probably rare adverse Infection is secondary to bone necrosis and loss of overlying mucosa. reaction to bisphosphonates Treatment: minimal surgical debridement, chlorohexidine rinses, antibiotics (e.g. PIP-TZ). NEJM 355:2278, 2006. Prosthetic joint See prosthetic joint, page 29 Spinal implant infection S. aureus, Onset within 30 days Onset after 30 days remove For details: CID 44:913, 2007. coag-neg staphylococci, culture, treat & then implant, culture & treat gram-neg bacilli suppress until fusion occurs NAI Sternum, post-op S. aureus, S. epidermidis Vanco 1 gm IV q12h; if over Linezolid 600 mg po/IV bid Sternal debridement for cultures & removal of necrotic bone. 100 kg, 1.5 gm IV q12h. For S. aureus options: Hem. Osteo. Specific Therapy, page 4. Contiguous Osteomyelitis With Vascular Insufficiency. Ref.: CID S115–22, 2004 Most pts are diabetics with Polymicrobic [Gm+ cocci Debride overlying ulcer & submit bone for histology & Diagnosis of osteo: Culture bone biopsy (gold standard). Poor concordance peripheral neuropathy & infected (to include MRSA) (aerobic culture. Select antibiotic based on culture results & treat of culture results between swab of ulcer and bone – need bone. (CID 42:57, skin ulcers (see Diabetic foot, & anaerobic) and Gm-neg. for 6 weeks. No empiric therapy unless acutely ill. If 63, 2006). Sampling by needle puncture inferior to biopsy (CID 48:888, 2009). 2 page 14) bacilli (aerobic & anaerobic)] acutely ill, see suggestions, Diabetic foot, page 14. Osteo more likely if ulcer >2 cm , positive probe to bone, ESR >70 & Revascularize if possible. abnormal plain x-ray (JAMA 299:806, 2008). Treatment: (1) Revascularize if possible; (2) Culture bone; (3) Specific antimicrobial(s). Chronic Osteomyelitis: S. aureus, Enterobacteria- Empiric rx not indicated. Base systemic rx on results of Important adjuncts: removal of orthopedic hardware, surgical debridement, Specific therapy ceae, P. aeruginosa culture, sensitivity testing. If acute exacerbation of chronic vascularized muscle flaps, distraction osteogenesis (Ilizarov) techniques. By definition, implies presence of osteo, rx as acute hematogenous osteo. Surgical Antibiotic-impregnated cement & hyperbaric oxygen adjunctive. dead bone. Need valid cultures debridement important. NOTE: RIF + (vanco or β-lactam) effective in animal model and in a clinical trial of S. aureus chronic osteo (SMJ 79:947, 1986). BREAST: Mastitis—Obtain culture; need to know if MRSA present. Review with definitions: Ob & Gyn Clin No Amer 29:89, 2002 Postpartum mastitis Mastitis without abscess S. aureus; less often NO MRSA: MRSA Possible: If no abscess, ↑ freq of nursing may hasten response; discuss age-specific Ref.: JAMA 289:1609, 2003 S. pyogenes (Gp A or B), Outpatient: Dicloxacillin Outpatient: TMP-SMX-DS risks to infant of drug exposure through breast milk with pediatrician. Coryne- E. coli, bacteroides species, 500 mg po qid or cepha- tabs 1-2 po bid or, if bacterium sp. assoc. with chronic granulomatous mastitis (CID 35:1434, maybe Corynebacterium lexin 500 mg po qid. susceptible, clinda 300 mg 2002). Bartonella henselae infection reported (Ob & Gyn 95:1027, 2000). sp., & selected coagulase- Inpatient: Nafcillin/oxacil- po