Publications by authors named "Haim Ben-Zvi"

49 Publications

Secondary bacterial infection in COVID-19 patients is a stronger predictor for death compared to influenza patients.

Sci Rep 2021 Jun 16;11(1):12703. Epub 2021 Jun 16.

Department of Clinical Microbiology and Immunology, The Sackler Faculty of Medicine, Tel Aviv University, 6997801, Tel Aviv, Israel.

Secondary bacterial infections are a potentially fatal complication of influenza infection. We aimed to define the impact of secondary bacterial infections on the clinical course and mortality in coronavirus disease 2019 (COVID-19) patients by comparison with influenza patients. COVID-19 (n = 642) and influenza (n = 742) patients, admitted to a large tertiary center in Israel and for whom blood or sputum culture had been taken were selected for this study. Bacterial culture results, clinical parameters, and death rates were compared. COVID-19 patients had higher rates of bacterial infections than influenza patients (12.6% vs. 8.7%). Notably, the time from admission to bacterial growth was longer in COVID-19 compared to influenza patients (4 (1-8) vs. 1 (1-3) days). Late infections (> 48 h after admission) with gram-positive bacteria were more common in COVID-19 patients (28% vs. 9.5%). Secondary infection was associated with a higher risk of death in both patient groups 2.7-fold (1.22-5.83) for COVID-19, and 3.09-fold (1.11-7.38) for Influenza). The association with death remained significant upon adjustment to age and clinical parameters in COVID-19 but not in influenza infection. Secondary bacterial infection is a notable complication associated with worse outcomes in COVID-19 than influenza patients. Careful surveillance and prompt antibiotic treatment may benefit selected patients.
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http://dx.doi.org/10.1038/s41598-021-92220-0DOI Listing
June 2021

Evidence for increased breakthrough rates of SARS-CoV-2 variants of concern in BNT162b2-mRNA-vaccinated individuals.

Nat Med 2021 Jun 14. Epub 2021 Jun 14.

The Shmunis School of Biomedicine and Cancer Research, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.

The BNT162b2 mRNA vaccine is highly effective against SARS-CoV-2. However, apprehension exists that variants of concern (VOCs) may evade vaccine protection, due to evidence of reduced neutralization of the VOCs B.1.1.7 and B.1.351 by vaccine sera in laboratory assays. We performed a matched cohort study to examine the distribution of VOCs in infections of BNT162b2 mRNA vaccinees from Clalit Health Services (Israel) using viral genomic sequencing, and hypothesized that if vaccine effectiveness against a VOC is reduced, its proportion among breakthrough cases would be higher than in unvaccinated controls. Analyzing 813 viral genome sequences from nasopharyngeal swabs, we showed that vaccinees who tested positive at least 7 days after the second dose were disproportionally infected with B.1.351, compared with controls. Those who tested positive between 2 weeks after the first dose and 6 days after the second dose were disproportionally infected by B.1.1.7. These findings suggest reduced vaccine effectiveness against both VOCs within particular time windows. Our results emphasize the importance of rigorously tracking viral variants, and of increasing vaccination to prevent the spread of VOCs.
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http://dx.doi.org/10.1038/s41591-021-01413-7DOI Listing
June 2021

Evaluation of Seropositivity Following BNT162b2 Messenger RNA Vaccination for SARS-CoV-2 in Patients Undergoing Treatment for Cancer.

JAMA Oncol 2021 May 28. Epub 2021 May 28.

Davidoff Center, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.

Importance: Patients with cancer undergoing treatment are at high risk of COVID-19 following SARS-CoV-2 infection; however, their ability to produce an adequate antibody response to messenger RNA SARS-CoV-2 vaccines is unclear.

Objective: To evaluate rates of antispike (anti-S) antibody response to a BNT162b2 vaccine in patients with cancer who are undergoing systemic treatment vs healthy controls.

Design, Setting, And Participants: This prospective cohort study included 102 adult patients with solid tumors undergoing active intravenous anticancer treatment and 78 controls who received the second dose of the BNT162b2 vaccine at least 12 days before enrollment. The controls were taken from a convenience sample of the patients' family/caregivers who accompanied them to treatment. The study was conducted between February 22, 2021, and March 15, 2021 at Davidoff Cancer Center at Beilinson Hospital (Petah Tikva, Israel).

Interventions: Blood samples were drawn from the study participants. Serum samples were analyzed and the titers of the IgG antibodies against SARS-CoV-2 spike receptor-binding domain were determined using a commercially available immunoassay. Seropositivity was defined as 50 or greater AU/mL.

Main Outcomes And Measures: The primary outcome was the rate of seropositivity. Secondary outcomes included comparisons of IgG titers and identifying factors that were associated with seropositivity using univariate/multivariable analyses.

Results: The analysis included 180 participants, which comprised 102 patients with cancer (median [interquartile range (IQR)] age, 66 [56-72] years; 58 men [57%]) and 78 healthy controls (median [IQR] age, 62 [49-70] years; 25 men [32%]). The most common tumor type was gastrointestinal (29 [28%]). In the patient group, 92 (90%) were seropositive for SARS-CoV 2 antispike IgG antibodies after the second vaccine dose, whereas in the control group, all were seropositive. The median IgG titer in the patients with cancer was significantly lower than that in the controls (1931 [IQR, 509-4386] AU/mL vs 7160 [IQR, 3129-11 241] AU/mL; P < .001). In a multivariable analysis, the only variable that was significantly associated with lower IgG titers was treatment with chemotherapy plus immunotherapy (β, -3.5; 95% CI, -5.6 to -1.5).

Conclusions And Relevance: In this cohort study of patients with cancer who were receiving active systemic therapy, 90% of patients exhibited adequate antibody response to the BNT162b2 vaccine, although their antibody titers were significantly lower than those of healthy controls. Further research into the clinical relevance of lower titers and their durability is required. Nonetheless, the data support vaccinating patients with cancer as a high priority, even during therapy.
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http://dx.doi.org/10.1001/jamaoncol.2021.2155DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8164144PMC
May 2021

Early humoral response among lung transplant recipients vaccinated with BNT162b2 vaccine.

Lancet Respir Med 2021 06 5;9(6):e52-e53. Epub 2021 May 5.

