Enterobacter Infections Medication
- Author: Susan L Fraser, MD; Chief Editor: Burke A Cunha, MD more...
Medication Summary
The goals of pharmacotherapy are to eradicate the infection, to reduce morbidity, and to prevent complications.
Antibiotics
Class Summary
The antimicrobials most indicated in Enterobacter infections include carbapenems, fourth-generation cephalosporins, aminoglycosides, fluoroquinolones, and TMP-SMZ.
Carbapenems continue to have the best activity against E cloacae, E aerogenes, and other Enterobacter species.[33] They are not affected by ESBLs. Imipenem-cilastatin and meropenem are used most often. Ertapenem, approved more recently, is gaining clinical experience.[34] Doripenem, approved in the United States in 2007, appears to be as effective as the other carbapenems.
First-generation and second-generation cephalosporins are inactive against Enterobacter infections. Third-generation cephalosporins frequently show good in vitro activity against these organisms, but, as explained above, a significant risk of developing full resistance during therapy exists. Resistance develops much less frequently with fourth-generation cephalosporins because they are relatively stable to AmpC beta-lactamase but not (so far) to the less frequently encountered ESBLs (see Medical Care). Third-generation cephalosporins are not indicated for the treatment of severe Enterobacter infections, perhaps with the notable exception of uncomplicated infections.
Fluoroquinolones have good bactericidal activity against gram-negative bacilli; their bioavailability ranges from very good to excellent (with the exception of norfloxacin). Newer quinolones have increased their spectrum toward gram-positive organisms and, in some cases, toward anaerobes. Ciprofloxacin and levofloxacin have the best activity against gram-negative bacilli and should generally be selected over the newer fluoroquinolones if clinically indicated.
Polymyxin B
Binds to phospholipids, alters permeability, and damages bacterial cytoplasmic membrane.
Levofloxacin (Levaquin)
In addition to ciprofloxacin, levofloxacin is an alternative choice. It has the advantage of once daily dosing, whether administered IV or PO.
Used for pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.
Doripenem (Doribax)
Carbapenem antibiotic. Doripenem is a new alternative choice. Has spectrum of activity similar to that of imipenem and meropenem (Fritsche, 2005; Mushtaq, 2004).
Elicits activity against a wide range of gram-positive and gram-negative bacteria. Indicated as a single agent for complicated intra-abdominal infections caused by susceptible strains of E coli, K pneumoniae, P aeruginosa, Bacteroides caccae, Bacteroides fragilis, Bacteroides thetaiotaomicron, Bacteroides uniformis, Bacteroides vulgatus, Streptococcus intermedius, Streptococcus constellatus, and Peptostreptococcus micros.
Imipenem/cilastatin (Primaxin)
For treatment of multiple-organism infections in which other agents do not have wide-spectrum coverage or are contraindicated because of potential toxicity. DOC for severe Enterobacter infections, except for meningitis and other CNS infections because of some reports indicating higher seizure potential. Hydrolyzed by the renal dehydropeptidase-1. To overcome this urinary inactivation, cilastatin, an inhibitor of this renal enzyme, is administered in equal amounts.
Meropenem (Merrem IV)
Alternative to imipenem for severe Enterobacter infections. Carbapenem of choice for meningitis and for patients at risk for seizures. Bactericidal broad-spectrum carbapenem antibiotic that inhibits cell wall synthesis. Effective against most gram-positive and gram-negative bacteria. Not degraded by renal dehydropeptidase-1. Has slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci compared to imipenem.
Cefepime (Maxipime)
Fourth-generation cephalosporin with good gram-negative coverage. Similar to third-generation cephalosporins but has better gram-positive coverage.
Ciprofloxacin (Cipro)
Fluoroquinolone with good activity against pseudomonads and most gram-negative organisms, but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth. Among fluoroquinolones, ciprofloxacin has the best activity against the gram-negative bacilli (including Enterobacter). IV and PO formulations available. Oral bioavailability is approximately 80%.