qid Mastitis with abscess With abscess, d/c nursing. I&D standard; needle aspiration reported neg. staphylococci (e.g., lin 2 gm IV q4h Inpatient: Vanco 1 gm IV successful (Am J Surg 182:117, 2001). Resume breast feeding from affected S. lugdunensis) q12h; if over 100 kg, 1.5 gm breast as soon as pain allows. IV q12h. Non-puerperal mastitis with abscess S. aureus; less often Bacter- See regimens for If subareolar & odoriferous, most likely anaerobes; need to add metro oides sp., peptostreptococ- Postpartum mastitis, page 5. 500 mg IV/po tid. If not subareolar, staph. Need pretreatment cus, & selected coagulase- aerobic/anaerobic cultures. Surgical drainage for abscess. neg. staphylococci Breast implant infection Acute: S. aureus, S. Acute: Vanco 1 gm Chronic: Await culture results. Lancet Infect Dis 5:94, 462, 2005. Coag-negative staph also common pyogenes. TSS reported. IV q12h; if over 100 kg, See Table 12 for mycobacteria (Aesthetic Plastic Surg 31:325, 2007). Chronic: Look for rapidly 1.5 gm q12h. treatment. growing Mycobacteria Abbreviations on page 2. NOTE: All dosage recommendations are for adults (unless otherwise indicated) and assume normal renal function. 6 TABLE 1A (3) ANATOMIC SITE/DIAGNOSIS/ ETIOLOGIES SUGGESTED REGIMENS* ADJUNCT DIAGNOSTIC OR THERAPEUTIC MEASURES MODIFYING CIRCUMSTANCES (usual) § AND COMMENTS PRIMARY ALTERNATIVE CENTRAL NERVOUS SYSTEM Brain abscess Primary or contiguous source Streptococci (60–70%), bac- P Ceph 3 ([cefotaxime Pen G 3-4 million units IV q4h If CT scan suggests cerebritis or abscesses <2.5 cm and pt neurologically Ref.: CID 25:763, 1997 teroides (20–40%), Entero- 2 gm IV q4h or ceftriaxone + metro 7.5 mg/kg q6h or stable and conscious, start antibiotics and observe. Otherwise, surgical drainage bacteriaceae (25–33%), S. 2 gm IV q12h) + (metro 15 mg/kg IV q12h necessary. Experience with Pen G (HD) + metro without ceftriaxone or aureus (10–15%), S. milleri. 7.5 mg/kg q6h or nafcillin/oxacillin has been good. We use ceftriaxone because of frequency Rare: Nocardia (below) 15 mg/kg IV q12h)] of isolation of Enterobacteriaceae. S. aureus rare without positive blood Listeria (CID 40:907, 2005) culture; if S. aureus, include vanco until susceptibility known. Strep. milleri Duration of rx unclear; treat until response by neuroimaging group esp. prone to produce abscess. (CT/MRI) Post-surgical, post-traumatic S. aureus, Enterobacteria- For MSSA: (Nafcillin or For MRSA: Vanco 1 gm IV ceae oxacillin) 2 gm IV q4h + q12h + (ceftriaxone or (ceftriaxone or cefotaxime) cefotaxime) HIV-1 infected (AIDS) Toxoplasma gondii See Table 13A, page 134 Nocardia: Haematogenous N. asteroides & N. TMP-SMX: 15 mg/kg/day of TMP-SMX + amikacin as in Measure peak sulfonamide levels: target 100-150 mcg/mL 2 hrs post dose. basiliensis TMP & 75 mg/kg/day of primary and add IMP 500 mg Linezolid 600 mg po bid reported effective (Ann Pharmacother 41:1694, abscess SMX, IV/po div in 2-4 doses IV q6h. 2007). For in vitro susceptibility testing: Wallace (+1) 903-877-7680 or U.S. Ref: Can Med J 171:1063, 2004 + ceftriaxone 2 gm IV CDC (+1) 404-639-3158. If sulfonamide resistant or sulfa-allergic, amikacin q12h. If multiorgan plus one of: IMP, MER, ceftriaxone