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Secular Trends in Gram-Negative Resistance among Urinary Tract Infection Hospitalizations in the United States, 2000–2009

  • Marya D. Zilberberg (a1) (a2) and Andrew F. Shorr (a3)

Urinary tract infections (UTIs) are common among hospitalized patients. Selection of an appropriate antibiotic for this infection requires knowledge of both its general microbiology and the epidemiology of drug-resistant organisms. We sought to determine secular trends in UTI hospitalizations that involve gram-negative (GN) multidrug-resistant Pseudomonas aeruginosa (MDR-PA), extended-spectrum β-lactamase (ESBL)-producing Escherichia coli (EC) and Klebsiella pneumoniae(KP), and carbapenem-resistant Enterobacteriaceae (CRE).




Patients with UTI in US hospitals between 2000 and 2009.


We first derived the total number of UTI hospitalizations in the United States from the Healthcare Cost and Utilization Project Nationwide Inpatient Sample database years 2000–2009. Based on a literature review, we then determined what proportion of all UTIs arise due to each of the organisms of interest, irrespective of resistance pattern. Finally, we assessed the prevalence of resistance within each pathogen based on the Eurofins Surveillance Network database 2000–2009. Susceptibility patterns served as phenotypic surrogates for resistance.


Between 2000 and 2009, the frequency of UTI hospitalizations increased by approximately 50%, from 53 to 77 cases per 1,000 hospitalizations. Infections due to all GN bacteria followed a similar trajectory, whereas those caused by resistant GN pathogens increased by approximately 50% (MDR-PA) to approximately 300% (ESBL). CRE emerged and reached 0.5 cases per 1,000 hospitalizations in this 10-year period.


The epidemiology and microbiology of GN UTI hospitalizations has shifted over the past decade. The proportion of all hospitalizations involving this infection has climbed. Resistant GN bacteria are becoming more prevalent and are implicated in an increasing proportion of UTIs among hospitalized patients.

