Monkeypox DNA levels correlate with virus infectivity in clinical samples, Israel, 2022.

The current monkeypox virus global spread and lack of data regarding clinical specimens' infectivity call for examining virus infectivity, and whether this correlates with results from PCR, the available diagnostic tool. We show strong correlation between viral DNA amount in clinical specimens and virus infectivity toward BSC-1 cell line. Moreover, we define a PCR threshold value (Cq ≥ 35, ≤ 4,300 DNA copies/mL), corresponding to negative viral cultures, which may assist risk-assessment and decision-making regarding protective-measures and guidelines for patients with monkeypox.

Microbiome Characterization of Infected Diabetic Foot Ulcers in Association With Clinical Outcomes: Traditional Cultures Versus Molecular Sequencing Methods.

Background: Infected diabetic foot ulcers (IDFU) are a major complication of diabetes mellitus. These potentially limb-threatening ulcers are challenging to treat due to impaired wound healing characterizing diabetic patients and the complex microbial environment of these ulcers. Aim: To analyze the microbiome of IDFU in association with clinical outcomes. Methods: Wound biopsies from IDFU were obtained from hospitalized patients and were analyzed using traditional microbiology cultures, 16S rRNA sequencing and metagenomic sequencing. Patients' characteristics, culture-based results and sequencing data were analyzed in association with clinical outcomes. Results: A total of 31 patients were enrolled. Gram-negative bacteria dominated the IDFU samples (79%, 59% and 54% of metagenomics, 16S rRNA and cultures results, respectively, p<0.001). 16S rRNA and metagenomic sequencing detected significantly more anaerobic bacteria, as compared to conventional cultures (59% and 76%, respectively vs. 26% in cultures, p=0.001). Culture-based results showed that Staphylococcus aureus was more prevalent among patients who were treated conservatively (p=0.048). In metagenomic analysis, the Bacteroides genus was more prevalent among patients who underwent amputation (p<0.001). Analysis of metagenomic-based functional data showed that antibiotic resistance genes and genes related to biofilm production and to bacterial virulent factors were more prevalent in IDFU that resulted in amputation (p<0.001). Conclusion: Sequencing tools uncover the complex biodiversity of IDFU and emphasize the high prevalence of anaerobes and Gram-negative bacteria in these ulcers. Furthermore, sequencing results highlight possible associations among certain genera, species, and bacterial functional genes to clinical outcomes.

Characteristics of pelvic inflammatory disease caused by sexually transmitted disease - An epidemiologic study.

INTRODUCTION: Pelvic inflammatory disease (PID) is an infection of the upper genital organs, diagnosed by clinical findings. The nucleic acid amplification test (NAAT) identify sexually transmitted (STD) pathogens from endocervical swabs, via real time PCR. This study explored the prevalence of STD detected by NAAT for women with PID. We also aimed to identify predictive characteristics for positive test. MATERIAL & METHODS: This retrospective cohort study explored the prevalence of positive NAAT for women with clinically diagnosed PID, 2016-2019, in a secondary referral center. The primary outcome was the prevalence of positive STD tests and specific pathogens. The secondary outcome was predictive clinical and laboratory parameters for positive NAAT. RESULTS: Among the 610 women in our cohort, 103 had a positive STD PCR, which accounts for 17%. Most of the patients had Urea parvum (39.4%) Mycoplasma hominis (17.2%) or Urea urealyticum (15.7%). Other pathogens with lower incidence were Chlamydia trachomatis (9.8%), Trichomonas vaginalis (3.4%), Mycoplasma genitalium (2.1%) and the lowest rate was for Neisseria gonorrhea (1.5%). CONCLUSION: In our population, we found lower prevalence of Chlamydia trachomatis and Neisseria gonorrhea compared to other large populations. This may be due to a high prevalence of married and religious women and also due to administration of a wide range of empirical antibiotic treatment, even for a low suspicion of PID. The study also gives reassurance that our empirical antibiotic protocol is adjusted to the endemic PID pathogens found in our population.

