Nationwide Outbreak of Candida auris Infections Driven by COVID-19 Hospitalizations, Israel, 2021-2022

We report an outbreak of Candida auris across multiple healthcare facilities in Israel. For the period of May 2014-May 2022, a total of 209 patients with C. auris infection or colonization were identified. The C. auris incidence rate increased 30-fold in 2021 (p = 0.00015), corresponding in time with surges of COVID-19-related hospitalization. Multilocus sequence typing revealed hospital-level outbreaks with distinct clones. A clade III clone, imported into Israel in 2016, accounted for 48.8% of typed isolates after January 2021 and was more frequently resistant to fluconazole (100% vs. 63%; p = 0.00017) and voriconazole (74% vs. 5.2%; p<0.0001) than were non-clade III isolates. A total of 23% of patients had COVID-19, and 78% received mechanical ventilation. At the hospital level, outbreaks initially involved mechanically ventilated patients in specialized COVID-19 units and then spread sequentially to ventilated non-COVID-19 patients and nonventilated patients.

The Impact of Thrombocytopenia and Lymphopenia on Mortality in Patients Infected with Influenza Virus: A Retrospective Cohort Study.

INTRODUCTION: Influenza virus causes significant global annual morbidity and mortality. Thrombocytopenia is recognized as a poor prognostic factor in sepsis and is associated with mortality, while lymphopenia has been established as a poor prognostic factor in other viral infections. We aimed to assess the incidence of thrombocytopenia and lymphopenia in seasonal influenza and their effect on clinical outcomes. METHODS: This single-center, retrospective, cohort study included consecutive adult patients, hospitalized in Rabin Medical Center between October 2017 and April 2018, with laboratory-confirmed influenza. Patients were grouped according to blood counts on admission: (1) thrombocytopenia (<150 K/mL), (2) lymphopenia (<0.5 K/mL), and (3) both thrombocytopenia and lymphopenia. Patients without thrombocytopenia and lymphopenia were designated as controls. The primary outcome was 30-day all-cause mortality. Risk factors were identified by univariable and multivariable analyses, using logistic regression and reported as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: A total of 625 patients were included, 112 (18%) had thrombocytopenia, 98 (15.6%) had lymphopenia, and 107 (17%) had both. The crude 30-day all-cause mortality was 7.6% (48/625). Mortality rates were 7.1% (8/112) for the thrombocytopenia group, 11.2% (11/98) for the lymphopenia group, and 14.9% (16/107) for patients with both versus 4.2% (13/308) in the control (p = 0.000 for all). In a multivariable regression model, significant thrombocytopenia (<100 K/µL) [OR 5.07 (95% CI 1.5-16.2)], age [OR 1.07 (95% CI 1.02-1.11)], time to oseltamivir [OR 1.006 (95% CI 1.002-1.11)], and significant respiratory support [OR 8.85 (3.4-22.6)] were associated with 30-day all-cause mortality. CONCLUSION: Patients hospitalized with seasonal influenza and thrombocytopenia <100 K/mL on admission, have an increased 30-day all-cause mortality.

External Validity of a Randomized Controlled Trial on Duration of Antibiotics for the Treatment of Gram-Negative Bacteremia.

INTRODUCTION: Reports regarding the external validity of randomized controlled trials (RCTs) are scarce. We aimed to assess the population external validity of an investigator-initiated RCT on the duration of antibiotics for the treatment of Gram-negative bacteremia by comparing patients included in the RCT to patients that were not included in the trial. METHODS: Hospitalized patients with Gram-negative bacteremia were recruited into an RCT and randomized to receive 7 or 14 days of covering antibiotic therapy in Israel and Italy from 2013 to 2017. In a concomitant observational study, RCT participants were compared with patients who fulfilled the inclusion criteria but were not included in the trial due to participation in other trials, discharge before approached by researchers, refusal to participate, or unwillingness of the treating physician to allow participants' recruitment. RESULTS: Six hundred and four RCT patients were compared with 613 nonincluded patients. Almost 50% of nonincluded patients (288/613) were dependent on others for activities of daily living at baseline compared to 37.7% of RCT participants (228/604). Dementia was nearly 2-fold more frequent in nonincluded patients than those included (5.9% [36/613] versus 3.6% [22/604], p = 0.07). Patients who were not included in the RCT were more likely to acquire their infection in the hospital (53.3% [327/613] versus 29.1% [176/604], p < 0.001). The primary composite outcome of mortality, clinical failure, readmissions, or extended hospitalization at 90 days occurred in 353 of 613 nonincluded patients (57.6%) compared to 299 of 604 RCT participants (49.6%), p = 0.005. However, on multivariate analysis noninclusion in the RCT was not an independent risk factor for clinical failure and mortality. CONCLUSIONS: RCTs, even with broad eligibility criteria, do not represent the whole spectrum of patients and leave out a population with more severe illness for whom the evidence is lacking.