Trimethoprim-sulfamethoxazole (Septra, Bactrim)
Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Antibacterial activity of TMP-SMZ includes common urinary tract pathogens, except P aeruginosa. Susceptibility of Enterobacter generally good but varies among centers.
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 various beta-lactamases, including penicillinases, cephalosporinases, and extended-spectrum beta-lactamases. Hydrolyzed by metallo-beta-lactamases.
Tigecycline (Tygacil)
This drug is FDA approved for complicated intra-abdominal or skin and soft-tissue infections. 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. Complicated intra-abdominal infections caused by C freundii, E cloacae, E coli, K oxytoca, K pneumoniae, E faecalis (vancomycin-susceptible isolates only), S aureus (methicillin-susceptible isolates only), S anginosus group (includes S anginosus, S intermedius, S constellatus), B fragilis, B thetaiotaomicron, B uniformis, B vulgatus, C perfringens, and P micros.
Lockhart SR, Abramson MA, Beekmann SE, et al. Antimicrobial resistance among Gram-negative bacilli causing infections in intensive care unit patients in the United States between 1993 and 2004. J Clin Microbiol. Oct 2007;45(10):3352-9. [Medline].
Hidron AI, Edwards JR, Patel J, Horan TC, Sievert DM, Pollock DA. NHSN annual update: antimicrobial-resistant pathogens associated with healthcare-associated infections: annual summary of data reported to the National Healthcare Safety Network at the Centers for Disease Control and Prevention, 2006-2007. Infect Control Hosp Epidemiol. Nov 2008;29(11):996-1011. [Medline].
National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) report, data summary from October 1986-April 1997, issued May 1997. A report from the NNIS System. Am J Infect Control. Dec 1997;25(6):477-87. [Medline].
National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System report, data summary from January 1990-May 1999, issued June 1999. Am J Infect Control. Dec 1999;27(6):520-32. [Medline].
National Nosocomial Infections Surveillance System. National Nosocomial Infections Surveillance (NNIS) System Report, data summary from January 1992 through June 2004, issued October 2004. Am J Infect Control. Dec 2004;32(8):470-85. [Medline].
National Nosocomial Infections Surveillance System. Intensive Care Antimicrobial Resistance Epidemiology (ICARE) Surveillance Report, data summary from January 1996 through December 1997: A report from the National Nosocomial Infections Surveillance (NNIS) System. Am J Infect Control. Jun 1999;27(3):279-84. [Medline].
Rossi F, Baquero F, Hsueh PR, et al. In vitro susceptibilities of aerobic and facultatively anaerobic Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: 2004 results from SMART (Study for Monitoring Antimicrobial Resistance Trends). J Antimicrob Chemother. Jul 2006;58(1):205-10. [Medline].
Chow JW, Satishchandran V, Snyder TA, et al. In vitro susceptibilities of aerobic and facultative gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: the 2002 Study for Monitoring Antimicrobial Resistance Trends (SMART). Surg Infect (Larchmt). Winter 2005;6(4):439-48. [Medline].
Deal EN, Micek ST, Ritchie DJ, et al. Predictors of in-hospital mortality for bloodstream infections caused by Enterobacter species or Citrobacter freundii. Pharmacotherapy. Feb 2007;27(2):191-9. [Medline].
Ye Y, Li JB, Ye DQ, et al. Enterobacter bacteremia: Clinical features, risk factors for multiresistance and mortality in a Chinese University Hospital. Infection. Oct 2006;34(5):252-7. [Medline].
Gallagher PG, Ball WS. Cerebral infarctions due to CNS infection with Enterobacter sakazakii. Pediatr Radiol. 1991;21(2):135-6. [Medline].
Drudy D, Mullane NR, Quinn T, et al. Enterobacter sakazakii: an emerging pathogen in powdered infant formula. Clin Infect Dis. Apr 1 2006;42(7):996-1002. [Medline].
Iversen C, Lehner A, Mullane N, Marugg J, Fanning S, Stephan R, et al. Identification of "Cronobacter" spp. (Enterobacter sakazakii). J Clin Microbiol. Nov 2007;45(11):3814-6. [Medline].
