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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
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>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
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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
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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