Clinical Outcomes of Hospitalized Patients with SARS-CoV-2 Omicron Variant vs. Influenza A During Influenza Season 2021 to 2022: A Retrospective Observational Study.

BACKGROUND: Influenza and coronavirus disease 2019 (COVID-19) are respiratory diseases with similar modes of transmission. In December 2021, influenza re-emerged after it had been undetected since March 2020 and the Omicron variant replaced the Delta variant. Data directly comparing the two diseases are scarce. OBJECTIVES: To compare the outcomes of patients with both the Omicron variant and influenza during 2021-2022. METHODS: We performed a retrospective study conducted in Beilinson hospital, Israel, from December 2021 to January 2022. We included all hospitalized patients with either laboratory-confirmed COVID-19 or influenza. The primary outcome was 30-day mortality. RESULTS: We identified 167 patients diagnosed with Omicron and 221 diagnosed with Influenza A. The median age was 71 years for Omicron and 65 years for influenza. Patients with Omicron had a significantly higher Charlson Comorbidity Index score (4 vs. 3, P < 0.001). Patients with Omicron developed more respiratory failure that needed mechanical ventilation (7% vs. 2%, P = 0.05) and vasopressors (14% vs. 2%, P < 0.001) than patients with influenza. In a multivariate model, 30-day mortality was lower in patients diagnosed with influenza than in patients diagnosed with Omicron (19/221 [9%] vs. 44/167 [26%], hazard ratio 0.45, 95% confidence interval 0.25-0.81). CONCLUSIONS: Patients diagnosed with Omicron had higher mortality than patients diagnosed with seasonal influenza. This finding could be due to differences in co-morbidities, the virus pathogenicity, and host responses to infection.

The Effect of Macrolides on Mortality in Bacteremic Pneumococcal Pneumonia: A Retrospective, Nationwide Cohort Study, Israel, 2009-2017.

BACKGROUND: Previous cohort studies of pneumonia patients reported lower mortality with advanced macrolides. Our aim was to characterize antibiotic treatment patterns and assess the role of quinolones or macrolides in empirical therapy. MATERIALS: An historical cohort, 1 July 2009 to 30 June 2017, included, through active surveillance, all culture-confirmed bacteremic pneumococcal pneumonia (BPP) among adults in Israel. Cases without information on antibiotic treatment were excluded. Logistic regression analysis was used to assess independent predictors of in-hospital mortality. RESULTS: A total of 2016 patients with BPP were identified. The median age was 67.2 years (interquartile range [IQR] 53.2-80.6); 55.1% were men. Lobar pneumonia was present in 1440 (71.4%), multi-lobar in 576 (28.6%). Median length of stay was 6 days (IQR 4-11). A total of 1921 cases (95.3%) received empiric antibiotics with anti-pneumococcal coverage: ceftriaxone, in 1267 (62.8%). Coverage for atypical bacteria was given to 1159 (57.5%), 64% of these, with macrolides. A total of 372 (18.5%) required mechanical ventilation, and 397 (19.7%) died. Independent predictors of mortality were age (odds ratio [OR] 1.051, 95% confidence interval [CI] 1.039, 1.063), being at high-risk for pneumococcal disease (OR 2.040, 95% CI 1.351, 3.083), multi-lobar pneumonia (OR 2.356, 95% CI 1.741, 3.189). Female sex and macrolide therapy were predictors of survival: (OR 0.702, 95% CI .516, .955; and OR 0.554, 95% CI .394, .779, respectively). Either azithromycin or roxithromycin treatment for as short as two days was predictor of survival. Quinolone therapy had no effect. CONCLUSIONS: Empirical therapy with macrolides reduced odds for mortality by 45%. This effect was evident with azithromycin and with roxithromycin. The effect did not require a full course of therapy.

