Infectious Diseases in Critical Care Medicine

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Patients with MDRP. aeruginosaurosepsis following urological instrumentation/procedures
may be effectively treated with colistin, polymyxin B, or doripenem (6–10).
For the empiric treatment of NP/VAP whereP. aeruginosa is the most important
therapeutic consideration, a variety of anti-pseudomonal antibiotics may be used with
susceptible strains. Piperacillin/tazobactam plus amikacin, meropenem, or cefepime may be
used for the empiric treatment of MDRP. aeruginosapresumed NP/VAP. There are relatively
few anti-pseudomonal antibiotics that are effective and reach therapeutic concentrations in the
lung. Empiric treatment of potential MDR P. aeruginosaNP/VAP may be initially with
meropenem. If the MDRP. aeruginosaisolate is meropenem resistant, then doripenem, colistin,
or polymyxin B may be effective (6,7,11–16).


MDRK. pneumoniae


Epidemiological Considerations
K. pneumoniaeis an aerobic GNB that colonizes respiratory secretions and urine. It is a common
cause of severe community-acquired pneumonia (CAP) in alcoholics, but not nonalcoholics.
K. pneumoniaeis also among the aerobic GNB pathogens causing NP/VAP. It is an infrequent,
but important cause of central venous catheter (CVC) infections as withP. aeruginosa.
Excluding IV line infections,K. pneumoniaeis a common colonizer and an infrequent pathogen
in immunocompetent hosts (7,17,18).
K. pneumoniaecauses a more slowly cavitating necrotic pneumonia than MSSA/MRSA or
P. aeruginosa.On CXR/chest CT,cavitation withK. pneumoniaeCAP or NP occurs after three to
five days.K. pneumoniaemay cause NP in normal hosts but only causes CAP in alcoholics.
WhenKlebsiella pneumoniaeis the pathogen,K. pneumoniaeis difficult to eradicate because it
produces abundant material that resists phagocytosis and antibiotic penetration (7,10).


K. pneumoniae Infections
K. pneumoniaeCAP or NP/VAP may be treated optimally using monotherapy with third-
generation cephalosporin (excludingceftazidime) or a carbapenem. The addition of another
antibiotic for possible synergy, i.e., an aminoglycoside, azthreonam, fluoroquinolone is
unnecessary and may be antagonistic or may increase resistance potential.
For K. pneumoniae urosepsis amikacin, third-generation cephalosporins (excluding
ceftazidime) or meropenem are useful. ForK. pneumoniae CAB, oral cephalosporins are
usually effective after urinary catheter removal/replacement. ForK. pneumoniaeCVC line
infections, the primary therapeutic intervention is CVC removal. When the CVC is removed,
antimicrobial therapy should be continued for seven days post-CVC removal (7,17,18).


Antibiotic Therapy of MDR K. pneumoniae Infections
Classically,K. pneumoniaeis susceptible to cephalosporins and aminoglycosides. Aminoglyco-
sides have modest anti-Klebsiella activity but cephalosporins are highly active against
K. pneumoniae. Traditionally, double-drug antibiotic therapy was used to treat serious systemic
K. pneumoniaeinfections because the available antibiotics, i.e., aminoglycosides, had limited
anti-K. pneumoniaeactivity and first-generation cephalosporins were combined with amino-
glycosides for potential synergy. Currently, the anti-K. pneumoniaeactivity of third-generation
cephalosporins, or carbapenems, and tigecycline provide the optimal therapy.
Most strains of community-acquiredK. pneumoniaeare susceptible and not MDR variety.
Nosocomial K. pneumoniae infections, i.e., NP/VAP, urosepsis, and particularly, CAB
infections are often of the MDR variety. MDRK. pneumoniaeare often extended-spectrum
beta-lactamases (ESBL) or carbapenemase (KPC) producers. In some cases metallobeta-
lactamases are an emerging problem among MDRK. pneumoniaeisolates. Such highly resistant
MDRK. pneumoniaestrains are often almost pan-antibiotic resistant. Frequently such MDRK.
pneumoniaestrains are susceptible only to gentamicin or tigecycline (6,7,10,17,18).
For MDRK. pneumoniaenosocomial urosepsis or NP/VAP due to empiric therapy with
tigecyclinegentamicin is effective and often is the only choice available. Because*33% of
tigecycline is excreted into the urine, therapeutic urinary concentrations may not be achievable
with the usual tigecycline dosing, i.e., 100 mg (IV)1 dose followed by 50 mg (IV) q12h. Since


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