or cefotaxime. involvement some add amikacin 7.5 mg/kg q12h. After 3-6 wks of IV therapy, switch to po therapy. Immunocompetent pts: TMP-SMX, minocycline or AM-CL x 3+ months. Immunocompromised pts: Treat with 2 drugs for at least one year. Subdural empyema: In adult 60–90% are extension of sinusitis or otitis media. Rx same as primary brain abscess. Surgical emergency: must drain (CID 20:372, 1995). Review in LnID 7:62, 2007. Encephalitis/encephalopathy Herpes simplex, arbo- Start IV acyclovir while awaiting results of CSF PCR for H. Newly recognized strain of bat rabies. May not require a break in the skin to IDSA Guideline: CID 47:303, 2008. viruses, rabies, West Nile simplex. For amebic encephalitis see Table 13A. infect. Eastern equine encephalitis causes focal MRI changes in basal ganglia (For Herpes see Table 14A page 147, and other flaviruses. Rarely: and thalamus (NEJM 336:1867, 1997). Cat-scratch ref.: PIDJ 23:1161, 2004. and for rabies, Table 20D, page 199) listeria, cat-scratch disease; Ref. on West Nile & related viruses: NEJM 351:370, 2004. Parvovirus B19 amebic (CID 48:879, 2009). (CID 48:1713, 2009). Meningitis, “Aseptic”: Pleocytosis Enteroviruses, HSV-2, LCM, For all but leptospirosis, IV fluids and analgesics. D/C drugs If available, PCR of CSF for enterovirus. HSV-2 unusual without concomitant of 100s of cells, CSF glucose HIV, other viruses, drugs that may be etiologic. For lepto (doxy 100 mg IV/po q12h) genital herpes. Drug-induced aseptic meningitis: Inf In Med 25:331, 2008. normal, neg. culture for bacteria (NSAIDs, metronidazole, or (Pen G 5 million units IV q6h) or (AMP 0.5–1 gm IV q6h). For lepto, positive epidemiologic history and concomitant hepatitis, (see Table 14A, page 143) carbamazepine, TMP-SMX, Repeat LP if suspect partially-treated bacterial meningitis. conjunctivitis, dermatitis, nephritis. For complete list of implicated drugs: Inf Ref: CID 47:783, 2008 IVIG), rarely leptospirosis Med 25:331, 2008. Abbreviations on page 2. NOTE: All dosage recommendations are for adults (unless otherwise indicated) and assume normal renal function. 7 TABLE 1A (4) ANATOMIC SITE/DIAGNOSIS/ ETIOLOGIES SUGGESTED REGIMENS* ADJUNCT DIAGNOSTIC OR THERAPEUTIC MEASURES MODIFYING CIRCUMSTANCES (usual) § AND COMMENTS PRIMARY ALTERNATIVE CENTRAL NERVOUS SYSTEM (continued) Meningitis, Bacterial, Acute: Goal is empiric therapy, then CSF exam within 30 min. If focal neurologic deficit, give empiric therapy, then head CT, then LP. (NEJM 354:44,2006; Ln ID 7:191, 2007; IDSA Pract. Guid., CID 39:1267, 2004) NOTE: In children, treatment caused CSF cultures to turn neg. in 2 hrs with meningococci & partial response with pneumococci in 4 hrs (Peds 108:1169, 2001) Empiric Therapy—CSF Gram stain is negative—immunocompetent Age: Preterm to <1 mo Group B strep 49%, AMP + cefotaxime AMP + gentamicin Primary & alternative reg active vs Group B strep, most coliforms, & listeria. Ln 361:2139, 2003 E. coli 18%, listeria 7%, If premature infant with long nursery stay, S. aureus, enterococci, and resistant Intraventricular treatment not recommended. misc. Gm-neg. 10%, coliforms potential pathogens. Optional empiric regimens: [nafcillin + Repeat CSF exam/culture 24–36 