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Epidemiology of ciprofloxacin resistance and its relationship to extended-spectrum β-lactamase production in Proteus mirabilis bacteremia.
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MedLine Citation:
PMID:  21437168     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND/AIMS: We evaluated the clinical features of ciprofloxacin-resistant Proteus mirabilis bacteremia and risk factors for ciprofloxacin resistance.
METHODS: From October 2000 to July 2009, 37 patients with clinically significant P. mirabilis bacteremia were identified and data from patients with ciprofloxacin-resistant and ciprofloxacin-susceptible P. mirabilis bacteremia were compared.
RESULTS: The most common underlying diseases were neurologic disease (37.8%) and solid tumors (29.7%). The most common site of infection was the urinary tract (35.1%). Ten of the 37 patients (27.0%) were infected with ciprofloxacin-resistant isolates, and univariate analysis revealed a significant relationship between ciprofloxacin-resistant P. mirabilis bacteremia and neurologic disease, recent operation, L-tube insertion, percutaneous tube use, and extended-spectrum β-lactamase (ESBL) production (all p < 0.05). ESBL was detected in six of 10 (60%) ciprofloxacin-resistant isolates, while only three of 27 (11%) ciprofloxacin-susceptible isolates produced ESBL (p = 0.005). In a logistic regression analysis, ESBL production remained a significant factor associated with ciprofloxacin resistance, after adjusting for other variables.
CONCLUSIONS: These data indicate a close association between ciprofloxacin resistance and ESBL-production in P. mirabilis bacteremia. This association is particularly troublesome because the therapeutic options for serious infections caused by ESBL-producing P. mirabilis are severely restricted.
Authors:
Kyung Mok Sohn; Cheol-In Kang; Eun-Jeong Joo; Young Eun Ha; Doo Ryeon Chung; Kyong Ran Peck; Nam Yong Lee; Jae-Hoon Song
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-03-03
Journal Detail:
Title:  The Korean journal of internal medicine     Volume:  26     ISSN:  2005-6648     ISO Abbreviation:  Korean J. Intern. Med.     Publication Date:  2011 Mar 
Date Detail:
Created Date:  2011-03-25     Completed Date:  2011-08-05     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  8712418     Medline TA:  Korean J Intern Med     Country:  Korea (South)    
Other Details:
Languages:  eng     Pagination:  89-93     Citation Subset:  IM    
Affiliation:
Division of Infectious Diseases, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Anti-Infective Agents / pharmacology*
Bacteremia / drug therapy*
Ciprofloxacin / pharmacology*
Drug Resistance, Bacterial
Female
Humans
Male
Middle Aged
Proteus Infections / drug therapy*
Proteus mirabilis / drug effects*,  enzymology
Risk Factors
beta-Lactamases / biosynthesis*
Chemical
Reg. No./Substance:
0/Anti-Infective Agents; 85721-33-1/Ciprofloxacin; EC 3.5.2.6/beta-Lactamases
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-ta): Korean J Intern Med
Journal ID (publisher-id): KJIM
ISSN: 1226-3303
ISSN: 2005-6648
Publisher: The Korean Association of Internal Medicine
Article Information
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Copyright © 2011 The Korean Association of Internal Medicine
Received Day: 06 Month: 5 Year: 2010
Revision Received Day: 30 Month: 8 Year: 2010
Accepted Day: 28 Month: 9 Year: 2010
Print publication date: Month: 3 Year: 2011
Electronic publication date: Day: 03 Month: 3 Year: 2011
Volume: 26 Issue: 1
First Page: 89 Last Page: 93
ID: 3056262
PubMed Id: 21437168
DOI: 10.3904/kjim.2011.26.1.89

Epidemiology of Ciprofloxacin Resistance and Its Relationship to Extended-Spectrum β-Lactamase Production in Proteus mirabilis Bacteremia
Kyung Mok Sohn12
Cheol-In Kang1
Eun-Jeong Joo1
Young Eun Ha1
Doo Ryeon Chung1
Kyong Ran Peck1
Nam Yong Lee3
Jae-Hoon Song1
1Division of Infectious Diseases, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
2Division of Infectious Diseases, Department of Internal Medicine, Chungnam National University Hospital, Daejeon, Korea.
3Department of Laboratory Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Correspondence: Correspondence to Cheol-In Kang, M.D. Division of Infectious Diseases, Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul 135-710, Korea. Tel: 82-2-3410-0324, Fax: 82-2-3410-0064, collacin@hotmail.com

INTRODUCTION

Proteus mirabilis can cause a variety of community- or hospital-acquired infections, including urinary tract, intraabdominal, and bloodstream infections [1,2]. Antimicrobial resistance has been reported increasingly for this species, and increased resistance to extended-spectrum cephalosporins due to the production of extended-spectrum β-lactamases (ESBLs) has become of great concern [1,3,4]. Consequently, carbapenem has emerged as the agent of choice for the treatment of serious infections caused by ESBL-producing pathogens. Fluoroquinolones may be an effective alternative antimicrobial therapy. However, similar to Escherichia coli and Klebsiella pneumoniae, the incidence of ciprofloxacin resistance in P. mirabilis isolates is increasing [5,6].