Does accepted definition of Clostridioides difficile infection (CDI) severity predict poor outcomes in older adults?

BACKGROUND: Advanced age is an important factor affecting Clostridioides difficile infection (CDI) risk and outcome. While fever and leukocytosis are prominent findings in young individuals with CDI, they are usually blunted in the elderly. Furthermore, chronic kidney disease often exists among this population prior to the CDI episode onset. AIM: We aimed to examine whether the accepted definition of severe CDI (leukocytosis ≥ 15,000 cells/µl or serum creatinine > 1.5 mg/dl) predicts poor outcomes in the elderly. METHODS: All CDI hospitalized individuals between January-2013 and May-2020 were included. The study population was dichotomized into older group (≥ 65 years) and younger group (< 65 years). Primary composite outcome was 30-day mortality, colectomy due to severe colitis, or intensive care unit admission. The older group was divided according to the primary outcome to evaluate the effect of CDI severity criteria. RESULTS: The study included 853 patients. Of them, 571 were in the older group and 282 in the younger one. The primary outcome was significantly more common in the older group (93/571, 16% vs. 31/282, 11%; p = 0.04). Ninety days mortality was significantly higher in the older group [116/571, 20% vs. 30/282, 11%; p < 0.01]. In multivariate analysis, accepted CDI severity criteria were not significantly associated with poor outcomes (odds ratio [OR] = 1.2, 95% confidence interval [CI] 0.7-2.2, p = 0.5). Advanced dementia and low serum albumin were significant predictors of poor outcomes (OR = 3, 95%CI 1.5-6, p = 0.002 and OR = 3.1, 95%CI 1.7-5.8, p < 0.01). CONCLUSION: The accepted definition of CDI severity was not useful in predicting CDI poor outcomes in older adults. In this population, we suggest advanced dementia and low albumin among others as CDI severity markers.

The impact of obesity on seasonal influenza: a single-center, retrospective study conducted in 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/m2) 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.

The significance of acute kidney injury in Clostridioides difficile infection.

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.

Cat Scratch Disease Presenting as Fever of Unknown Origin Is a Unique Clinical Syndrome.

BACKGROUND: Fever of unknown origin (FUO) is a rare manifestation of cat scratch disease (CSD). Data regarding CSD-associated FUO (CSD-FUO), particularly in adults, are limited. We aimed to study disease manifestations and long-term clinical outcome. METHODS: A national CSD surveillance study has been conducted in Israel since 1991. Data are obtained using questionnaires, review of medical records, and telephone interviews. FUO was defined as fever of ≥14 days without an identifiable cause. CSD-FUO patients were identified in the 2004-2017 CSD national registry. Follow-up included outpatient clinic visits and telephone/e-mail surveys. RESULTS: The study included 66 CSD-FUO patients. Median age was 35.5 years (range, 3-88). Median fever duration was 4 weeks (range, 2-9). Relapsing fever pattern was reported in 52% of patients, weight loss in 57%, and night sweats in 48%. Involvement of ≥1 organs occurred in 59% of patients; hepatosplenic space-occupying lesions (35%), abdominal/mediastinal lymphadenopathy (20%), ocular disease (18%), and multifocal osteomyelitis (6%) were the most common. Malignancy, particularly lymphoma, was the initial radiological interpretation in 21% of patients; 32% underwent invasive diagnostic procedures. Of the 59 patients available for follow-up (median duration, 31 weeks; range, 4-445), 95% had complete recovery; 3 patients remained with ocular sequelae. CONCLUSION: This is the first attempt to characterize CSD-FUO as a unique syndrome that may be severe and debilitating and often mimics malignancy. Relapsing fever is a common clinical phenotype. Multiorgan involvement is common. Recovery was complete in all patients except in those with ocular disease.

Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia: A Noninferiority Randomized Controlled Trial.

