Khetam Hussein

Carbapenem Resistance Among Klebsiella pneumoniae Isolates: Risk Factors, Molecular Characteristics, and Susceptibility Patterns

BACKGROUNDnCarbapenem resistance among isolates of Klebsiella pneumoniae has been unusual.nnnOBJECTIVESnTo identify risk factors for infection with carbapenem-resistant K. pneumoniae (CRKP) and to characterize microbiological aspects of isolates associated with these infections.nnnDESIGNnRetrospective case-control study.nnnSETTINGnA 900-bed tertiary care hospital.nnnRESULTSnFrom January 2006 through April 2007, K. pneumoniae was isolated from 461 inpatients; 88 had CRKP infection (case patients), whereas 373 had carbapenem-susceptible K. pneumoniae infection (control subjects). The independent risk factors for infection with CRKP were prior fluoroquinolone use (odds ratio [OR], 1.87 [95% confidence interval [CI], 1.07-3.26]; P=.026), previous receipt of a carbapenem drug (OR, 1.83 [95% CI, 1.02-3.27]; P=.042), admission to the intensive care unit (OR, 4.27 [95% CI, 2.49-7.31]; P<.001), and exposure to at least 1 antibiotic drug before isolation of K. pneumoniae (OR, 3.93 [95% CI, 1.15-13.47]; P=.029). All CRKP isolates carried the bla(KPC) gene. Approximately 90% of the tested isolates carried the bla(KPC-2) allele, suggesting patient-to-patient transmission. Almost all CRKP isolates were resistant to all antibiotics, except to colistin (resistance rate, 4.5%), gentamicin (resistance rate, 7%), and tigecycline (resistance rate, 15%).nnnCONCLUSIONSnCRKP should be regarded as an emerging clinical threat. Because these isolates are resistant to virtually all commonly used antibiotics, control of their spread is crucial.

Decreased Macrophage Paraoxonase 2 Expression in Patients With Hypercholesterolemia Is the Result of Their Increased Cellular Cholesterol Content: Effect of Atorvastatin Therapy

Objective—To analyze paraoxonase2 (PON2) expression in human monocyte-derived macrophages (HMDM) from patients with hypercholesterolemia in relation to cellular cholesterol and oxidative stress. Methods and Results—Ten healthy subjects (controls) and 10 patients with hypercholesterolema who received 20-mg/d atorvastatin participated in the study. The patients’ versus controls’ HMDM demonstrated increased cholesterol content (270%) and oxidative stress (30% to 45%). Atorvastatin therapy reduced these parameters (59% and 25%, respectively). The patients’ versus controls’ macrophage-PON2 mRNA expression and PON2 activity were lower (100% and 40%, respectively), and atorvastatin therapy increased these parameters (76% and 200%, respectively). Untreated patient HMDM incubation with atorvastatin (0 to 10 &mgr;mol/L) resulted in a dose-dependent reduction in cellular cholesterol content and in cell-mediated low-density lipoprotein (LDL) oxidation up to 79% and 66%, respectively. In parallel, PON2 mRNA expression and PON2 activity increased dose-dependently up to 3.6- and 2.1-fold, respectively. On incubation of control HMDM with acetylated-LDL or aggregated-LDL, cellular cholesterol content increased (77% and 100%), and macrophage-PON2 activity decreased (49% and 22%), respectively. In contrast, oxidized LDL increased both cellular oxidative stress and PON2 expression. Conclusions—HMDM-PON2 expression is reduced in patients with hypercholesterolemia as a result of their increased cellular cholesterol content. Atorvastatin therapy reduced both macrophage oxidative stress and cholesterol content, and upregulated PON2 expression, thus contributing to attenuation of foam cells formation.

Impact of carbapenem resistance on the outcome of patients' hospital-acquired bacteraemia caused by Klebsiella pneumoniae