Palmer DL, Kuritsky JN, Lapham SC, et al. Enterobacter mediastinitis following cardiac surgery. Infect Control. Mar 1985;6(3):115-9. [Medline].
Tunkel AR, Fisch MJ, Schlein A, et al. Enterobacter endocarditis. Scand J Infect Dis. 1992;24(2):233-40. [Medline].
Durand ML, Calderwood SB, Weber DJ, et al. Acute bacterial meningitis in adults. A review of 493 episodes. N Engl J Med. Jan 7 1993;328(1):21-8. [Medline].
Maki DG, Weise CE, Sarafin HW. A semiquantitative culture method for identifying intravenous-catheter-related infection. N Engl J Med. Jun 9 1977;296(23):1305-9. [Medline].
Paterson DL. Resistance in gram-negative bacteria: enterobacteriaceae. Am J Med. Jun 2006;119(6 Suppl 1):S20-8; discussion S62-70. [Medline].
Ratnam I, Franklin C, Spelman DW. In vitro activities of 'new' and 'conventional' antibiotics against multi-drug resistant Gram negative bacteria from patients in the intensive care unit. Pathology. Dec 2007;39(6):586-8. [Medline].
Reinert RR, Low DE, Rossi F, et al. Antimicrobial susceptibility among organisms from the Asia/Pacific Rim, Europe and Latin and North America collected as part of TEST and the in vitro activity of tigecycline. J Antimicrob Chemother. Nov 2007;60(5):1018-29. [Medline].
Halstead DC, Abid J, Dowzicky MJ. Antimicrobial susceptibility among Acinetobacter calcoaceticus-baumannii complex and Enterobacteriaceae collected as part of the Tigecycline Evaluation and Surveillance Trial. J Infect. Jul 2007;55(1):49-57. [Medline].
DiPersio JR, Dowzicky MJ. Regional variations in multidrug resistance among Enterobacteriaceae in the USA and comparative activity of tigecycline, a new glycylcycline antimicrobial. Int J Antimicrob Agents. May 2007;29(5):518-27. [Medline].
Ritchie DJ, Alexander BT, Finnegan PM. New antimicrobial agents for use in the intensive care unit. Infect Dis Clin North Am. Sep 2009;23(3):665-81. [Medline].
Jacoby GA. AmpC beta-lactamases. Clin Microbiol Rev. Jan 2009;22(1):161-82, Table of Contents. [Medline].
Bush K, Jacoby GA, Medeiros AA. A functional classification scheme for beta-lactamases and its correlation with molecular structure. Antimicrob Agents Chemother. Jun 1995;39(6):1211-33. [Medline].
Woodford N, Dallow JW, Hill RL, et al. Ertapenem resistance among Klebsiella and Enterobacter submitted in the UK to a reference laboratory. Int J Antimicrob Agents. Apr 2007;29(4):456-9. [Medline].
Souli M, Kontopidou FV, Papadomichelakis E, et al. Clinical experience of serious infections caused by Enterobacteriaceae producing VIM-1 metallo-beta-lactamase in a Greek University Hospital. Clin Infect Dis. Mar 15 2008;46(6):847-54. [Medline].
Pintado V, San Miguel LG, Grill F, et al. Intravenous colistin sulphomethate sodium for therapy of infections due to multidrug-resistant gram-negative bacteria. J Infect. Mar 2008;56(3):185-90. [Medline].
Gupta S, Govil D, Kakar PN, Prakash O, Arora D, Das S. Colistin and polymyxin B: A re-emergence. Indian J Crit Care Med. Apr-Jun 2009;13(2):49-53. [Medline].
Lo-Ten-Foe JR, de Smet AM, Diederen BM, et al. Comparative evaluation of the VITEK 2, disk diffusion, etest, broth microdilution, and agar dilution susceptibility testing methods for colistin in clinical isolates, including heteroresistant Enterobacter cloacae and Acinetobacter baumannii strains. Antimicrob Agents Chemother. Oct 2007;51(10):3726-30. [Medline].
