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We report 8 cases of persistent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia in patients previously treated with anti-CD20 monoclonal antibodies. Polymerase chain reaction of nasopharyngeal swabs for SARS-CoV-2 was negative in most cases; viral cell cultures confirmed that viable SARS-Co-2 virus was present. Four patients were treated with anti-SARS-CoV-2 hyperimmune globulins with rapid resolution of disease. [ABSTRACT FROM AUTHOR]

Background It is unknown whether convalescent immunoglobulins (cIgGs) are better than convalescent plasma (CP) for patients with coronavirus 2019 (COVID-19). Methods In this randomized controlled trial, we assigned high risk COVID-19 patients with ≤10 days of symptoms, to receive cIgGs or CP. The primary endpoint was improvement on day 14 according to the World Health Organization scale. Secondary endpoints were survival on day 14, and improvement, survival, and percent of ventilated patients on day 28, and treatment response in unvaccinated and vaccinated patients. Results A total of 319 patients were included: 166 received cIgGs and 153 CP. Median age was 64 to 66 years. A total of 112 patients (67.5%) in the cIgG group and 103 patients (67.3%) in the CP group reached the primary endpoint. Difference between groups was 0.1 (95% confidence interval, −10.1 to 10.4; P =.026), failing to reach noninferiority. More patients receiving cIgG improved by day 28 (136 patients [81.9%] and 108 patients [70.6%], respectively; 95% confidence interval, 1.9–20.7; P <.001; for superiority P =.018). Seventeen patients in the cIgG group (10.2%) and 25 patients (16.3%) in the CP group required mechanical ventilation (P =.136). Sixteen (9.6%) and 23 (15%) patients, respectively, died (P =.172). More unvaccinated patients improved by day 28 in the cIgG group (84.1% vs 66.1%; P =.024), and survival was better in the cIgG group (89.9% vs 77.4%; P =.066). Conclusions cIgGs failed to reach the primary noninferiority endpoint on day 14 but was superior to CP on day 28. Survival and improvement by day 28 in unvaccinated patients treated with cIgGs were better. In the face of new variants, cIgGs are a viable option for treating COVID-19. Trial registration number My Trials MOH_2021-01-14_009667. [ABSTRACT FROM AUTHOR]

Background Fosmanogepix is a first-in-class antifungal targeting the fungal enzyme Gwt1, with broad-spectrum activity against yeasts and moulds, including multidrug-resistant fungi, formulated for intravenous (IV) and oral administration. Methods This global, multicenter, non-comparative study evaluated the safety and efficacy of fosmanogepix for first-line treatment of candidaemia in non-neutropenic adults. Participants with candidaemia, defined as a positive blood culture for Candida spp. within 96 h prior to study entry, with ≤ 2 days of prior systemic antifungals, were eligible. Participants received fosmanogepix for 14 days: 1000 mg IV twice daily on Day 1, followed by maintenance 600 mg IV once daily, and optional switch to 700 mg orally once daily from Day 4. Eligible participants who received at least one dose of fosmanogepix and had confirmed diagnosis of candidaemia (<96 h of treatment start) composed the modified intent-to-treat (mITT) population. Primary efficacy endpoint was treatment success at the end of study treatment (EOST) as determined by the Data Review Committee. Success was defined as clearance of Candida from blood cultures with no additional antifungal treatment and survival at the EOST. Results Treatment success was 80% (16/20, mITT; EOST) and Day 30 survival was 85% (17/20; 3 deaths unrelated to fosmanogepix). Ten of 21 (48%) were switched to oral fosmanogepix. Fosmanogepix was well tolerated with no treatment-related serious adverse events/discontinuations. Fosmanogepix had potent in vitro activity against baseline isolates of Candida spp. (MICrange: CLSI, 0.002–0.03 mg/L). Conclusions Results from this single-arm Phase 2 trial suggest that fosmanogepix may be a safe, well-tolerated, and efficacious treatment for non-neutropenic patients with candidaemia, including those with renal impairment. [ABSTRACT FROM AUTHOR]

Background Waning immunity and an increased incidence of coronavirus disease 2019 (COVID-19) during the Omicron outbreak led the Israeli Ministry of Health to recommend a fourth vaccine dose for high-risk individuals. In this study, we assessed its effect for hospitalized patients with severe breakthrough COVID-19. Methods In this multicenter cohort study of hospitalized adults with severe COVID-19 in Israel, from 15 to 31 January 2022, cases were divided according to the number of vaccinations received. Poor outcome was defined as mechanical ventilation or in-hospital death and was compared between 3- and 4-dose vaccinees using logistic regression. Results Included were 1049 patients, median age 80 years. Among them, 394 were unvaccinated, 386 and 88 had received 3 or 4 doses, respectively. The 3-dose group was older, included more males, and immunosuppressed patients but with similar outcomes, 49% vs 51% compared with unvaccinated patients (P =.72). Patients who received 4 doses were similarly older and immunosuppressed but had better outcomes compared with unvaccinated patients, 34% vs 51% (P <.01). We examined independent predictors for poor outcome in patients who received either 3 or 4 doses a median of 161 days or 14 days before diagnosis, respectively. Receipt of the fourth dose was associated with protection (odds ratio, 0.51; 95% confidence interval,.3–.87), as was remdesivir. Male sex, chronic renal failure, and dementia were associated with poor outcomes. Conclusions Among hospitalized patients with severe breakthrough COVID-19, a recent fourth dose was associated with significant protection against mechanical ventilation or death compared with 3 doses. [ABSTRACT FROM AUTHOR]