BACKGROUND: Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited. METHODS: This was a randomized, multicenter, open-label, noninferiority trial. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 days (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative, or distant complications; and readmission or extended hospitalization (>14 days). The noninferiority margin was set at 10%. RESULTS: We included 604 patients (306 intervention, 298 control) between January 2013 and August 2017 in 3 centers in Israel and Italy. The source of the infection was urinary in 411 of 604 patients (68%); causative pathogens were mainly Enterobacteriaceae (543/604 [90%]). A 7-day difference in the median duration of covering antibiotics was achieved. The primary outcome occurred in 140 of 306 patients (45.8%) in the 7-day group vs 144 of 298 (48.3%) in the 14-day group (risk difference, -2.6% [95% confidence interval, -10.5% to 5.3%]). No significant differences were observed in all other outcomes and adverse events, except for a shorter time to return to baseline functional status in the short-course therapy arm. CONCLUSIONS: In patients hospitalized with gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was noninferior to 14 days. Reducing antibiotic treatment for uncomplicated gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention. CLINICAL TRIALS REGISTRATION: NCT01737320.

Chronic use of oral iron supplements is associated with poor clinical outcomes in patients with gram-negative bacteremia.

An unabsorbed dietary iron supplementation can modify the colonic microbiota equilibrium and favor the growth of pathogenic strains over barrier strains. Nevertheless, the impact of oral iron supplements (OIS) use on the clinical outcomes of patients with gram-negative bacteremia (GNB) has not been evaluated. To explore the impact of OIS on the outcomes of patients with GNB. A retrospective study conducted in a tertiary hospital including patients with GNB during 2011-2016. The entire cohort was divided into chronic OIS users (study group) and nonusers (control group). The two groups were compared for the study outcomes, septic shock at presentation, length of hospital stay (LOS), and short-term mortality. The study cohort included 232 patients; 44 patients in the study group and 188 in the control one. There was no any significant difference in demographic and comorbidities characteristics between the two groups. Escherichia coli comprised the majority of bacteria (69%), while the urinary tract was the main source of the bacteremia. OIS alone and after adjustment was significantly associated with septic shock at presentation (OR = 2, CI95% [1.03-5], p = 0.04 and OR = 5, CI95% [1.4-15], p = 0.01, respectively). By multivariate analysis, OIS was significantly associated with 30-day mortality (OR = 3, CI95% [1.05-7], p = 0.04), but had no impact on LOS (16 + 23 vs. 12 + 15, p = 0.9). There is a significant association between chronic OIS exposure and increased adverse outcomes in patients with GNB. These findings might have important clinical implications.

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

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.

Molecular-based diagnosis of Clostridium difficile infection is associated with reduced mortality.

Polymerase chain reaction (PCR) for the diagnosis of Clostridium difficile infection (CDI) might result in overdiagnosis. The clinical outcomes of symptomatic CDI patients diagnosed by PCR remain uncertain. We aimed to determine whether patients whose diagnosis of CDI was based on PCR had different characteristics and clinical outcomes than those diagnosed by toxin immunoassay. Consecutive CDI patients, hospitalized at Rabin Medical Center, Beilinson Hospital, Petah Tikva, Israel, between January 2013 and January 2016, were identified retrospectively and included in the study. Diagnosis of CDI was based on PCR or diagnosis by immunoassay for C. difficile toxin. The main outcome was 30- and 90-day all-cause mortality. The PCR group included 165 patients and the immunoassay group included 157 patients. In comparison to the immunoassay group, patients in the PCR group were more likely to be younger, to be independent, to undergo previous abdominal surgery, and to use laxatives. The 30-day mortality rate in the PCR group was significantly lower than that in the immunoassay group, 29/165 (18%) vs 49/157 (31%), respectively; p = 0.028. On multivariate analysis, PCR diagnosis was associated with reduced mortality, OR 0.48 (95% CI 0.26-0.88). PCR-based diagnosis of CDI is associated with reduced all-cause mortality rates. Further studies are needed to determine the management of patients with discrepant immunoassay and PCR diagnosis of CDI.

Gram-negative bloodstream infections in hemodialysis patients: A retrospective study
.

