The Prognostic Value of Serology in Persistent Q Fever Infection.

Background: Q fever has significant consequences for patients with persistent localized infection. A combination of doxycycline with hydroxychloroquine, for at least 18-24 months, is the first-line therapy. The use of serology as a prognostic marker during therapy is controversial. Methods: A retrospective, observational cohort study in two outpatient clinics in northern Israel. All adults with persistent Q fever (2015-2021) were included in the study. Clinical failure was defined as relapse or death related to Q fever after end of treatment (EOT). Serological cure was defined as phase 1 IgG ≤800 or a four-fold decrease at EOT. Results: Twenty-two patients were included in the study, with a median follow up of 40 months (IQR = 28.5-63.5), and median treatment duration of 28.5 months (IQR = 21.8-50.5). Clinical cure occurred in 18 patients (82%), serological cure in 10 (45%). Phase 1 IgG at presentation was significantly higher in the clinical failure group (median 9600 vs. 3200 in the clinical cure group, p = 0.019), and at 6-12 months after EOT (median 6400 vs. 800 respectively, p = 0.03). Phase 1 IgG levels at 1 year and EOT were similar in both groups. Positive phase 2 IgM after one year of therapy correlated with clinical failure (p = 0.038), but not at EOT or after EOT. Conclusion: Phase 1 IgG levels at presentation, phase 2 IgM at 1 year, and Phase 1 IgG 6-12 months after EOT were associated with clinical failure in patients with persistent Q fever.

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.

High rate of bacterial respiratory tract co-infections upon admission amongst moderate to severe COVID-19 patients.

BACKGROUND: The role of bacterial and viral co-infection in the current COVID-19 pandemic remains elusive. The aim of this study was to describe the rates and features of co-infection on admission of COVID-19 patients, based on molecular and routine laboratory methods. METHODS: A retrospective study of COVID-19 and non-COVID-19 patients undergoing Biofire®, FilmArray® Pneumonia Panel, bioMérieux, and routine cultures during the first 3 days from admission, between June 2019 and March 2021. RESULTS: FilmArray tests were performed in 115 COVID-19 and in 61 non-COVID-19 patients. Most (>99%) COVID-19 patients had moderate-critical illness, 37% required mechanical ventilation. Sputa and endotracheal aspirates were the main samples analyzed. Positive FilmArray tests were found in 60% (70/116) of the tests amongst COVID-19 patients and 62.5% (40/64) amongst non-COVID-19 patients. All 70 cases were positive for bacterial targets, while one concomitant virus (Rhinovirus/Enterovirus) and one Legionella spp. were detected. The most common bacterial targets were Haemophilus influenzae (36%), Staphylococcus aureus (23%), Streptococcus pneumoniae (10%) and Enterobacter cloacae (10%). Correlation between FilmArray and cultures was found in 81% and 44% of negative and positive FA tests, respectively. Positive FilmArray results typically (81%) triggered the administration of antibiotic therapy and negative results resulted in antimicrobials to be withheld in 56% of cases and stopped in 8%. Bacterial cultures of COVID-19 patients were positive in 30/88 (34%) of cases. CONCLUSIONS: Bacterial co-infection is common amongst moderate-critical COVID-19 patients on admission while viral and atypical bacteria were exceedingly rare. Positive FilmArray results could trigger potentially unnecessary antibiotic treatment.KEY POINTWe found high rates of on-admission bacterial co-infection amongst hospitalized moderate to severe COVID-19 patients. Molecular tests (Biofire, FilmArray) and routine microbiological tests revealed 60% and 34% bacterial co-infection, respectively, while viral and fungal co-infections were rare.

High Rates of Bacterial Pulmonary Co-Infections and Superinfections Identified by Multiplex PCR among Critically Ill COVID-19 Patients.