Background Severe acute respiratory syndrome coronavirus 2 infection is responsible for the coronavirus disease 2019 (COVID-19) pandemics. Omicron (B.1.1.529) variant is the cause for the surge of the COVID-19 pandemics of the end of 2021 and the beginning of 2022, although its subvariants are responsible for the following daily increase of COVID-19 cases in July 2022. Early reports of Omicron variant confirmed patients indicated less severe disease course compared with the disease caused by previously encountered variants with absence of data regarding cardiac involvement by Omicron. Case summary A 42-year-old male who tested positive for Omicron was admitted on January 2022 with chest pain and ST-segment elevation in the inferior leads. Coronary angiography revealed non-significant coronary artery disease. Cardiac magnetic resonance imaging demonstrated features consistent with myocarditis with involvement of 22% of the left ventricular mass by late gadolinium enhancement involving both the lateral and the septal walls. The second patient is a 60-year-old male presented following syncope and palpitations after he was confirmed with Omicron infection. Upon emergency department arrival he had ventricular tachycardia of 250 beats/minute and underwent urgent cardioversion. During his hospitalization, there was no recurrence of malignant arrhythmia, coronary angiography revealed non-obstructive disease. Cardiac magnetic resonance imaging demonstrated imaging features suggesting acute myocarditis with involvement of 19% of the left ventricular mass. Discussion This is the first report of myocarditis cases as a possible complication associated with Omicron variant. Despite preliminary reports of less severe disease clinicians should be vigilant for potential deleterious cardiac complications of Omicron. [ABSTRACT FROM AUTHOR]

Background: Despite high vaccine coverage, an increase in breakthrough coronavirus disease 2019 (COVID-19) infections, prompted administration of a third BNT162b2 dose to people aged >60 years in Israel since July 2021. Here, we report real-world immunogenicity following third dose.Methods: Overall, 208 healthcare workers aged >60 years were included. Paired pre- and post-second and/or third dose immunoglobulin G (IgG) and neutralizing antibody titers were compared. A subpopulation of low responders to the second dose was also tested for T-cell activation. For 25 paired serum samples, we tested neutralization of wild-type vs neutralization of Delta and Lambda variants, pre- and post-third dose. Active surveillance of vaccine adverse events was conducted through surveys.Results: A pronounced immune response was observed following the third dose, including a 33-fold and 51-fold increase in IgG and neutralizing antibody, respectively. The neutralizing antibody levels post-third dose were 9.34 times higher than post-second dose (geometric mean titer, 2598 [95% confidence interval {CI}, 2085-3237] vs 207 [95% CI, 126-339]). Nine previously low responders had a significant antibody increase post-third dose, and 7 of 9 showed increase in T-cell activation. Additionally, sera obtained post-third dose highly and comparably neutralized the wild-type and Delta and Lambda variants. Of 1056 responders to the adverse-event survey, none had serious events.Conclusions: We demonstrate a rapid and broad immune response to the third BNT162b2 dose in individuals >60 years of age. [ABSTRACT FROM AUTHOR]

Background Hematopoietic-cell transplant (HCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. We evaluated the RSV fusion inhibitor presatovir in a randomized, double-blind, Phase II trial in HCT recipients with RSV upper respiratory tract infections. Methods Patients were stratified by lymphopenia (<200/µL) and ribavirin use; were randomized, stratified by lymphopenia (<200/μL) and ribavirin use, to receive oral presatovir at 200 mg or a placebo on Days 1, 5, 9, 13, and 17, and were followed through Day 28. The coprimary efficacy endpoints were the time-weighted average change in the nasal RSV viral load between Days 1 and 9 and the proportion of patients developing lower respiratory tract complications (LRTCs) through Day 28. Results From 23 January 2015 to 16 June 2017, 189 patients were randomly assigned to treatment (96 to presatovir and 93 to the placebo). Presatovir treatment, compared with the placebo treatment, did not significantly affect (prespecified α = 0.01) a time-weighted average decline in the RSV viral load from Day 1 to 9 (treatment difference, −0.33 log10 copies/mL; 95% confidence interval [CI] −.64 to −.02 log10 copies/mL; P =.040) or the progression to LRTC (11.2% vs 19.5%, respectively; odds ratio, 0.50; 95% CI,.22–1.18; P =.11). In a post hoc analysis among patients with lymphopenia, presatovir decreased LRTC development by Day 28 (2/15 [13.3%] vs 9/14 [64.3%], respectively; P =.008), compared with the placebo. Adverse events were similar for patients receiving presatovir and the placebo. Conclusions Presatovir had a favorable safety profile in adult HCT recipients with RSV but did not achieve the coprimary endpoints. Exploratory analyses suggest an antiviral effect among patients with lymphopenia. Clinical Trials Registration NCT02254408; EUDRA-CT#2014-002474-36. [ABSTRACT FROM AUTHOR]

