Membrane stripping in group B streptococcus carriers does not impede adequate intrapartum antibiotic prophylaxis: a retrospective study.

Objective: Membrane stripping in group B streptococcus (GBS) carriers poses an increased risk of inadequate antibiotic prophylaxis, potentially due to accelerated labor, thereby potentially impacting the management of GBS colonization during delivery. We compared the adequacy of intrapartum antibiotic prophylaxis between pregnant women colonized with GBS, who underwent membrane stripping and those who did not. The study aimed to determine whether the performance of membrane stripping, by potentially shortening labor duration, increases the risk of inadequate antibiotic prophylaxis dispensation. Study design: A retrospective cohort study was conducted on GBS screen-positive women with a full-term singleton pregnancy in cephalic presentation, who were eligible for vaginal delivery. The exposed group consisted of women who underwent membrane stripping, while the unexposed group consisted of women who did not undergo membrane stripping. The primary outcome was defined as inadequate duration of antibiotic prophylaxis during labor, wherein less than 4 h of beta-lactam antibiotics were administered prior to delivery. Neonatal outcome was compared between the groups. Results: This retrospective cohort study comprised 1,609 women, with 129 in the exposed group (stripping group) and 1,480 in the unexposed group (no stripping group). Adequate intrapartum antibiotic prophylaxis was received by 64.3% (83/129) of the exposed group, compared to 46.9% (694/1,480) of the unexposed group (p = 0.003). Membrane stripping was associated with increased odds of receiving adequate prophylaxis (OR 1.897, 95% CI 1.185-3.037, p = 0.008). After excluding women who presented to the labor ward in active labor and delivered in less than 4 h, both the exposed and unexposed groups had similarly high rates of adequate intrapartum antibiotic prophylaxis (87.5% vs. 85.8%, respectively). No significant difference was observed in adverse neonatal outcomes between the groups. Conclusion: The provision of membrane stripping did not impede adequate intrapartum antibiotic prophylaxis and was correlated with a higher rate of sufficient prophylaxis in comparison to non-swept patients. These observations suggest that membrane stripping can be considered a safe option for ensuring adequate antibiotic prophylaxis in women colonized with GBS.

Pseudomonas aeruginosa ventricular assist device infections: findings from ineffective phage therapies in five cases.

Left ventricular assist devices (LVAD) are increasingly used for management of heart failure; infection remains a frequent complication. Phage therapy has been successful in a variety of antibiotic refractory infections and is of interest in treating LVAD infections. We performed a retrospective review of four patients that underwent five separate courses of intravenous (IV) phage therapy with concomitant antibiotic for treatment of endovascular Pseudomonas aeruginosa LVAD infection. We assessed phage susceptibility, bacterial strain sequencing, serum neutralization, biofilm activity, and shelf-life of phage preparations. Five treatments of one to four wild-type virulent phage(s) were administered for 14-51 days after informed consent and regulatory approval. There was no successful outcome. Breakthrough bacteremia occurred in four of five treatments. Two patients died from the underlying infection. We noted a variable decline in phage susceptibility following three of five treatments, four of four tested developed serum neutralization, and prophage presence was confirmed in isolates of two tested patients. Two phage preparations showed an initial titer drop. Phage biofilm activity was confirmed in two. Phage susceptibility alone was not predictive of clinical efficacy in P. aeruginosa endovascular LVAD infection. IV phage was associated with serum neutralization in most cases though lack of clinical effect may be multifactorial including presence of multiple bacterial isolates with varying phage susceptibility, presence of prophages, decline in phage titers, and possible lack of biofilm activity. Breakthrough bacteremia occurred frequently (while the organism remained susceptible to administered phage) and is an important safety consideration.

Towards Standardization of Phage Susceptibility Testing: The Israeli Phage Therapy Center "Clinical Phage Microbiology"-A Pipeline Proposal.

