Haim Ben-Zvi

Trends in Secondary Antibiotic Resistance of Helicobacter pylori from 2007 to 2014: Has the Tide Turned?

ABSTRACT The current guidelines recommend culture and antibiotic susceptibility testing of Helicobacter pylori following two failed eradication attempts. Where testing is unavailable, epidemiological data for secondary H. pylori resistance are essential to allow for the rational use of antibiotics. The aim of this study was to describe the temporal changes in antibiotic resistance among adults previously treated for H. pylori infections and to identify predictors of resistance. Between 2007 and 2014, consecutive patients undergoing gastroscopy with H. pylori culture and susceptibility testing at our institution following at least two treatment failures were retrospectively identified. Antibiotic susceptibilities were recorded and linked to the demographic data. A total of 1,042 patients were identified, including 739 (70.9%) males, aged 39.3 ± 18.9 years. Resistance to clarithromycin, metronidazole, and levofloxacin was found in 57.2%, 64.4%, and 5.1% of isolates, respectively. Dual resistance to clarithromycin and metronidazole was seen in 39.9%. Over the study period, clarithromycin resistance increased annually in a linear manner (odds ratio [OR], 1.09; 95% confidence interval [CI], 1.03 to 1.14; P < 0.01), levofloxacin resistance decreased annually (OR, 0.78; 95% CI, 0.61 to 0.92; P < 0.01), and metronidazole resistance was nonlinear. Age was an independent predictor of resistance to all antibiotics. Time elapsed predicted resistance for clarithromycin and levofloxacin and dual resistance for clarithromycin-metronidazole. Secondary resistance of H. pylori to clarithromycin and metronidazole remains high. The low secondary resistance to levofloxacin makes it an attractive treatment option in our region for patients following two failed eradication attempts.

Monomicrobial necrotizing fasciitis in a single center: the emergence of Gram-negative bacteria as a common pathogen

BACKGROUNDnNecrotizing fasciitis (NF) is a life-threatening soft tissue infection. It is usually caused by Streptococcus pyogenes and other Gram-positive bacteria. Several reports, however, emphasize the importance of Gram-negative rods in this infection.nnnMETHODSnWe retrospectively studied all cases of monomicrobial necrotizing fasciitis hospitalized in our center during the years 2002-2012. We compared clinical characteristics and outcomes of patients with Gram-negative versus Gram-positive infection.nnnRESULTSnForty-five cases were reviewed, 19 caused by Gram-negative organisms, 10 of them Escherichia coli, and 26 caused by Gram-positive organisms, 10 of them S. pyogenes. Compared to Gram-positive infections, patients with Gram-negative infections were more likely to have a baseline malignancy (9/19, 47.4%) or to have undergone recent surgery (4/19, 42.3%). The 30-day mortality was higher among Gram-negative infected patients (8/19, 42.1% vs. 8/26, 30.8%). Creatine phosphokinase (CPK) was elevated in a minority of patients with Gram-negative necrotizing fasciitis, and its absolute value was lower than in Gram-positive necrotizing fasciitis.nnnCONCLUSIONSnIn our center, 42% of monomicrobial necrotizing fasciitis cases were found to be caused by Gram-negative organisms, mostly E. coli. These infections usually appeared in immunocompromised or postoperative patients, often presented with normal CPK levels, and were associated with high mortality rates.

Empirical Antibiotic Treatment Does Not Improve Outcomes in Catheter-Associated Urinary Tract Infection: Prospective Cohort Study

BackgroundnCatheter associated urinary tract infection (CAUTI) is the most common healthcare-associated acquired infection. We aimed to describe the short- and long-term survival of patients with CAUTI and the impact of the empirical antibiotic treatment on survival rates.nnnMethodsnIn this prospective observational study we included consecutive adult patients with a chronic indwelling catheter-associated UTI and sepsis hospitalized in medical departments. The primary outcomes were 30-days all-cause mortality and long-term survival at end of the follow-up. A multivariate analysis using logistic regression and Cox proportional hazard model was performed to identify independent risk factors for an adverse outcome. A propensity-score model for receiving appropriate empirical antibiotic therapy was constructed and used to match patients.nnnResultsnOverall, 315 consecutive patients with CAUTI were enrolled. The cohort consisted of elderly to very old patients (mean age 79.2 ± 11.5). The crude 30-day all-cause mortality rate was 30.8% (97/315). The median survival time was 82 days (interquartile range [IQR] 22-638). Appropriate early empirical treatment had no statistically significant association with 30-day mortality, propensity score-matched odds ratio (OR) 1.39 (0.76-2.55). Similarly, in the propensity-matched cohort, appropriate empirical treatment was not statistically associated with long-term survival (hazard ratio [HR] = 0.99, 95% confidence interval [CI] 0.75-1.3).nnnConclusionsnIn our setting, patients with CAUTI had poor short- and long-term prognosis regardless of appropriate empirical antibiotic treatment. Avoiding empirical antibiotics for CAUTI might be an important antibiotic stewardship intervention in hospitals.

