Short-term outcome of pregnant women vaccinated with BNT162b2 mRNA COVID-19 vaccine.

OBJECTIVES: To determine the immunogenicity and reactogenicity of the Pfizer/BioNTech BNT162b2 mRNA coronavirus disease 2019 (COVID-19) vaccine among pregnant women compared with non-pregnant women, and to evaluate obstetric outcome following vaccination. METHODS: This was an observational case-control study of pregnant women who were vaccinated with a two-dose regimen of the BNT162b2 vaccine during gestation between January and February 2021 (study group) and age-matched non-pregnant women who received the vaccine during the same time period (control group). Participants received a digital questionnaire 1-4 weeks after the second dose and were asked to provide information regarding demographics, medication, medical history, history of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, timing of COVID-19 vaccine doses and side effects after each vaccine dose. A second digital questionnaire, regarding current pregnancy and delivery outcomes, was sent to patients in the study group after the calculated due date. All recruited women were offered a serology blood test for SARS-CoV-2 immunoglobulin G (IgG) following the second vaccination dose and SARS-CoV-2 IgG levels were compared between the two groups. RESULTS: Of 539 pregnant women who were recruited after completion of the two-dose regimen of the vaccine, 390 returned the digital questionnaire and were included in the study group and compared to 260 age-matched non-pregnant vaccinated women. The rates of rash, fever and severe fatigue following vaccination among pregnant women were comparable to those in non-pregnant women. Myalgia, arthralgia and headache were significantly less common among pregnant women after each dose, local pain or swelling and axillary lymphadenopathy were significantly less common among pregnant women after the first and second doses, respectively, while paresthesia was significantly more common among the pregnant population after the second dose. Among pregnant women, there were no significant differences in the rates of side effects according to whether the vaccine was administered during the first, second or third trimester of pregnancy, except for local pain/swelling, which was significantly less common after the first dose when administered during the third trimester, and uterine contractions, which were significantly more common after the second dose when administered during the third trimester. The rates of obstetric complications, including uterine contractions (1.3% after the first dose and 6.4% after the second dose), vaginal bleeding (0.3% after the first dose and 1.5% after the second dose) and prelabor rupture of membranes (0% after the first dose and 0.8% after the second dose), were very low following vaccination. All serum samples in both groups were positive for SARS-CoV-2 IgG. However, pregnant women had significantly lower serum SARS-CoV-2 IgG levels compared to non-pregnant women (signal-to-cut-off ratio, 27.03 vs 34.35, respectively; P < 0.001). Among the 57 pregnant women who delivered during the study period and who completed the second questionnaire, median gestational age at delivery was 39.5 (interquartile range, 38.7-40.0) weeks, with no cases of preterm birth < 37 weeks, no cases of fetal or neonatal death and two (3.5%) cases of admission to the neonatal intensive care unit for respiratory support. CONCLUSIONS: The adverse-effect profile and short-term obstetric and neonatal outcomes among pregnant women who were vaccinated with the BNT162b2 vaccine at any stage of pregnancy do not indicate any safety concerns. The vaccine is effective in generating a humoral immune response in pregnant women, although SARS-CoV-2 IgG levels were lower than those observed in non-pregnant vaccinated women. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Environmental shedding of toxigenic Clostridioides difficile by asymptomatic carriers: A prospective observational study.

OBJECTIVES: The aim was to compare the burden of environmental shedding of toxigenic Clostridioides difficile among asymptomatic carriers, C. difficile-infected (CDI) patients and non-carriers in an inpatient non-epidemic setting. METHODS: C. difficile carriage was determined by positive toxin-B PCR from rectal swabs of asymptomatic patients. Active CDI was defined as a positive two-step enzyme immunoassay/polymerase chain reaction (EIA/PCR) test in patients with more than three unformed stools/24 hr. C. difficile environmental contamination was assessed by obtaining specimens from ten sites in the patients' rooms. Toxigenic strains were identified by PCR. We created a contamination scale to define the overall level of room contamination that ranged from clean to heavy contamination. RESULTS: One hundred and seventeen rooms were screened: 70 rooms inhabited by C. difficile carriers, 30 rooms by active CDI patients and 17 rooms by non C. difficile -carriers (control). In the carrier rooms 29 (41%) had more than residual contamination, from which 17 (24%) were heavily contaminated. In the CDI rooms 12 (40%) had more than residual contamination from which three (10%) were heavily contaminated, while in the control rooms, one room (6%) had more than residual contamination and none were heavily contaminated. In a multivariate analysis, the contamination score of rooms inhabited by carriers did not differ from rooms of CDI patients, yet both were significantly more contaminated than those of non-carriers odd ratio 12.23 and 11.16 (95% confidence interval 1.5-99.96 p 0.0195, and 1.19-104.49 p 0.035), respectively. DISCUSSION: Here we show that the rooms of C. difficile carriers are as contaminated as those of patients with active CDI and significantly more than those of non-carriers.