Using phages as salvage therapy for nonhealing infections is gaining recognition as a viable solution for patients with such infections. The escalating issue of antibiotic resistance further emphasizes the significance of using phages in treating bacterial infections, encompassing compassionate-use scenarios and clinical trials. Given the high specificity of phages, selecting the suitable phage(s) targeting the causative bacteria becomes critical for achieving treatment success. However, in contrast to conventional antibiotics, where susceptibility-testing procedures were well established for phage therapy, there is a lack of standard frameworks for matching phages from a panel to target bacterial strains and assessing their interactions with antibiotics or other agents. This review discusses and compares published methods for clinical phage microbiology, also known as phage susceptibility testing, and proposes guidelines for establishing a standard pipeline based on our findings over the past 5 years of phage therapy at the Israeli Phage Therapy Center.

Phages and phage-borne enzymes as new antibacterial agents.

BACKGROUND: Persistent and resistant infections caused by bacteria are increasing in numbers and pose a treatment challenge to the medical community and public health. However, solutions with new agents that will enable effective treatment are lacking or delayed by complex development and authorizations. Bacteriophages are known as a possible solution for invasive infections for decades but were seldom used in the Western world. OBJECTIVES: To provide an overview of the current status and emerging use of bacteriophage therapy and phage-based products, as well as touch on the socioeconomic and regulatory issues surrounding their development. SOURCES: Peer-reviewed articles and authors' first-hand experience. CONTENT: Although phage therapy is making a comeback since its early discovery, there are many hurdles to its current use. The lack of appropriate standardized bacterial susceptibility testing; lack of a simple business model and authorization for the need of many phages to treat a single species infection; and the lack of knowledge on predictable outcome measures are just a few examples. In this review, we explore the possible routes for phage use, either based on local specialty centres or by industry; the current status of phage therapy, which is mainly based on single-centre or single-bacterial cohorts, and emerging clinical trials; local country-level frameworks for phage utilization even without full authorization; and the use of phage-derived products as alternatives to antibiotics. We also explore what may be the current indications based on the possible availability of phages. IMPLICATIONS: Although phages are emerging as a potential treatment for non-resolving and life-threatening infections, the models for their use and production still need to be defined by the medical community, regulatory bodies, and industry. Bacteriophages may have a great potential for infection treatment but many aspects still need to be defined before their routine use in the clinic.

Refractory Pseudomonas aeruginosa infections treated with phage PASA16: A compassionate use case series.

BACKGROUND: A growing number of compassionate phage therapy cases were reported in the last decade, with a limited number of clinical trials conducted and few unsuccessful clinical trials reported. There is only a little evidence on the role of phages in refractory infections. Our objective here was to present the largest compassionate-use single-organism/phage case series in 16 patients with non-resolving Pseudomonas aeruginosa infections. METHODS: We summarized clinical phage microbiology susceptibility data, administration protocol, clinical data, and outcomes of all cases treated with PASA16 phage. In all intravenous phage administrations, PASA16 phage was manufactured and provided pro bono by Adaptive Phage Therapeutics. PASA16 was administered intravenously, locally to infection site, or by topical use to 16 patients, with data available for 15 patients, mainly with osteoarticular and foreign-device-associated infections. FINDINGS: A few minor side effects were noted, including elevated liver function enzymes and a transient reduction in white blood cell count. Good clinical outcome was documented in 13 out of 15 patients (86.6%). Two clinical failures were reported. The minimum therapy duration was 8 days with a once- to twice-daily regimen. CONCLUSIONS: PASA16 with antibiotics was found to be relatively successful in patients for whom traditional treatment approaches have failed previously. Such pre-phase-1 cohorts can outline potential clinical protocols and facilitate the design of future trials. FUNDING: The study was funded in part by The Israeli Science Foundation IPMP (ISF_1349/20), Rosetrees Trust (A2232), United States-Israel Binational Science Foundation (2017123), and the Milgrom Family Support Program.

Compassionate Use of Bacteriophages for Failed Persistent Infections During the First 5 Years of the Israeli Phage Therapy Center.