Healthcare-associated Pneumocystis jirovecii Pneumonia (PJP) Infection in HIV-negative Adults: a Multicenter Study.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is an opportunistic infection in immunocompromised patients. Clusters of PJP, especially among organ transplant recipients in clinic settings were described. Data regarding nosocomial PJP infection among inpatients are limited. OBJECTIVES: To assess the magnitude and characteristics of inpatient healthcare-associated PJP infection (HCA-PJP) in HIV-negative patients. METHODS: A retrospective chart review of hospitalized PJP patients was performed to identify HCA-PJP. The study was performed at six medical centers in Israel from 2006 to 2016. HCA-PJP was defined as cases of hospital-onset or those with documented contact with a PJP patient. We reviewed and cross-matched temporal and spatial co-locations of patients. Clinical laboratory characteristics and outcomes were compared. RESULTS: Seventy-six cases of PJP were identified. Median age was 63.7 years; 64% men; 44% hematological malignancies; 18% inflammatory diseases; and 61% steroid usage. Thirty-two patients (42%) were defined as HCA-PJP: 18/32 (23.6%) were hospitalized at onset and 14/32 (18.4%) had a previous encounter with a PJP patient. Time from onset of symptoms to diagnosis was shorter in HCA-PJP vs. community-PJP (3.25 vs. 11.23 days, P = 0.009). In multivariate analysis, dyspnea at presentation (odds ratio [OR] 16.79, 95% confidence interval [95%CI] 1.78-157.95) and a tendency toward higher rate of ventilator support (72% vs. 52%, P = 0.07, OR 5.18, 95%CI 0.7-30.3) were independently associated with HCA-PJP, implying abrupt disease progression in HCA-PJP. CONCLUSIONS: HCA-PJP was common. A high level of suspicion for PJP among selected patients with nosocomial respiratory infection is warranted. Isolation of PJP patients should be considered.

Improving urinary tract infection treatment through a multifaceted antimicrobial stewardship intervention in the emergency department.

BACKGROUND: Urinary tract infection (UTI) is frequently encountered in the emergency department (ED). We assessed an antibiotic stewardship intervention tailored for the ED. The primary objective was improving overall adherence to agent choice and treatment duration. The secondary objective was a decrease in fluoroquinolone prescription. METHODS: This pre-post study included patients discharged from the ED with a UTI diagnosis. The intensive intervention period lasted three months and involved dissemination of guidelines, short lectures, incorporation of order sets into electronic ED charts and weekly personal audit and feedback. The following 11-month phase was a booster period consisting of monthly text messages of the treatment protocol. Assessment of adherence to the protocol was compared between the three-month pre-intervention period and the last two months of the intensive intervention period, as well as with the last two months of the booster period. RESULTS: A total of 177 patients were included in the pre-intervention period, 156 in the intervention period, and 94 in the late follow-up assessing the booster period. Median age was 49 (18-94) years, 78.2% were female, 84.8% had cystitis. During the intervention period, protocol adherence with antibiotic selection and duration increased from 41% to 84% (p < 0.001). Adherence remained high in the late follow-up period (73.4% vs. 41%, p < 0.001). Fluoroquinolone use decreased from 19.1% pre-intervention, to 5% in the intervention and 7.4% in the late follow-up periods (p < 0.001). CONCLUSIONS: An antibiotic stewardship intervention in a busy ED resulted in adherence to treatment protocols, including a decrease in fluoroquinolone use. A monthly reminder preserved most of the effect for a year.

Rituximab identified as an independent risk factor for severe PJP: A case-control study.

OBJECTIVE: Pneumocystis jirovecii pneumonia (PJP) was reported among immunosuppressed patients with deficits in cell-mediated immunity and in patients treated with immunomodulatory drugs. The aim of this study was to identify risk-factors for PJP in noninfected HIV patients. METHODS: This retrospective, test negative, case-control study was conducted in six hospitals in Israel, 2006-2016. Cases were hospitalized HIV-negative patients with pneumonia diagnosed as PJP by bronchoalveolar lavage. Controls were similar patients negative for PJP. RESULTS: Seventy-six cases and 159 controls were identified. Median age was 63.7 years, 65% males, 34% had hematological malignancies, 11% inflammatory diseases, 47% used steroids and 9% received antilymphocyte monoclonal antibodies. PJP was independently associated with antilymphocyte monoclonal antibodies (OR 11.47, CI 1.50-87.74), high-dose steroid treatment (OR 4.39, CI 1.52-12.63), lymphopenia (OR 8.13, CI 2.48-26.60), low albumin (OR 0.15, CI 0.40-0.54) and low BMI (OR 0.80, CI 0.68-0.93). CONCLUSION: In conclusion, rituximab, which is prescribed for a wide variety of malignant and inflammatory disorders, was found to be significant risk-factor for PJP. Increased awareness of possible PJP infection in this patient population is warranted.