Background In phase 3 MODIFY I/II trials, bezlotoxumab significantly reduced recurrence of Clostridioides (Clostridium) difficile infection (rCDI) over 12 weeks. Choice of CDI antibacterial treatment may affect CDI-related outcomes; therefore, this prespecified analysis assessed if the magnitude of bezlotoxumab-induced rCDI reduction was influenced by the antibiotic administered. Methods In MODIFY I/II (NCT01241552/NCT01513239), participants received a single infusion of bezlotoxumab (10 mg/kg) or placebo during anti-CDI treatment. Using pooled data from MODIFY I/II, initial clinical cure (ICC) and rCDI were assessed in metronidazole-, vancomycin-, and fidaxomicin-treated subgroups. Results Of 1554 participants in MODIFY I/II, 753 (48.5%) received metronidazole, 745 (47.9%) vancomycin, and 56 (3.6%) fidaxomicin. Fewer participants receiving metronidazole had a prior CDI episode in the previous 6 months (12.9%) or ≥1 risk factor for rCDI (66.0%) vs participants receiving vancomycin (41.2% and 83.6%, respectively) and fidaxomicin (55.4% and 89.3%, respectively). ICC rates were similar in the bezlotoxumab (metronidazole, 81.0%; vancomycin, 78.5%; fidaxomicin, 86.7%) and placebo groups (metronidazole, 81.3%; vancomycin, 79.6%; fidaxomicin, 76.9%). In placebo-treated participants, the rCDI was lower in the metronidazole subgroup vs the vancomycin and fidaxomicin subgroups (metronidazole, 28.0%; vancomycin, 38.4%; fidaxomicin, 35.0%). When analyzed by subsets based on history of CDI, rCDI rates were similar in the metronidazole and vancomycin groups. rCDI rates were lower in all antibiotic subgroups for bezlotoxumab vs placebo (metronidazole: rate difference [RD], –9.7%; 95% confidence interval [CI], –16.4% to –3.1%; vancomycin: RD, –15.4%; 95% CI, –22.7% to –8.0%; fidaxomicin: RD, –11.9%; 95% CI, –38.1% to 14.3%). Conclusion Bezlotoxumab reduces rCDI vs placebo in participants receiving metronidazole and vancomycin, with a similar effect size in participants receiving fidaxomicin. [ABSTRACT FROM AUTHOR]

The incidence of invasive fungal diseases (IFDs) with central nervous system (CNS) involvement is increasing due to the rising numbers of immunocompromised individuals, such as patients receiving chemotherapy, transplantation procedures, or immune-modulating therapies. CNS IFDs cause significant morbidity and mortality, and treatments are complicated by difficulties in identifying fungal pathogens and delivering antifungal agents to the CNS. Isavuconazole is a novel triazole with broad-spectrum activity that has shown good blood–brain barrier penetration in animal models. We present a retrospective analysis of isavuconazole in the treatment of patients with CNS IFDs and who either participated in the phase III VITAL or SECURE clinical trials, or were included in a named-patient program. A total of 36 patients were identified, including 27 patients from the clinical trials. Of these patients, 47.2% had hematologic malignancies, while 13.9% had no identifiable underlying conditions. Mucorales, Aspergillus species, and Cryptococcus species accounted for 30.6%, 22.2%, and 13.9% of infections, respectively. The overall survival rate was 80.6% at day 42 and 69.4% at day 84, and at the end of treatment, a complete or partial clinical response was achieved in 58.3% of patients. Isavuconazole exhibited clinical activity in a variety of CNS IFDs. [ABSTRACT FROM AUTHOR]

Salmonella enterica serovar Infantis (S. Infantis) is one of the dominant serovars of the bacterial pathogen S. enterica. In recent years, the number of human infections caused by S. Infantis has been increasing in many countries, and often the emerging population harbors a unique virulence-resistant megaplasmid called plasmid of emerging S. Infantis (pESI). Here, we report the complete gap-free genome sequence of the S. Infantis Israeli emerging clone and compare its chromosome and pESI sequences with other complete S. Infantis genomes. We show a conserved presence of the Salmonella pathogenicity islands 1–6, 9, 11, 12, and CS54 and a common integration of five bacteriophages in the S. Infantis chromosome. In contrast, we found variable presence of additionally three chromosomally integrated phages and eight modular regions in pESI, which contribute to the genetic and phenotypic diversity (including antimicrobial resistance) of this ubiquitous foodborne pathogen. [ABSTRACT FROM AUTHOR]