Pulmonary Division, Rabin Medical Center, Petach Tikva 49100, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

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http://dx.doi.org/10.1016/S2213-2600(21)00184-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8099313PMC
June 2021

Immunogenicity of the BNT162b2 mRNA vaccine in heart transplant recipients - a prospective cohort study.

Eur J Heart Fail 2021 May 8. Epub 2021 May 8.

Department of Cardiology, Rabin Medical Center, Petah Tikva, Israel.

Aims: To assess the short-term immunogenicity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine in a population of heart transplant (HTx) recipients. A prospective single-centre cohort study of HTx recipients who received a two-dose SARS-CoV-2 mRNA vaccine (BNT162b2, Pfizer-BioNTech).

Methods And Results: Whole blood for anti-spike IgG (S-IgG) antibodies was drawn at days 21-26 and at days 35-40 after the first vaccine dose. Geometric mean titres (GMT) ≥50 AU/mL were interpreted positive. Included were 42 HTx recipients at a median age of 61 [interquartile range (IQR) 44-69] years. Median time from HTx to the first vaccine dose was 9.1 (IQR 2.6-14) years. Only 15% of HTx recipients demonstrated the presence of positive S-IgG antibody titres in response to the first vaccine dose [GMT 90 (IQR 54-229) AU/mL]. Overall, 49% of HTx recipients induced S-IgG antibodies in response to either the first or the full two-dose vaccine schedule [GMT 426 (IQR 106-884) AU/mL]. Older age [68 (IQR 59-70) years vs. 46 (IQR 34-63) years, P = 0.034] and anti-metabolite-based immunosuppression protocols (89% vs. 44%, P = 0.011) were associated with low immunogenicity. Importantly, 36% of HTx recipients who were non-responders to the first vaccine dose became S-IgG seropositive in response to the second vaccine dose. Approximately a half of HTx recipients did not generate S-IgG antibodies following SARS-CoV-2 two-dose vaccine.

Conclusions: The generally achieved protection from SARS-CoV-2 mRNA vaccination should be regarded with caution in the population of HTx recipients. The possible benefit of additive vaccine should be further studied.
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http://dx.doi.org/10.1002/ejhf.2199DOI Listing
May 2021

Antibody response to SARS-CoV-2 mRNA vaccine among kidney transplant recipients: a prospective cohort study.

Clin Microbiol Infect 2021 May 3. Epub 2021 May 3.

Department of Nephrology and Hypertension, Rabin Medical Center, Petah-Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel; Department of Transplantation, Rabin Medical Center, Beilinson Campus, Petah-Tikva, Israel.

Objectives: We aimed to evaluate the rates of antibody response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) mRNA vaccine among kidney transplant recipients, and to identify factors associated with reduced immunogenicity.

Methods: This was a prospective cohort study including consecutive kidney transplant recipients in a single referral transplant centre. Participants were tested for anti-spike (anti-S) antibodies 2-4 weeks after a second vaccine dose. Primary outcome was rate of seropositivity. Univariate and multivariate analyses were conducted to identify factors associated with seropositivity.

Results: Of 308 kidney transplant recipients included, only 112 (36.4%) tested positive for anti-S antibodies 2-4 weeks after receiving the second dose of BNT162b2 vaccine. Median antibody titre was 15.5 AU/mL (interquartile range (IQR) 3.5-163.6). Factors associated with antibody response were higher estimated glomerular filtration rate (eGFR) (odds ratio (OR) 1.025 per mL/min/1.73 m, 95% confidence interval (CI) 1.014-1.037, p < 0.001), lower mycophenolic acid dose (OR 2.347 per 360 mg decrease, 95%CI 1.782-3.089, p < 0.001), younger age (OR 1.032 per year decrease, 95%CI 1.015-1.05, p < 0.001) and lower calcineurin inhibitor (CNI) blood level (OR 1.987, 95%CI 1.146-3.443, p 0.014). No serious adverse events resulting from the vaccine were reported.

Conclusions: Kidney transplant recipients demonstrated an inadequate antibody response to SARS-CoV-2 mRNA vaccination. Immunosuppression level was a significant factor in this response. Strategies to improve immunogenicity should be examined in future studies.
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http://dx.doi.org/10.1016/j.cmi.2021.04.028DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8091803PMC
May 2021

Excluded versus included patients in a randomized controlled trial of infections caused by carbapenem-resistant Gram-negative bacteria: relevance to external validity.

BMC Infect Dis 2021 Mar 31;21(1):309. Epub 2021 Mar 31.

Sackler Faculty of Medicine, Tel Aviv University, Ramat-Aviv, Tel Aviv, Israel.

Background: Population external validity is the extent to which an experimental study results can be generalized from a specific sample to a defined population. In order to apply the results of a study, we should be able to assess its population external validity. We performed an investigator-initiated randomized controlled trial (RCT) (AIDA study), which compared colistin-meropenem combination therapy to colistin monotherapy in the treatment of patients infected with carbapenem-resistant Gram-negative bacteria. In order to examine the study's population external validity and to substantiate the use of AIDA study results in clinical practice, we performed a concomitant observational trial.

Methods: The study was conducted between October 1st, 2013 and January 31st, 2017 (during the RCTs recruitment period) in Greece, Israel and Italy. Patients included in the observational arm of the study have fulfilled clinical and microbiological inclusion criteria but were excluded from the RCT due to receipt of colistin for > 96 h, refusal to participate, or prior inclusion in the RCT. Non-randomized cases were compared to randomized patients. The primary outcome was clinical failure at 14 days of infection onset.

Results: Analysis included 701 patients. Patients were infected mainly with Acinetobacter baumannii [78.2% (548/701)]. The most common reason for exclusion was refusal to participate [62% (183/295)]. Non-randomized and randomized patients were similar in most of the demographic and background parameters, though randomized patients showed minor differences towards a more severe infection. Combination therapy was less common in non-randomized patients [31.9% (53/166) vs. 51.2% (208/406), p = 0.000]. Randomized patients received longer treatment of colistin [13 days (IQR 10-16) vs. 8.5 days (IQR 0-15), p = 0.000]. Univariate analysis showed that non-randomized patients were more inclined to clinical failure on day 14 from infection onset [82% (242/295) vs. 75.5% (307/406), p = 0.042]. After adjusting for other variables, non-inclusion was not an independent risk factor for clinical failure at day 14.