Gales AC, Jones RN, Sader HS. Global assessment of the antimicrobial activity of polymyxin B against 54 731 clinical isolates of Gram-negative bacilli: report from the SENTRY antimicrobial surveillance programme (2001-2004). Clin Microbiol Infect. Apr 2006;12(4):315-21. [Medline].
Walkty A, DeCorby M, Nichol K, Karlowsky JA, Hoban DJ, Zhanel GG. In vitro activity of colistin (polymyxin E) against 3,480 isolates of gram-negative bacilli obtained from patients in Canadian hospitals in the CANWARD study, 2007-2008. Antimicrob Agents Chemother. Nov 2009;53(11):4924-6. [Medline].
Hawser SP, Bouchillon SK, Hoban DJ, Badal RE. In vitro susceptibilities of aerobic and facultative anaerobic Gram-negative bacilli from patients with intra-abdominal infections worldwide from 2005-2007: results from the SMART study. Int J Antimicrob Agents. Dec 2009;34(6):585-8. [Medline].
Bassetti M, Righi E, Fasce R, et al. Efficacy of ertapenem in the treatment of early ventilator-associated pneumonia caused by extended-spectrum beta-lactamase-producing organisms in an intensive care unit. J Antimicrob Chemother. Aug 2007;60(2):433-5. [Medline].
Abbott SL, Janda JM. Enterobacter cancerogenus ("Enterobacter taylorae") infections associated with severe trauma or crush injuries. Am J Clin Pathol. Mar 1997;107(3):359-61. [Medline].
Alhambra A, Cuadros JA, Cacho J, et al. In vitro susceptibility of recent antibiotic-resistant urinary pathogens to ertapenem and 12 other antibiotics. J Antimicrob Chemother. Jun 2004;53(6):1090-4. [Medline].
Caplan ES, Hoyt NJ. Identification and treatment of infections in multiply traumatized patients. Am J Med. Jul 15 1985;79(1A):68-76. [Medline].
Clark NM, Patterson J, Lynch JP 3rd. Antimicrobial resistance among gram-negative organisms in the intensive care unit. Curr Opin Crit Care. Oct 2003;9(5):413-23. [Medline].
Cosgrove SE, Kaye KS, Eliopoulous GM, et al. Health and economic outcomes of the emergence of third-generation cephalosporin resistance in Enterobacter species. Arch Intern Med. Jan 28 2002;162(2):185-90. [Medline].
Cunha BA. Antibiotic Essentials. 9th ed. Sudbury, MA: Jones & Bartlett; 2010.
Cunha BA. Enterobacter: Colonization & infection. Infect Dis Pract. 1999;23:41-3.
Cunha BA. Once-daily tigecycline therapy of multidrug-resistant and non-multidrug-resistant gram-negative bacteremias. J Chemother. Apr 2007;19(2):232-3. [Medline].
Cunha BA. Pharmacokinetic considerations regarding tigecycline for multidrug-resistant (MDR) Klebsiella pneumoniae or MDR Acinetobacter baumannii urosepsis. J Clin Microbiol. May 2009;47(5):1613. [Medline].
Cunha BA, McDermott B, Nausheen S. Single daily high-dose tigecycline therapy of a multidrug-resistant (MDR) Klebsiella pneumoniae and Enterobacter aerogenes nosocomial urinary tract infection. J Chemother. Dec 2007;19(6):753-4. [Medline].
Cunha BA, Theodoris AC, Yannelli B. Enterobacter cloacae graft infection/bacteremia in a hemodialysis patient. Am J Infect Control. Apr 2000;28(2):181-3. [Medline].
De Champs C, Sirot D, Chanal C, et al. A 1998 survey of extended-spectrum beta-lactamases in Enterobacteriaceae in France. The French Study Group. Antimicrob Agents Chemother. Nov 2000;44(11):3177-9. [Medline].
Donati L, Scamazzo F, Gervasoni M, et al. Infection and antibiotic therapy in 4000 burned patients treated in Milan, Italy, between 1976 and 1988. Burns. Aug 1993;19(4):345-8. [Medline].
Foster DR, Rhoney DH. Enterobacter meningitis: organism susceptibilities, antimicrobial therapy and related outcomes. Surg Neurol. Jun 2005;63(6):533-7; discussion 537. [Medline].
