Article

Risk factors for fluoroquinolone resistance in Enterococcus urinary tract infections in hospitalized patients

Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania School of Medicine, 423 Guardian Drive, Philadelphia, PA 19104-6021, USA.
Epidemiology and Infection (Impact Factor: 2.49). 06/2011; 139(6):955-61. DOI: 10.1017/S095026881000186X
Source: PubMed

ABSTRACT Past studies exploring risk factors for fluoroquinolone (FQ) resistance in urinary tract infections (UTIs) focused only on UTIs caused by Gram-negative pathogens. The epidemiology of FQ resistance in enterococcal UTIs has not been studied. We conducted a case-control study at two medical centres within the University of Pennsylvania Health System in order to identify risk factors for FQ resistance in enterococcal UTIs. Subjects with positive urine cultures for enterococci and meeting CDC criteria for healthcare-acquired UTI were eligible. Cases were subjects with FQ-resistant enterococcal UTI. Controls were subjects with FQ-susceptible enterococcal UTI and were frequency matched to cases by month of isolation. A total of 136 cases and 139 controls were included from 1 January 2003 to 31 March 2005. Independent risk factors [adjusted OR (95% CI)] for FQ resistance included cardiovascular diseases [2·24 (1·05-4·79), P=0·037], hospitalization within the past 2 weeks [2·08 (1·05-4·11), P=0·035], hospitalization on a medicine service [2·15 (1·08-4·30), P<0·030], recent exposure to β-lactamase inhibitors (BLIs) [14·98 (2·92-76·99), P<0·001], extended spectrum cephalosporins [9·82 (3·37-28·60), P<0·001], FQs [5·36 (2·20-13·05), P<0·001] and clindamycin [13·90 (1·21-10·49), P=0·035]. Use of BLIs, extended spectrum cephalosporins, FQs and clindamycin was associated with FQ resistance in enterococcal uropathogens. Efforts to curb FQ resistance should focus on optimizing use of these agents.