Universal screening for Clostridioides difficile in a tertiary hospital: risk factors for carriage and clinical disease.

OBJECTIVES: The role of asymptomatic carriers in Clostridioides difficile infection (CDI) epidemiology is not fully understood. Our aim was to evaluate CD carriage prevalence on admission, associated risk factors, and the risk of developing CDI. METHODS: A 10-week surveillance program for CD carriage of all medical patients admitted to the Sheba Medical Centre was implemented, utilizing an admission rectal swab PCR. Healthcare facility-onset CDI (HO-CDI) was recorded and divided into HO-CDI diagnosed in CD carriers and non-carriers. RESULTS: A total of 4601 admissions were recorded in 3803 patients; 2368 patients had technically analysable rectal swabs, of whom 81 (3.4%) were CD carriers. A multivariate logistic regression model showed that previous hospitalization, old age (>85 years) and low Norton scores were significant independent predictors of CD carriage. Carriers were more likely to receive antimicrobial therapy during hospitalization than non-carriers were. The incidence of HO-CDI in non-carriers was 4.6 cases per 10 000 patient-days; the incidence of HO-CDI in carriers was 76.7 cases per 10 000 patient-days (RR 16.6, 95% CI 4.0-69.1, p .002). CONCLUSIONS: In a prospective study, the rate of CD carriage on admission in medical patients was 3.4%. CD carriers were older, frailer, and more likely to have been hospitalized recently. HO-CDI incidence was significantly higher among CD carriers than among non-carriers, with at least a third of CDI in screened patients developing in carriers. Targeted screening of high-risk groups for CD carriage should be further considered.

Clinical outcomes and treatment approach for community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections in Israel.

Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) infections are increasingly documented worldwide. We recently identified two major CA-MRSA clones in Israel: USA300 and t991. Here, we assessed clinical outcomes by CA-MRSA clones and the physicians' treatment approach to CA-MRSA infections. All community-onset, clinical MRSA isolates detected during 2011-2013 by Maccabi Healthcare Services were collected and characterized phenotypically and genotypically; data were collected retrospectively from electronic medical records. Of 309 patients with MRSA infections, 64 were identified as CA-MRSA (21 %). Of the CA-MRSA infections, 72 % had skin and soft tissue infections (SSTIs), 38 % were Panton-Valentine leukocidin (PVL)+, the major clone being USA300 (n = 13, 54 %). Of PVL- isolates (n = 40, 62 %), t991 was the major clone. Age was the only predictor for PVL+ CA-MRSA infection (p < 0.001). Patients with PVL+ CA-MRSA had higher incidence of SSTI recurrences (1.061 vs. 0.647 events per patient/per year, p < 0.0001) and were more likely to have the SSTI drained (64 % vs. 21 %, p = 0.003) when compared to PVL- CA-MRSA. USA300 was more common among adults, while t991 was more common among children (p = 0.002). The physician's referral to culture results and susceptibility were the only predictors of appropriate antibiotic therapy (p < 0.001). However, only a minority of physicians referred to culture results, regardless of subspecialties. PVL+ CA-MRSA isolates caused significantly more recurrences of SSTIs and increased the need for drainage compared with PVL- isolates. Physicians' awareness of CA-MRSA as a cause of SSTIs in the community was suboptimal. Culturing of pus-producing SSTIs is crucial for providing adequate antimicrobials and elucidating MRSA epidemiology.

Molecular epidemiology of community-onset methicillin-resistant Staphylococcus aureus infections in Israel.

Data on community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) in Israel are scarce. The objective of this study was to characterize the major CA-MRSA clones in Israel. All clinical MRSA isolates detected in the community during a period of 2.5 years (2011-2013) from individuals insured by a major health maintenance organization in Israel were collected, with additional data from medical records. Antibiotic susceptibility patterns and staphylococcal chromosomal cassette mec (SCCmec) typing were determined. SCCmec IV and V isolates were further typed by pulsed-field gel electrophoresis (PFGE), spa typing, and detection of a panel of toxin genes. MRSA were detected in 280 patients, mostly from skin infections. Patients with SCCmec IV (n = 120, 43 %) were younger (p < 0.0001) and reported less contact with healthcare facilities. Almost all isolates were trimethoprim-sulfamethoxazole susceptible (98 %). spa-CC032, a typical nosocomial MRSA clone, accounted for 28 % of SCCmec IV. The two major CA-MRSA clones were t008 USA300 (13 %) and t991 (10 %); t991 was isolated mainly from children (75 %), was Panton-Valentine leukocidin (PVL) negative but eta-positive, and was typically susceptible to most antibiotic groups. PVL-positive strains (n = 31) included mainly USA300 (52 %) and t019 (13 %). While multiple genetic lineages were evident among community-onset MRSA in Israel, approximately 20 % are typical CA-MRSA clones, mainly USA300 and a local clone, t991.