BACKGROUND: Bloodstream infections (BSIs) are an important cause of hospitalizations and mortality among hemodialysis (HD) patients. Epidemiology of these infections is changing, with increasing rates of Gram-negative pathogens, including resistant ones. Few studies have focused on the characteristics and outcomes of these infections. OBJECTIVE: We aimed to document the causative pathogens of BSIs in HD patients and their clinical outcomes during 2008 - 2015, and to compare risk factors, clinical features, appropriateness of therapy, and outcomes between patients with Gram-negative vs. Gram-positive BSIs. MATERIALS AND METHODS: A single-center retrospective cohort study. Charts of 120 HD patients hospitalized with first BSI were reviewed. RESULTS: A total of 120 patients were included, 61 episodes of Gram-negative (51.8%) and 59 episodes of Gram-positive bacteria (49.2%). Source of infection was significantly more likely to be urinary or abdominal among patients with Gram-negative infection. Otherwise, no statistically significant differences were documented between groups in terms of baseline characteristics, presentation of infection and outcomes. Most Gram-negative BSIs were caused by enterobacteriaceae, followed by Pseudomonas spp. Previous clinical or surveillance cultures added little to accurate prediction of the causative organism. CONCLUSION: In a cohort of HD patients with BSI, no significant differences were found between Gram-negative and Gram-positive BSIs, besides source of infection. A urinary or abdominal source strongly suggests a Gram-negative pathogen. Otherwise, patient's characteristics, clinical presentation, and previous cultures, all cannot accurately predict the causative pathogen of BSI, and broad-spectrum antibiotics should be used empirically.
.

[THE ASSOCIATION BETWEEN URINE RESIDUAL VOLUME AT ADMISSION AND THE OUTCOMES OF HOSPITALIZED ELDERLY MEN WITH URINARY TRACT INFECTION].

BACKGROUND: Early assessment of urine residual volume (URV) at admission is essential in elderly men with urinary tract infection (UTI). Large URV might predispose these patients to subsequent complications; nevertheless, only scarce data are available concerning the impact of URV on the outcomes of elderly men with UTI. OBJECTIVES: To determine the impact of URV on the outcomes of elderly men hospitalized with UTI, including:  bacteremia rates, length of hospital stay, short and long-term mortality. METHODS: Eligible subjects were hospitalized men aged ≥ 65 years with a discharge diagnosis of UTI whose URV was assessed at presentation. The clinical parameters and outcomes of patients with urinary retention (≥400ml) and ones without (URV ≤ 400ml) were compared. RESULTS: Eighty out of 184 patients (43.5%) had urinary retention while 104 (56.5%) did not. The two groups didn't differ in their demographic and clinical parameters. Large URV at admission was significantly associated with increased 30-day mortality [OR=4 (95% CI 1.15-14), p=0.03] without significant impact on bacteremia rates and length of hospitalization. CONCLUSIONS: Large URV at admission in elderly men with UTI is associated with increased 30-day mortality. Further prospective studies with different URV cutoffs are needed to explore this association and its pathophysiology.

Trimethoprim/sulfamethoxazole versus vancomycin in the treatment of healthcare/ventilator-associated MRSA pneumonia: a case-control study.

Objectives: Therapeutic options available to treat MRSA pneumonia are limited. Trimethoprim/sulfamethoxazole is an attractive treatment because of its bactericidal anti-MRSA activity, oral and parenteral formulations and good penetration to the lung tissue. We aimed to compare the efficacy and safety of trimethoprim/sulfamethoxazole with vancomycin in the treatment of healthcare/ventilator-associated MRSA pneumonia. Methods: We carried out a retrospective case-control study of all consecutive hospitalized adult patients diagnosed with MRSA pneumonia at Beilinson Hospital during 2010-15 and treated with either vancomycin or trimethoprim/sulfamethoxazole. The primary outcomes were all-cause mortality at 30 days and clinical failure at the end of treatment. In order to reduce bias affecting the decision to use a specific antibiotic and as a sensitivity analysis, a propensity-score model for choosing between vancomycin and trimethoprim/sulfamethoxazole was used. Results: We identified 42 patients with MRSA pneumonia treated with trimethoprim/sulfamethoxazole and 39 treated with vancomycin. There were no significant differences in the baseline characteristics between the groups. Vancomycin-treated patients showed significantly higher 30 day mortality on both multivariate analysis (HR = 5.28; 95% CI = 1.50-18.60; P < 0.05) and sensitivity analysis with propensity score [vancomycin 13/24 (54.1%) versus trimethoprim/sulfamethoxazole 4/24 (16.7%); P < 0.05], and higher clinical failure rates [vancomycin 23/39 (59%) versus trimethoprim/sulfamethoxazole 15/42 (35.7%); P < 0.05], also in the sensitivity analysis with propensity score [vancomycin 14/24 (58.3%) versus trimethoprim/sulfamethoxazole 6/24 (25%); P < 0.05]. The rates of side effects in both arms were comparable. Conclusions: Trimethoprim/sulfamethoxazole appears to be superior to vancomycin in the treatment of MRSA pneumonia. A large-scale randomized controlled trial is needed to evaluate these findings.