BACKGROUND: The role of bacterial co-infection and superinfection among critically ill COVID-19 patients remains unclear. The aim of this study was to assess the rates and characteristics of pulmonary infections, and associated outcomes of ventilated patients in our facility. METHODS: This was a retrospective study of ventilated COVID-19 patients between March 2020 and March 2021 that underwent BioFire®, FilmArray® Pneumonia Panel, testing. Community-acquired pneumonia (CAP) was defined when identified during the first 72 h of hospitalization, and ventilator-associated pneumonia (VAP) when later. RESULTS: 148 FilmArray tests were obtained from 93 patients. With FilmArray, 17% of patients had CAP (16/93) and 68% had VAP (64/93). Patients with VAP were older than those with CAP or those with no infection (68.5 vs. 57-59 years), had longer length of stay and higher mortality (51% vs. 10%). The most commonly identified FilmArray target organisms were H. influenzae, S. pneumoniae, M. catarrhalis and E. cloacae for CAP and P. aeruginosa and S. aureus for VAP. FilmArray tests had high negative predictive values (99.6%) and lower positive predictive values (~60%). CONCLUSIONS: We found high rates of both CAP and VAP among the critically ill, caused by the typical and expected organisms for both conditions. VAP diagnosis was associated with poor patient outcomes.

Epidemiological, clinical and laboratory features of acute Q fever in a cohort of hospitalized patients in a regional hospital, Israel, 2012-2018.

INTRODUCTION: Acute Q fever is endemic in Israel, yet the clinical and laboratory picture is poorly defined. METHODS: A retrospective study reviewing the medical records of acute Q fever patients, conducted in a single hospital in the Sharon district, Israel. Serum samples from suspected cases were preliminary tested by a qualitative enzyme immunoassay (EIA). Confirmatory testing at the reference laboratory used an indirect immunofluorescence assay (IFA). Positive cases were defined as fever with at least one other symptom and accepted laboratory criteria such as a single-phase II immunoglobulin G (IgG) antibody titer ≥1:200. Cases not fulfilling these criteria and in which acute Q fever was excluded, served as a control group. RESULTS: Between January 2012 and May 2018, 484 patients tested positive. After confirmatory testing, 65 (13.4%) were positive for acute Q fever (with requisite clinical picture), 171 (35.3%) were definitely not infected, the remaining 248 were excluded because of past/chronic/undetermined infection. The average age was 58 years and 66% were males. Most resided in urban areas with rare animal exposure. Pneumonia was seen in 57% of cases and a combination with headache/hepatitis was highly suggestive of acute Q fever diagnosis. Syncope/presyncope, fall and arthritis were more common in acute Q fever cases. Laboratory indexes were similar to the control group, except for erythrocyte sedimentation rate (ESR) which was more common and higher in the study group. CONCLUSION: Acute Q fever in the Sharon district could be better diagnosed by using a syndromic approach in combination with improved rapid diagnostic testing.

Spotted Fever Group Rickettsioses in Israel, 2010-2019.

In a multicenter, nationwide, retrospective study of patients hospitalized with spotted fever group rickettsiosis in Israel during 2010-2019, we identified 42 cases, of which 36 were autochthonous. The most prevalent species was the Rickettsia conorii Israeli tick typhus strain (n = 33, 79%); infection with this species necessitated intensive care for 52% of patients and was associated with a 30% fatality rate. A history of tick bite was rare, found for only 5% of patients; eschar was found in 12%; and leukocytosis was more common than leukopenia. Most (72%) patients resided along the Mediterranean shoreline. For 3 patients, a new Rickettsia variant was identified and had been acquired in eastern, mountainous parts of Israel. One patient had prolonged fever before admission and clinical signs resembling tickborne lymphadenopathy. Our findings suggest that a broad range of Rickettsia species cause spotted fever group rickettsiosis in Israel.

Humoral Response to the Pfizer BNT162b2 Vaccine in Patients Undergoing Maintenance Hemodialysis.