BACKGROUNDnCarbapenem-resistant Enterobacteriaceae, especially Klebsiella spp., have become a major health problem recently worldwide. Since 2006 the incidence of carbapenem-resistant Klebsiella pneumoniae (CRKP) infections has increased substantially in Israel. Bloodstream infections (BSIs) caused by these strains have been associated with high rates of treatment failure and mortality.nnnAIMnThis study was designed to identify risk factors for carbapenem resistance among patients with healthcare-related (HCR) K.xa0pneumoniae bacteraemia and predictors of mortality associated with HCR-CRKP bacteraemia compared with carbapenem-susceptible K.xa0pneumoniae (CSKP).nnnMETHODSnIn this retrospective case-control study, all cases of K.xa0pneumoniae bacteraemia during 2006-2008 were identified. Resistance patterns, underlying morbidities, risk factors for drug resistance and mortality rates were compared for patients with CRKP and CSKP bacteraemia.nnnFINDINGSnTwo hundred and fourteen patients with CSKP bacteraemia were compared with 103 patients with CRKP bacteraemia. Severe, chronic comorbidities and prior antibiotic use were more frequent among patients with CRKP bacteraemia. On multivariate analysis prior use of macrolides and antibiotic exposure for ≥14 days remained the only independent factors associated with CRKP bacteraemia. Mortality rates of CRKP patients were significantly higher than those of CSKP patients. On multivariate analyses: bedridden status, chronic liver disease, Charlson comorbidity index ≥5, mechanical ventilation, and haemodialysis remained independently associated with mortality among patients with K.xa0pneumoniae bacteraemia. Carbapenem resistance was not a risk factor for mortality.nnnCONCLUSIONSnPrevious antibiotic exposure is a risk factor for CRKP-BSI. Mortality among patients with K.xa0pneumoniae bacteraemia is associated with serious comorbidities, but not with carbapenem resistance.

Natural history and decolonization strategies for ESBL/carbapenem-resistant Enterobacteriaceae carriage: systematic review and meta-analysis

BACKGROUNDnESBL-producing Enterobacteriaceae and carbapenem-resistant Enterobacteriaceae (CRE) are rapidly spreading worldwide. Their natural reservoir is intestinal.nnnMETHODSnWe carried out a systematic review and meta-analysis to estimate CRE and ESBL carriage duration and to evaluate the effect of decolonization therapy. We included cohort and comparative studies examining the natural history of CRE/ESBL colonization, examining rates of carriage following decolonization or comparing decolonization and no decolonization conducted in the healthcare setting or in the community. A comprehensive search was conducted until November 2015. We compiled carriage rates at 1, 3, 6 and 12 months with and without decolonization therapy and assessed the effect of decolonization.nnnRESULTSnThirty-seven studies fulfilled inclusion criteria. In healthcare settings, pooled ESBL/CRE colonization rates decreased without intervention from 76.7% (95% CIu200a=u200a69.3%-82.8%) at 1 month to 35.2% (95% CIu200a=u200a28.2%-42.9%) at 12 months of follow-up. Following decolonization, the rate was 37.1% (95% CIu200a=u200a27.5%-47.7%) at end of therapy and 57.9% (95% CIu200a=u200a43.1%-71.4%) at 1 month. In two randomized trials, carriage was significantly reduced at end of therapy (risk ratiou200a=u200a0.42, 95% CIu200a=u200a0.25-0.65), but the effect was not significant after 1 month (risk ratiou200a=u200a0.72, 95% CIu200a=u200a0.48-1.05), with no longer follow-up. Heterogeneity was explained by surveillance methodology, with no differences observed between ESBLs and CREs. Among community dwellers, ESBL colonization decreased from 52.3% (95% CIu200a=u200a29.5%-74.2%) at 1 month to 19.2% (95% CIu200a=u200a9.7%-34.4%) at 6 months.nnnCONCLUSIONSnA significant proportion of ESBL and CRE carriers remain colonized up to 1 year in the healthcare setting. While short-term decolonization therapy reduces carriage during therapy, its longer-term effects are unclear.

Risk Factors for Recurrence of Carbapenem-Resistant Enterobacteriaceae Carriage: Case-Control Study

BACKGROUNDnThe natural history of carbapenem-resistant Enterobacteriaceae (CRE) carriage and the timing and procedures required to safely presume a CRE-free status are unclear.nnnOBJECTIVEnTo determine risk factors for recurrence of CRE among presumed CRE-free patients.nnnMETHODSnCase-control study including CRE carriers in whom CRE carriage presumably ended, following at least 2 negative screening samples on separate days. Recurrence of CRE carriage was identified through clinical samples and repeated rectal screening in subsequent admissions to any healthcare facility in Israel. Patients with CRE recurrence (cases) were compared with recurrence-free patients (controls). The duration of follow-up was 1 year for all surviving patients.nnnRESULTSnIncluded were 276 prior CRE carriers who were declared CRE-free. Thirty-six persons (13%) experienced recurrence of CRE carriage within a year after presumed eradication. Factors significantly associated with CRE recurrence on multivariable analysis were the time in months between the last positive CRE sample and presumed eradication (odds ratio, 0.94 [95% CI, 0.89-0.99] per month), presence of foreign bodies at the time of presumed eradication (4.6 [1.64-12.85]), and recurrent admissions to healthcare facilities during follow-up (3.15 [1.05-9.47]). The rate of CRE recurrence was 25% (11/44) when the carrier status was presumed to be eradicated 6 months after the last known CRE-positive sample, compared with 7.5% (10/134) if presumed to be eradicated after 1 year.nnnCONCLUSIONSnWe suggest that the CRE-carrier status be maintained for at least 1 year following the last positive sample. Screening of all prior CRE carriers regardless of current carriage status is advised.