The use of bacteriophages (phages) is reemerging as a potential treatment option for antibiotic-resistant or nonresolving bacterial infections. Phages are bacteria-specific viruses that may serve as a personalized therapeutic option with minimal collateral damage to the patient or the microbiome. In 2018 we established the Israeli Phage Therapy Center (IPTC) as a shared initiative of the Hadassah Medical Center and the Hebrew University of Jerusalem, aiming to conduct all of the steps required for phage-based solutions, from phage isolation and characterization to treatments, for nonresolving bacterial infections. So far, a total of 159 requests for phage therapy arrived to the IPTC; 145 of them were from Israel and the rest from other countries. This number of registered requests is growing annually. Multidrug-resistant bacteria accounted for 38% of all phage requests. Respiratory and bone infections were the most prevalent among clinical indications and accounted for 51% of the requests. To date, 20 phage therapy courses were given to 18 patients by the IPTC. In 77.7% (n = 14) of the cases, a favorable clinical outcome of infection remission or recovery was seen. Clearly, establishing an Israeli phage center has led to an increased demand for compassionate use of phages with favorable outcomes for many previously failed infections. As clinical trials are still lacking, publishing patient data from cohort studies is pertinent to establish clinical indications, protocols, and success and failure rates. Last, workflow processes and bottlenecks should be shared to enable faster availability and authorization of phages for clinical use.

Viral and Bacterial Respiratory Pathogens during the COVID-19 Pandemic in Israel.

BACKGROUND: previous worldwide reports indicated a substantial short-term reduction in various respiratory infections during the early phase of the SARS-CoV-2 pandemic. AIMS: exploring the long-term impact of the COVID-19 pandemic on respiratory pathogens. METHODS: retrospective analysis of bacterial and viral positivity rate in respiratory samples, between 1 January 2017-30 June 2022 in a tertiary hospital in Jerusalem, Israel. RESULTS: A decline in overall respiratory tests and positivity rate was observed in the first months of the pandemic. Respiratory isolations of Hemophilus influenza and Streptococcus pneumoniae were insignificantly affected and returned to their monthly average by November 2020, despite a parallel surge in COVID-19 activity, while Mycoplasma pneumoniae was almost eliminated from the respiratory pathogens scene. Each viral pathogen acted differently, with adenovirus affected only for few months. Human-metapneumovirus and respiratory-syncytial-virus had reduced activity for approximately a year, and influenza A virus resurged in November 2021 with the elimination of Influenza-B. CONCLUSIONS: After an immediate decline in non-SARS-CoV-2 respiratory infections, each pathogen has a different pattern during a 2-year follow-up. These patterns might be influenced by intrinsic factors of each pathogen and different risk reduction behaviors of the population. Since some of these measures will remain in the following years, we cannot predict the timing of return to pre-COVID-19 normalcy.

Are Healthcare Workers Infected with SARS-CoV-2 at Home or at Work? A Comparative Prevalence Study.

Prior to the widespread use of vaccinations, healthcare workers (HCWs) faced the double burden of caring for unprecedented numbers of critically ill COVID-19 patients while also facing the risk of becoming infected themselves either in healthcare facilities or at home. In order to assess whether SARS-CoV-2-positivity rates in HCWs reflected or differed from those in their residential areas, we compared the SARS-CoV-2-positivity rates during 2020 among HCWs in Hadassah Hebrew University Medical Centers (HHUMC), a tertiary medical center in Jerusalem, Israel, to those of the general population in Jerusalem, stratified by neighborhood. Additionally, we compared the demographic and professional parameters in every group. Four percent of the adult population (>18 years) in Jerusalem tested positive for SARS-CoV-2 during 2020 (24,529/605,426) compared to 7.1% of HHUMC HCWs (317/4470), rate ratio 1.75 (95% CI 1.57-1.95), with wide variability (range 0.38-25.0) among different neighborhoods. Of the 30 neighborhoods with more than 50 infected HCWs, 25 showed a higher positivity rate for HCWs compared to the general population. The higher risk of HCWs compared to residents representing the general population in most neighborhoods in Jerusalem may be explained by their behavior in and out of the hospital.

Phage Therapy in Israel, Past, Present, and Future.

The fascinating scientific history of phage therapy has been documented in numerous publications. In this study, however, we focus on an angle of the story that hitherto has remained relatively neglected, namely, phage therapy treatments, and the protagonists that conducted these in Mandatory-Palestine and subsequently the state of Israel, as part of a global trend. We complete the story by describing efforts in the new era of phage therapy in present-day Israel.

Mycoplasma pneumoniae detections before and during the COVID-19 pandemic: results of a global survey, 2017 to 2021.