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    ABSTRACT: This review summarizes data on the fluoroquinolone resistance epidemiology published in the previous 5 years. The data reviewed are stratified according to the different prescription patterns by either primary- or tertiary-care givers and by indication. Global surveillance studies demonstrate that fluoroquinolone- resistance rates increased in the past several years in almost all bacterial species except Staphylococcus pneumoniae and Haemophilus influenzae causing community-acquired respiratory tract infections (CARTIs), as well as Enterobacteriaceae causing community-acquired urinary tract infections. Geographically and quantitatively varying fluoroquinolone resistance rates were recorded among Gram-positive and Gram-negative pathogens causing healthcare-associated respiratory tract infections. One- to two-thirds of Enterobacteriaceae producing extended-spectrum β-lactamases (ESBLs) were fluoroquinolone resistant too, thus, limiting the fluoroquinolone use in the treatment of community- as well as healthcare-acquired urinary tract and intra-abdominal infections. The remaining ESBL-producing or plasmid-mediated quinolone resistance mechanisms harboring Enterobacteriaceae were low-level quinolone resistant. Furthermore, 10-30 % of H. influenzae and S. pneumoniae causing CARTIs harbored first-step quinolone resistance determining region (QRDR) mutations. These mutants pass susceptibility testing unnoticed and are primed to acquire high-level fluoroquinolone resistance rapidly, thus, putting the patient at risk. The continued increase in fluoroquinolone resistance affects patient management and necessitates changes in some current guidelines for the treatment of intra-abdominal infections or even precludes the use of fluoroquinolones in certain indications like gonorrhea and pelvic inflammatory diseases in those geographic areas in which fluoroquinolone resistance rates and/or ESBL production is high. Fluoroquinolone resistance has been selected among the commensal flora colonizing the gut, nose, oropharynx, and skin, so that horizontal gene transfer between the commensal flora and the offending pathogen as well as inter- and intraspecies recombinations contribute to the emergence and spread of fluoroquinolone resistance among pathogenic streptococci. Although interspecies recombinations are not yet the major cause for the emergence of fluoroquinolone resistance, its existence indicates that a large reservoir of fluoroquinolone resistance exists. Thus, a scenario resembling that of a worldwide spread of β-lactam resistance in pneumococci is conceivable. However, many resistance surveillance studies suffer from inaccuracies like the sampling of a selected patient population, restricted geographical sampling, and undefined requirements of the user, so that the results are biased. The number of national centers is most often limited with one to two participating laboratories, so that such studies are point prevalence but not surveillance studies. Selected samples are analyzed predominantly as either hospitalized patients or patients at risk or those in whom therapy failed are sampled; however, fluoroquinolones are most frequently prescribed by the general practitioner. Selected sampling results in a significant over-estimation of fluoroquinolone resistance in outpatients. Furthermore, the requirements of the users are often not met; the prescribing physician, the microbiologist, the infection control specialist, public health and regulatory authorities, and the pharmaceutical industry have diverse interests, which, however, are not addressed by different designs of a surveillance study. Tools should be developed to provide customer-specific datasets. Consequently, most surveillance studies suffer from well recognized but uncorrected biases or inaccuracies. Nevertheless, they provide important information that allows the identification of trends in pathogen incidence and antimicrobial resistance.
    Infection 03/2012; 40(3):239-62. DOI:10.1007/s15010-012-0257-2 · 2.86 Impact Factor
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    ABSTRACT: Urinary tract infection (UTI) is one of the most prevalent bacterial infections, and fluoroquinolone therapy is a well-known standard regimen for UTI. The prevalence and risk factor analysis of fluoroquinolone resistance in enterococcal UTIs are not well documented. The aim of this study was to evaluate the antimicrobial susceptibility and risk factors for ciprofloxacin resistance in Enterococcus faecalis strains isolated from patients with complicated UTI. We evaluated 81 E. faecalis strains isolated from 81 male patients at a single teaching hospital over 3 years. The Vitek 2 automatic system was used for antimicrobial susceptibility analysis. Antimicrobial resistance rates were rare for ampicillin/sulbactam, imipenem, and vancomycin in E. faecalis. Forty-six percent of the E. faecalis strains were resistant to levofloxacin, 47% were resistant to ciprofloxacin, and 58% were resistant to norfloxacin. E. faecalis strains were highly resistant to erythromycin (92%) and ftetracycline (96%). The risk factor analysis revealed that age intervals, the underlying diseases, catheterization, and the number of admissions did not increase the risk of ciprofloxacin resistance, whereas patients with hospital-acquired infection (odds ratio [OR], 18.15; 95% confidence interval [CI], 3.46 to 95.13; p=0.001), patients who were treated in a urological department (OR, 6.15; 95% CI, 1.5 to 25.41; p=0.012), and patients who were transferred from health care centers (OR, 7.393; 95% CI, 1.32 to 41.22; p=0.023) had an increased risk of ciprofloxacin resistance compared with the matched controls. Ciprofloxacin is no longer a recommended therapy for E. faecalis from complicated UTI in men with risk factors. We suggest that ampicillin/sulbactam can be recommended as alternatives for treating ciprofloxacin-resistant E. faecalis strains associated with UTI in Korea.
    Korean journal of urology 06/2013; 54(6):388-393. DOI:10.4111/kju.2013.54.6.388
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    ABSTRACT: This paper on the fluoroquinolone resistance epidemiology stratifies the data according to the different prescription patterns by either primary or tertiary caregivers and by indication. Global surveillance studies demonstrate that fluoroquinolone resistance rates increased in the past years in almost all bacterial species except S. pneumoniae and H. influenzae, causing community-acquired respiratory tract infections. However, 10 to 30% of these isolates harbored first-step mutations conferring low level fluoroquinolone resistance. Fluoroquinolone resistance increased in Enterobacteriaceae causing community acquired or healthcare associated urinary tract infections and intraabdominal infections, exceeding 50% in some parts of the world, particularly in Asia. One to two-thirds of Enterobacteriaceae producing extended spectrum β-lactamases were fluoroquinolone resistant too. Furthermore, fluoroquinolones select for methicillin resistance in Staphylococci. Neisseria gonorrhoeae acquired fluoroquinolone resistance rapidly; actual resistance rates are highly variable and can be as high as almost 100%, particularly in Asia, whereas resistance rates in Europe and North America range from <10% in rural areas to >30% in established sexual networks. In general, the continued increase in fluoroquinolone resistance affects patient management and necessitates changes in some guidelines, for example, treatment of urinary tract, intra-abdominal, skin and skin structure infections, and traveller's diarrhea, or even precludes the use in indications like sexually transmitted diseases and enteric fever.
    Interdisciplinary Perspectives on Infectious Diseases 01/2012; 2012:976273. DOI:10.1155/2012/976273

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