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1.Haley RW, Hooton TM, Culver DH, et al.Nosocomial infections in U.S. hospitals, 1975-1976: estimated frequency by selected characteristics of patients. Am J Med 1981;70:947959.
2.Haley RW, Culver DH, White JW, Morgan WM, Emori TG. The nationwide nosocomial infection rate: a new need for vital statistics. Am J Epidemiol 1985;121:159167.
3.Saint S, Meddings JA, Calfree D, Kowalski CP, Krein SL. Catheter-associated urinary tract infection and the Medicare rule changes. Ann Int Med 2009;150:877884.
4.Gandhi T, Flanders SA, Markovitz E, Saint S, Kaul DR. Importance of urinary tract infection to antibiotic use among hospitalized patients. Infect Control Hosp Epidemiol 2009;30:193195.
5.Lewis JS 2nd, Herrera M, Wiekes B, Patterson JE, Jorgensen JH. First report of the emergence of CTX-M-type extended-spectrum β-lactamases (ESBLs) as the predominant ESBL isolated in a U.S. health care system. Antimicrob Agents Chemother 2007; 51:40154021.
6.Moland ES, Hanson ND, Black JA, Hossain A, Song W, Thomson KS. Prevalence of newer β-lactamases in gram-negative clinical isolates collected in the United States from 2001 to 2002. J Clin Microbiol 2006;44:33183324.
7.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 2007;45:33523359.
8.Gaynes R, Edwards JR; National Nosocomial Infections Surveillance (NNIS) System. Overview of nosocomial infections caused by gram-negative bacilli. Clin Infect Dis 2005;41:848854.
9.Hidron AI, Edwards JR, Patel J, et al.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 Hospital Epidemiol 2008;29:9961011.
10.Kuehnert MJ, Hill HA, Kupronis BA, Tokars JI, Solomon SL, Jernigan DB. Methicillin-resistant Staphylococcus aureus hospitalizations, United States. Emerg Infect Dis 2005;11:868872.
11.Klein E, Smith DL, Laxminarayan R. Hospitalizations and deaths caused by methicillin-resistant Staphylococcus aureus, United States, 1999-2005. Emerg Infect Dis 2007.
12. Healthcare Cost and Utilization Project (HCUP). HCUP Nationwide Inpatient Sample. Rockville, MD: Agency for Healthcare Research and Quality, 2012. Accessed December 17, 2012.
13.Meddings J, Saint S, McMahon LF. Hospital-acquired catheter-associated urinary tract infection: documentation and coding issues may reduce financial impact of Medicare's new payment policy. Infect Control Hosp Epidemiol 2010;31:627633.
14.Naber KG, Llorens L, Kaniga K, Kotey P, Hedrich D, Redman R. Intravenous doripenem at 500 milligrams versus levofloxacin at 250 milligrams, with an option to switch to oral therapy, for treatment of complicated lower urinary tract infection and pyelonephritis. Antimicrob Agents Chemother 2009;53:37823792.
15.Peterson J, Kaul S, Khashab M, Fisher A, Kahn JB. Identification and pretherapy susceptibility of pathogens in patients with complicated urinary tract infection or acute pyelonephritis enrolled in a clinical study in the United States from November 2004 through April 2006. Clin Therapeutics 2007;29:22152221.
16.Wells WG, Woods GL, Jiang Q, Gesser RM. Treatment of complicated urinary tract infection in adults: combined analysis of two randomized, double-blind, multicenter trials comparing er-tapenem and ceftriaxone followed by appropriate oral therapy. J Antimicrobial Chemother 2004;53:ii67ii74.
17.Micek ST, Kollef KE, Reichley RM, et al.Health care-associated pneumonia and community-acquired pneumonia: a single-center experience. Antimicrob Agents Chemother 2007;51:35683573.
18.Iregui M, Ward S, Sherman G, et al.Clinical importance of delays in the initiation of appropriate antibiotic treatment for ventilator-associated pneumonia. Chest 2002;122:262268.
19.Alvarez-Lerma F; Intensive Care Unit-Acquired Pneumonia Study Group. Modification of empiric antibiotic treatment in patients with pneumonia acquired in the intensive care unit. Intensive Care Med 1996;22:387394.
20.Zilberberg MD, Shorr AF, Micek MT, Mody SH, Kollef MH. Antimicrobial therapy escalation and hospital mortality among patients with HCAP: a single center experience. Chest 2008:134: 963968.
21.Shorr AF, Micek ST, Welch EC, Doherty JA, Reichley RM, Kollef MH. Inappropriate antibiotic therapy in gram-negative sepsis increases hospital length of stay. Crit Care Med 2011;39:4651.
22.Kollef MH, Sherman G, Ward S, Fraser VJ. Inadequate antimicrobial treatment of infections: a risk factor for hospital mortality among critically ill patients. Chest 1999;115:462474.
23.Garnacho-Montero J, Garcia-Garmendia JL, Barrero-Almodo-var A, Jimenez-Jimenez FJ, Perez-Paredes C, Ortiz-Leyba C. Impact of adequate empirical antibiotic therapy on the outcome of patients admitted to the intensive care unit with sepsis. Crit Care Med 2003;31:27422751.
24.Harbarth S, Garbino J, Pugin J, Romand JA, Lew D, Pittet D. Inappropriate initial antimicrobial therapy and its effect on survival in a clinical trial of immunomodulating therapy for severe sepsis. Am J Med 2003;115:529535.
25.Ferrer R, Artigas A, Suarez D, et al.Effectiveness of treatments for severe sepsis: a prospective, multicenter, observational study. Am J Respir Crit Care Med 2009;180:861866.
26.Arias CA, Murray BE, Antibiotic-resistant bugs in the 21st century: a clinical super-challenge. N Engl J Med 2009;360:439443.
27.Boucher H, Talbot GH, Bradley JS, et al.Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin Infect Dis 2009;48:112.
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Infection Control & Hospital Epidemiology
  • ISSN: 0899-823X
  • EISSN: 1559-6834
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