BackgroundMycoplasma pneumoniae respiratory infections are transmitted by aerosol and droplets in close contact.AimWe investigated global M. pneumoniae incidence after implementation of non-pharmaceutical interventions (NPIs) against COVID-19 in March 2020.MethodsWe surveyed M. pneumoniae detections from laboratories and surveillance systems (national or regional) across the world from 1 April 2020 to 31 March 2021 and compared them with cases from corresponding months between 2017 and 2020. Macrolide-resistant M. pneumoniae (MRMp) data were collected from 1 April 2017 to 31 March 2021.ResultsThirty-seven sites from 21 countries in Europe, Asia, America and Oceania submitted valid datasets (631,104 tests). Among the 30,617 M. pneumoniae detections, 62.39% were based on direct test methods (predominantly PCR), 34.24% on a combination of PCR and serology (no distinction between methods) and 3.37% on serology alone (only IgM considered). In all countries, M. pneumoniae incidence by direct test methods declined significantly after implementation of NPIs with a mean of 1.69% (SD ± 3.30) compared with 8.61% (SD ± 10.62) in previous years (p < 0.01). Detection rates decreased with direct but not with indirect test methods (serology) (-93.51% vs + 18.08%; p < 0.01). Direct detections remained low worldwide throughout April 2020 to March 2021 despite widely differing lockdown or school closure periods. Seven sites (Europe, Asia and America) reported MRMp detections in one of 22 investigated cases in April 2020 to March 2021 and 176 of 762 (23.10%) in previous years (p = 0.04).ConclusionsThis comprehensive collection of M. pneumoniae detections worldwide shows correlation between COVID-19 NPIs and significantly reduced detection numbers.

Perceived support and preparedness for the next pandemic among Israeli social workers in hospital settings during the COVID-19 pandemic.

This study describes the conditions under which Israeli social workers in hospital settings operated s during the COVID-19 pandemic, and assesses their perceived support (informal and organizational support) and preparedness for the next pandemic. It further assesses correlates for perceived support and associations between perceived support and preparedness. The participants were 163 social workers from four hospitals who completed an on-line survey. The findings revealed that the level of exposure to COVID-19 and fear of contracting COVID-19 were unrelated to perceived informal and organizational support. Age and having children who are minors living at home moderated the relationship between fear of contracting COVID-19 and both types of perceived support. Each type of perceived support was significantly associated with preparedness beyond age, having minors at home, exposure to COVID-19, and fear of contracting COVID-19. Implications for research and practice are discussed.

Nurses' and Physicians' Responses to a New Active Antimicrobial Stewardship Program: A Two-Phase Study of Responses and Their Underlying Perceptions and Values.

BACKGROUND: Successful implementation of an antimicrobial stewardship program (ASP) depends on staff members' response to it. We introduced at the Hadassah Medical Center in Israel a significant change to our long-standing handshake ASP. As before, the new ASP involved a dialogue between the treating physician and the infectious disease physician over the appropriate antibiotic therapy. The main change was that the infectious disease physician's decision was now integrated into the patient's electronic medical record (EMR). Our purpose in this study was to uncover the concerns and expectations of physicians and nurses towards the new ASP, before and after its implementation, and link these with their basic perceptions of the ASP and their personal values. METHODS: We used open-ended questions and Likert-type scales to study staff members' personal values, basic perceptions of the new system, and attitudes towards it, both before (N = 143), and one year after (N = 103) the system's implementation. Relationships of the system's perceptions and personal values with attitudes toward the system were tested using correlations and multiple regression analyses. RESULTS: Prior to its implementation, physicians and nurses had multiple concerns about the new ASP's demandingness and inefficiency and its threat to physicians' autonomy and expertise. They also had positive expectations for benefits to the hospital, the patients and society. A year later, following the system's implementation, concerns dissipated, whereas the perceived benefits remained. Moreover, staff members' attitudes tended to be more positive among those who value conformity. CONCLUSION: Introducing new ASPs is a challenging process. Our findings suggest that hospital staff's initial concerns about the new ASP were primarily about its ease of use and demandingness. These concerns, which diminished over time, were linked with perceived satisfaction with the system. Conformity values had an indirect effect in predicting satisfaction with the system, mediated by perceptions of the system as straightforward.

Complete Genome Sequence of Pseudomonas aeruginosa Bacteriophage PASA16, Used in Multiple Phage Therapy Treatments Globally.

