Jacob Strahilevitz

Hebrew University of Jerusalem, Yerushalayim, Jerusalem, Israel

Are you Jacob Strahilevitz?

Claim your profile

Publications (47)231.81 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Patients receiving chemotherapy for hematological malignancies are at high risk for febrile neutropenia (FN). Garlic extracts (GEs) are natural food substances showing antimicrobial effects in vivo. We explored whether adding GE may be efficacious in reducing the risk or severity of infections. This was a placebo-controlled double-blind randomized study. Of 95 patients randomized to receive GE or placebo following chemotherapy, a febrile episode was documented in 50% of patients receiving GE and 63.3% receiving placebo (P = .89). There was a higher risk of developing a third and fourth febrile episode in the GE group (P = .01). However, among those at a lower risk for FN, those receiving GE developed fewer FN episodes (P = .075), especially those with severe neutropenia (P = .05). Major adverse events were distributed equally, but nonadherence was more common in the GE than in the placebo group: 19.5% versus 4%, respectively (P = .05). GE was safe and did not reduce FN risk in the entire cohort, but yet appeared to exert a protective effect in the lower-risk subgroup. We do not recommend the use of GE for FN prevention in higher-risk patients. A larger-scale clinical trial for the lower-risk subgroup of patients is advocated. (This trial was registered at www.clinicaltrials.gov as NCT00247039.). © The Author(s) 2015.
    Integrative Cancer Therapies 06/2015; DOI:10.1177/1534735415588928 · 2.01 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Candida infective endocarditis is a rare disease with a high mortality rate. Our understanding of this infection is derived from case series, case reports, and small prospective cohorts. The purpose of this study was to evaluate the clinical features and use of different anti-fungal treatment regimens for Candida infective endocarditis. This prospective cohort study was based on 70 cases of Candida infective endocarditis from the International Collaboration on Endocarditis (ICE)-Prospective Cohort Study and ICE-Plus databases collected between 2000 and 2010. The majority of infections were acquired nosocomially (67%). Congestive heart failure (24%), prosthetic heart valve (46%), and previous infective endocarditis (26%) were common comorbidities. Overall mortality was high with 36% mortality in-hospital and 59% at 1 year. On univariate analysis, older age, heart failure at baseline, persistent candidemia, nosocomial acquisition, heart failure as a complication, and intracardiac abscess were associated with higher mortality. Mortality was not affected by use of surgical therapy or choice of antifungal agent. A sub-group analysis was performed on 33 patients for whom specific antifungal therapy information was available. In this sub-group, 11 patients received amphotericin B based therapy and 14 received echinocandin based therapy. Despite a higher percentage of older patients and nosocomial infection in the echinocandin group, mortality was similar between the two groups. In conclusion, Candida infective endocarditis is associated with a high mortality rate that was not impacted by choice of antifungal therapy or by adjunctive surgical intervention. Additionally, echinocandin therapy was as effective as amphotericin B based therapy in the small sub-group analysis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.
    Antimicrobial Agents and Chemotherapy 02/2015; 59(4). DOI:10.1128/AAC.04867-14 · 4.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: -Use of surgery for the treatment of IE as related to surgical indications and operative risk for mortality has not been well defined. -The International Collaboration on Endocarditis-PLUS (ICE-PLUS) is a prospective cohort of consecutively enrolled patients with definite IE from 29 centers in 16 countries. We included patients from ICE-PLUS with definite left-sided, non-cardiac device related IE who were enrolled between September 1, 2008 and December 31, 2012. 1,296 patients with left-sided IE were included. Surgical treatment was performed in 57% of the overall cohort and in 76% of patients with a surgical indication. Reasons for non-surgical treatment included poor prognosis (33.7%), hemodynamic instability (19.8%), death before surgery (23.3%), stroke (22.7%), and sepsis (21%). Among patients with a surgical indication, surgical treatment was independently associated with the presence of severe aortic regurgitation, abscess, embolization prior to surgical treatment, and transfer from an outside hospital. Variables associated with non-surgical treatment were a history of moderate/severe liver disease, stroke prior to surgical decision, and S. aureus etiology. The integration of surgical indication, STS-IE score, and use of surgery was associated with 6-month survival in IE. -Surgical decision-making in IE is largely consistent with established guidelines, although nearly one-quarter of patients with surgical indications do not undergo surgery. Operative risk assessment by STS-IE score provides prognostic information for survival beyond the operative period. S. aureus IE was significantly associated with non-surgical management.