Background: Salmonella enterica serovar Infantis (S. Infantis) is one of the ubiquitous serovars of the bacterial pathogen S. enterica and recently has been emerging in many countries worldwide. Nonetheless, not much is known about its epidemiology, host adaptation, and virulence.Methods: Epidemiological and molecular approaches were used together with tissue-culture and mouse models to conduct phenotypic comparison with the model S. enterica serovar Typhimurium.Results: We show that S. Infantis is more frequently associated with infections in infants <2 years old and prone to cause significantly less invasive infections than serovar Typhimurium. Moreover, although S. Infantis adheres better to host cells and highly colonizes mouse intestines soon after infection, it is significantly less invasive and induces much lower inflammation and disease in vivo than S. Typhimurium. These differences were associated with lower expression of Salmonella pathogenicity island (SPI) 1 genes in S. Infantis than in S. Typhimurium.Conclusions: Our results demonstrate previously unknown differences in the epidemiology, virulence pathway expression, and pathogenicity between two highly abundant Salmonella serovars and suggest that native variation in the expression of the SPI-1 regulon is likely to contribute to epidemiological and virulence variation between genetically similar nontyphoidal Salmonella serovars. [ABSTRACT FROM AUTHOR]

Background Isavuconazole was compared to caspofungin followed by oral voriconazole in a Phase 3, randomized, double-blind, multinational clinical trial for the primary treatment of patients with candidemia or invasive candidiasis. Methods Adult patients were randomized 1:1 to isavuconazole (200 mg intravenous [IV] three-times-daily [TID] for 2 days, followed by 200 mg IV once-daily [OD]) or caspofungin (70 mg IV OD on day 1, followed by 50 mg IV OD [70 mg in patients > 80 kg]) for a maximum of 56 days. After day 10, patients could switch to oral isavuconazole (isavuconazole arm) or voriconazole (caspofungin arm). Primary efficacy endpoint was successful overall response at the end of IV therapy (EOIVT) in patients with proven infections who received ≥1 dose of study drug (modified-intent-to-treat [mITT] population). The pre-specified noninferiority margin was 15%. Secondary outcomes in the mITT population were successful overall response at 2 weeks after the end of treatment, all-cause mortality at days 14 and 56, and safety. Results Of 450 patients randomized, 400 comprised the mITT population. Baseline characteristics were balanced between groups. Successful overall response at EOIVT was observed in 60.3% of patients in the isavuconazole arm and 71.1% in the caspofungin arm (adjusted difference -10.8, 95% confidence interval -19.9–-1.8). The secondary endpoints, all-cause mortality, and safety were similar between arms. Median time to clearance of the bloodstream was comparable between groups. Conclusions This study did not demonstrate non-inferiority of isavuconazole to caspofungin for primary treatment of invasive candidiasis. Secondary endpoints were similar between both groups. Clinical Trials Registration NCT00413218. [ABSTRACT FROM AUTHOR]

Background Bezlotoxumab is a human monoclonal antibody against Clostridium difficile toxin B indicated to prevent C. difficile infection (CDI) recurrence (rCDI) in adults at high risk for rCDI. This post hoc analysis of pooled monocolonal antibodies for C. difficile therapy (MODIFY) I/II data assessed bezlotoxumab efficacy in participants with characteristics associated with increased risk for rCDI. Methods The analysis population was the modified intent-to-treat population who received bezlotoxumab or placebo (n = 1554) by risk factors for rCDI that were prespecified in the statistical analysis plan: age ≥65 years, history of CDI, compromised immunity, severe CDI, and ribotype 027/078/244. The proportion of participants with rCDI in 12 weeks, fecal microbiota transplant procedures, 30-day all cause and CDI-associated hospital readmissions, and mortality at 30 and 90 days after randomization were presented. Results The majority of enrolled participants (75.6%) had ≥1 risk factor; these participants were older and a higher proportion had comorbidities compared with participants with no risk factors. The proportion of placebo participants who experienced rCDI exceeded 30% for each risk factor compared with 20.9% among those without a risk factor, and the rCDI rate increased with the number of risk factors (1 risk factor: 31.3%; ≥3 risk factors: 46.1%). Bezlotoxumab reduced rCDI, fecal microbiota transplants, and CDI-associated 30-day readmissions in participants with risk factors for rCDI. Conclusions The risk factors prespecified in the MODIFY statistical analysis plan are appropriate to identify patients at high risk for rCDI. While participants with ≥3 risk factors had the greatest reduction of rCDI with bezlotoxumab, those with 1 or 2 risk factors may also benefit. Clinical Trials Registration NCT01241552 (MODIFY I) and NCT01513239 (MODIFY II). [ABSTRACT FROM AUTHOR]

Background. Atovaquone-proguanil is considered causal prophylaxis (inhibition of liver-stage schizonts) for Plasmodium falciparum; however, its causal prophylactic efficacy for Plasmodium vivax is not known. Travelers returning to nonendemic areas provide a unique opportunity to study P. vivax prophylaxis. Methods. In a retrospective observational study, for 11 years, Israeli rafters who had traveled to the Omo River in Ethiopia, a highly malaria-endemic area, were followed for at least 1 year after their return. Malaria prophylaxis used during this period included mefloquine, doxycycline, primaquine, and atovaquone-proguanil. Prophylaxis failure was divided into early (within a month of exposure) and late malaria. Results. Two hundred fifty-two travelers were included in the study. Sixty-two (24.6%) travelers developed malaria, 56 (91.9%) caused by P. vivax, with 54 (87.1%) cases considered as late malaria. Among travelers using atovaquone-proguanil, there were no cases of early P. falciparum or P. vivax malaria. However, 50.0% of atovaquone-proguanil users developed late vivax malaria, as did 46.5% and 43.5% of mefloquine and doxycycline users, respectively; only 2 (1.4%) primaquine users developed late malaria (P < .0001). Conclusions. Short-course atovaquone-proguanil appears to provide causal (liver schizont stage) prophylaxis for P. vivax, but is ineffective against late, hypnozoite reactivation–related attacks. These findings suggest that primaquine should be considered as the chemoprophylactic agent of choice for areas with high co-circulation of P. falciparum and P. vivax. [ABSTRACT FROM AUTHOR]

