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Microbiology: Treatment of CNS and Respiratory Tract Infections (Pogue) BACTERIAL MENINGITIS: General Treatment Considerations: o IV therapy at MAX dose o Bactericidal drugs preferred o BBB decreases amount of drug that gets to the site of action (to a variable degree, depending on the drug) o Fast, appropriate therapy saves lives Antibiotic Penetration into CSF: o Probably Sufficient Agents: 3rd/4th generation cephalosporins (as good as it gets) Penicillin (not benzathine) Apicillin Vancomycin TMP/SMX FQs Metronidazole o Probably Insufficient Agents: Tetracyclines Aminiglycosides Polymixins Treatment Broken Down by Age: <1 Month: o Causative Agents: S.agalactiae (GBS) E.coli L.monocytogenes Klebsiella o Empiric Therapy: Important Point: children less than 1 month old do NOT have an intact BBB (do not have to worry about selecting drugs that will penetrate well) Possibilities: Ampicillin + gentamicin Ampicillin + cefotaxime (NOT CEFTRIAXONE, because of contraindication( 1-23 Months: o Causative Agents: S.pneumoniae N.meningitidis S.agalactiae H.influenzae (maybe, depends on vaccination status) E.coli o Empiric Therapy: Vancomycin + 3rd generation cephalosporin Vancomycin added for S.pneumo that is slightly resistant (elevated MICs) to 3rd generation cephalosporins While this is normally not an issue in other infections (recall= 3 rd gens can overcome resistance by binding tighter to PBP), this IS an issue in CNS infections because of variable penetration of the BBB 2-50 Years: o Causative Agents: N.meningitidis S.pneumoniae H.influenzae (if unvaccinated) o Empiric Therapy: Vancomcyin + 3rd generation cephalosphorin + dexamethasone o Dexamethasone: IV steroid give 4 x a day for 4 days Given to decrease inflammation in subarachnoid space to decrease neurologic sequelae Mortality benefit thought to outweigh immunossupression Important Point: need to give PRIOR to first antibiotic dose; if already received, don’t give - >50 Years: o Causative Agents: S.pneumoniae N.meningitidis L.monogytogenes Gram negatives o Empiric Therapy: Vancomycin + 3rd generation cephalosporin + ampicillin (for Listeria) Listeria (Important Points): - HELPS Bug: o Ampicillin is DOC o Others: TMP/SMX Meropenem Gentamicin sometimes added as adjunct (despite penetration issues) Summary: o Most common causative agents for most patients: S.pneumo and N.meningitidis High dose 3rd generation cephalosporins (ceftriaxone) High dose vancomycin added to cover for ceftriaxone resistant S.pneumo o Extremes of age need Listeria coverage: High dose ampicillin o Avoid ceftriaxone in neonates o Duration of Treatment: between 7-21 days and vary by bug (generally 14-21) Prophylaxis: o N.meningitidis: Who: treat household contacts and people exposed to oral secretions DOC: ciprofloxacin 500 mg x 1 dose Others: Rifampin x 2 days IM Ceftriaxone o H.influenzae: Who: everyone in the household with unvaccinated children DOC: rifampin CNS Shunt Infections (Special Populations): o Causative Agents: most often skin bugs Mostly: coagulase negative staph Others: S.aureus, GNR, streptococci Note: staph species account for ~75% of infections o Treatment: Gram stain for pathogen and start on broad spectrum antibiotics Vancomycin + cefepime Vancomycin + pip/tazo May use intraventricular antibiotics as adjunctive therapy Remove shunt if possible (gets rid of source of infection) Once cultures come back, de-escalate therapy to target specific organism o Duration: treat for 7-21 days then put shunt back in if possible Fungal CNS Infections: o Cryptococcal Meningitis: often seen in HIV patients Treatment: Lipid Amphotericin B + Flucystine for 2 weeks THEN Fluconazole 400mg PO once daily for 8 weeks o Blastomycoses and Histoplasmosis: Treatment: Lipid Amphotericin B for 4-6 weeks THEN Oral azole (flu, itra, vori) for 12 months (long treatment because associated with relapse) o Coccidiomycoses: Treatment: high dose fluconazole (although some clinicians will still use amphotericin B) ACUTE BRONCHITIS: Basics: o Vast majority of cases are viral: antibiotics will NOT help; in this case, symptomatic treatment is mainstay o Exceptions: Bordetella pertussis Influenza Mycoplasma Chlamydia Treatment: o Influenza: vaccination is key (minimal efficacy with antivirals) o B.pertussis: Standard: macrolides Others: tetracyclines, TMP/SMX o Mycoplasma and Chlamydia: addressed in next section COPD EXACERBATION: Only some get antibiotics: need to have 3 