    Circulation 12/2014; 131(2). DOI:10.1161/CIRCULATIONAHA.114.012461 · 14.95 Impact Factor
  • Source
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: The optimal therapy for Candida infective endocarditis (IE) is unknown, and treatment guidelines are based largely on single site case series and case reports. The current guidelines have added echinocandins as a treatment option. We sought to compare amphotericin B based therapy to echinocandin based therapy, using two large, prospective, international, multi-center cohorts of patients with definite IE. Methods: We identified cases of definite Candida IE presenting between June 1, 2000 and September 30, 2011 from the International Collaboration on Endocarditis – Prospective Cohort Study (ICE-PCS) and the International Collaboration on Endocarditis Plus (ICE-Plus). A supplemental case report form was sent to enrolling sites to gather detailed information on antifungal therapy. We compared clinical characteristics and outcomes based on antifungal regimen received. Results: 72 cases of definite Candida IE were identified of which 33 had supplemental data on antifungal therapy available. The most common infecting species were C. albicans (n=13) and C. parapsilosis (n=12). Most patients received either an amphotericin B based regimen (33%) or an echinocandin based regimen (42%). Nearly half received combination antifungal therapy (45%) and surgical therapy was used in 13 patients (39%). There was no difference in either 42 day or 1 year mortality between those receiving an amphotericin B based regimen vs. those receiving an echinocandin based regimen (36% vs. 36% and 64% vs. 69%, respectively, p=1). Conclusion: This is one of the largest prospective series of Candida endocarditis patients to date. In this cohort, there was no difference in mortality with echinocandin based therapy as compared to amphotericin B based therapy. This study is limited by small sample size and observational data, however it lends support to the current recommendation of echinocandin based therapy as a viable treatment option for Candida endocarditis. Table 1. Amphotericin B (N=11) Echinocandin (N=14) p-value Combination therapy 6 (54%) 6 (43%) 0.56 Surgery 6 (54%) 5 (36%) 0.35 Duration antifungal, days (median) 78 50 0.89 Suppressive therapy 5 (45%) 6 (43%) 0.90 Mortality 42 d 4 (36%) 5 (36%) 1 1 y 7 (64%) 9 (69%) 1
    IDWeek 2014 Meeting of the Infectious Diseases Society of America; 10/2014
  • Maya Korem, Itzhack Polacheck, Jacob Strahilevitz
    Journal of Clinical Microbiology 07/2014; 52(7):2744. DOI:10.1128/JCM.01164-14 · 4.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Epidemiological features of infective endocarditis have changed during the last decades because of increases in the prevalence of health care exposure and of Staphylococcus aureus bloodstream infection. Consequently, the role of surgery is evolving. We aim to provide a contemporary profile of epidemiological, microbiological, and clinical features of infective endocarditis in a tertiary medical center, and identify predictors of mortality. Methods: A prospective observational cohort study of consecutive adult patients with definite endocarditis according to the modified Duke criteria. Data were collected from January 1, 2009 through October 31, 2011 following a predefined case report form designed by the ICE-PCS. Results: Among 70 endocarditis episodes, 25.7% involved prosthetic valves and 11.5% were device related. Forty-four percent of episodes were health-care associated. The predominant causative microorganism on native valve, prosthetic valve and device related endocarditis was Staphylococcus aureus (33.3%). Viridans group streptococci accounted for the majority of community-acquired endocarditis (36.1%). At least one complication occurred in 50% of the episodes. One third of the patients who had an indication for surgery were operated upon. Six month case fatality ratio was 40%. Sixty-five percent of patients with a contraindication to surgery died, compared with 9% and 28.5% who were treated surgically and medically, respectively. In multivariable analysis, age was a predictor of mortality. Conclusion: Compared with other series, we observed more health-care associated endocarditis, and a higher mortality. Nearly half of all deaths were in patients who had a contraindication to surgery. Careful evaluation of contraindications to surgery is warranted.
    European Journal of Internal Medicine 06/2014; 25(6). DOI:10.1016/j.ejim.2014.05.011 · 2.30 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Abstract Infective endocarditis and hepatosplenic abscesses are rare manifestations of cat scratch disease (CSD), especially among immunocompetent adults. An otherwise healthy woman who presented with fever and abdominal pain was diagnosed with multiple abscesses in the spleen and the liver, as well as a mitral valve vegetation. PCR on spleen tissue was positive for Bartonella henselae. Prolonged treatment with doxycycline and gentamicin led to complete recovery. Review of the literature revealed 18 cases of hepatosplenic CSD in immunocompetent adults; the majority presented with fever of unknown origin and abdominal pain. In most cases the causative organism was B. henselae and the pathological findings were necrotizing granulomas, similar to the pathological features in classic CSD. Concomitant endocarditis was diagnosed in one case. Because Bartonella is one of the leading pathogens of culture-negative endocarditis, we raise the question of whether a comprehensive evaluation for endocarditis is needed in cases of systemic CSD.