hr after start of therapy misc. Gm-pos. 10% (ceftazidime or cefotaxime)]. If high risk of MRSA, use vanco + cefotaxime. For dosage, see Table 16 Alter regimen after culture/sensitivity data available. Age: 1 mo– 50 yrs S. pneumo, meningococci, Adult dosage: [(Cefotaxime [(MER 2 gm IV q8h) (Peds: For pts with severe pen. allergy: Chloro 12.5 mg/kg IV q6h (max. 4 gm/day) 1 See footnote for empiric H. influenzae now very rare, 2 gm IV q4–6h OR 40 mg/kg IV q8h)] + IV (for meningococcus) + TMP-SMX 5 mg/kg q6–8h (for listeria if immunocom- listeria unlikely if young & ceftriaxone 2 gm IV q12h)] dexamethasone + vanco promised) + vanco. Rare meningococcal isolates chloro-resistant (NEJM treatment rationale. 2 immuno-competent (add + (dexamethasone) + (see footnote ) 339:868, 1998). High chloro failure rate in pts with resistant S. pneumo (Ln 339: For meningococcal 2 3 ampicillin if suspect listeria: vanco (see footnote ). Peds: see footnote 405, 1992; Ln 342:240, 1993). So far, no vanco-resistant S. pneumo. immunization, 3 2 gm IV q4h) Peds: see footnote Value of dexamethasone documented in children with H. influenzae and see Table 20A, page 195. adults with S. pneumo (NEJM 347:1549 & 1613, 2002; NEJM 357:2431 & Dexamethasone: 0.15 mg/kg IV q6h x 2–4 days. Give with st 2441, 2007; LnID 4:139, 2004). Decreased inflammatory markers in adults or just before 1 dose of antibiotic to block TNF st (CID 49:1387, 2009). Give 1 dose 15–20 min. prior to or con-comitant production (see Comment). st 3 with 1 dose of antibiotic. Dose: 0.15 mg/kg IV q6h x 2–4 days. See footnote for rest of ped. dosage Age: >50 yrs or alcoholism S. pneumo, listeria, Gm-neg. (AMP 2 gm IV q4h) + MER 2 gm IV q8h + vanco + Severe penicillin allergy: Vanco 500–750 mg IV q6h + TMP-SMX 5 mg/kg or other debilitating assoc bacilli. (ceftriaxone 2 gm IV q12h IV dexamethasone. q6–8h pending culture results. Chloro has failed vs resistant S. pneumo diseases or impaired Note absence of meningo- or cefotaxime 2 gm IV q6h) For severe pen. Allergy, (Ln 342:240, 1993). cellular immunity coccus. + vanco + IV see Comment dexamethasone 2 For vanco dose, see footnote . Dexamethasone: st 0.15 mg/kg IV q6h x 2–4 days; 1 dose before or st concomitant with 1 dose of antibiotic. Post-neurosurgery, post- S. pneumoniae most Vanco (until known not MER 2 gm IV q8h + vanco Vanco alone not optimal for S. pneumo. If/when suscept. S. pneumo 2 head trauma, or post- common, esp. if CSF leak. MRSA) 500–750 mg IV q6h 1 gm IV q6–12h identified, quickly switch to ceftriaxone or cefotaxime. cochlear implant Other: S. aureus, coliforms, + (cefepime or ceftaz- If coliform or pseudomonas meningitis, some add intrathecal gentamicin (NEJM 349:435, 2003) P. aeruginosa idime 2 gm IV q8h)(see (4 mg q12h into lateral ventricles). Cure of acinetobacter meningitis with Comment) intraventricular or intrathecal colistin (JAC 53:290, 2004; JAC 58:1078, 2006). st Ventriculitis/meningitis due S. epidermidis, S. aureus, Vanco 500–750 mg IV q6h Vanco 500–750 mg IV q6h + Usual care: 1 , remove infected shunt & culture; external ventricular catheter to infected ventriculo- coliforms, diphtheroids + (cefepime or ceftazi- MER 2 gm IV q8h for drainage/pressure control; antimicrobic for 14 days. For timing of new peritoneal (atrial) shunt (rare), P. acnes dime 2 gm IV q8h) shunt, see CID 39:1267, 2004. If unable to remove shunt, consider intraventricular therapy; 4 for dosages, see footnote 1 Rationale: Hard to get adequate CSF concentrations of anti-infectives, hence MIC criteria for in vitro susceptibility are lower for CSF isolates (ArIM 161:2538, 2001). 