BACKGROUND AND OBJECTIVES: Coronavirus disease 2019 (COVID-19) is associated with higher morbidity and mortality in patients on maintenance hemodialysis. Patients on dialysis tend to have a reduced immune response to infection or vaccination. We aimed to assess, for the first time to the best of our knowledge, the humoral response following vaccination with the BNT162b2 vaccine in patients on maintenance hemodialysis and the factors associated with it. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The study included 56 patients on maintenance hemodialysis (dialysis group) and a control group composed of 95 health care workers. All participants had received two doses of the BNT162b2 (Pfizer-BioNTech) vaccine. The serology testing was done using Quant II IgG anti-Spike severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) assay by Abbott a median of 30 days after receipt of the second dose of the vaccine. RESULTS: All subjects in the control group developed an antibody response compared with 96% (54 of 56) positive responders in the dialysis group. The IgG levels in the dialysis group (median, 2900; interquartile range, 1128-5651) were significantly lower than in the control group (median, 7401; interquartile range, 3687-15,471). A Mann-Whitney U test indicated that this difference was statistically significant (U=1238; P<0.001). There was a significant inverse correlation of age and IgG levels in both groups. The odds of being in the lower quartile were significantly higher for older individuals (odds ratio, 1.11 per year of age; 95% confidence interval, 1.08 to 1.20; P=0.004) and for the dialysis group compared with the control group (odds ratio, 2.7; 95% confidence interval, 1.13 to 7.51; P=0.05). Within the dialysis group, older age and lower lymphocyte count were associated with antibody response in the lower quartile (odds ratio, 1.22 per 1-year older; 95% confidence interval, 1.13 to 1.68; P=0.03 and odds ratio, 0.83 per 10-e3/µl-higher lymphocyte count; 95% confidence interval, 0.58 to 0.97; P=0.05). CONCLUSIONS: Although most patients on maintenance hemodialysis developed a substantial humoral response following the BNT162b2 vaccine, it was significantly lower than controls. Age was an important factor in the humoral response, regardless of chronic medical conditions.

Molecular Epidemiology of Methicillin-Resistant Staphylococcus aureus Clinical Isolates during 7.5 Years in One Regional Hospital in Israel.

Background: The clonal repertoire of community-associated Methicillin-resistant Staphylococcus aureus (CA-MRSA) strains appear to differ between hospitals and geographic locations. We aimed to study the molecular epidemiology of MRSA infections in our regional hospital in Israel. Methods: A retrospective analysis of MRSA isolates from hospitalized patients, which underwent spa typing between 2012 and 2019. Mainly, MRSA-bloodstream isolates were typed. Isolates were grouped into healthcare-associated (HcA) or community-associated (CA). HcA were further divided into hospital-related or long-term care facility- (LTCF-) related. Several representatives underwent SCCmec typing. Results: We analyzed 166 clinical MRSA isolates: 115 (70%) bloodstream, 42 (25%) wounds/abscesses, and 9 (5%) screening isolates. 145 (87%) were HcA, and 21 (13%) were CA. Common (72%) spa types were t002, t032, t008, t001, and t065. Eighty (55%) isolates were attributed to LTCFs and 65 isolates to our hospital, both showing similar spa types distribution. The most prevalent spa type among patients with HcA infection was t002 (50 isolates, 32%), followed by t032, t065, t578, t008, and t001. Most (88/115, 77%) bloodstream infections (BSIs) were HcA, typically occurring in the same facility in which the infection was acquired. In 27 cases (23%), the BSI developed in the community setting, and in half of these cases, a previous healthcare system exposure was evident. Conclusions: The MRSA clonal population in this longitudinal study was stable and consisted mainly of molecular lineages widespread in Europe. SCCmec-IV strains play a major role in causing MRSA infections in the healthcare settings, especially in LTCFs. Community-acquired MRSA BSIs without any previous healthcare exposure are still relatively rare.

Chronic schistosomiasis in African immigrants in Israel: Lessons for the non-endemic setting.

To study the clinical presentation of Chronic Schistosomiasis (CS) in immigrants from East Africa to Israel and the tests that were useful in confirming the diagnosis.A retrospective study of all medical notes pertaining to hospitalized patients who were immigrants from East Africa with a pathological or microscopic confirmation of CS. Literature review was also conducted focusing on diagnosis of schistosomiasis among immigrants from endemic countries.We identified 32 suspected and 11 confirmed cases of CS. Most of the patients (82%) presented with gastrointestinal symptoms. Sensitivity of stool smear, serology and tissue diagnosis (by histopathology or microscopy) were 14%, 100%, 89%, respectively. Patients have undergone extensive diagnostic evaluation with long hospitalization stays (median 10 days, range 4 to 33 days).CS has multiple presentations and is seen in Israel among refugees from Eritrea and Sudan. Most of the manifestations are gastrointestinal, suggestive of infection with Schistosoma mansoni (S. mansoni). Standard diagnostic techniques used in endemic countries, such as microscopy for ova and parasites were unhelpful, necessitating more advanced procedures like colonoscopic or liver biopsy. We propose a diagnostic algorithm for CS in this patient population in order to make an accurate diagnosis and avoid unnecessary invasive procedures.