    Vector borne and zoonotic diseases (Larchmont, N.Y.) 02/2014; DOI:10.1089/vbz.2012.1279 · 2.53 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: PCV7 was introduced as universal childhood vaccination in Israel in July 2009 and PCV13 in November 2010. Here we report data on adult invasive pneumococcal disease (IPD), two years post PCV7 implementation and before an expected effect of PCV13. An ongoing nationwide active-surveillance (all 27 laboratories performing blood cultures in Israel), providing all blood & CSF S. pneumoniae isolates from persons >18 y was initiated in July 2009. Capture-recapture method assured reporting of >95% cases. All isolates were serotyped in one central laboratory. IPD outcome and medical history were recorded in 90%. Second year post PCV implementation is compared to the first year. During July 2009 to June 2011, 970 IPD cases were reported (annual incidence [/100,000] of 9.17 and 10.16 in the two consecutive years, respectively). Respective case fatality rates (CFRs) were 20% and 19.1%. Incidence of IPD and CFR increased with age and number of comorbidities. Incidence rate was significantly greater during the second winter, 7.79/100,000 vs. 6.14/100,000 in first winter, p = 0.004, with a non-significant decrease during summer months (3.02 to 2.48/100,000). The proportion of IPD cases due to PCV7-serotypes decreased from 27.5% to 13.1% (first to second year) (p<0.001). Yet, non-PCV13-strains increased from 32.7% to 40.2% (p = 0.017). The increase in non-PCV13-strains was highly significant in immunocompromised patients and to a lesser degree in non-immunocompromised at risk or in older patients (>64 y). Among younger/healthier patients serotype 5 was the major increasing serotype. Penicillin and ceftriaxone resistance decreased significantly in the second year. While overall annual incidence of IPD did not change, the indirect effect of PCV7 vaccination was evident by the significant decrease in PCV7 serotypes across all age groups. Increase in non-VT13 strains was significant in immunocompromised patients. A longer follow-up is required to appreciate the full effect of infant vaccination on annual IPD.
    PLoS ONE 02/2014; 9(2):e88406. DOI:10.1371/journal.pone.0088406 · 3.53 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Repeat episodes of infective endocarditis (IE) can occur in patients who survive an initial episode. We analysed risk factors and 1-year mortality of patients with repeat IE. 1874 patients enrolled in the International Collaboration on Endocarditis-Prospective Cohort Study between January 2000 and December 2006 (ICE-PCS) who had definite native or prosthetic valve IE and 1-year follow-up. Multivariable analysis was used to determine risk factors for repeat IE and 1-year mortality. Of 1874 patients, 1783 (95.2%) had single episode IE and 91 (4.8%) had repeat IE: 74/91(81%) with new infection and 17/91 (19%) with presumed relapse. On bivariate analysis, repeat IE was associated with haemodialysis (p=0.002), HIV (p=0.009), injection drug use (IDU) (p<0.001), Staphylococcus aureus IE (p=0.003), health-care acquisition (p=0.006) and previous IE before ICE enrolment (p=0.001). On adjusted analysis, independent risk factors were haemodialysis (OR 2.5, 95% CI, 1.2-5.3), IDU (OR 2.9, 95% CI 1.6- 5.4), previous IE (OR 2.8, 95% CI, 1.5-5.1) and North American region (OR 1.9, 95% CI 1.1- 3.4). Patients with repeat IE had higher 1-year mortality than those with single episode IE (p=0.003). Repeat IE is associated with IDU, previous IE, and haemodialysis. Clinicians should be aware of these risk factors in order to recognize patients who are at risk for repeat IE. This article is protected by copyright. All rights reserved.