Fluorescence Lifetime Imaging Microscopy, a Novel Diagnostic Tool for Metastatic Cell Detection in the Cerebrospinal Fluid of Children with Medulloblastoma

In pediatric brain tumours, dissemination of malignant cells within the central nervous system confers poor prognosis and determines treatment intensity, but is often undetectable by imaging or cytology. This study describes the use of fluorescence lifetime (FLT) imaging microscopy (FLIM), a novel diagnostic tool, for detection of metastatic spread. The study group included 15 children with medulloblastoma and 2 with atypical teratoid/rhabdoid tumour. Cells extracted from the tumour and the cerebrospinal fluid (CSF) 2 weeks postoperatively and repeatedly during chemo/radiotherapy were subjected to nuclear staining followed by FLT measurement and cytological study. Control CSF samples were collected from patients with infectious/inflammatory disease attending the same hospital. Median FLT was prolonged in tumour cells (4.27u2009±u20090.28u2009ns; Pu2009<u20092.2*10−16) and CSF metastatic cells obtained before chemo/radiotherapy (6.28u2009±u20090.22u2009ns; Pu2009<u20092.2*10−16); normal in inflammatory control cells (2.6u2009±u20090.04u2009ns) and cells from children without metastasis before chemo/radiotherapy (2.62u2009±u20090.23u2009ns; Pu2009=u20090.858) and following treatment (2.62u2009±u20090.21u2009ns; Pu2009=u20090.053); and short in CSF metastatic cells obtained after chemo/radiotherapy (2.40u2009±u20090.2u2009ns; Pu2009<u20092.2*10−16). FLIM is a simple test that can potentially identify CSF spread of brain tumours. FLT changes in accordance with treatment, with significant prolonged median values in tumours and metastases. More accurate detection of metastatic cells may guide personalised treatment and improve the therapeutic outcome.

Positive IgM in Congenital CMV Infection

Neonatal serum detection of cytomegalovirus (CMV) immunoglobulin M (IgM) has low sensitivity in identifying congenital cytomegalovirus (cCMV). Several reports have endeavored to associate the presence/absence of IgM to disease severity. Data were collected for all infants with cCMV followed in our clinic. Infant outcome after birth was compared between infants who tested positive or negative. Sensitivity of positive IgM in diagnosing cCMV was 40.7%. The rate of symptomatic disease in those who tested positive was statistically higher (67.7%, P < .001). Odds ratio for symptomatic disease in infants with positive IgM born after a maternal primary infection was 3.47 (95% confidence interval = 1.7-7.1). Positive IgM was found in only 48.8% of symptomatic and 22.1% of asymptomatic children. Our results demonstrated a low sensitivity of IgM in diagnosing cCMV. However, while a positive IgM antibody for CMV is associated with a more symptomatic disease, it does not serve as a precise laboratory marker for a severity.

Frequency domain fluorescence lifetime imaging microscopy system for detecting inflammatory cells

Characterizing different pathological states in the cellular level with a high throughput diagnostic tool is one of the main interests today. In previously works, we demonstrated how the frequency domain (FD) fluorescence lifetime imaging microscopy (FLIM) technique could be utilized to implement that in variety of examples. Among them was to classify between different chromosomal abnormalities in patients with b-cell chronic lymphocytic leukemia (B-CLL) and between metastatic cells and inflammation cells in the cerebral spinal fluid of patients with Medulloblastoma. This research describes the use of FD-FLIM system to differentiate between patients diagnosed without any disease (controls) that showed a normal median FLT (2.65±0.11ns) and patients diagnosed with inflammation (viruses and bacteria) that showed a prolong median FLT and a larger distribution (3.18±0.44ns in viruses and 3.28±0.45ns). The study group of this research included 43 samples divided into 4 groups: 9 samples diagnosed with different types of bacteria, 16 samples diagnosed with different types of viruses, 12 samples diagnosed with no any bacteria or virus and 5 samples diagnosed without any disease that served as controls. Furthermore, we studied a group of patients without detection of inflammation that were sick. We found that this group was divided into two groups; one group had the same median FLT as the controls, and the other group had the same median FLT as the inflammatory patients. As a result, we believe the FD-FLIM system can suggest a faster and more accurate diagnostic technique than the methods used today. The correlations of the FLT distribution pattern with the different groups are presented.

Risk factors for early invasive fungal infections in paediatric liver transplant recipients

Invasive fungal infections (IFIs) postliver transplantation are a frequent cause of morbidity and mortality; however, studies reporting on these infections in the paediatric population are scarce. To investigate the incidence and risk factors of IFIs in paediatric liver transplant recipients during the early posttransplantation period (≤3 months). Data were collected for all paediatric liver transplant recipients registered in a national transplantation center from 2004 to 2014. Using a stepwise logistic regression to identify independent risk factors for IFIs, a predictive model was formulated. Ten IFIs were identified in 81 liver transplant recipients (12.3%) all occurring during the first month posttransplantation. Candida species were responsible for nine cases (90%), of which four were non‐albicans Candida (44%). Significant risk factors were identified; recipient of multiple blood product transfusions during transplantation, prolonged use of indwelling intravenous catheter, prolonged IV antibiotic treatment, surgical complications, pulse steroid treatment and living donor liver transplantation. The predictive model used two clinical parameters to define high‐risk patients: a living donor transplantation and duration of IV antibiotic treatment (area under the ROC curve 0.918). IFIs are a significant complication occurring in the first month posttransplantation. Future studies are required to assess efficacy of targeted antifungal prophylaxis in high risk patients.