Background. Although chronic infections by typhoidal Salmonella are well-known, prolonged human infections by nontyphoidal Salmonella (NTS) are poorly characterized. Methods. We retrospectively analyzed 48 345 culture-confirmed NTS infections that occurred in Israel 1995-2012. A casecontrol study was performed to identify risk factors associated with persistent infections. Whole-genome-sequencing, pulsed-field gel electrophoresis (PFGE), and a mouse infection model were used to study genetic and phenotypic differences between samepatient persistent, recurring isolates. Results. In total, 1047 cases of persistent NTS infections, comprising 2.2% of all reported cases of salmonellosis, were identified. The persistence periods ranged between 30 days to 8.3 years. The majority (93%) of the persistently infected patients were immunocompetent, and 65% were symptomatic with relapsing diarrhea, indicating a distinct clinical manifestation from the asymptomatic carriage of typhoidal Salmonella. Four NTS serovars (Mbandaka, Bredeney, Infantis and Virchow) were found to be significantly more frequently associated with persistence than others. Comparative genomics between early and later isolates obtained from the same patients confirmed clonal infection and showed 0 to 10 SNPs between persistent isolates. A different composition of mobile genetic elements ( plasmids and phages) or amino acid substitutions in global regulators was identified in multiple cases. These changes resulted in differences in phenotype and virulence between early and later same-patient isolates. Conclusions. These results illuminate the overlooked clinical manifestation of persistent salmonellosis that can serve as a human reservoir for NTS infections. Additionally, we demonstrate mechanisms of in-host microevolution and exhibit their potential to shape Salmonella pathogenicity, antimicrobial resistance and host-pathogen interactions. [ABSTRACT FROM AUTHOR]

Background: Since 2001, we have observed patients with a clinical picture consistent with West Nile virus (WNV) infection, which was defined as nonprimary infection (NPI) owing to the presence of highly elevated serum immunoglobulin G antibody titers with a high avidity index (≥ 55%), absent or low titers of serum and cerebrospinal fluid (CSF) immunoglobulin M, and occasionally positive results of WNV-specific real-time reverse-transcription polymerase chain reaction analysis of CSF and/or blood specimens.Methods: We investigated 124 patients with a diagnosis of primary WNV infection (PI) or NPI during 2005-2007 at Sheba Medical Center (Tel-Hashomer, Israel). Logistic regression was used to evaluate the association of variables with PI and NPI and with in-hospital mortality.Results: A total of 68 and 50 patients with PI and NPI, respectively were included; 6 patients had incomplete data. In multivariate models, NPI was significantly associated with underlying psychiatric disorders (adjusted odds ratio [aOR], 13.73; 95% confidence interval [CI], 2.28-82.56; P = .004), hospitalization during winter and spring (aOR, 8.82; 95% CI, 1.59-48.87; P = .013), and fever (aOR, 0.61; 95% CI, .39-.95; P = .031). In-hospital mortality was significantly associated with NPI (aOR, 3.86; 95% CI, 1.12-13.28; P = .032) and a higher Charlson comorbidity index (aOR, 1.37; 95% CI, 1.03-1.83; P = .032).Conclusions: The possibility that NPI may be an emerging clinical entity with a high mortality rate must be considered seriously. [ABSTRACT FROM AUTHOR]

Human infection with typhoidal Salmonella serovars causes a febrile systemic disease, termed enteric fever. Here we establish that in response to a temperature equivalent to fever (39°C-42°C) Salmonella enterica serovars Typhi, Paratyphi A, and Sendai significantly attenuate their motility, epithelial cell invasion, and uptake by macrophages. Under these feverlike conditions, the residual epithelial cell invasion of S. Paratyphi A occurs in a type III secretion system (T3SS) 1-independent manner and results in restrained disruption of epithelium integrity. The impaired motility and invasion are associated with down-regulation of T3SS-1 genes and class II and III (but not I) of the flagella-chemotaxis regulon. In contrast, we demonstrate up-regulation of particular Salmonella pathogenicity island 2 genes (especially spiC) and increased intraepithelial growth in a T3SS-2- dependent manner. These results indicate that elevated physiological temperature is a novel cue controlling virulence phenotypes in typhoidal serovars, which is likely to play a role in the distinct clinical manifestations elicited by typhoidal and nontyphoidal salmonellae. [ABSTRACT FROM AUTHOR]