    Clinical Microbiology and Infection 09/2013; 20(6). DOI:10.1111/1469-0691.12395 · 5.20 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective. To identify predictors of community-onset extended-spectrum β-lactamase (ESBL)-producing Escherichia coli infection. Design. Prospective case-control study. Setting. Acute care hospitals and ambulatory clinics in the Chicago, Illinois, region. Patients. Adults with E. coli clinical isolates cultured in ambulatory settings or within 48 hours of hospital admission. Methods. Cases were patients with ESBL-producing E. coli clinical isolates cultured in ambulatory settings or within 48 hours of admission, and controls were patients with non-ESBL-producing E. coli isolates, matched to cases by specimen, location, and date. Clinical variables were ascertained through interviews and medical record review. Molecular methods were used to identify ESBL types, sequence type ST131, and aac(6')-Ib-cr. Results. We enrolled 94 cases and 158 controls. Multivariate risk factors for ESBL-producing E. coli infection included travel to India in the past year (odds ratio [OR], 14.40 [95% confidence interval (CI), 2.92-70.95]), ciprofloxacin use (OR, 3.92 [95% CI, 1.90-8.1]), and age (OR, 1.04 [95% CI, 1.02-1.06]). Case isolates exhibited high prevalence of CTX-M-15 (78%), ST131 (50%), and aac(6')-Ib-cr (66% of isolates with CTX-M-15). Conclusions. Providers should be aware of the increased risk of ESBL-producing E. coli infection among returned travelers, especially those from India.
    Infection Control and Hospital Epidemiology 09/2013; 34(9):947-53. DOI:10.1086/671725 · 3.94 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Exserohilum rostratum is the most common pathogen in the current US outbreak of fungal central nervous system infection, septic arthritis and localized spinal or paraspinal infections (1).…
    Journal of clinical microbiology 05/2013; DOI:10.1128/JCM.00955-13 · 4.23 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: PURPOSE: Colistin is increasingly used as the last-resort treatment option against infections caused by multidrug-resistant (MDR) Gram-negative pathogens, but its nephrotoxicity is of concern, especially in severely ill patients. The aim of this study was to analyze the toxicity of colistin therapy in adults and children with hematological malignancies (HM) and hematopoietic stem cell transplantation (HSCT) recipients. METHODS: Data on HSCT recipients and HM patients, treated with intravenous colistin (2.5-5 mg/kg/day in children and 3-6 million international units (IU) in adults, adjusted to renal function) during the period 2008-2011 in our center, were retrospectively collected and analyzed. Nephrotoxicity was defined according to the RIFLE criteria (Risk, Injury, Failure, Loss, and End-stage kidney disease). RESULTS: Twenty-nine children and adults received 38 courses of intravenous colistin (2.5-5 mg/kg/day in children and 3-6 × 10(6) IU in adults, adjusted to renal function) [allogeneic HSCT (22 courses) and HM (16 courses)] for 3-28 days (median 10 days) for empirical therapy for nosocomial clinical sepsis (28) or local infection (6), and bacteremia with MDR Gram-negative rods (4). Nephrotoxicity was observed at the end of 4 (10.5 %) courses. In 32 (84 %) courses, nephrotoxic medications were concomitantly administered. Two patients had convulsions, probably unrelated to colistin. Seven patients (18 %) died while on colistin therapy. No death was attributed to an adverse effect of colistin. CONCLUSIONS: Treatment with intravenous colistin, with dosage adjusted to renal function, was relatively safe for HM/HSCT patients, even with concomitantly administered nephrotoxic medications. Concern about nephrotoxicity should not justify a delay in initiating empirical colistin treatment in situations where infection with MDR Gram-negative rods is likely.
    Infection 05/2013; 41(5). DOI:10.1007/s15010-013-0471-6 · 2.86 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pneumococcal infections in adults vary in severity and incidence is affected by childhood vaccination policy. Here, we try to define the host determinants and the interaction with specific serotypes that result in invasive pneumococcal disease (IPD) before an expected effect of pneumococcal conjugate vaccines. A nationwide active surveillance was initiated on July 2009, at the time of national implementation of PCV7 in Israel. The surveillance included all 27 laboratories and medical centers performing blood cultures in Israel, providing all blood and CSF pneumococcal isolates from persons =18y. Capture-recapture method assured that >95% of all cases were reported. IPD outcome and medical history were recorded and isolates were serotyped. Four hundred and sixty IPD cases were reported (annual incidence [/100,000] of 9.25). Incidence increased with age, from 2.6 among 18-34y to 66.8 among =85y. The most common diagnosis was pneumonia (72.4%), followed by bacteremia with no apparent focus (20.2%). Case fatality rate increased with age and number of comorbidities (34.5% for =75y or those with =3 comorbidities vs. 9.2-11.2% among <65y or those with no comorbidities; p=0.015). Variables independently associated with mortality were: age =75, chronic renal failure, malignancy, neurosurgery, alcohol abuse, multi-lobar pneumonia and sepsis with no apparent focus. The predominant serotypes in patients 18-49y were 1, 5, 8, 7F and 9V (constituting 56.3% in this age-group vs. 11.9% in =75y; p<0.01). The predominant serotypes among patients =75y were 3, 19A, 23F and 14 (40.3% of this age-group vs. 12.9% of 18-49y; p<0.01). Overall, PCV7 and PCV13 covered 25.6% and 63.7% of isolates, respectively, and 30.9% and 67.9% of isolates in mortality cases respectively. This nationwide active surveillance provides the baseline incidence, mortality rates and risk group distributions of IPD in adults before expected PCV effect.