Treatment of Carbapenem-Resistant Acinetobacter baumannii Ventilator-Associated Pneumonia: Retrospective Comparison Between Intravenous Colistin and Intravenous Ampicillin-Sulbactam.

Carbapenem-resistant Acinetobacter baumannii has been increasingly reported as the causative agent of ventilator-associated pneumonia (VAP) among patients in the intensive care units. However, there are insufficient data to guide the appropriate treatment for such infection. Our aim was to compare the outcome of carbapenem-resistant A. baumannii VAP treated with colistin or with ampicillin–sulbactam. We conducted a retrospective study of patients diagnosed with carbapenem-resistant A. baumannii VAP during 2008 and 2009. Clinical and microbiologic cure rates, 30-day mortality, and change in renal function were compared between patients treated with colistin versus those treated with ampicillin–sulbactam. The association between treatment and mortality was examined through multivariable logistic regression analysis. Of the 98 patients diagnosed with carbapenem-resistant A. baumannii VAP, 66 were treated with colistin and 32 with ampicillin–sulbactam. Baseline characteristics of patients were similar, except for a longer intensive care unit stay and lower creatinine clearance test before VAP diagnosis among patients treated with colistin. Clinical cure rates were similar in the 2 groups. In the colistin group, microbiologic failure rates were higher at 7 days [16/33 (48%) vs. 3/17 (18%); P = 0.03]; patients had a more significant elevation in creatinine (+0.2 ± 1.0 mg/dL vs. −0.3 ± 1.1 mg/dL; P = 0.021), and treatment was associated with an increased 30-day mortality (adjusted-odds ratio, 6.5; 95% confidence interval, 1.348–31.342; P = 0.02). In conclusion, patients treated with colistin or ampicillin–sulbactam had similar clinical cure rates. However, colistin was associated with higher rates of microbiologic failure, reduction in renal function, and an increased 30-day mortality. A prospective study comparing high-dose colistin and ampicillin–sulbactam for the treatment of carbapenem-resistant A. baumannii VAP is warranted.

Acute cytomegalovirus infection associated with the onset of inflammatory bowel disease

A 29-year-old man was admitted with high-grade fever, crampy abdominal pain, and watery diarrhea that had persisted for 2 weeks before his admission. Symptomatic treatment (acetaminophen only) was of no benefit. On physical examination, there was diffuse abdominal tenderness. Laboratory tests showed a leukomoid reaction with atypical lymphocytosis, and serology tests revealed acute cytomegalovirus infection. Abdominal computed tomography and colonoscopy revealed an inflammatory process involving the large intestine. On histologic examinations of intestinal biopsy samples, there was an active inflammation with no inclusion bodies. The patient was treated with ganciclovir with only mild improvement. Adding 5-aminosalicylic acid caused little further improvement. Repeated colonoscopy performed 2 months later showed severe chronic ulcerative colitis. Only the addition of systemic steroids caused complete resolution of the symptoms. On review of the literature (Medline search for cytomegalovirus colitis in immunocompetent patients), 18 cases were found. On follow-up, 10 of these patients were found to have inflammatory bowel disease.