cardinal symptoms (only need 2/3 if one is increased purulence) o Increased dyspnea o Increased sputum volume o Increased sputum purulence Common causative agents: o S.pneumo o H.influenzae o M.cattarhalis o Chlamydia pneumo o Mycoplasma pneumo Treatment: o Oral therapy for mild-moderate infection: Amoxicillin (+/- clavulanic acid) Doxycyclin TMP/SMX Macrolides FQs o IV therapy considered for patients with risk factors for poor outcome: co-morbidities, severe COPD, frequent exacerbations, recent antimicrobial use Ampicillin/sulbactam 2nd/3rd generation cephalosporins FQs o If risk factors for P.aeruginosa exist: Oral FQs (only cipro and levo; if oral therapy is indicated) Many other options with IV therapy o Duration: correlates with clinical improvement, generally 3-7 days (can be very short) PNEUMONIA: CAP: Causative Agents (“the big 6”): o S.pneumo o H.influenzae o M.cattarhalis o M.pneumo o C.pneumo o Legionella pneumophilia Others: o S.aureus (increasing incidence of CA-MRSA; needs to be considered in some cases) Post-influenza infection (secondary staph infection) Severe or necrotizing infections o Oral anaerobes (aspiration pneumonia) - Outpatient Therapy: o If previously healthy and no risk for drug-resistant S.pneumo: Macrolide (azithro) Doxycycline o If presence of co-morbidities, Immunosuppression or recent antibiotic exposures: at risk for more drug resistant forms of S.pneumo B-lactam + macrolide B-lactam + doxyclcine High dose amoxicillin (+/- clavulanic acid) High dose 2nd/3rd generation cephalosporins o Some areas have high macrolide resistance: avoid using them in these areas Inpatient Therapy: o Non-ICU: 3rd generation cephalosporin + macrolide/doxycycline Respiratory FQ (moxi or levo) o ICU: IV therapy is necessary 3rd generation cephalosporin + macrolide (no doxy substitution) Add vancomycin if concern for MRSA Aspiration Pneumonia: o Need to cover for oral anaerobes: recall that metronidazole is NOT good at this (but clindamycin is) o Outpatient: Clindamycin Amox/clav Moxifloxacine o Inpatient: Amp/sulbactam Clindamycin Moxifloxacin Duration of Therapy: o Minimum of 5 days o Once past 5 days, discontinue if: Afebrile for 48-72 hours No more than one CAP related sign of instability: Fever Leukocytosis Heart rate Respiratory rate HAP/HCAP/VAP: Basics: o All caused by the same agents o Start treatment broadly (appropriate empiric therapy saves lives) o Obtain cultures to de-escalate therapy Causative Agents: o P.aerugiosa o S.aureus (MRSA) o E.coli o K.pneumoniae o Enterobacter spp. o Serratia o A.baumannii Empiric Therapy: o 3 drug combination: Anti-pseudomonal B-lactam: cefepime, ceftazadime, pip/tazo, meropenem, doripenem, imipenem, aztreonam PLUS Anti-pseudomonal FQ of AMG: cipro, levo, gentamicin, tobramicin, amikacin PLUS MRSA agent: vancomycin or linezolid Note on Acinetobacter baumannii: o Resistant to most Abx: if it is prevalent where you are, your empiric regimen may be different - Duration of Therapy: o New Guidelines: 7-8 day course if infection is caused by agent other than pseudoomas or acinetobacter 14 days if caused by pseudomonas or acinetobacter De-escalation once cultures come back: o If not MRSA: ditch the Gram (+) coverage (get rid of vanco/linezolid) o Do I keep patient on both G (-) drugs? Generally, streamline down to ONE drug: most narrow spectrum agent possible Possible exception is pseudomonas: In vitro synergy has been shown (although not shown in patients) Resistance development common Important point: some doctors WILL use 2 agents for pseudomonas, but there has never been any data to show this is effective (just use one!) Strenotropomonas maltophilia: sometimes seen in hospital setting as cause of nosocomial pneumonia o DOC: TMP/SMX o Others: Ticarcillin/clavulanic acid Moxifloxacin Tigecycline Cystic Fibrosis Patients: o Have extremely high metabolism rate for antimicrobials: doses often exceed what we generally consider max doses o Aerosolized antibiotics: directly inhaled; goal is often suppression of organism (not eradication), and aerosolized Abx have been shown to be useful for this o Odd organisms may be seen: due to the high number of antibiotics they receive Burkholderia cepacia INFLUENZA: Vaccination: key to preventing acquisition/transmission Treatment: only modestly effective o Few agents o High resistance o Must start treatment early in disease course o Will only decrease duration and severity o Severely ill patients will often get longer courses of antivirals