Fritsche TR, Stilwell MG, Jones RN. Antimicrobial activity of doripenem (S-4661): a global surveillance report (2003). Clin Microbiol Infect. Dec 2005;11(12):974-84. [Medline].
Fritsche TR, Strabala PA, Sader HS, et al. Activity of tigecycline tested against a global collection of Enterobacteriaceae, including tetracycline-resistant isolates. Diagn Microbiol Infect Dis. Jul 2005;52(3):209-13. [Medline].
Gallagher PG. Enterobacter bacteremia in pediatric patients. Rev Infect Dis. Sep-Oct 1990;12(5):808-12. [Medline].
Hanna H, Afif C, Alakech B, Boktour M, et al. Central venous catheter-related bacteremia due to gram-negative bacilli: significance of catheter removal in preventing relapse. Infect Control Hosp Epidemiol. Aug 2004;25(8):646-9. [Medline].
Hoffmann H, Sturenburg E, Heesemann J, et al. Prevalence of extended-spectrum beta-lactamases in isolates of the Enterobacter cloacae complex from German hospitals. Clin Microbiol Infect. Apr 2006;12(4):322-30. [Medline].
Jiang X, Ni Y, Jiang Y, et al. Outbreak of infection caused by Enterobacter cloacae producing the novel VEB-3 beta-lactamase in China. J Clin Microbiol. Feb 2005;43(2):826-31. [Medline].
Kang CI, Kim SH, Park WB, et al. Bloodstream infections caused by Enterobacter species: predictors of 30-day mortality rate and impact of broad-spectrum cephalosporin resistance on outcome. Clin Infect Dis. Sep 15 2004;39(6):812-8. [Medline].
Kaye KS, Cosgrove S, Harris A, et al. Risk factors for emergence of resistance to broad-spectrum cephalosporins among Enterobacter spp. Antimicrob Agents Chemother. Sep 2001;45(9):2628-30. [Medline].
Larson EL, Cimiotti JP, Haas J, et al. Gram-negative bacilli associated with catheter-associated and non-catheter-associated bloodstream infections and hand carriage by healthcare workers in neonatal intensive care units. Pediatr Crit Care Med. Jul 2005;6(4):457-61. [Medline].
Leverstein-van Hall MA, Blok HE, et al. Extensive hospital-wide spread of a multidrug-resistant enterobacter cloacae clone, with late detection due to a variable antibiogram and frequent patient transfer. J Clin Microbiol. Feb 2006;44(2):518-24. [Medline].
Liu CP, Wang NY, Lee CM, et al. Nosocomial and community-acquired Enterobacter cloacae bloodstream infection: risk factors for and prevalence of SHV-12 in multiresistant isolates in a medical centre. J Hosp Infect. Sep 2004;58(1):63-77. [Medline].
Livermore DM. beta-Lactamases in laboratory and clinical resistance. Clin Microbiol Rev. Oct 1995;8(4):557-84. [Medline].
Livermore DM, Oakton KJ, Carter MW, et al. Activity of ertapenem (MK-0826) versus Enterobacteriaceae with potent beta-lactamases. Antimicrob Agents Chemother. Oct 2001;45(10):2831-7. [Medline].
Luzzaro F, Docquier JD, Colinon C, et al. Emergence in Klebsiella pneumoniae and Enterobacter cloacae clinical isolates of the VIM-4 metallo-beta-lactamase encoded by a conjugative plasmid. Antimicrob Agents Chemother. Feb 2004;48(2):648-50. [Medline].
Markowitz SM, Smith SM, Williams DS. Retrospective analysis of plasmid patterns in a study of burn unit outbreaks of infection due to Enterobacter cloacae. J Infect Dis. Jul 1983;148(1):18-23. [Medline].
Mushtaq S, Ge Y, Livermore DM. Comparative activities of doripenem versus isolates, mutants, and transconjugants of Enterobacteriaceae and Acinetobacter spp. with characterized beta-lactamases. Antimicrob Agents Chemother. Apr 2004;48(4):1313-9. [Medline].