Time trends in Staphylococcus aureus bacteremia, 1988-2010, in a tertiary center with high methicillin resistance rates.

INTRODUCTION: Changes in the epidemiology of Staphylococcus aureus bacteremia (SAB) have been described in recent decades. Decreased mortality has been reported over time, mostly from countries with low methicillin resistance rates. We aimed to describe time trends in SAB in a tertiary center with high methicillin resistance rates. METHODS: We retrospectively analyzed 1692 patients with SAB, and compared between three time periods: 1988-1994 (342 patients), 1998-2004 (597 patients) and 2005-2010 (753 patients). RESULTS: In our cohort, 30 days mortality increased significantly with time, reaching 42.9 % during 2005-2010. The latter period was characterized by higher rates of older patients (35.1 % aged 80 years and older), with lower functional capacity (46.5 % bedridden) and higher rates of comorbidities (33.6 % renal disease, 24.8 % heart failure, 19.0 % dementia). These patients were more likely to be ventilated (18.7 %) and carry a urinary catheter at presentation (46.6 %); present with septic shock (15.9 %) and have pneumonia (20.5 %) or endocarditis (7.2 %) as source. Similar characteristics were found among patients younger than 50 years and with independent functional status. No significant increase in methicillin resistant Staph aureus (MRSA) rates or inappropriate empirical therapy was demonstrated during 2005-2010. CONCLUSIONS: In our cohort, increased mortality in recent years in patients with SAB can be explained by baseline condition of patients. MRSA or inappropriate empiric therapy did not explain the increase in mortality. The patients afflicted with SAB changed over time. Epidemiology and outcomes of SAB vary with time and according to geographical location. External validity of studies should be taken into consideration.

Clinical presentation, management and outcomes of Staph aureus bacteremia (SAB) in older adults.

AIM: The incidence of Staphylococcus aureus bacteremia (SAB) increases with advancing age with higher mortality reported in older adults. We aimed to describe the clinical presentation, management and outcomes of older patients with SAB. METHODS: We analyzed data from a retrospectively collected database including 1692 patients with SAB, and compared 1158 older patients (≥65 years) with 534 younger patients (<65 years) in terms of clinical features, management of infection, and outcomes. RESULTS: Older patients were significantly less likely to be febrile on presentation, with 37.5 % (415/1106) of older patients presenting with normal body temperature [versus 29.2 % (152/520) of younger patients]. Older patients were however, more likely to have leukocytosis, septic shock, lower heart rate and lower diastolic blood pressure compared with younger patients. Management of older patients included significantly less imaging studies, performance of transesophageal echocardiogram (TEE) and infectious diseases consultation. TEE was performed less in older patients [124/726 (17.1 %) versus 72/285 (25.3 %)]. Mortality was significantly higher in older patients [550/1158 (47.5 %) versus 124/534 (23.2 %)], with predictors for mortality for the entire cohort in multivariate analysis including older age, higher Charlson comorbidity index, female sex, impaired functional capacity, pneumonia or primary bacteremia, and non-performance of TEE. CONCLUSIONS: Mortality rates in older patients with SAB are higher compared with younger patients. Several diagnostic and therapeutic procedures in the management of SAB were less likely to be performed in older patients in our cohort. These may have implications on outcome and should not be dismissed on the basis of age alone.