PASA16 is a Pseudomonas aeruginosa phage isolated from a soil sample and used to treat several patients suffering from persistent infections in various countries. PASA16's genome was sequenced, analyzed, and deposited in GenBank.

A Case Report of Mycoplasma hominis Subdural Empyema Following Decompressive Craniotomy, and a Review of Central Nervous System Mycoplasma hominis Infections.

Background: Mycoplasma hominis is a small cell-wall-free organism, part of the normal microbiota of the genitourinary tract. It is rarely involved in extragenital infections, mainly joint, surgical-site, and respiratory infections. Methods: We describe a case of M. hominis subdural empyema and lower limb surgical site infections, following decompressive craniotomy, after traumatic brain and extremities injury. In addition, a literature review of 34 cases M. hominis CNS infections was done. Results: Our case depicts a 25-years old patient who developed subdural empyema and surgical site infections in his cranium and fibula. Both sites were cultured, and small pinpoint colonies grew on blood agar. MALDI-TOF MS identified M. hominis. Simultaneously 16S-rDNA PCR from CSF detected M. hominis. Antimicrobial treatment was switched to doxycycline with improvement. Literature review revealed 21 adults and 13 pediatric cases of M. hominis CNS infection. Risk factors in adults were head trauma, neurosurgery, or post-partum period. Conclusions: Based upon the literature reviewed, we postulate that adult patients with head trauma or neurosurgical procedure, rarely are infected either through direct contamination during the trauma, or by undergoing urgent, urinary catheterization, and may experience distant infection due to translocation of M. hominis into the bloodstream. In such cases diagnosis is delayed due to difficulties in growing and identifying the bacteria. Empiric antimicrobials are usually not effective against mycoplasmas. These factors contributed to the mortality in adult cases (15%). Our rare case highlights the necessity of combining classical microbiology routines with advanced molecular techniques to establish a diagnosis in complicated cases.

The effect of a third BNT162b2 vaccine on breakthrough infections in health care workers: a cohort analysis.

OBJECTIVES: In August 2021, 6 months after mass vaccination of the Israeli population with the two-dose BNT162b2 mRNA vaccine, a surge of coronavirus disease 2019 infections, mostly from the delta variant, appeared also among the vaccinated. In response, the Israeli Ministry of Health initiated a booster (third dose) vaccination program. We assessed the protective effect of the third dose among health care workers (HCWs). METHODS: Infections with severe acute respiratory syndrome coronavirus 2 are monitored systematically among HCWs at the Hadassah tertiary care medical centre in Jerusalem, Israel. In this cohort, we included breakthrough infections, defined as those occurring >180 days since the second vaccine dose. The follow-up period lasted 120 days. We compared infection rates between HCWs who received the booster dose and those who received only the two-dose regimen. RESULTS: The rate of breakthrough infections among HCWs who received only the two-dose regimen was 21.4% (85 of 398). The rate in the boosted group was 0.7% (35/4973; relative risk 30, 95% CI 20-50). Those results were seen in all age groups. DISCUSSION: The significantly lower rate of breakthrough infections in boosted HCWs indicates substantial protection by a third vaccine dose.

Erratum: Corridengum to: Self-Rated Smell Ability Enables Highly Specific Predictors of COVID-19 Status: A Case-Control Study in Israel.

[This corrects the article DOI: 10.1093/ofid/ofaa589.].

Expanding clinical phage microbiology: simulating phage inhalation for respiratory tract infections.

Phage therapy is a promising antibacterial strategy for resistant respiratory tract infections. Phage inhalation may serve this goal; however, it requires a careful assessment of their delivery by this approach. Here we present an in vitro model to evaluate phage inhalation. Eight phages, most of which target pathogens common in cystic fibrosis, were aerosolised by jet nebuliser and administered to a real-scale computed tomography-derived 3D airways model with a breathing simulator. Viable phage loads reaching the output of the nebuliser and the tracheal level of the model were determined and compared to the loaded amount. Phage inhalation resulted in a diverse range of titre reduction, primarily associated with the nebulisation process. No correlation was found between phage delivery to the phage physical or genomic dimensions. These findings highlight the need for tailored simulations of phage delivery, ideally by a patient-specific model in addition to proper phage matching, to increase the potential of phage therapy success.