Background. Telavancin is a lipoglycopeptide bactericidal against gram-positive pathogens.Methods. Two methodologically identical, double-blind studies (0015 and 0019) were conducted involving patients with hospital-acquired pneumonia (HAP) due to gram-positive pathogens, particularly methicillin-resistant Staphylococcus aureus (MRSA). Patients were randomized 1:1 to telavancin (10 mg/kg every 24 h) or vancomycin (1 g every 12 h) for 7–21 days. The primary end point was clinical response at follow-up/test-of-cure visit.Results. A total of 1503 patients were randomized and received study medication (the all-treated population). In the pooled all-treated population, cure rates with telavancin versus vancomycin were 58.9% versus 59.5% (95% confidence interval [CI] for the difference, –5.6% to 4.3%). In the pooled clinically evaluable population (n = 654), cure rates were 82.4% with telavancin and 80.7% with vancomycin (95% CI for the difference, –4.3% to 7.7%). Treatment with telavancin achieved higher cure rates in patients with monomicrobial S. aureus infection and comparable cure rates in patients with MRSA infection; in patients with mixed gram-positive/gram-negative infections, cure rates were higher in the vancomycin group. Incidence and types of adverse events were comparable between the treatment groups. Mortality rates for telavancin-treated versus vancomycin-treated patients were 21.5% versus 16.6% (95% CI for the difference, –0.7% to 10.6%) for study 0015 and 18.5% versus 20.6% (95% CI for the difference, –7.8% to 3.5%) for study 0019. Increases in serum creatinine level were more common in the telavancin group (16% vs 10%).Conclusions. The primary end point of the studies was met, indicating that telavancin is noninferior to vancomycin on the basis of clinical response in the treatment of HAP due to gram-positive pathogens. [ABSTRACT FROM AUTHOR]

Background. Heteroresistant vancomycin-intermediate Staphylococcus aureus (hVISA) infections are emerging, but their clinical significance remains unclear. Our objective was to compare patients who had hVISA bacteremia with patients who had methicillin-resistant S. aureus (MRSA) bacteremia. Methods. A total of 27 case patients with hVISA bacteremia were compared with 223 control patients with MRSA bacteremia. Medical records of all patients were reviewed, and factors independently associated with infection-related mortality were assessed by logistic regression. Results. Patients with hVISA bacteremia were not significantly different from those with MRSA bacteremia with respect to age, comorbidities, duration of hospital stay, and infection-attributable mortality. However, the median duration of bacteremia among patients with hVISA was significantly longer than that among patients with MRSA (12 vs. 2 days; P = .005), and patients with hVISA had a greater prevalence of complications, such as endocarditis (18.5% vs. 3.6%; P = .007) and osteomyelitis (25.9% vs. 7.2%, respectively; P = .006). Rifampin resistance emerged more frequently among hVISA isolates than among MRSA isolates (44% vs. 5.9%; P < .001). Factors independently associated with infection-related mortality in all patients were age, Charlson comorbidity index, female sex, and being bedridden. Conclusions. hVISA bacteremia was significantly associated with prolonged bacteremia duration, greater rates of complications, and emergence of rifampin resistance, compared with MRSA bacteremia. However, no significant difference in mortality existed between patients with hVISA bacteremia and those with MRSA bacteremia. [ABSTRACT FROM AUTHOR]

Background. Surgical wound infections caused by rapidly growing mycobacteria developed in 15 women after insertion of breast implants from August to November 2003 at a single medical center. Methods. A case-control study was conducted that included the identified patients, as well as women who underwent breast operations at the same center who did not develop infections. The study was accompanied by an extensive environmental investigation. Isolates were identified by standard bacteriological methods and by comparison of their 16S rRNA, HSP65, RPOB, SODA, and RECA gene sequences. Isolates were compared by random amplified polymorphic DNA analysis and by pulsed-field gel electrophoresis. Results. The risk factors for infection included surgery performed by 1 specific surgeon (odds ratio, 21.3; 95% confidence interval, 3.64–125.6). Identical strains of mycobacteria were isolated from the infected wounds of the patients; from the eyebrows, hair, face, nose, ears, and groin of this particular surgeon; and from this surgeon's outdoor whirlpool. The isolates exhibited a biochemical profile overlapping that of Mycobacterium wolinskyi, but their sequences of 16S rRNA and HSP65, RPOB, SODA, and RECA genes differed. We propose the name ဘMycobacterium jacuzzii’ for this new species. DNA fingerprints of cultured isolates from the surgical wounds, areas of the surgeon's body that grow hair, and the surgeon's whirlpool were identical. When the surgeon discontinued his use of the whirlpool and began cleaning the hairy areas of his body with a shampoo containing triclosan, the outbreak ended. Conclusions. This outbreak brings to light the possibility of the colonization of human skin and human-tohuman transmission of environmental mycobacteria during surgery that involves implant insertion. [ABSTRACT FROM AUTHOR]