Although the occurrence of ciprofloxacin resistance in E. coli and K. pneumoniae isolates is well-established, little is known of the epidemiology of P. mirabilis bacteremia caused by ciprofloxacin-resistant isolates. Thus, in this study, we evaluated the clinical features of ciprofloxacin-resistant P. mirabilis bacteremia to clarify the risk factors for ciprofloxacin resistance in P. mirabilis isolates causing bacteremia.


METHODS

The database in our clinical microbiology laboratory (Samsung Medical Center, Seoul, Korea; a 1,950-bed, tertiary-care university hospital and referral center) was reviewed to identify patients > 16 years of age diagnosed with P. mirabilis bacteremia from October 2000 to July 2009. Only the first episode for each patient was included in the analysis. Antibiotic susceptibility was tested using the VITEK II automated system (bioMérieux, Hazelwood, MO, USA) using the standard modified broth microdilution method. Minimum inhibitory concentration (MIC) breakpoints and quality control protocols were used according to standards established by the Clinical and Laboratory Standards Institute [7]. For the purposes of this study, isolates showing in vitro resistance to cefotaxime, ceftriaxone, or ceftazidime were classified as ESBL-producing organisms. Strains showing an 'intermediate' result to the tested antibiotics were considered resistant.

We compared the clinical features of patients with ciprofloxacin-resistant and ciprofloxacin-susceptible P. mirabilis bacteremia. The data collected included age, gender, underlying disease, primary site of infection, acquisition site, and antimicrobial regimen. The presence of the following comorbid conditions was also documented: recent operation, corticosteroid use, indwelling urinary catheter, L-tube insertion, percutaneous tube use, prior invasive procedure, and prior use of antibiotics. Nosocomial acquisition of infection was defined as an infection that occurred > 48 hours after hospital admission, while infections diagnosed within the first 48 hours of hospitalization were classified as community-onset infection, based on the time the culture samples were obtained. Because many cases of Proteus bacteremia that are present or incubating on admission to the hospital are nonetheless healthcare-associated, we refer to non-nosocomial bacteremia as community-onset rather than community-acquired. Community-onset infection was further classified as community-associated and healthcare-associated, as previously suggested [8]. The site of infection was determined by physicians, based on the isolation of P. mirabilis from the presumed portal of entry and clinical evaluation.

Student's t test was used to compare continuous variables, and χ2 or Fisher's exact tests were used to compare categorical variables. A logistic regression analysis was performed to evaluate ESBL production as a factor associated with ciprofloxacin resistance. The odds ratio (OR) and 95% confidential interval (CI) were calculated. All p values were two-tailed, and p < 0.05 was considered to indicate statistical significance.


RESULTS

Thirty-seven patients with P. mirabilis bacteremia were identified. Their demographic and clinical characteristics are shown in Table 1. The most common underlying diseases were neurologic diseases (38%) and solid tumors (30%). The most common site of infection was the urinary tract (35%). Ten (27%) of the 37 patients were infected with ciprofloxacin-resistant isolates and nine (24%) were infected with ESBL-producers. Among the 27 patients determined to have community-onset infections, five (19%) had ciprofloxacin-resistant bacteremia. Among the ten patients identified as having a nosocomial-acquired infection, five (50%) had ciprofloxacin-resistant bacteremia (p = 0.094).

Risk factors associated with ciprofloxacin-resistant P. mirabilis are listed in Table 2. Univariate analysis revealed a significant relationship between ciprofloxacin-resistant P. mirabilis bacteremia and neurologic disease, recent operation, L-tube insertion, percutaneous tube use, and ESBL production (all p < 0.05). ESBL was detected in six (60%) of ten ciprofloxacin-resistant P. mirabilis isolates. In comparison, only three (11%) of 27 ciprofloxacin-susceptible P. mirabilis isolates were ESBL producers. ESBL production was significantly associated with ciprofloxacin resistance among P. mirabilis isolates causing bacteremia (OR, 12.00; 95% CI, 2.10 to 68.6; p = 0.005). In a logistic regression analysis, ESBL production remained a significant factor associated with ciprofloxacin resistance, after adjusting for nosocomial infection, neurologic disease, or recent operation (OR, 13.93; 95% CI, 1.04 to 186.07; p = 0.046).