    Vaccine 03/2013; DOI:10.1016/j.vaccine.2013.02.059 · 3.49 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A bla(KPC-9) carbapenemase variant was discovered in isolates of Klebsiella pneumoniae and Escherichia coli from a single patient. It differed from bla(KPC-3) by one amino acid substitution (Val239Ala). The K. pneumoniae isolate was typed as ST258, as was the epidemic Israeli KPC-3 clone. bla(KPC-9) was found on a plasmid indistinguishable from pKpQIL that carries bla(KPC-3) in the epidemic clone. Compared to KPC-3, KPC-9 conferred less resistance to carbapenems and higher resistance to ceftazidime.
    Antimicrobial Agents and Chemotherapy 09/2012; 56(11):6057-9. DOI:10.1128/AAC.01156-12 · 4.45 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: A refractory epidemic of carbapenem-resistant Klebsiella pneumoniae (CRKP) emerged in the adult population at our hospital in 2005, as in most Israeli hospitals. Contemporaneously, a different clone of CRKP caused an easily contained outbreak in a paediatric long-term care facility (LTCF) in Jerusalem. While previously identified host-related risk factors for colonization by these organisms undoubtedly contributed to these outbreaks, it is very likely that bacterial factors might be crucial in explaining the striking differences in transmissibility between the implicated strains. We therefore sought bacterial factors associated with these different epidemiological behaviours. Seven CRKP isolated at our hospital and the LTCF during 2008-09 were examined by antimicrobial susceptibility testing and PFGE, and further analyses of these two clones was done using multilocus sequence typing and competition experiments. Plasmids were analysed by conjugation, restriction mapping, PCR and sequencing. Both clones were multidrug resistant and harboured identical plasmids carrying the bla(KPC-3) gene. The hyper-transmissible epidemic clone carried additional antibiotic resistance genes and hosted an additional plasmid. The clone from the LTCF did not demonstrate hyper-transmissible properties despite its presence in an institution of a type commonly plagued by the epidemic clone. Competition assays showed the more easily contained strain to be fitter. These findings suggest that neither the presence of the plasmid carrying the bla(KPC-3) gene nor relative survival fitness account for the hyper-transmissibility of the epidemic strain. The role of patient age in susceptibility to colonization by the epidemic strain should be investigated.
    Journal of Antimicrobial Chemotherapy 04/2012; 67(7):1651-4. DOI:10.1093/jac/dks115 · 5.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We characterized distinctive features of a hypertransmissible carbapenem-resistant Klebsiella pneumoniae (CRKP) clone that emerged at Hadassah Hospital, Ein-Kerem, Jerusalem, Israel, in 2006. Eleven CRKP isolated at Hadassah Hospital during 2005-09 were examined by antimicrobial susceptibility testing, PFGE and multilocus sequence typing (MLST). Plasmids were analysed by conjugation, restriction mapping, PCR and sequencing. Divergence from the national epidemic sequence type (ST) ST258 to ST512 was observed early on. Carbapenem resistance was conferred by bla(KPC-3) carried on a plasmid apparently closely related to pKpQIL, also from Israel. This clone also carried a 15 kb plasmid, designated pAAC154, that carries a Tn1331 derivative containing the aac(6')-Ib gene. pAAC154 does not carry a bla(KPC) gene, but is similar to pS15, a plasmid from New York that carries bla(KPC-2). A single CRKP clone ST512 has spread efficiently in our region. In this clone, aac(6')-Ib, common in CRKP strains, is carried on a different plasmid from bla(KPC-3).