Background. In March 2002, a patient in Tel Aviv, Israel, died of endocarditis caused by Phialernonium curvaturn. As part of his therapy for erectile dysfunction, the patient had been trained to self-inject a compound of vaso active drugs provided by an impotence clinic into his penile corpus cavernosous. Methods. We identified the used prefilled syringes as the source of his infection. Similar cases were investigated as a putative outbreak of P. curvaturn invasive disease among customers of this impotence clinic. B curvaturn isolates, cultured from samples obtained from the patients and from prefilled syringes, were compared by DNA sequencing of the nuclear ribosomal internal transcribed spacer. Results. We identified 2 additional customers at the impotence clinic who had P. curvaturn endocarditis. In addition, cultures of unused, prefilled syringes and bottles provided by the same clinic to 5 asymptomatic customers tested positive for pathogenic molds (B curvaturn in 4 cases and Paecilornyces lilacinus in 1). All P. curvaturn isolates were of a single genetic type that is known only from this outbreak but is closely related to 3 other P. curvaturn genotypes associated with pathogenicity in humans. Conclusions. P. curvaturn is an emerging pathogen that can be readily isolated from blood. We identified an outbreak of B curva turn endocarditis among men who had erectile dysfunction treated by intracavernous penile injections from contaminated prefilled syringes. [ABSTRACT FROM AUTHOR]

Objectives: to determine the incidence and the dynamics of asymptomatic bacteriuria in ambulatory' nursing home residents, and to characterise bacteria according to their phenotype and genotype. Design: an 18 months prospective longitudinal study. Subjects: 42 nursing home residents (31 female, 11 males) without indwelling catheters. Methods: urine was sampled every 3 months. Antibiograms, biotyping and ribotyping were performed. Results: the cumulative percent of infection for females and males was 75% and 27% respectively. Osteoporosis was associated with bacteriuria. Ribotypes of consecutive Escherichia coli isolates indicated that each patient harboured a different strain. Conclusions: asymptomatic bacteriuria in the elderly is a dynamic and transient phenomenon. Osteoporosis is common among this population. Ribotyping is a powerful tool in the elucidation of the epidemiology of this bacteriuria. [ABSTRACT FROM AUTHOR]

Rhinocerebral mucormycosis (zygomycosis) primarily affects diabetic or immunosuppressed patients and typically progresses rapidly, necessitating surgical excision and antifungal therapy with amphotericin B. Large doses of amphotericin B are required for cure, causing significant renal toxicity. Amphotericin B colloidal dispersion (ABCD; Amphocil, Sequus Pharmaceuticals, Menlo Park, CA) is a 1:1 complex of cholesteryl sulfate and amphotericin B, which results in significant reduction of toxicity, especially nephrotoxicity. We describe three patients with life-threatening rhinocerebral mucormycosis treated with ABCD. All patients had high serum creatinine levels due to prior treatment with amphotericin B; these levels reverted to normal during treatment with ABCD. Two patients with diabetes mellitus were cured after receiving a combination of surgery and ABCD therapy. The third patient, who had myelodysplastic syndrome, had an initial good response, with cure of the fungal infection; however, he eventually died of his primary illness. To the best of our knowledge, this is the first detailed clinical description of the treatment of mucormycosis with ABCD. [ABSTRACT FROM PUBLISHER]

During 10 months at our hospital, 413 patients underwent extracorporeal shock-wave lithotripsy (ESWL). The occurrence of complications was examined in the 126 (30.5%) of these patients who had sterile urine before the procedure and who had neither indwelling catheters nor stents. No patient received prophylactic antibiotics. After ESWL, nine patients (7%) developed bacteriuria, which was usually transient and required no therapy. Seven of the nine cases developed within 2 weeks of ESWL. In no case did other complications follow bacteriuria. Patients in whom bacteriuria was suspected because of fever all proved to have sterile urine. Our results indicate that patients whose urine is sterile before ESWL do not need antimicrobial prophylaxis. [ABSTRACT FROM PUBLISHER]

Background Rectovaginal colonization during pregnancy with Group B Streptococcus (GBS) is a risk factor for early neonatal sepsis, and may also cause chorioamnionitis and fetal death. In Israel, the reported colonization rate in pregnant women is low, and therefore routine screening of pregnant women for GBS colonization is not recommended. We noticed higher rates of early-onset disease (EOD) due to GBS in newborns of women hospitalized in Maayaney Hayeshua Medical Center, which serves an Orthodox Jewish Community (OJC) in Israel. Therefore, our aim was to investigate molecular patterns of GBS strains from mothers and neonates hospitalized in Maayaney Hayeshua. Methods During 2017, GBS isolates were collected from asymptomatic pregnant women (280/1,074), neonates with EOD (n = 7), and intrauterine fetal death remains (IUFD) (n = 7). We serotyped isolates from vaginal carriage (n = 203), EOD (n = 7), IUFD (n = 7) and EOD isolates obtained from the Ministry of Health (n = 11). Multilocus sequence typing (MLST) was performed on isolates from asymptomatic pregnant women (n = 14), EOD (n = 7) and IUFD (n = 7). Antibiotic susceptibilities were determined. Results GBS carriage rate was 26.1%. In asymptomatic pregnant women the dominant serotype was VI [84 women (41.3%)], followed by III, IV and V in 32 (15.7%), 23 (11.3%) and 21 (10.3%) women, respectively. The dominant serotype in EOD was III [15/18 (83.3%)] and in IUFD VI [5 (71.4%)]. ST-17 was expressed mainly by serotype III, and was associated with EOD. ST-1, expressed mainly by serotype VI, was associated with IUFD. See Tables 1 and 2 and Figure 1. Resistance to erythromycin and clindamycin was 19.3% and 18.2% while resistance in invasive isolates was 45.5% to both antibiotics. Conclusion GBS vaginal colonization rate in an OJC was significantly higher than the reported carriage rate of 21.6% reported in Israeli pregnant women. Serotypes VI was dominant in carriage and in cases of IUFD while EOD was exclusively associated with serotype III. Resistance rates to erythromycin clindamycin were high, particularly in invasive disease. These results advocate routine GBS screening in this population and caution against empirical treatment with macrolides or clindamycin in penicillin-allergic women. Disclosures All authors: No reported disclosures. [ABSTRACT FROM AUTHOR]