Screening asymptomatic households for Streptococcus pyogenes pharyngeal carriage as a part of in-hospital investigation of puerperal sepsis.

BACKGROUND: Invasive group A streptococcal (iGAS) infection in the peripartum setting is a rare but devastating disease occasionally occurring as a health care-associated infection (HAI). Current guidelines suggest enhanced surveillance and streptococcal isolate storage after a single case of iGAS, as well as a full epidemiological investigation that includes screening health care workers (HCWs) from several sites after 2 cases. Current guidelines do not recommend routine screening of household members of a patient with iGAS. METHODS: We conducted studies of 3 patients with iGAS puerperal sepsis and related epidemiologic and molecular investigations. RESULTS: Identical GAS emm gene types were found in pharyngeal cultures of 3 asymptomatic spouses of patients with iGAS puerperal sepsis. HCWs screened negative for GAS, and emm typing indicated that other iGAS cases from this hospital were sporadic and not related to the puerperal cases. CONCLUSIONS: The concurrent presence of the same emm type in a household member practically excludes the option of an inadvertent HAI or facility outbreak. Hence, we suggest that screening close family members for asymptomatic GAS carriage should be performed early as a part of infection prevention measures, as doing so would have significant utility in saving time and resources related to a full epidemiological inquiry.

Characteristics of hospitalized adult patients with laboratory documented Influenza A, B and Respiratory Syncytial Virus - A single center retrospective observational study.

INTRODUCTION: The epidemiology, clinical features and outcomes of hospitalized adult patients with Influenza A (FluA), Influenza B (FluB) and Respiratory Syncytial Virus (RSV) have not been thoroughly compared. The aim of this study was to describe the differences between these viruses during 3 winter seasons. METHODS: A retrospective observational study was conducted consisting of all the polymerase chain reaction (PCR)-based diagnoses of FluA, FluB and RSV among adults during 2015-2018, in one regional hospital. Epidemiology, clinical symptoms and outcome-related data were comparatively analyzed. RESULTS: Between November 2015 and April 2018, 759 patients were diagnosed with FluA, FluB or RSV. Study cohort included 539 adult patients (306 FluA, 148 FluB and 85 RSV). FluB was predominant during the winter of 2017-18. RSV caused 15.7% of hospitalizations with diagnosed viral infection and in comparison to influenza, had distinct epidemiological, clinical features and outcomes, including older age (74.2 vs 66.2, p = 0.001) and higher rates of co-morbidities; complications including bacterial pneumonia (31 vs 18%, p = 0.02), mechanical ventilation (20 vs 7%, p = 0.001), and viral-related death (13 vs 6.6%, p = 0.04). FluA and FluB had similar epidemiology, clinical symptoms and outcomes, but vaccinated patients were less prone to be hospitalized with FluB as compared with FluA (3 vs 14%, p = 0.001). Paroxysmal atrial fibrillation and falls were common (8.7 and 8.5% respectively). CONCLUSIONS: FluA and FluB had similar epidemiological, clinical features and contributed equally to hospitalization burden and complications. RSV had a major impact on hospitalizations, occurring among the more elderly and sick populations and causing significantly worse outcomes, when compared to influenza patients. Vaccination appeared as a protective factor against hospitalizations with FluB as compared with FluA.

Disseminated "Haemophilus quentini" infection in a patient with multiple myeloma - a case report and review of the literature.

We describe a case report of a 56-year-old male with undiagnosed multiple myeloma who had severe sepsis associated with pneumonia, meningitis, polyarthritis, and osteomyelitis related to invasive "Haemophilus quentini" infection. The genus was misidentified as H. influenzae by the common bacterial identification systems including newly introduced syndromic PCR-based methods. We review the epidemiological, clinical, and laboratory aspects of this rare, cryptic species of Haemophilus.

Streptococcus pyogenes bacteremia and toxic shock syndrome related to Strongyloides stercoralis hyperinfection: a case report.