2 Low & erratic penetration of vanco into the CSF (PIDJ 16:895, 1997); children’s dosage 15 mg/kg IV q6h (2x standard adult dose). In adults, max dose of 2-3 gm/day is suggested: 500–750 mg IV q6h. 3 Dosage of drugs used to treat children ≥1 mo of age: Cefotaxime 200 mg/kg per day IV div. q6–8h; ceftriaxone 100 mg/kg per day IV div. q12h; vanco 15 mg/kg IV q6h. 4 Dosages for intraventricular therapy. The following are daily adult doses in mg: amikacin 30, gentamicin 4–8, polymyxin E (Colistin) 10, tobramycin 5–20, vanco 10–20. Ref.: CID 39:1267, 2004. Abbreviations on page 2. NOTE: All dosage recommendations are for adults (unless otherwise indicated) and assume normal renal function. 8 TABLE 1A (5) ANATOMIC SITE/DIAGNOSIS/ ETIOLOGIES SUGGESTED REGIMENS* ADJUNCT DIAGNOSTIC OR THERAPEUTIC MEASURES MODIFYING CIRCUMSTANCES (usual) § AND COMMENTS PRIMARY ALTERNATIVE CENTRAL NERVOUS SYSTEM/Meningitis, Bacterial, Acute (continued) Empiric Therapy—Positive CSF Gram stain Gram-positive diplococci S. pneumoniae Either (ceftriaxone 2 gm IV q12h or cefotaxime 2 gm IV Alternatives: MER 2 gm IV q8h or Moxi 400 mg IV q24h. Dexamethasone q4–6h) + vanco 500–750 mg IV q6h + timed dexametha- does not block penetration of vanco into CSF (CID 44:250, 2007). sone 0.15 mg/kg q6h IV x 2–4 days. Gram-negative diplococci N. meningitidis (Cefotaxime 2 gm IV q4–6h or ceftriaxone 2 gm IV q12h) Alternatives: Pen G 4 mill. units IV q4h or AMP 2 gm q4h or Moxi 400 mg IV q24h or chloro 1 gm IV q6h Gram-positive bacilli or Listeria monocytogenes AMP 2 gm IV q4h ± gentamicin 2 mg/kg loading dose then If pen-allergic, use TMP-SMX 5 mg/kg q6–8h or MER 2 gm IV q8h coccobacilli 1.7 mg/kg q8h Gram-negative bacilli H. influenzae, coliforms, (Ceftazidime or cefepime 2 gm IV q8h) + gentamicin Alternatives: CIP 400 mg IV q8–12h; MER 2 gm IV q8h st P. aeruginosa 2 mg/kg 1 dose then 1.7 mg/kg q8h Specific Therapy—Positive culture of CSF with in vitro susceptibility results available. Interest in monitoring/reducing intracranial pressure: CID 38:384, 2004 H. influenzae β-lactamase positive Ceftriaxone (peds): 50 mg/kg IV q12h Pen. allergic: Chloro 12.5 mg/kg IV q6h (max. 4 gm/day.) Listeria monocytogenes AMP 2 gm IV q4h ± gentamicin 2 mg/kg loading dose, Pen. allergic: TMP-SMX 20 mg/kg per day div. q6–12h. One report of (CID 43:1233, 2006) then 1.7 mg/kg q8h greater efficacy of AMP + TMP-SMX as compared to AMP + gentamicin (JID 33:79, 1996). Alternative: MER 2 gm IV q8h. Success reported with linezolid + RIF (CID 40:908, 2005). N. meningitidis Pen MIC 0.1–1 mcg per mL Ceftriaxone 2 gm IV q12h x 7 days (see Comment); if β-lactam Rare isolates chloro-resistant (NEJM 339:868 & 917, 1998). allergic, chloro 12.5 mg/kg (up to 1 gm) IV q6h Alternatives: MER 2 gm IV q8h or Moxi 400 mg q24h. S. pneumoniae Pen G MIC Pen G 4 million