Conclusion: The similarity between the observational arm and RCT patients has strengthened our confidence in the population external validity of the AIDA trial. Adding an observational arm to intervention studies can help increase the population external validity and improve implementation of study results in clinical practice.

Trial Registration: The trial was registered with ClinicalTrials.gov, number NCT01732250 on November 22, 2012.
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http://dx.doi.org/10.1186/s12879-021-05995-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8010276PMC
March 2021

A real-life setting evaluation of the effect of remdesivir on viral load in COVID-19 patients admitted to a large tertiary centre in Israel.

Clin Microbiol Infect 2021 Jun 9;27(6):917.e1-917.e4. Epub 2021 Mar 9.

Department of Medicine D, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel; The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objectives: The effectiveness of remdesivir, a Food and Drug Administration-approved drug for severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has been repeatedly questioned during the current coronavirus disease 2019 (COVID-19) pandemic. Most of the recently reported studies were randomized controlled multicentre clinical trials. Our goal was to test the efficiency of remdesivir in reducing nasopharyngeal viral load and hospitalization length in a real-life setting in patients admitted to a large tertiary centre in Israel.

Methods: A total of 142 COVID-19 patients found to have at least three reported SARS-CoV-2 quantitative RT-PCR tests during hospitalization were selected for this study. Of these, 29 patients received remdesivir, while the remaining non-treated 113 patients served as controls.

Results: Among the tested parameters, the control and remdesivir groups differed significantly only in the intubation rates. Remdesivir treatment did not significantly affect nasopharyngeal viral load, as determined by comparing the differences between the first and last cycle threshold values of the SARS-CoV-2 quantitative RT-PCR tests performed during hospitalization (cycle threshold 7.07 ± 6.85 vs. 7.08 ± 7.27, p 0.977 in the control and treated groups, respectively). Remdesivir treatment shortened hospitalization length by less than a day compared with non-treated controls and by 3.1 days when non-intubated patients from both groups were compared. These differences, however, were not statistically significant, possibly because of the small size of the remdesivir group.

Discussion: Remdesivir was not associated with nasopharyngeal viral load changes, but our study had a significant disease severity baseline imbalance and was not powered to detect viral load or clinical differences.
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http://dx.doi.org/10.1016/j.cmi.2021.02.029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7939997PMC
June 2021

Diarrheal Morbidity During Hematopoietic Cell Transplantation: The Diagnostic Yield of Stool Cultures.

Infect Dis Ther 2021 Jun 4;10(2):1023-1032. Epub 2021 Mar 4.

Institute of Hematology, Davidoff Cancer Center, Rabin Medical Center, Petah Tikva, Israel.

Introduction: Diarrhea affects a significant proportion of patients undergoing hematopoietic cell transplantation (HCT). We explored the diagnostic yield of stool cultures for enteric pathogens among patients undergoing HCT.

Methods: This is a single-center, retrospective study. Between 5/2007 and 4/2020, consecutive patients who underwent HCT were included if inpatient bacterial stool cultures were collected. Patient characteristics, results, and timing of stool cultures obtained during hospitalization were collected.

Results: A total of 1072 individuals underwent autologous (n = 603) and allogeneic (n = 469) HCT. Overall, 947 stool culture samples were obtained from 561 (52%) patients with diarrheal illness during hospitalization for HCT. Most (99%) samples were obtained beyond 3 days of admission, mainly (77%) during neutropenia. Overall, only four (0.42%) (autologous, n = 3; allogeneic, n = 1) patients had a positive stool culture and in all cases Campylobacter spp. were the pathogens identified. The number of stool cultures needed-to-test to diagnose one case of bacterial infection was 237. The cost of diagnosing one case of bacterial diarrhea was US $8770. Patients with a positive stool culture did not have discerning characteristics.

Conclusions: In our experience, the yield of stool cultures for enteropathogens in patients undergoing HCT is extremely low and thus should be avoided in most cases.
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http://dx.doi.org/10.1007/s40121-021-00415-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8116365PMC
June 2021

Clinical Features and Comparison of Kingella and Non-Kingella Endocarditis in Children, Israel.

Emerg Infect Dis 2021 Mar;27(3):703-709

Kingella spp. have emerged as an important cause of invasive pediatric diseases. Data on Kingella infective endocarditis (KIE) in children are scarce. We compared the clinical features of pediatric KIE cases with those of Streptococcus species IE (StIE) and Staphylococcus aureus IE (SaIE). A total of 60 patients were included in the study. Throughout the study period, a rise in incidence of KIE was noted. KIE patients were significantly younger than those with StIE and SaIE, were predominately boys, and had higher temperature at admission, history of oral aphthae before IE diagnosis, and higher lymphocyte count (p<0.05). Pediatric KIE exhibits unique features compared with StIE and SaIE. Therefore, in young healthy children <36 months of age, especially boys, with or without a congenital heart defect, with a recent history of oral aphthae, and experiencing signs and symptoms compatible with endocarditis, Kingella should be suspected as the causative pathogen.
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http://dx.doi.org/10.3201/eid2703.203022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7920667PMC
March 2021

The impact of obesity on seasonal influenza: a single-center, retrospective study conducted in Israel.

Eur J Clin Microbiol Infect Dis 2021 Jul 11;40(7):1471-1476. Epub 2021 Feb 11.

Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.

Obesity is associated with an increased susceptibility to infections. Several studies have reported adverse clinical outcomes of influenza among obese individuals. Our aim was to examine the association between obesity and the clinical outcomes of hospitalized adult patients ill with seasonal influenza. Consecutive hospitalized adult patients between 10/2017 and 4/2018 with laboratory confirmed influenza A and B were divided into an obese group (body mass index (BMI) ≥ 30 kg/m) and controls. The primary outcome was a composite endpoint of 30-day all-cause mortality, vasopressor use, mechanical ventilation, ICU admission, and severe influenza complication (myocarditis and encephalitis). Secondary outcomes encompassed all the components of the primary outcome, 90-day all-cause mortality, occurrence of pneumonia, length of hospital stay, and 90-day readmission rates. The study comprised 512 hospitalized adults diagnosed with laboratory-confirmed influenza A (195/512) and B (317/512). Within this group, 17% (86/512) were classified obese; the remaining 83% (426/512) were controls. Results of the composite outcome (7/85, 8% vs. 45/422, 11%; p=0.5) and the crude 30-day all-cause mortality rate (5/86, 6% vs. 34/426, 8%, p=0.5) were similar between the two groups. The multivariate analysis demonstrated that obesity was not a significant risk factor for influenza adverse events (OR=1.3, CI 95% 0.3-3.3; p=0.5), whereas advanced age, chronic kidney disease, and hypoalbuminemia were significant risk factors (OR=1.03, OR=2.7, and OR=5.4, respectively). Obesity was not associated with influenza-related morbidity and mortality among the hospitalized adults during the 2017-2018 influenza season. Further studies researching different influenza seasons are essential.
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http://dx.doi.org/10.1007/s10096-021-04174-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877522PMC
July 2021

Morbidity and mortality of respiratory syncytial virus infection in hospitalized adults: Comparison with seasonal influenza.