BACKGROUND: We describe a patient with Strongyloides stercoralis hyperinfection associated with Streptococcus pyogenes and with streptococcal toxic shock syndrome. To the best of our knowledge this association has not been previously described. CASE PRESENTATION: A 78 year-old Israeli man, who was born in Iraq but lived in Israel for 66 years, presented with multi-organ failure including acute kidney and hepatic injury, coagulopathy, and lactic acidosis. He had a medical history including aortic valve replacement, diabetes mellitus, spinal stenosis, and low back pain treated with repeated local steroid injections. Blood cultures were positive for Streptococcus pyogenes and antibiotic treatment was switched to penicillin G, clindamycin, and intravenous immunoglobulins. Repeated physical examinations failed to identify the source of the bacteremia. On day 12 of hospitalization the serology results for Strongyloides stercoralis sent on admission, because of chronic eosinophilia, came back positive. A microscopic stool examination and stool polymerase chain reaction were positive for Strongyloides stercoralis. Ivermectin therapy was commenced and continued for a total of 4 weeks. He was discharged for rehabilitation after 25 days. He had no exposure to endemic countries or to immigrants. During many years he had multiple gastrointestinal symptoms, respiratory symptoms, cutaneous symptoms, chronic eosinophilia, and high immunoglobulin E levels. He underwent several operative procedures and numerous hospitalizations and medical encounters with different experts but a parasitic infection was not considered. His asymptomatic daughter was also found to be serologically positive. CONCLUSIONS: Strongyloides stercoralis hyperinfection associated with Streptococcus pyogenes bacteremia and toxic shock is described for the first time. The case also highlights the importance of history taking and reviewing past laboratory results, the utility of serological tests for Strongyloides stercoralis, and the importance of screening asymptomatic family members of an infected patient. Strongyloides stercoralis hyperinfection must be considered in the differential diagnosis of any patient with Streptococcus pyogenes bacteremia or toxic shock of no clear source as well as in symptomatic patients with chronic or intermittent eosinophilia, even without any epidemiological risk factors.

Case Report: Typhoid Fever and Spotted Fever Group Rickettsiosis Presenting Concomitantly in an Indian Immigrant.

We present a rare case of an Indian immigrant suffering from concomitant infection of Salmonella typhi and spotted fever group Rickettsia. We discuss the scarce reports of dual infections from the developing world and the related diagnostic challenges.

Cryptococcosis as a cause of nephrotic syndrome? A case report and review of the literature.

We present a case of a 74 years old male with cutaneous cryptococcosis of the right forearm. Cryptococcus neoformans var. neoformans was cultivated from the skin and from the bloodstream. He was diagnosed with nephrotic syndrome (focal segmental glomerulosclerosis) 21 months prior to admission, which was steroid-dependent. He was treated with prednisone and cyclosporine A. Concurrently with his renal disease he was also diagnosed as having disseminated severe tinea mannum, tinea corporis and tinea cruris; onychomycosis, skin eczema and psoriasis. After a prolonged course of anti-fungal therapy, his skin lesions as well as his nephrotic syndrome recovered completely. Follow up after 7 months without any anti-fungal or immunosuppression showed no skin or renal recurrence. We assume that the renal disease was related to the pre-existing cutaneous cryptococcosis, aggravated by immunosuppression, and discuss the close association between cutaneous cryptococcosis and nephrotic syndrome, as well as similar case reports in the literature.

Two Cases of Israeli Spotted Fever with Purpura Fulminans, Sharon District, Israel.

We report a series of 5 case-patients who had Israeli spotted fever, of whom 2 had purpura fulminans and died. Four case-patients were given a diagnosis on the basis of PCR of skin biopsy specimens 3-4 days after treatment with doxycycline; 1 case-patient was given a diagnosis on the basis of seroconversion. Rickettsia spp. from the 2 case-patients who died were sequenced and identified as Rickettsia conorii subsp. israelensis. Purpura fulminans has been described in association with R. rickettsii and R. indica, but rarely with R. conorii subsp. israelensis.

Streptococcus anginosus endocarditis and multiple liver abscesses in a splenectomised patient.

An unusual case of infective endocarditis and concurrent multiple liver abscesses both caused by Streptococcus anginosus in a splenectomised patient is reported. The microorganism is a very rare cause of endocarditis and its presentation with multiple liver abscesses is highly unusual. It was initially misdiagnosed as Streptococcus sanguinis and issues relating to the different clinical presentations of S. anginosus including the rare cases of endocarditis, the role of the patient's splenectomy and problems that may contribute to its potential laboratory misidentifications are discussed.