units IV q4h or AMP 2 gm IV q4h Alternatives: Ceftriaxone 2 gm IV q12h, chloro 1 gm IV q6h <0.1 mcg/mL NOTES: 1. Assumes dexamethasone 0.1–1 mcg/mL Ceftriaxone 2 gm IV q12h or cefotaxime 2 gm IV q4–6h Alternatives: Cefepime 2 gm IV q8h or MER 2 gm IV q8h st just prior to 1 dose & ≥2 mcg/mL Vanco 500–750 mg IV q6h + (ceftriaxone or cefotaxime Alternatives: Moxi 400 mg IV q24h x 4 days. as above) 2. If MIC ≥1, repeat CSF exam after 24–48h. Ceftriaxone MIC ≥1 mcg/mL Vanco 500–750 mg IV q6h + (ceftriaxone or cefotaxime Alternatives: Moxi 400 mg IV q24h 3. Treat for 10–14 days as above) If MIC to ceftriaxone >2 mcg/mL, add RIF 600 mg 1x/day. E. coli, other coliforms, or P. Consultation advised— (Ceftazidime or cefepime 2 gm IV q8h) ± gentamicin Alternatives: CIP 400 mg IV q8–12h; MER 2 gm IV q8h. aeruginosa need susceptibility results For discussion of intraventricular therapy: CID 39:1267, 2004 Prophylaxis for H. influenzae and N. meningitides Haemophilus influenzae type b Children: RIF 20 mg/kg po (not to exceed 600 mg) q24h Household: If there is one unvaccinated contact ≤4 yr in the household, give Household and/or day care contact: residing with index x 4 doses. RIF to all household contacts except pregnant women. Child Care Facilities: case or ≥4 hrs. Day care contact: same day care as index Adults: RIF 600 mg q24h x 4 days With 1 case, if attended by unvaccinated children ≤2 yr, consider prophylaxis + case for 5–7 days before onset vaccinate susceptibles. If all contacts >2 yr: no prophylaxis. If ≥2 cases in 60 days & unvaccinated children attend, prophylaxis recommended for children & personnel (Am Acad Ped Red Book 2006, page 313). Abbreviations on page 2. NOTE: All dosage recommendations are for adults (unless otherwise indicated) and assume normal renal function. 9 TABLE 1A (6) ANATOMIC SITE/DIAGNOSIS/ ETIOLOGIES SUGGESTED REGIMENS* ADJUNCT DIAGNOSTIC OR THERAPEUTIC MEASURES MODIFYING CIRCUMSTANCES (usual) § AND COMMENTS PRIMARY ALTERNATIVE CENTRAL NERVOUS SYSTEM/Meningitis, Bacterial, Acute/Prophylaxis for H. influenzae and N. meningitides (continued) Prophylaxis for Neisseria meningitidis exposure [CIP (adults) 500 mg po single dose] OR Spread by respiratory droplets, not aerosols, hence close contact req. ↑ risk if (close contact) [Ceftriaxone 250 mg IM x 1 dose (child <15 yr 125 mg close contact for at least 4hrs during wk before illness onset (e.g., housemates, NOTE: CDC reports CIP-resistant group B IM x 1)] OR day care contacts, cellmates) or exposure to pt’s nasopharyngeal secretions meningococcus from selected counties in N. Dakota [RIF 600 mg po q12h x 4 doses. (Children >1 mo 10 mg/kg (e.g., kissing, mouth-to-mouth resuscitation, intubation, nasotracheal & Minnesota. Use ceftriaxone, RIF, or single 500 mg dose po q12h x 4 doses, <1 mo 5 mg/kg q12h x 4 doses)] suctioning). Since RIF-resistant N. meningitidis documented, post-exposure of azithro (MMWR 57:173, 2008). OR prophylaxis with CIP or ceftriaxone preferred (EID 11:977, 2005). NUS Spiramycin 500 mg po q6h x 5 days. Primary prophylactic regimen in many European countries. Children 10 mg/kg po q6h x 5 days. Meningitis, chronic M. tbc 40%, cryptococcosis Treatment depends on etiology. No urgent