Medication Summary
The following is a discussion on the specific agents used in the antimicrobial therapy of Klebsiella infections. In vitro data show that a wide range of beta-lactams, aminoglycosides, quinolones, and other antibiotics are useful for treatment of klebsiellae infections. [19, 20, 21]
Cephalosporins have been widely used as monotherapy and in combination with aminoglycosides. Cephalosporins should be avoided if ESBL strains are present. In such instances, the carbapenems, especially imipenem, are effective.
Aztreonam and quinolones are useful in patients allergic to penicillin, and rifampin has been used for treatment of rhinoscleroma. TMP/SMZ is not used in primary treatment of pneumonia. They may be used as initial treatment in uncomplicated UTI and as second-line agents for ozena.
For isolates that produce ESBLs and carbapenemases, see Treatment.
Antibiotics
Class Summary
Therapy must cover all likely pathogens in the context of this clinical setting. Antibiotic selection should be guided by culture and sensitivity results whenever feasible.
Cefotaxime (Claforan)
Useful for most Klebsiella infections. Third-generation cephalosporin with gram-negative activity. Arrests bacterial cell wall synthesis, which, in turn, inhibits bacterial growth.
Ceftriaxone
Effective for K pneumoniae meningitis and other Klebsiella infections. Third-generation cephalosporin with broad-spectrum, gram-negative activity and higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.
Gentamicin
Aminoglycoside antibiotic for gram-negative coverage. Bactericidal drug that may be used synergistically with third-generation cephalosporins. Works by binding the bacterial 30S ribosomal subunit, thereby inhibiting protein synthesis. Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be given IV/IM. Monitoring may be required because of the potential to cause cochlear, vestibular, and tubular damage.
Amikacin
For gram-negative bacterial coverage of infections resistant to gentamicin and tobramycin. Irreversibly binds to 30S subunit of bacterial ribosomes, blocks recognition step in protein synthesis, and causes growth inhibition. The same principles of drug monitoring for gentamicin apply to amikacin.
Piperacillin/tazobactam (Zosyn)
Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication.
Imipenem/cilastatin (Primaxin)
When given alone, this beta-lactam carbapenem antibiotic is metabolized by renal dehydropeptidase I, resulting in metabolites toxic to the proximal tubule. Cilastatin is an inhibitor of this enzyme, ensuring adequate levels of imipenem.
Ciprofloxacin (Cipro)
Indicated for a variety of Klebsiella infections. May be used PO or IV. Inhibits bacterial DNA synthesis and, consequently, growth.
Aztreonam (Azactam)
Monobactam inhibits cell wall synthesis during bacterial growth. Active against gram-negative bacilli. Bactericidal.
Rifampin (Rifadin)
Inhibits DNA-dependent bacterial RNA polymerase. Indicated as second-line agent in select klebsiellae infections.
Trimethoprim/sulfamethoxazole (Bactrim, Bactrim DS, Sulfatrim Pediatric)
Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens except Pseudomonas aeruginosa. Indicated as second-line agent for select infections. Not used for routine treatment of pneumonia.
Ampicillin/sulbactam (Unasyn)
This agent features ampicillin combined with a beta-lactamase inhibitor. It interferes with bacterial cell wall synthesis during active replication, causing bactericidal activity against susceptible organisms.
Ceftazidime (Fortaz, Tazicef)
Ceftazidime is a third-generation cephalosporin with broad-spectrum activity against gram-negative organisms, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms. By binding to 1 or more of the penicillin-binding proteins, it arrests bacterial cell wall synthesis and inhibits bacterial replication.
Cefepime (Maxipime)
Cefepime is a fourth-generation cephalosporin. Its gram-negative coverage is comparable to ceftazidime, but it has better gram-positive coverage (comparable to ceftriaxone). Cefepime is a zwitterion; it rapidly penetrates gram-negative cells. Cefepime is the best beta-lactam for intramuscular administration. Its poor capacity to the cross blood-brain barrier precludes its use for meningitis.
Meropenem (Merrem)
Meropenem is a bactericidal broad-spectrum carbapenem antibiotic. Inhibits bacterial cell wall synthesis by binding to several of the penicillin-binding proteins, which in turn inhibits cell wall biosynthesis. It is effective against most gram-positive and gram-negative bacteria.
Ertapenem (Invanz)
Bactericidal activity results from inhibition of cell wall synthesis and is mediated through ertapenem binding to penicillin-binding proteins. Stable against hydrolysis by a variety of beta-lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases. Hydrolyzed by metallo-beta-lactamases.
Ceftazidime/avibactam (Avycaz)
Indicated for the treatment of complicated intra-abdominal infections, in combination with metronidazole, and complicated UTI caused by designated susceptible microorganisms.
Meropenem/vaborbactam (Vabomere)
Indicated for complicated urinary tract infections (cUTI) caused by carbapenem-resistant Enterobacteriaceae (CRE). Vaborbactam is a nonsuicidal beta-lactamase inhibitor that protects meropenem from degradation by certain serine beta-lactamases such as K pneumoniae carbapenemase (KPC). Vaborbactam does not have any antibacterial activity and does not decrease the activity of meropenem against meropenem-susceptible organisms.
Levofloxacin (Levaquin, Levofloxacin)
Levofloxacin is a second-generation quinolone that acts by interfering with DNA gyrase in bacterial cells. It is bactericidal and is highly active against gram-negative and gram-positive organisms, including Pseudomonas aeruginosa.
Moxifloxacin (Avelox)
Inhibits the A subunits of DNA gyrase, resulting in inhibition of bacterial DNA replication and transcription. Its activity is similar to that of ciprofloxacin and levofloxacin.
Colistin (Coly Mycin M)
Prodrug hydrolyzed to colistin, which acts as cationic detergent and damages bacterial cytoplasmic membrane, causing leaking of intracellular substances and cell death.
Tigecycline (Tygacil)
A glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. Inhibits bacterial protein translation by binding to 30S ribosomal subunit and blocks entry of amino-acyl tRNA molecules in ribosome A site. Indicated for complicated skin and skin structure infections.
Metronidazole (Flagyl, Flagyl ER, Metro)
An imidazole ring-based antibiotic that is active against anaerobes. It is usually given in combination with other antimicrobial agents, except in the setting of Clostridium difficile enterocolitis, in which monotherapy is appropriate.
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This scanning electron micrograph (SEM) reveals some of the ultrastructural morphologic features of Klebsiella pneumoniae. Courtesy of CDC/Janice Carr.