Diagnosis of HIV-1 infection: Performance of Xpert Qual and Geenius supplemental assays in fourth generation ELISA-reactive samples

BACKGROUNDnArchitect (AR) and Vidas (VD) fourth generation HIV screening immunoassays, which identify early stages of HIV infections, could have false positive results especially at low signal/cutoff (S/C) AR values. Geenius HIV1/2 (GS) is a specific confirmation line immunoassay that is not highly sensitive to early HIV infections. An HIV-1 RNA assay may better detect such infections.nnnOBJECTIVESnTo evaluate all AR-VD reactive samples with GS results, and to assess Xpert Qual HIV-1 RNA assay (XQ) as an alternative to GS, in the first low S/C AR-VD-reactive samples from a tested individual.nnnSTUDY DESIGNnFirst AR-VD-reactive-GS-tested results from all individuals with resolved HIV status, collected between March 2015 and March 2017 (nu202f=u202f749), were retrospectively assessed. Samples with AR-VD-reactive-GS-discordant results and those with low S/C AR-VD-reactive results, were tested by XQ. Receiver operating characteristic (ROC) analysis of GS and XQ sensitivity/specificity was performed.nnnRESULTSnOverall, 94.1% (705/749) of AR-VD-reactive results were true HIV-1 positive. All samples with <3u202fS/C AR values were false positive. XQ resolved all first samples with AR-VD-reactive-GS-discordant results. The diagnostic accuracy of XQ in low (≤33u202fS/C) AR-VD-reactive samples was better than that of GS (97.6%, 81/83 versus 73.5%, 61/83, pu202f<u202f0.01). ROC analysis for low S/C AR samples was optimal for pooled XQ and GS results.nnnCONCLUSIONSnIncorporating XQ in the current screening algorithm for the first AR-VD-reactive-GS-discordant samples may significantly reduce overall turn-around time of HIV-1 diagnosis.

Influence of GeneXpert MRSA/SA test implementation on clinical outcomes of Staphylococcus aureus bacteremia — a before–after retrospective study

Use of GeneXpert MRSA/SA in diagnostic algorithms of Staphylococcus aureus bacteremia may influence both patients clinical outcomes and antibiotic stewardship. We evaluated these outcomes in a retrospective cohort before (1/6/2015-31/5/2016) and after (1/6/2016-31/8/2017) the introduction of the test in adult patients with Gram-positive cocci in clusters in blood cultures. We included 254 patients (125 preintervention, 129 postintervention). No significant difference in 30-day mortality or clinical success was demonstrated between periods. Appropriate antibiotic therapy rates were significantly higher in the postintervention group, and vancomycin use was significantly reduced (80.6% vs 53.6%, Pu202f<u202f0.01; 2.3±0.38 vs 2.98±1.02 defined daily doses/100 patient days, Pu202f=u202f0.026, respectively). Appropriate beta-lactam use was also significantly higher (56.7% postintervention vs 23.1% preintervention, Pu202f<u202f0.01). Use of GeneXpert MRSA/SA test has a positive effect on antibiotic stewardship measures, though it has no significant effect on clinical outcomes including mortality in this fatal infection.

Characterization of hepatitis B and delta coinfection in Israel

BackgroundCharacteristics of hepatitis B (HBV) and delta (HDV) coinfection in various geographical regions, including Israel, remain unclear. Here we studied HDV seroprevalence in Israel, assessed HDV/HBV viral loads, circulating genotypes and hepatitis delta antigen (HDAg) conservation.MethodsSerological anti HDV IgG results from 8969 HBsAg positive individuals tested in 2010-2015 were retrospectively analyzed to determine HDV seroprevalence. In a cohort of HBV/HDV coinfected (n=58) and HBV monoinfected (n=27) patients, quantitative real-time PCR (qRT-PCR) and sequencing were performed to determine viral loads, genotypes and hepatitis delta antigen (HDAg) protein sequence.Results6.5% (587/8969) of the HBsAg positive patients were positive for anti HDV antibodies. HDV viral load was >2 log copies/ml higher than HBV viral load in most of the coinfected patients with detectable HDV RNA (86%, 50/58). HDV genotype 1 was identified in all patients, most of whom did not express HBV. While 66.6% (4/6) of the HBV/HDV co-expressing patients carried HBV-D2 only 18.5% (5/27) of the HBV monoinfections had HBV-D2 (p=0.03). Higher genetic variability in the HDAg protein sequence was associated with higher HDV viral load.ConclusionsThe overall significant prevalence of HDV (6.5%) mandates HDV RNA testing for all coinfected patients. Patients positive for HDV RNA (characterized by low HBV DNA blood levels) carried HDV genotype 1. Taken together, the significant HDV seroprevalence and the lack of effective anti-HDV therapy, necessitates strict clinical surveillance especially in patients with higher HDV viral loads and increased viral evolution.