need for empiric Long list of possibilities: bacteria, parasites, fungi, viruses, neoplasms, Defined as symptoms + CSF 7%, neoplastic 8%, Lyme, therapy, but when TB suspected treatment should be vasculitis, and other miscellaneous etiologies—see chapter on chronic pleocytosis for ≥4 wks syphilis, Whipple’s disease expeditious. meningitis in latest edition of Harrison’s Textbook of Internal Medicine. Whipple’s: JID 188:797 & 801, 2003. Meningitis, eosinophilic Angiostrongyliasis, gnatho- Corticosteroids Not sure antihelminthic 1/3 lack peripheral eosinophilia. Need serology to confirm diagnosis. Steroid LnID 8:621, 2008 stomiasis, baylisascaris therapy works ref.: CID 31:660, 2001; LnID 6:621, 2008. Automated CSF count may not correctly identify eosinophils (CID 48: 322, 2009). Meningitis, HIV-1 infected (AIDS) As in adults, >50 yr: also If etiology not identified: For crypto rx, see Table 11A, C. neoformans most common etiology in AIDS patients. H. influenzae, See Table 11, Sanford Guide to consider cryptococci, M. treat as adult >50 yr + page 106 pneumococci, Tbc, syphilis, viral, histoplasma & coccidioides also need to be HIV/AIDS Therapy tuberculosis, syphilis, HIV obtain CSF/serum crypto- considered. Obtain blood cultures. L. monocytogenes risk >60x ↑, ¾ present aseptic meningitis, Listeria coccal antigen as meningitis (CID 17:224, 1993). monocytogenes (see Comments) EAR External otitis Chronic Usually 2° to seborrhea Eardrops: [(polymyxin B + neomycin + hydrocortisone Control seborrhea with dandruff shampoo containing selenium sulfide qid) + selenium sulfide shampoo] (Selsun) or [(ketoconazole shampoo) + (medium potency steroid solution, triamcinolone 0.1%)]. Fungal Candida species Fluconazole 200 mg po x 1 dose & then 100 mg po x 3-5 days. “Malignant otitis externa” Pseudomonas aeruginosa (IMP 0.5 gm IV q6h) or (MER 1 gm IV q8h) or [CIP CIP po for treatment of early disease. Debridement usually required. R/O Risk groups: Diabetes mellitus, in >90% 400 mg IV q12h (or 750 mg po q12h)] or (ceftaz 2 gm IV osteomyelitis: CT or MRI scan. If bone involved, treat for 4–6 wks. PIP without AIDS, chemotherapy. Ref: q8h) or (CFP 2 gm q12h) or (PIP 4–6 gm IV q4–6h + tobra) Tazo may be hard to find: extended infusion of PIP-TZ (4 hr infusion of Oto Clinics N Amer 41:537, 2008 or (TC 3 gm IV q4h + tobra dose Table 10D) 3.375 gm every 8h) may improve efficacy (CID 44:357, 2007). “Swimmer’s ear” Pseudomonas sp., Entero- Eardrops: Oflox 0.3% soln bid or [(polymyxin B + neo- Rx includes gentle cleaning. Recurrences prevented (or decreased) PIDJ 22:299, 2003 bacteriaceae, Proteus sp. mycin + hydrocortisone) qid] or (CIP + hydrocortisone by drying with alcohol drops (1/3 white vinegar, 2/3 rubbing alcohol) after (Fungi rare.) Acute infection bid) --active vs gm-neg bacilli. swimming, then antibiotic drops or 2% acetic acid solution. Ointments should usually 2° S. aureus For acute disease: dicloxacillin 500 mg po 4x/day. If MRSA not be used in ear. Do not use neomycin drops if tympanic membrane a concern, use TMP-SMX, doxy or clinda punctured. Abbreviations on page 2. NOTE: All dosage recommendations are for adults (unless otherwise indicated) and assume normal renal function.