Prevalence and genetic relatedness of community-acquired methicillin-resistant Staphylococcus aureus in Israel.

The aims of the study presented here were to determine the prevalence of Staphylococcus aureus carriage and, specifically, community-acquired methicillin-resistant S. aureus (CA-MRSA) carriage in children and their parents in Israel and to determine the genetic relatedness of these isolates. S. aureus was isolated from 580 of 3,373 (17.2%) individuals screened. The predominant type identified by pulsed-field gel electrophoresis was strain ST45-MSSA (25%). Five MRSA isolates were detected, and two of these were classified as CA-MRSA, based on the following criteria: no previous contact with a healthcare facility, absence of a multidrug-resistant (MDR) phenotype, and presence of SCCmec type IV. Isolates were negative for pvl and were classified as ST-45-MRSA. Although CA-MRSA is still rare in Israel, the genetic relatedness of the strains found in this study to a successful MSSA clone warrants close follow up.

Characteristics of candidaemia with Candida-albicans compared with non-albicans Candida species and predictors of mortality.

Candidaemia due to non-albicans Candida species is increasing in frequency. We describe 272 episodes of candidaemia, define parameters associated with Candida albicans and other Candida species, and analyse predictors associated with mortality. Patients with C. albicans (55%) had the highest fatality rate and frequently received immunosuppressive therapy, while patients with Candida parapsilosis (16%) had the lowest fatality and complication rates. Candida tropicalis (16%) was associated with youth, severe neutropenia, acute leukaemia or bone marrow transplantation, Candida glabrata (10%) was associated with old age and chronic disease, and Candida krusei (2%) was associated with prior fluconazole therapy. The overall fatality rate was 36%, and predictors of death by multi-variate analysis were shock, impaired performance status, low serum albumin and congestive heart failure. Isolation of non-albicans Candida species, prior surgery and catheter removal were protective factors. When shock was excluded from analysis, antifungal therapy was shown to be protective. Unlike previous concerns, infection with Candida species other than C. albicans has not been shown to result in an increased fatality rate.

Short report: a consideration of primaquine dose adjustment for radical cure of Plasmodium vivax malaria.

Relapse of Plasmodium vivax malaria following standard primaquine dosing has been reported from many areas, and more recently from sub-Saharan Africa. In this report we describe eight episodes (in five patients) of treatment failure in non-immune Israeli travelers returning from Ethiopia. Retrospective calculation of the primaquine dose per kilogram of body weight for 23 treatment courses showed a lower total dose per kilogram in heavier patients. The mean calculated dose (95% CI) in the eight failed treatments was 2.5 +/- 0.3 mg/kg compared with 4.4 +/- 0.5 mg/kg in the 15 successful treatment courses. Weight-adjusted dosing regimens may prevent inadvertent subtherapeutic drug failure, and thus apparent primaquine failure. In these cases, no relapses were observed in those who received > 3.5 mg/kg. Consideration should be given to adjusting the dose of primaquine according to body weight. For those infected by strains from Ethiopia a dose > 3.5 mg/kg is preferable.

Primaquine as prophylaxis for malaria for nonimmune travelers: A comparison with mefloquine and doxycycline.

Malaria prophylaxis for travelers is a controversial issue. The commonly used regimens are associated with side effects, low compliance, or low efficacy, which have raised concern regarding their use. In addition, they are inefficient against the tissue stage of the parasite and thus do not prevent relapses of Plasmodium vivax infection. Primaquine is aimed at the pre-erythrocytic stage and thus may be a potential causal-prophylactic treatment that can abolish the need for long postexposure therapy. During 1995-1998, we followed retrospectively travelers who joined rafting trips to an area in Ethiopia where both P. vivax and Plasmodium falciparum are hyperendemic. Of the 106 travelers who received primaquine, 5.7% developed malaria; of the 19 doxycycline recipients, 53% developed malaria; and of the 25 mefloquine recipients, 52% developed P. vivax malaria (>/=3 months after return from the area of endemicity). Primaquine was well tolerated, and only 1 withdrawal from therapy (due to gastrointestinal symptoms) was reported. Primaquine was shown to be a safe and effective prophylactic drug against both P. falciparum malaria and P. vivax malaria in travelers.