Campylobacter bacteraemia: 16 years of experience in a single centre

Abstract Background: Campylobacter bacteraemia (CB) is rare and usually occurs in immune-compromised patients. In this study we examined the incidence and epidemiology of CB in one institution over 15.5 years. Methods: The medical records of all the consecutive patients with CB admitted to our hospital from 2000 to 2015 were retrospectively reviewed. Clinical characteristics, microbiologic and outcome data were collected. Results: During the study period, 65 patients with CB were identified. The majority of the patients were middle aged and immune-compromised. Campylobacter jejuni was the most commonly identified species (33/47, 70%). The main underlying conditions were haematological malignancies (43%) and chronic liver disease (14%). Fifty-seven percent of the patients were receiving immunosuppressive therapy at the time of bacteraemia. The most common presenting symptoms were fever (85%), diarrhoea (40%), abdominal pain (40%), and nausea and vomiting (40%). Of the isolates tested, 97% were susceptible to macrolides, and only 35% were susceptible to quinolones. Susceptibility to quinolones decreased over the years. Most patients did not receive adequate empiric antibiotic treatment (81.5%) and about 20% never received directed therapy. Mortality and relapse rates were low (5% each). There was no association between adequate empirical or definitive antibiotic therapy and adverse outcomes. Conclusion: The main predisposing factor for Campylobacter bacteraemia in our cohort was immunosuppression. Prognosis was generally favourable regardless of appropriateness of antibiotic therapy.

The association between infection control interventions and carbapenem-resistant Enterobacteriaceae incidence in an endemic hospital

BACKGROUNDnIsrael experienced a national outbreak of carbapenem-resistant Enterobacteriaceae (CRE) starting in 2006.nnnAIMnTo assess the association between infection control (IC) interventions implemented in a referral hospital in Israel and CRE incidence.nnnMETHODSnRetrospective quasi-experimental study of prospectively collected data. CRE incidence, defined as the number of patients newly acquiring CRE in surveillance or clinical samples per 100,000 hospital-days, was plotted quarterly between 2005 and 2016. IC interventions were applied at different time-points throughout this period. Data were collected on IC staffing, number of rectal surveillance cultures, and carbapenem consumption. Autocorrelated segmented linear regression analysis was used to assess the time-points at which a significant change in the CRE incidence trend occurred, and the association between the timing of IC intervention implementation and observed CRE trends was assessed. Trends between time-points were expressed as quarterly percent change (QPC) with 95% confidence intervals (CIs).nnnFINDINGSnBetween 2005 and 2008, CRE incidence increased significantly (QPC: 19.7%; CI: 11.5-28.4), reaching a peak of 186.6 new acquisitions per 100,000 hospital-days. From mid-2011 until the end of follow-up, there was a significantly decreasing incidence trend (QPC:xa0-4.5; CI: -6.4 to -2.5). Cohorting of patients, screening of contacts and high-risk patients on admission were insufficient to control the epidemic. Improved hand hygiene compliance, cohorting with dedicated nursing staff, addition of regular screening in high-risk departments, and carbapenem restriction were required. Decreasing CRE incidence was observed with an infectious diseases/IC staffing of 1.2-1.5 per 100 beds and 20,000-36,000 yearly CRE surveillance samples.nnnCONCLUSIONnA multi-faceted hospital-wide intervention programme is required to control CRE in hospital settings.

Risk factors for mortality among carbapenem-resistant enterobacteriaceae carriers with focus on immunosuppression

OBJECTIVESnTo identify risk factors for mortality in a cohort of carbapenem-resistant enterobacteriaceae (CRE) carriers, focusing on immunosuppression and other risk factors known at the time of CRE carriage detection.nnnMETHODSnWe prospectively followed all new and known CRE carriers admitted between June 2016 and June 2017 to a single tertiary center in Israel. Patients were included in the study after confirmation of the carrier state. Demographic and clinical data were documented on admission or CRE acquisition and patients were followed prospectively post-discharge until January 2018 or death. Risk factors for mortality known at the time of the first encounter with a CRE carrier were sought. Adjusted hazard ratios (HR) for mortality at end of follow-up with 95% confidence intervals (CI) were assessed using Cox regression analysis.nnnRESULTSnA total of 115 patients were included in the analysis. During the study period, 66 (57.4%) patients died. Immunosuppression was associated with mortality (HR 1.95, CI 95% 1.12-3.44), adjusted to the Charlson co-morbidity score, functional status, chronic renal disease and Klebsiella pneumonia CRE, the latter three also significantly associated with mortality. CRE bacteremia occurred among 24 (20.9%) carriers during follow up, more frequently among immunosuppressed patients and was significantly associated with mortality at end of follow-up (pu202f=u202f0.015).nnnCONCLUSIONnImmunosuppression is independently associated with mortality among CRE carriers, possibly related to CRE bacteremia that is frequent among these patients. Further research is needed on interventions to prevent deaths among CRE carriers.