Paterson DL, Rossi F, Baquero F, et al. In vitro susceptibilities of aerobic and facultative Gram-negative bacilli isolated from patients with intra-abdominal infections worldwide: the 2003 Study for Monitoring Antimicrobial Resistance Trends (SMART). J Antimicrob Chemother. Jun 2005;55(6):965-73. [Medline].
Pitout JD, Nordmann P, Laupland KB, et al. Emergence of Enterobacteriaceae producing extended-spectrum beta-lactamases (ESBLs) in the community. J Antimicrob Chemother. Jul 2005;56(1):52-9. [Medline].
Pitout JD, Thomson KS, Hanson ND, et al. Plasmid-mediated resistance to expanded-spectrum cephalosporins among Enterobacter aerogenes strains. Antimicrob Agents Chemother. Mar 1998;42(3):596-600. [Medline].
Ristuccia PA, Cunha BA. Enterobacter. Infect Control. Mar 1985;6(3):124-8. [Medline].
Rupp ME, Fey PD. Extended spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae: considerations for diagnosis, prevention and drug treatment. Drugs. 2003;63(4):353-65. [Medline].
Sader HS, Jones RN, Dowzicky MJ, et al. Antimicrobial activity of tigecycline tested against nosocomial bacterial pathogens from patients hospitalized in the intensive care unit. Diagn Microbiol Infect Dis. Jul 2005;52(3):203-8. [Medline].
Sader HS, Jones RN, Stilwell MG, et al. Tigecycline activity tested against 26,474 bloodstream infection isolates: a collection from 6 continents. Diagn Microbiol Infect Dis. Jul 2005;52(3):181-6. [Medline].
Sanders CC, Sanders WE Jr. beta-Lactam resistance in gram-negative bacteria: global trends and clinical impact. Clin Infect Dis. Nov 1992;15(5):824-39. [Medline].
Sanders WE Jr, Sanders CC. Enterobacter spp.: pathogens poised to flourish at the turn of the century. Clin Microbiol Rev. Apr 1997;10(2):220-41. [Medline].
Siegel JD, Rhinehart E, Jackson M, Chiarello L and the HICPAC. Guideline for Isolation Precautions: Preventing Transmission of Infectious Agents in Healthcare SEttings 2007. Centers for Disease Contol. Available at http://www.cdc.gov/ncidod/dhqp/pdf/guidelines/Isolation2007.pdf. Accessed 1 April 12008.
Siegel JD, Rhinehart E, Jackson M, Chiarello L, HICPAC. Management of Multidrug-Resistant Organisms In Healthcare Settings, 2006. Centers for Disease Control. Available at http://www.cdc.gov/ncidod/dhqp/pdf/ar/mdroGuideline2006.pdf. accessed 1 April 2008.
Tresoldi AT, Padoveze MC, Trabasso P, et al. Enterobacter cloacae sepsis outbreak in a newborn unit caused by contaminated total parenteral nutrition solution. Am J Infect Control. Jun 2000;28(3):258-61. [Medline].
v Dijk Y, Bik EM, Hochstenbach-Vernooij S, v d Vlist GJ, Savelkoul PH, Kaan JA, et al. Management of an outbreak of Enterobacter cloacae in a neonatal unit using simple preventive measures. J Hosp Infect. May 2002;51(1):21-6. [Medline].
Watson JT, Jones RC, Siston AM, et al. Outbreak of catheter-associated Klebsiella oxytoca and Enterobacter cloacae bloodstream infections in an oncology chemotherapy center. Arch Intern Med. Dec 12-26 2005;165(22):2639-43. [Medline].
Wendt C, Lin D, von Baum H. Risk factors for colonization with third-generation cephalosporin-resistant enterobacteriaceae. Infection. Oct 2005;33(5-6):327-32. [Medline].
Wisplinghoff H, Bischoff T, Tallent SM, et al. Nosocomial bloodstream infections in US hospitals: analysis of 24,179 cases from a prospective nationwide surveillance study. Clin Infect Dis. Aug 1 2004;39(3):309-17. [Medline].