Four (40%) of ten patients with ciprofloxacin-resistant bacteremia received inappropriate initial antimicrobial therapy, while three (11%) of 27 patients with ciprofloxacin-susceptible bacteremia received inappropriate initial antimicrobial therapy (p = 0.069). Of 32 patients whose outcomes could be evaluated, eight (25%) died within 30 days; no significant difference was found between ciprofloxacin-resistant (1/9, 11%) and -susceptible (7/23, 30%) patients (p = 0.386). When factors associated with mortality were evaluated, solid tumor was found to be the only significant factor associated with mortality (p = 0.005).


DISCUSSION

This study revealed that neurologic disease, recent operation, L-tube insertion, and percutaneous tube were significant risk factors associated with the development of bacteremia caused by ciprofloxacin-resistant P. mirabilis. Ciprofloxacin resistance in K. pneumoniae has been reported to be closely associated with ESBL production [9]. Several studies have examined the relationship between quinolone resistance and ESBL production in E. coli and K. pneumoniae [10,11]. Ciprofloxacin-resistant Enterobacter bacteremia is closely associated with broad-spectrum cephalosporin resistance [12]. Consistent with the latter study, we also observed a close association of ciprofloxacin-resistant P. mirabilis bacteremia with broad-spectrum cephalosporin resistance conferred by ESBL.

This association is of great concern because ESBL-producing P. mirabilis isolates are usually resistant to penicillins and cephalosporins. Thus, ciprofloxacin resistance severely limits already restricted treatment options. Additionally, the marked increase in the incidence of ESBL-producing P. mirabilis isolates in recent years is of great concern [1,3,13]. Although carbapenems remain the most effective option for treating serious infection caused by ESBL-producing P. mirabilis, the increasing use of carbapenems has been paralleled by the rapid emergence of carbapenem resistance in nosocomial pathogens [14,15].

What is the explanation for the coexistence of these two resistance mechanisms in Gram-negative bacilli? The relationship between ciprofloxacin resistance and ESBL production may be due to the interplay between prior heavy antibiotic use and conditions favoring patient-to-patient transfer of multidrug-resistant organisms, as described elsewhere [6,9,12]. Additionally, there are other potential explanations for the association between ciprofloxacin resistance and broad-spectrum cephalosporins resistance; these include active efflux and outer membrane protein alterations [16]. For ciprofloxacin resistance in K. pneumoniae and E. coli, transfer of the same plasmid has been suggested as a further possible explanation for the coexistence of the two resistance mechanisms [17,18]. Plasmid-mediated ciprofloxacin resistance has recently been reported in such strains [19,20]. Furthermore, a new plasmid-mediated quinolone resistance gene, qnrC, was reported in a clinical isolate of P. mirabilis [21]. However, the basis for the ciprofloxacin resistance combined with ESBL production is not yet fully understood. Further investigation of the possible mechanisms is needed.

Prior therapy with fluoroquinolones is an important risk factor for ciprofloxacin resistance in Gram-negative bacilli [22,23]. In this regard, we were unable to assess possible associations between ciprofloxacin resistance and prior use of antibiotics in this study because of the small number of cases. Additionally, we sought to delineate the clinical features of Proteus bacteremia, rather than focusing on microbiological analyses, and so did not characterize ESBL types. Thus, misclassification with regard to ESBL production may have been possible in several patients. Finally, because our study was conducted in a large tertiary-care hospital, the results may not necessarily be applicable to other institutions.

In conclusion, our investigation of risk factors for ciprofloxacin-resistant P. mirabilis bacteremia revealed a close association between ciprofloxacin resistance and ESBL production. This association is particularly troublesome because the therapeutic options for serious infections caused by ESBL-producing P. mirabilis are severely restricted.


Notes

No potential conflict of interest relevant to this article was reported.

Acknowledgements

This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health, Welfare & Family Affairs, Republic of Korea (Grant No. A084063).