    Journal of Antimicrobial Chemotherapy 01/2012; 67(4):898-901. DOI:10.1093/jac/dkr552 · 5.44 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Cytotoxic chemotherapy induces changes in the oral microflora that may cause oral and systemic infections in myelosuppressed cancer patients. These complications prompted us to assess the antimicrobial activity of a topical Iseganan HCl mouthwash vs. placebo on the aerobic and facultatively anaerobic oral flora in these patients. Two hundred and twenty-five chemotherapy patients were recruited into a randomized, double-blind, placebo-controlled trial, conducted at multiple centers. The study compared the antimicrobial efficacy of Iseganan HCl vs. placebo (95% of the Iseganan and 97% of the control group received myeloablative chemotherapy). Iseganan HCl 9 mg/3 ml was administered as a swish and swallow solution, six times daily for 21-28 days. Microbial cultures were made before and after the daily Iseganan mouth rinse on the first and final days of chemotherapy. The reduction in total microbial load after the first day of treatment was statistically significant (1.59 vs. 0.18 log10 CFU for the Iseganan HCl and placebo groups, respectively, P < 0.0001). Iseganan HCl rinse had a cumulative effect demonstrated by the significant difference between the two groups on the last day of the study (i.e. completion of Iseganan daily treatment) (P < 0.05). The reduction was mainly due to decreased densities of viridans streptococci, non-hemolytic streptococci, and yeasts. The minimal inhibitory concentration (MIC) of Iseganan HCl remained the same throughout the course of treatment. Topical Iseganan HCl significantly reduces the total oral aerobic bacterial, streptococcal, and yeast load. Its potential as an oral antimicrobial agent in preventing these types of infections is clear.
    Journal of Oral Pathology and Medicine 11/2011; 41(3):229-34. DOI:10.1111/j.1600-0714.2011.01094.x · 1.87 Impact Factor
  • Source
    Carlos Hidalgo-Grass, Jacob Strahilevitz
    [Show abstract] [Hide abstract]
    ABSTRACT: We have developed a simple PCR-based high-resolution melt curve analysis for identification of the quinolone resistance gene aac(6')-Ib-cr through regions encompassing the two defining single nucleotide mutations. Dissociation curves showed 100% concordance with DNA sequencing, including the identification of a strain where aac(6')-Ib and aac(6')-Ib-cr coexist.
    Antimicrobial Agents and Chemotherapy 05/2010; 54(8):3509-11. DOI:10.1128/AAC.00485-10 · 4.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Although plasmid-mediated quinolone resistance (PMQR) was thought not to exist before its discovery in 1998, the past decade has seen an explosion of research characterizing this phenomenon. The best-described form of PMQR is determined by the qnr group of genes. These genes, likely originating in aquatic organisms, code for pentapeptide repeat proteins. These proteins reduce susceptibility to quinolones by protecting the complex of DNA and DNA gyrase or topoisomerase IV enzymes from the inhibitory effect of quinolones. Two additional PMQR mechanisms were recently described. aac(6')-Ib-cr encodes a variant aminoglycoside acetyltransferase with two amino acid alterations allowing it to inactivate ciprofloxacin through the acetylation of its piperazinyl substituent. oqxAB and qepA encode efflux pumps that extrude quinolones. All of these genes determine relatively small increases in the MICs of quinolones, but these changes are sufficient to facilitate the selection of mutants with higher levels of resistance. The contribution of these genes to the emergence of quinolone resistance is being actively investigated. Several factors suggest their importance in this process, including their increasing ubiquity, their association with other resistance elements, and their emergence simultaneous with the expansion of clinical quinolone resistance. Of concern, these genes are not yet being taken into account in resistance screening by clinical microbiology laboratories.
    Clinical microbiology reviews 10/2009; 22(4):664-89. DOI:10.1128/CMR.00016-09 · 16.00 Impact Factor

Publication Stats

2k Citations
231.81 Total Impact Points

Institutions

  • 2008–2015
    • Hebrew University of Jerusalem
      Yerushalayim, Jerusalem, Israel
  • 2009–2014
    • Hadassah Medical Center
      • Division of Microbiology and Infectious Diseases
      Yerushalayim, Jerusalem, Israel
    • NorthShore University HealthSystem
      • Department of Medicine
      Chicago, Illinois, United States
  • 2005–2009
    • Tel Aviv University
      Tell Afif, Tel Aviv, Israel
  • 2006
    • Kenya Centers for Disease Control and Prevention
      Winam, Kisumu, Kenya
    • Harvard Medical School
      • Department of Medicine
      Boston, Massachusetts, United States
  • 2005–2006
    • Massachusetts General Hospital
      • Division of Infectious Diseases
      Boston, MA, United States
  • 2002
    • Sheba Medical Center
      • Department of Pathology
      Gan, Tel Aviv, Israel