Int J Infect Dis 2021 Feb 26;103:489-493. Epub 2020 Nov 26.

Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel; Internal Medicine Department A, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel.

Introduction: Respiratory syncytial virus (RSV) is considered a major pathogen that causes acute influenza-like illness. The objective of this study was to compare the clinical outcomes of patients with laboratory-confirmed RSV and patients with influenza infection.

Methods: Adults hospitalized in Beilinson Hospital (October 2017-April 2018) with laboratory-confirmed RSV or influenza were included. The primary outcome was the composite of RSV/influenza complications: 30-day mortality, pneumonia, mechanical ventilation, vasopressor support, intensive care unit admission, and myocarditis/encephalitis. Secondary outcomes were individual components of the primary outcome, 90-day mortality, 90-day readmission, and length of hospital stay.

Results: A total of 639 patients with RSV (n = 113) and influenza (n = 526) were included. The composite primary outcome was 21.4% (136/633), and was higher in RSV patients (30% (34/113) vs 19% (102/526), p = 0.002). Pneumonia was more common in RSV patients (21.2% (24/113) vs 9.1% (48/526), p = 0.001). On multivariable analysis, hypoalbuminemia (odds ratio (OR) 3.3, 95% confidence interval (CI) 2.1-5.3, p < 0.001), reduced room-air saturation (OR 1.1, 95% CI 1.02-1.1, p = 0.001), and infection with RSV (OR 1.67, 95% CI 1.01-2.76, p = 0.046) were predictors of complications.

Conclusions: RSV infection in hospitalized adults resulted in serious respiratory illness with complications that are comparable to those caused by influenza.
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http://dx.doi.org/10.1016/j.ijid.2020.11.185DOI Listing
February 2021

The significance of acute kidney injury in Clostridioides difficile infection.

Int J Clin Pract 2021 Mar 11;75(3):e13785. Epub 2020 Dec 11.

Infectious Disease Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel.

Objective: Clostridioides difficile infection (CDI) may present as sepsis with acute kidney injury (AKI). Herein, we aimed to evaluate the clinical outcomes of patients with AKI complicating CDI.

Methods: All consecutive adult patients hospitalized in Rabin Medical Center between 1 January 2013 and 31 December 2018 with laboratory confirmed CDI, were included in the study. Subjects were divided into two groups: patients with AKI and controls. Primary outcome was all-cause mortality at 30 days after the CDI episode. Secondary outcomes included number of patients with deteriorating renal functions at 90 days, 90-day all-cause mortality, length of hospital stay and readmission rates. A multivariable analysis adjusted for other risk factors for mortality and renal function deterioration was conducted. An analysis of subgroups based on baseline kidney function and AKI stage was also performed. Results are reported as odds ratios (OR) with 95% confidence intervals (95% CI).

Results: A total of 527 patients were included, amongst them 140 patients with AKI and 387 controls. Patients with AKI were significantly older, had more comorbidities, and more of them had chronic kidney disease (CKD) at any stage at baseline. On multivariable analysis, 30 days all-cause mortality was significantly higher in patients with AKI, OR 1.67, 95% CI 1.05-2.66. Mortality was also significantly associated with advanced age and baseline CKD. Among patients alive at 90 days, deterioration of renal function was significantly more common in patients with AKI (27/63 (42.8%) vs 22/191 (11.5%), P = .000). In a multivariable analysis, deterioration of renal function at 90 days was associated with AKI at presentation (OR 4.67, 95% CI 1.05-20.6). Early (at discharge) renal function recovery was not associated with protection from further deterioration of renal function at day 90.

Conclusions: CDI patients with AKI have an increased risk of mortality and further deterioration of renal function. Early renal function recovery does not infer protection from further deterioration of renal function at 3 months. Caution and nephrology follow-up should be considered after discharge for all patients who developed AKI during CDI, regardless of discharge creatinine levels.
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http://dx.doi.org/10.1111/ijcp.13785DOI Listing
March 2021

Diagnostic value of sputum cultures in children under 2 years of age with chronic suppurative lung diseases.

Pediatr Pulmonol 2020 12 12;55(12):3421-3428. Epub 2020 Oct 12.

Graub CF Center Pulmonary Institute, Schneider Children's Medical Center of Israel, Petach Tikva, Israel.

Background: Acquiring sputum cultures from infants is considered challenging. We describe their yield in infants with cystic fibrosis (CF) and other chronic suppurative lung diseases (CSLDs).

Methods: Retrospective medical record review over a 4-year period, for infants aged 0-2 years with ≥2 airway bacterial cultures acquired by deep suction or induced sputum ≥4 weeks apart. Data included demographics, culture results, and clinical status.

Results: A total of 98 infants (16 CF) were evaluated and 534 sputum cultures acquired, 201 in CF and 333 in CSLD. There were 12 (2-23), median (range) cultures/CF infant, and 3 (2-21)/CSLD infant. Age at first culture was 3.8 (1-19.5) months for CF and 10.4 (0.5-22) months for CSLD; p = .016. In total, 360 cultures (67%) were positive for any bacteria, with 170/234 (73%) positive during exacerbations, compared with 190/300 (63%) during routine visits; p = .05. More infants with CF than CSLD had cultures positive for Staphylococcus aureus (SA; 75% vs. 34%; p = .004) throughout the period. Pseudomonas aeruginosa (PA) was common in both CF and CSLD (56% and 44%, respectively; p = .42) and increased over time for CF but was high throughout for CSLD. The number of hospital days before PA acquisition was 6 (10.2) for CF and 28.8 (38.7) for CSLD (p = .003). No CF but 6/82 (7%) CSLD infants had chronic PA (p = .56).