References
1. Endimiani A,Luzzaro F,Brigante G,et al. Proteus mirabilis bloodstream infections: risk factors and treatment outcome related to the expression of extended-spectrum beta-lactamasesAntimicrob Agents ChemotherYear: 2005492598260515980325
2. O'Hara CM,Brenner FW,Miller JM. Classification, identification, and clinical significance of Proteus, Providencia, and MorganellaClin Microbiol RevYear: 20001353454611023955
3. Wu JJ,Chen HM,Ko WC,Wu HM,Tsai SH,Yan JJ. Prevalence of extended-spectrum beta-lactamases in Proteus mirabilis in a Taiwanese university hospital, 1999 to 2005: identification of a novel CTX-M enzyme (CTX-M-66)Diagn Microbiol Infect DisYear: 20086016917517913434
4. Uh Y,Hwang GY,Kwon O,Yoon KJ,Kim HY. Isolation frequency of extended spectrum beta-lactamase producing Escherichia coli, Klebsiella species, and Proteus mirabilisKorean J Clin MicrobiolYear: 200710119122
5. Hernandez JR,Martinez-Martinez L,Pascual A,Suarez AI,Perea EJ. Trends in the susceptibilities of Proteus mirabilis isolates to quinolonesJ Antimicrob ChemotherYear: 20004540740810702570
6. Saito R,Okugawa S,Kumita W,et al. Clinical epidemiology of ciprofloxacin-resistant Proteus mirabilis isolated from urine samples of hospitalised patientsClin Microbiol InfectYear: 2007131204120617850340
7. Clinical and Laboratory Standards InstitutePerformance Standards for Antimicrobial Susceptibility Testing: Seventeenth Informational Supplement (Document M100-S17)Year: 2007Wayne (PA)Clinical and Laboratory Standards Institute
8. Friedman ND,Kaye KS,Stout JE,et al. Health care--associated bloodstream infections in adults: a reason to change the accepted definition of community-acquired infectionsAnn Intern MedYear: 200213779179712435215
9. Paterson DL,Mulazimoglu L,Casellas JM,et al. Epidemiology of ciprofloxacin resistance and its relationship to extended-spectrum beta-lactamase production in Klebsiella pneumoniae isolates causing bacteremiaClin Infect DisYear: 20003047347810722430
10. Kang CI,Kim SH,Kim DM,et al. Risk factors for ciprofloxacin resistance in bloodstream infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniaeMicrob Drug ResistYear: 200410717615140397
11. Lautenbach E,Strom BL,Bilker WB,Patel JB,Edelstein PH,Fishman NO. Epidemiological investigation of fluoroquinolone resistance in infections due to extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniaeClin Infect DisYear: 2001331288129411565067
12. Kang CI,Kim SH,Park WB,et al. Clinical epidemiology of ciprofloxacin resistance and its relationship to broad-spectrum cephalosporin resistance in bloodstream infections caused by Enterobacter speciesInfect Control Hosp EpidemiolYear: 200526889215693414
13. Kim JY,Park YJ,Kim SI,Kang MW,Lee SO,Lee KY. Nosocomial outbreak by Proteus mirabilis producing extended-spectrum beta-lactamase VEB-1 in a Korean university hospitalJ Antimicrob ChemotherYear: 2004541144114715546971
14. Eagye KJ,Kuti JL,Nicolau DP. Risk factors and outcomes associated with isolation of meropenem high-level-resistant Pseudomonas aeruginosaInfect Control Hosp EpidemiolYear: 20093074675219583513
15. Tacconelli E,De Angelis G,Cataldo MA,et al. Antibiotic usage and risk of colonization and infection with antibiotic-resistant bacteria: a hospital population-based studyAntimicrob Agents ChemotherYear: 2009534264426919667289
16. Zavascki AP,Carvalhaes CG,Picão RC,Gales AC. Multidrug-resistant Pseudomonas aeruginosa and Acinetobacter baumannii: resistance mechanisms and implications for therapyExpert Rev Anti Infect TherYear: 20108719320014903
17. Jacoby G,Cattoir V,Hooper D,et al. qnr Gene nomenclatureAntimicrob Agents ChemotherYear: 2008522297229918426894
18. Martinez-Martinez L,Pascual A,Jacoby GA. Quinolone resistance from a transferable plasmidLancetYear: 19983517977999519952
19. Kim HB,Park CH,Kim CJ,Kim EC,Jacoby GA,Hooper DC. Prevalence of plasmid-mediated quinolone resistance determinants over a 9-year periodAntimicrob Agents ChemotherYear: 20095363964519064896
20. Wu JJ,Ko WC,Wu HM,Yan JJ. Prevalence of Qnr determinants among bloodstream isolates of Escherichia coli and Klebsiella pneumoniae in a Taiwanese hospital, 1999-2005J Antimicrob ChemotherYear: 2008611234123918356152
21. Wang M,Guo Q,Xu X,et al. New plasmid-mediated quinolone resistance gene, qnrC, found in a clinical isolate of Proteus mirabilisAntimicrob Agents ChemotherYear: 2009531892189719258263
22. Colodner R,Kometiani I,Chazan B,Raz R. Risk factors for community-acquired urinary tract infection due to quinolone-resistant E. coliInfectionYear: 200836414518193386
23. Levin PD,Fowler RA,Guest C,Sibbald WJ,Kiss A,Simor AE. Risk factors associated with resistance to ciprofloxacin in clinical bacterial isolates from intensive care unit patientsInfect Control Hosp EpidemiolYear: 20072833133617326025

Article Categories:
  • Original Article

Keywords: Proteus mirabilis, Ciprofloxacin, Drug resistance, Bacterial, Risk factors, Cephalosporin resistance.

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