Streptococcus pyogenes bacteremia occurred in 104 patients over a 6-year period, during which time the annual incidence remained constant. The clinical and epidemiologic characteristics are described for 90 of these patients. Of the 90 patients, 90% had community-acquired infection, and 77% had an underlying illness predisposing them to infection. Skin infection was the cause of bacteremia in 615r% of the cases. Septic shock developed in 13 patients. The overall mortality rate was 15%. An increased likelihood of death was associated with septic shock and diabetes mellitus. [ABSTRACT FROM PUBLISHER]

Background The optimum diagnostic test method for Clostridioides difficile infection (CDI) remains controversial due to variation in accuracy in identifying true CDI. This post hoc analysis examined the impact of CDI diagnostic testing methodology on efficacy outcomes in phase 3 MODIFY I/II trials. Methods In MODIFY I/II (NCT01241552/NCT01513239), participants received bezlotoxumab (10 mg/kg) or placebo during anti-CDI treatment for primary/recurrent CDI (rCDI). Using MODIFY I/II pooled data, initial clinical cure (ICC) and rCDI were assessed in participants diagnosed at baseline using direct detection methods (enzyme immunoassay [EIA]/cell cytotoxicity assay [CCA]) or indirect methods to determine toxin-producing ability (toxin gene polymerase chain reaction [tgPCR]/toxigenic culture). Results Of 1554 participants who received bezlotoxumab or placebo in MODIFY I/II, 781 (50.3%) and 773 (49.7%) were diagnosed by tgPCR/toxigenic culture and toxin EIA/CCA, respectively. Participants diagnosed by toxin EIA/CCA were more likely to be inpatients, older, and have severe CDI. In bezlotoxumab recipients, ICC rates were slightly higher in the toxin EIA/CCA subgroup (81.7%) vs tgPCR/toxigenic culture (78.4%). Bezlotoxumab significantly reduced the rCDI rate vs placebo in both subgroups; however, the magnitude of reduction was substantially larger in participants diagnosed by toxin EIA/CCA (relative difference, –46.6%) vs tgPCR/toxigenic culture (–29.1%). In bezlotoxumab recipients, the rCDI rate was lower in the toxin EIA/CCA subgroup (17.6%) vs tgPCR/toxigenic culture (23.6%; absolute difference, –6.0%; 95% confidence interval, –12.4 to 0.3; relative difference, –25.4%). Conclusions Diagnostic tests that detect fecal C. difficile toxins are of fundamental importance to accurately diagnosing CDI, including in clinical trial design, ensuring that therapeutic efficacy is not underestimated. [ABSTRACT FROM AUTHOR]

We describe a case of a young adult who had chronic recurrent multifocal osteomyelitis that was diagnosed by exclusion and review the distinct clinical course of this disease. It is important to make a correct diagnosis so that unnecessary repeated invasive diagnostic procedures and prolonged use of antibiotics, steroids, or other chemotherapeutic agents can be avoided. [ABSTRACT FROM PUBLISHER]

Timing of treatment for invasive fungal disease (IFD) is critical for making appropriate clinical decisions. Historically, many centres have treated at-risk patients prior to disease detection to try to prevent fungal colonization or in response to antibiotic-resistant fever. Many studies have indicated that a diagnostic-driven approach, using radiological tests and biomarkers to guide treatment decisions, may be a more clinically relevant and cost-effective approach. The Invasive Fungal Infections Cooperative Group of the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) defined host clinical and mycological criteria for proven, probable and possible classes of IFD, to aid diagnosis. However, some patients at risk of IFD do not meet EORTC/MSG criteria and have been termed Groups B (patients with persistent unexplained febrile neutropenia) and C (patients with non-definitive signs of IFD) in a study by Maertens et al. (Haematologica 2012; 97: 325–7). Consequently, we considered the most appropriate triggers (clinical or radiological signs or biomarkers) for treatment of all patient groups, especially the unclassified B and C groups, based on our clinical experience. For Group C patients, additional diagnostic testing is recommended before a decision to treat, including repeat galactomannan tests, radiological scans and analysis of bronchoalveolar lavage fluid. Triggers for stopping antifungal treatment were considered to include resolution of all clinical signs and symptoms. For Group B patients, it was concluded that better definition of risk factors predisposing patients to fungal infection and the use of more sensitive diagnostic tests are required to aid treatment decisions and improve clinical outcomes. [ABSTRACT FROM PUBLISHER]