Conclusions: Sputum cultures showed that infection, in particular PA, is common in CF and CSLD whereas SA is more common in CF. Prospective studies are warranted to elucidate the role of active surveillance in guiding antibiotic therapy.
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http://dx.doi.org/10.1002/ppul.25103DOI Listing
December 2020

Nasopharyngeal viral load predicts hypoxemia and disease outcome in admitted COVID-19 patients.

Crit Care 2020 09 1;24(1):539. Epub 2020 Sep 1.

Department of Clinical Microbiology and Immunology, The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

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http://dx.doi.org/10.1186/s13054-020-03244-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459243PMC
September 2020

Clinical correlates of nocardiosis.

Sci Rep 2020 08 31;10(1):14272. Epub 2020 Aug 31.

Department of Epidemiology and Preventive Medicine, Sackler Faculty of Medicine, School of Public Health, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.

Nocardia is an opportunistic pathogen that most frequently affects the lungs. Evidence is limited regarding the risk factors for nocardiosis. The current study assessed clinical correlates of nocardiosis. A retrospective study was conducted based on medical records of consecutive adult patients (N = 60) with nocardiosis hospitalized during 2007-2018 at a tertiary hospital in central Israel. A matched comparison group of 120 patients was randomly selected among hospitalized patients with community-acquired pneumonia. Multivariable conditional logistic regression models were fitted. Immunosuppressive pharmacotherapy was positively associated with nocardiosis (matched odds ratio [OR] 4.40, 95% confidence interval [CI] 2.25-8.62, p < 0.001), particularly corticosteroid therapy (matched OR 4.69, 95% CI 2.45-8.99, p < 0.001). Systemic corticosteroid therapy was strongly associated with pulmonary nocardiosis (matched OR 5.90, 95% CI 2.75-12.66, p < 0.001). The positive association between solid organ transplantation and nocardiosis was attenuated following adjustment for systemic corticosteroids in a multivariable model. The association between corticosteroid therapy and nocardiosis appeared stronger in patients with chronic pulmonary disease (OR 5.74, 95% CI 2.75-12.66, p < 0.001) than in the pooled analysis of all nocardiosis cases. In conclusion, corticosteroid therapy was strongly correlated with nocardiosis, particularly among individuals with chronic pulmonary disease and in pulmonary nocardiosis.
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http://dx.doi.org/10.1038/s41598-020-71214-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7459281PMC
August 2020

Treatment of Bacteremia Caused by spp.: Should the Potential for AmpC Induction Dictate Therapy? A Retrospective Study.

Microb Drug Resist 2021 Mar 17;27(3):410-414. Epub 2020 Aug 17.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Carbapenems are considered treatment of choice for bacteremia caused by potential AmpC-producing bacteria, including spp. We aimed to compare mortality following carbapenem vs. alternative antibiotics for the treatment of spp. bacteremia. We conducted a retrospective study in two centers in Israel. We included hospitalized patients with bacteremia treated with third-generation cephalosporins (3GC), piperacillin/tazobactam, quinolones, or carbapenem monotherapy as the main antibiotic in the first week of treatment, between 2010 and 2017. Cefepime was excluded due to nonavailability during study years. The primary outcome was 30-day all-cause mortality. Univariate and multivariate analyses were conducted, introducing the main antibiotic as an independent variable. Two hundred seventy-seven consecutive patients were included in the analyses. Of these, 73 were treated with 3GC, 39 with piperacillin/tazobactam, 104 with quinolones, and 61 with carbapenems. All-cause 30-day mortality was 16% (45 patients). The type of antibiotics was not significantly associated with mortality on univariate or multivariate analyses. With carbapenems as reference, adjusted odds ratios (ORs) for mortality were 0.708, 95% confidence interval (CI) 0.231-2.176 with 3GC; OR 1.172, 95% CI 0.388-3.537 with piperacillin/tazobactam; and OR 0.586, 95% CI 0.229-1.4 with quinolones. The main antibiotic was not associated with repeated growth of spp. in blood cultures or other clinical specimens. Resistance development was observed with 3GC and piperacillin/tazobactam. Carbapenem treatment was not advantageous to alternative antibiotics, including 3GC, among patients with spp. bacteremia in an observational study.
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http://dx.doi.org/10.1089/mdr.2020.0234DOI Listing
March 2021

The bacteriology of recurrent acute exacerbations of chronic rhinosinusitis: a longitudinal analysis.

Eur Arch Otorhinolaryngol 2020 Nov 4;277(11):3051-3057. Epub 2020 Jul 4.

Department of Otorhinolaryngology Head and Neck Surgery, Rabin Medical Center, Petah Tiqva, Israel.

Purpose: The purpose of this study was to describe the microbiology of recurrent acute exacerbations of chronic rhinosinusitis over time.

Methods: Retrospective review of patients with recurrent acute exacerbations of chronic rhinosinusitis who underwent endoscopic-guided cultures during acute exacerbations of chronic rhinosinusitis.

Results: 386 cultures were obtained from 112 patients during recurrent acute exacerbations of CRS. A change of bacterial isolates during the course of recurrent exacerbations was observed in 68% (76/112) of patients, necessitating a change of treatment in 40% (45/112). The main risk factor for the subsequent change in cultures was polymicrobial growth. Sinus surgery was not associated with subsequent change in cultured isolates. Resistant strains developed in 11.6% (13/112) of patients, of whom those with abnormal mucociliary clearance being at the highest risk.

Conclusion: Repeated middle meatal cultures should be considered in patients with recurrent exacerbations of CRS, particularly in cases not responding to standard therapy.
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http://dx.doi.org/10.1007/s00405-020-06157-7DOI Listing
November 2020

Institutional Burden of Carbapenemase-Producing Enterobacterales: The Effect of Changes in Surveillance Culture Methodology.

Microb Drug Resist 2020 Nov 7;26(11):1350-1356. Epub 2020 May 7.

Department of Epidemiology, Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

An essential part of the Israeli intervention program aimed to contain the spread of carbapenemase-producing Enterobacterales (CPE) has been the establishment of national surveillance system, where the institutional rates are determined by both clinical and surveillance cultures. The objectives of the study were to analyze the effect of changes in surveillance culture media on the rates and microbiological characteristics of CPE in a multicenter study. The rates were compared during 2 years in and between four centers. Two centers (Tel-Aviv and Beilinson) had changed their surveillance media to CHROMagar™ mSuperCARBA™ after 1 year, and two centers (Rambam and Hillel-Yaffe) had continued to use CHROMagar KPC. There was an increase in the rates of surveillance CPE in Tel-Aviv and Beilinson following the change in media, whereas the rates remained the same or declined in Rambam and Hillel-Yaffe, respectively. The rates of clinical CPE remained unchanged in Rambam and Hillel-Yaffe, declined in Tel-Aviv, and increased in Beilinson but to a lesser extent compared with the increase in surveillance CPE. The relative composition of the CPE mechanisms and species changed in Tel-Aviv, with an increase in non- species and in carbapenemase other than KPC. Our study shows that changes in surveillance media may contribute to significant changes in the rate of surveillance CPE that may be irrespective of actual epidemiological changes. Therefore, determination of institutional burden of CPE and the assessment of intervention results should be based primarily on the rate of clinical CPE rather than surveillance culture reports.
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http://dx.doi.org/10.1089/mdr.2019.0478DOI Listing
November 2020

Can we improve early identification of neonatal late-onset sepsis? A validated prediction model.

J Perinatol 2020 09 20;40(9):1315-1322. Epub 2020 Mar 20.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

Objective: No single test can accurately identify neonatal late-onset sepsis (LOS). Our aim was to use clinical evaluation with laboratory tests to rapidly assess sepsis risk.

Study Design: A retrospective case-control study was performed in a tertiary Neonatal Center during the years 2016-2019. Infants with bacteriologically confirmed LOS were compared with control infants. A clinical health evaluation score was assigned to each infant. A prediction model was developed and validated by multivariable analysis.

Results: The study included 145 infants, 48 with sepsis, and 97 controls. LOS was independently associated with: sick appearance (OR: 5.7, 95% CI: 1.1-29.1), C-reactive protein > 0.75 (OR: 5.4, 95% CI: 1.1-26.3), and neutrophil-to-lymphocyte ratio > 1.5 (OR: 6.7, 95% CI: 1.2-38.5). Our model had an area under the receiver operating characteristic curve of 0.92 (95% CI: 0.86-0.97).

Conclusions: Clinical evaluation with neutrophil-to-lymphocyte ratio and C-reactive protein can rapidly identify LOS enabling decreased health costs and antibiotic use.
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http://dx.doi.org/10.1038/s41372-020-0649-6DOI Listing
September 2020

Nocardia colonization in contrast to nocardiosis: a comparison of patients' clinical characteristics.

Eur J Clin Microbiol Infect Dis 2020 Apr 20;39(4):759-763. Epub 2019 Dec 20.

Department of Internal Medicine F-Recanati, Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel.

Information on Nocardia colonization of the lower respiratory tract is scarce. The current study is aimed at comparing clinical characteristics between individuals with Nocardia colonization and those with nocardiosis. All patients with Nocardia isolation between 2007 and 2018 at a tertiary hospital in Israel were included. Nocardia isolation was based on biochemical tests together with phenotypic susceptibility and resistance patterns until 2011 and on matrix-assisted laser desorption/ionization time-of-flight mass spectrometer from 2012. We defined nocardiosis as a clinically evident infection related to the isolation of the bacteria, which required antibiotic therapy. We defined colonization as Nocardia isolation with no clinical evidence of disease. The medical charts of all included individuals were independently reviewed by an infectious disease specialist to ensure adequate classification. Logistic regression models were fitted to compare clinical characteristics between the groups. Fifteen (20%) of the 75 Nocardia isolations met the criteria for colonization. Of those, 13 (87%) had background illnesses. Having a chronic pulmonary disease was associated with increased likelihood of Nocardia colonization, in contrast to nocardiosis (adjusted odds ratio [OR] 4.06, 95% confidence interval [CI] 1.06-15.48, p = 0.040), while an inverse association was found with corticosteroid therapy (adjusted OR 0.21, 95% CI 0.06-0.74, p = 0.015). Nocardia colonization of the lower respiratory tract accounts for a substantial proportion of all Nocardia isolations. Individuals colonized with Nocardia typically have chronic pulmonary disease and are less frequently treated with corticosteroid than patients with nocardiosis.
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http://dx.doi.org/10.1007/s10096-019-03796-5DOI Listing
April 2020

Clostridioides difficile infection in immunocompromised hospitalized patients is associated with a high recurrence rate.

Int J Infect Dis 2020 Jan 28;90:237-242. Epub 2019 Oct 28.

Infectious Disease Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.

Objective: Clostridioides difficile infection (CDI) may pose a serious threat to immunocompromised patients (IMC). Herein, we evaluated the clinical outcomes of IMC patients with CDI.

Methods: All consecutive hospitalized patients between January 1, 2013 and December 31, 2018 with laboratory confirmed CDI were included in the study. Subjects were divided into two groups: IMC patients and controls. Primary outcome was the recurrence rate of CDI (rCDI) at 30 and 90 days after the first CDI episode. Secondary outcomes included 30 and 90 day all-cause mortality, length of hospital stay (LOS) and readmission rates. A multivariate analysis adjusted other risk factors for recurrence. An analysis of IMC patient subgroups (based on type of IMC conditions) was also performed. Results are reported as odds ratios (OR) with a 95% confidence interval (95% CI).

Results: A total of 573 patients were included, amongst them 149 IMC patients (36 solid organ transplants, 38 undergoing chemotherapy, 62 haematological conditions, 13 receiving high dose prednisone) and 424 controls. IMC patients were younger, independent and exhibited less significant comorbidities. On multivariable analysis, the rate of rCDI was significantly higher in IMC patients (OR 2.7, 95% CI 1.6-5). rCDI was also associated with vancomycin therapy, haemodialysis and previous hospitalizations. Mortality, LOS, CDI complications and rehospitalization rates were similar in both.

Conclusions: IMC patients with CDI have an increased risk of 90 days rCDI. Vancomycin treatment for CDI endangers recurrence in IMC patients. Further research should explore other therapies for IMC patients with CDI with alternative agents such as Fidaxomicin and Bezlotoxumab.
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http://dx.doi.org/10.1016/j.ijid.2019.10.028DOI Listing
January 2020

Immunosuppression reduction in kidney transplant recipients during bacterial infection-A retrospective study.

Clin Transplant 2019 10 19;33(10):e13707. Epub 2019 Sep 19.

Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Israel.

Background: Immunosuppression reduction is a common practice in the management of bacterial infection among kidney transplant recipients (KTRs). This practice, however, is based on limited evidence.

Methods: Retrospective study comparing clinical outcomes of KTRs whose antimetabolite was discontinued vs continued during hospitalization due to bacterial infection, considering calcineurin inhibitors (CNI) levels. Primary outcome was a composite of clinical failure at day 5; all-cause mortality; and/or re-hospitalization at 90 days. Multivariable analysis of risk factors for the primary outcome was performed using a propensity-matched cohort.

Results: We included 183 KTRs hospitalized with bacterial infection. Neither discontinuation of antimetabolites nor lower levels of CNI at infection onset were associated with a significant decrease the composite primary outcome. No significant difference in graft loss or rejection was demonstrated between patients with low vs high CNI levels or discontinuation vs continuation of antimetabolite. In multivariable analysis, CNI levels and management of antimetabolite were not significantly associated with adverse outcome.

Conclusions: Immunosuppression reduction in hospitalized KTRs with bacterial infection did not offer a clinical advantage in terms of mortality, re-hospitalization, or clinical success. An interventional study evaluating continuation of immunosuppression vs reduction should be considered.
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http://dx.doi.org/10.1111/ctr.13707DOI Listing
October 2019

Flavobacteriaceae Bacteremia in Children: A Multicenter Study.

Pediatr Infect Dis J 2019 11;38(11):1096-1099

From the Department of Pediatrics B, Schneider Children's Medical Center, Petach Tikva, Israel.

Background: The Flavobacteriaceae family includes rare pathogens in children; Chryseobacterium indologenes and Elizabethkingia meningosepticum are the most common pathogenic species, with a wide range of clinical presentations and high mortality rate. Although rare, diagnosis is important due to inherent resistance to multiple antibiotics, especially those typically prescribed for empiric treatment of aerobic Gram-negative bacterial infections.

Methods: A multicenter retrospective study conducted in 5 Israeli hospitals, describing Flavobacteriaceae bacteremia confirmed by positive blood culture from 1998 to 2018.

Results: Thirteen cases were included; 9 isolates were C. indologenes. Bacteremia was nosocomial or healthcare-associated in all cases. Bacteremia was associated with young age (median, 1 year, range 24 days-17 years), with only 2 (15.4%) cases in neonates, Central line-associated bloodstream infection as a source (5/13, 38%) and malignancy (7/13, 54.8%). Thirty-day all-cause mortality was 23% (3/13). Ninety-one percent of isolates were susceptible to trimethoprim-sulfamethoxazole, 82% to piperacillin-tazobactam and 92% to ciprofloxacin.

Conclusions: C. indologenes and E. meningosepticum are rare, nosocomial- or healthcare-associated pediatric bacteremia pathogens. Bacteremia was associated with young age, but in contrast to the literature, the majority of our cases were older than the neonatal age period. In addition, they were associated with central line-associated bloodstream infection and malignancy. The most adequate antibiotics according to resistance patterns were ciprofloxacin, trimethoprim-sulfamethoxazole and piperacillin-tazobactam.
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http://dx.doi.org/10.1097/INF.0000000000002449DOI Listing
November 2019

Statins and outcomes of hospitalized patients with laboratory-confirmed 2017-2018 influenza.

Eur J Clin Microbiol Infect Dis 2019 Dec 28;38(12):2341-2348. Epub 2019 Aug 28.

Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

No studies evaluating the association between statins and outcomes of patients with seasonal influenza have been performed since the 2007-2008 and the 2009 pandemic H1N1 influenza seasons. All consecutive hospitalized patients between October 2017 and April 2018, diagnosed with laboratory-confirmed influenza A and B virus, were included. Patients were divided into two groups: statin and non-statin users. Outcomes were 30- and 90-day mortality, complications (pneumonia, myocarditis, encephalitis, intensive care unit (ICU) transfer, mechanical ventilation, vasopressor support), length of hospital stay, and readmission rates. A multivariate analysis was performed to adjust for mortality risk factors. To compare the groups, we matched patients to the nearest neighbor propensity score. Of the 526 patients ill with influenza A (201/526) and B (325/526), 36% (188/526) were statin users; 64% (338/526) were not. Statin users were older (78 vs.70; p = < 0.05) and suffered from more comorbidities (Charlson comorbidity scores of 6 vs.4; p < 0.005). The 30-day mortality rate among statin vs. non-statin users was 6% vs. 8% (p = 0.3). On multivariate analysis, statin use was not associated with mortality benefit (OR = 0.67 (0.29-1.36)). After propensity score matching, the results were unchanged (OR = 0.71 (0.29-1.71)). Statin users were diagnosed with less complicated diseases as they were less likely to receive vasopressor support, mechanical ventilation, and/or transfer to the ICU. Although statin users were significantly older and exhibited more comorbidities, 30-day mortality rates did not differ between statin users and non-users, which may signify a protective role of statins on seasonal influenza patients. Further studies performed during different influenza seasons and different subtypes are essential.
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http://dx.doi.org/10.1007/s10096-019-03684-yDOI Listing
December 2019

Clinical benefits of FilmArray meningitis-encephalitis PCR assay in partially-treated bacterial meningitis in Israel.

BMC Infect Dis 2019 Aug 13;19(1):713. Epub 2019 Aug 13.

Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Background: Management of partially-treated, community-acquired bacterial meningitis (PCBM) is commonly compromised by lack of microbiological diagnosis. We aimed to analyze the impact of FilmArray Meningitis-Encephalitis (FA-ME) PCR on the management of PCBM.

Methods: Comparison of treatment variables of PCBM cases between two periods, before (6.5 years, control group) and after (2 years, study group) the application of FA-ME PCR assay.

Results: The total duration of antimicrobial treatment in the study group (n = 8) was significantly shorter than the control group (n = 23) (9.5 ± 3.7 days vs. 15.2 ± 5 days, p = 0.007). The percentage of narrow-spectrum regimens was significantly higher in the study group (78 ± 11% vs. 40 ± 9%, p = 0.03). There was a significant difference in implementation of antimicrobial chemoprophylaxis for close contacts (4/8 (50%) vs. 1/23 (4%), p = 0.01).

Conclusions: The use of FA-ME PCR provides significant benefits in the management of PCBM by shortening duration of antibiotic treatment, increasing the use of narrow-spectrum regimens, and allowing proper administration of antimicrobial chemoprophylaxis.

Trial Registration: The study was approved and retrospectively registered by the Tel-Aviv Sourasky Medical Center ( 0378-17-TLV , 10/17/2017) and Rabin Medical Center ( 0270-18-RMC , 11/11/2018) Ethics committees and conforms to recognized standards.
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http://dx.doi.org/10.1186/s12879-019-4348-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6693273PMC
August 2019

and cytomegalovirus simultaneous detection in the filmarray meningitis/encephalitis panel and its clinical relevance.

IDCases 2019 9;17:e00516. Epub 2019 Mar 9.

Microbiology Laboratory, Rabin Medical Center, Beilinson Hospital, Israel.

A BioFire FilmArray Meningitis/Encephalitis test was performed on a 7-month old child suspected for bacterial meningitis. Two pathogens were detected, and cytomegalovirus (CMV). We verified the filmarray meningitis/encephalitis test by pan-bacterial assay to test for and CMV viral load test for the CMV detection. Pan-bacterial confirmed presence of , but CMV was not detected by the CMV viral load test. Together with the manifestations of high fever, vomiting, diffuse petechial rash, bulging fontanel, and leukocytosis, it is a clear case of meningococcal meningitis, while CMV detection had no clinical relevance.
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http://dx.doi.org/10.1016/j.idcr.2019.e00516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6536664PMC
March 2019

Predicting candidemia in the internal medicine wards: a comparison with gram-negative bacteremia-a retrospectives study.

Diagn Microbiol Infect Dis 2019 Sep 26;95(1):80-83. Epub 2019 Apr 26.

Infectious Disease Unit, Rabin Medical Center, Beilinson Hospital, Petah-Tikva, Israel; Sackler Faculty of Medicine, Tel Aviv University, Tel-Aviv, Israel.

Introduction: Risk factors for candidemia in the internal medicine wards (IMW) are poorly characterized. Their elucidation might assist in early diagnosis and treatment.

Objectives: We aimed to elucidate predictors of candidemia in the IMWs comparing them to patients with gram-negative bacteremia (GNB).

Methods: A retrospective study of consecutive patients with candidemia in IMWs in Beilinson hospital (2007-2016) was performed. Patient demographics, comorbidities, and clinical characteristics were documented. The comparator group was GNB patients.

Results: Sixty-two patients with candidemia were compared with 178 patients with GNB. Candidemic patients were younger and with less body mass index > 20 kg/m (73 ± 15 vs. 78 ± 10, P = 0.01; 44% vs. 60%, P = <0.0001,respectively). In multivariate model, underweight, prior cephalosporin use, and central venous catheters (CVCs) were significantly associated with candidemia [odds ratio (OR) = 0.2, 95% confidence interval (CI) 0.07-0.4; OR = 4, 95% CI 1.3-11; and OR = 4, 95% CI 1.5-12, respectively].

Conclusion: Underweight, recent cephalosporin exposure, and CVCs were statistically significant predictors of candidemia in the IMW. Using these predictors might aid in recognizing high-risk patients for candidemia in the IMWs, leading to earlier appropriate empirical treatment.
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http://dx.doi.org/10.1016/j.diagmicrobio.2019.04.007DOI Listing
September 2019

Risk factors for mortality due to bacteremia in patients with hematological malignancies - a retrospective study.

Leuk Lymphoma 2019 11 24;60(11):2787-2792. Epub 2019 Apr 24.

Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.

Carbapenem resistant (CRAB) is a significant cause of hospital acquired bloodstream infections in patients with hematological malignancies. Data regarding outcomes in this group of patients are limited. We retrospectively analyzed mortality risk factors of hospitalized hematological patients with CRAB bacteremia in our center. Among 46 included patients, overall 7-day mortality was 72% (33/46). Risk factors for 7-day mortality in multivariate analysis were higher infection severity score (SOFA score) at presentation (OR 1.481, 95% CI 1.091-2.012,  = .012) while appropriate antibiotic therapy within 48 h was protective (OR 0.052, 95% CI 0.005-0.590,  = .017). Inappropriate antibiotic therapy within 24 h was not significantly associated with 7-day mortality nor was absolute neutrophil count. Thirty-day mortality was 96% (44/46). CRAB bacteremia in hematological patients is associated with extremely high mortality, regardless of therapy. Infection control measures and antimicrobial stewardship aiming to prevent this infection of dismal prognosis are of major importance.
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http://dx.doi.org/10.1080/10428194.2019.1599113DOI Listing
November 2019

Perioperative prophylaxis with single-dose cefazolin for liver transplantation: a retrospective study.

Eur J Gastroenterol Hepatol 2019 Sep;31(9):1135-1140

General Intensive Care.

Background: Early infections are common during the first month after liver transplantation (LT), whereas no consensus exists on the optimal prophylactic antimicrobial therapy. We aimed to evaluate the effectiveness of cefazolin perioperative prophylaxis in LT.

Patients And Methods: We documented our experience with single-dose cefazolin as prophylaxis for LT. Infections occurring within 30 days following LT during 2006-2015 were documented retrospectively. Univariate and multivariate analyses of risk factors for infection were carried out.

Results: Among 113 LT recipients receiving cefazolin as prophylaxis, infections occurred in 50 (44%) patients, including surgical site infections (n=24, 21%) and bacteremia (n=14, 12%). Bacteria resistant to cefazolin were documented in 59/72 (82%) isolates. Enterococcal infections were documented in 6% (7/113). Almost half of the infections (44%) occurred in the first week following LT and the vast majority within 2 weeks. The 30-day mortality rate (7%, 8/113) was significantly higher among infected patients (7/50, 14% vs. 1/63, 1.6%, P=0.011). Model for End-stage Liver Disease score, age, and requirement for at least 5 U of packed red cells during transplantation were predictive for postoperative infections.

Conclusion: In our center, cefazolin was insufficient as perioperative prophylaxis in LT. We suggest that all LT recipients should receive antibiotic prophylaxis targeting microorganisms on the basis of local bacterial ecology and patterns of resistance irrespective of preoperative or intraoperative risk assessment.
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http://dx.doi.org/10.1097/MEG.0000000000001401DOI Listing
September 2019