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

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

Pneumococcal Meningitis in Adults after Introduction of PCV7 and PCV13, Israel, July 2009-June 20151.

The indirect effect of pneumococcal conjugate vaccine on adult pneumococcal meningitis has not been thoroughly investigated. We present data from active surveillance on pneumococcal meningitis in adults in Israel occurring during July 2009-June 2015. Pneumococcal meningitis was diagnosed for 221 patients, 9.4% of all invasive pneumococcal disease (IPD) cases. Although overall IPD incidence decreased during the study period, meningitis increased nonsignificantly from 0.66 to 0.85 cases/100,000 population. Incidence of vaccine type (VT) pneumococcal meningitis (VT13) decreased by 70%, but non-VT13 pneumococcal meningitis increased from 0.32 to 0.75 cases/100,000 population (incident rate ratio 2.35, 95% CI 1.27-4.35). Pneumococcal meningitis patients were younger and healthier than nonmeningitis IPD patients, and 20.2% had a history of previous head surgery or cerebrospinal fluid leak compared with <2.0% of nonmeningitis patients (p<0.0001). Non-VT13 types that rarely cause IPD (15B/C, 6C, 23A, 23B, 24F) seem to be emerging as common causes of meningitis.

Antibiotic Exposure in the Community and Resistance Patterns of Escherichia coli Community-Acquired Bloodstream Infection.

BACKGROUND: Increasing antibiotic resistance in the community results in greater use of empiric broad spectrum antibiotics for patients at hospital admission. As a measure of antibiotic stewardship it is important to identify a patient population that can receive narrow spectrum antibiotics. OBJECTIVES: To evaluate resistance patterns of Escherichia coli bloodstream infection (BSI) from strictly community-acquired infection and the impact of recent antibiotic use on this resistance. METHODS: This single center, historical cohort study of adult patients with E. coli BSI was conducted from January 2007 to December 2011. Patients had no exposure to any healthcare facility and no chronic catheters or chronic ulcers. Data on antibiotic use during the previous 90 days was collected and relation to resistance patterns was assessed. RESULTS: Of the total number of patients, 267 BSI cases met the entry criteria; 153 patients (57%) had bacteria sensitive to all antibiotics. Among 189 patients with no antibiotic exposure, 61% of isolates (116) were pan-sensitive. Resistance to any antibiotic appeared in 114 patients and 12 were extended-spectrum beta-lactamase (ESBL) producers. Quinolone use was the main driver of resistance to any antibiotic and to ESBL resistance patterns. In a multivariate analysis, older age (odds ratio 1.1) and quinolone use (odds ratio 7) were independently correlated to ESBL. CONCLUSIONS: At admission, stratification by patient characteristics and recent antibiotic use can help personalize primary empirical therapy.

The herd effects of infant PCV7/PCV13 sequential implementation on adult invasive pneumococcal disease, six years post implementation; a nationwide study in Israel.

BACKGROUND: Introduction of pneumococcal conjugate vaccine (PCV) has nearly eliminated vaccine-type (VT) invasive pneumococcal disease (IPD) in children, yet the reported resulting reduction of adult IPD is variable. We present the indirect impact of sequential PCV7/PCV13 implementation in Israel on adult IPD. METHODS: An ongoing nationwide active surveillance was initiated on July 2009 when PCV7 was implemented (with Catch-up). PCV7 was gradually replaced by PCV13 since November 2010. Comorbidity and outcome data were collected from medical files. Incidence rates were calculated for overall and vaccine-type IPD. RESULTS: A total of 2579 IPD cases were diagnosed among a population of 5.0-5.5 million adults >18y (2009-2015). Incidence rates were 9.15/100,000 and 10.16/100,000 in the first and second study years, respectively. However, after PCV13 implementation, the rates decreased to 7.19 within four years, and remained stable in the two following years. Within 6years, PCV7-VT-IPD incidence decreased from 2.52 to 0.52 (79%) and PCV13-VT-IPD from 6.15 to 1.81 (71%). Concurrently, non-VT13 incidence increased from 2.99 to 5.25. Approximately 50% of all patients were adults ≥65y, in whom the decrease in PCV13-VT-IPD incidence was smaller and slower (65% vs. >80% decrease in adults <50y). CONCLUSIONS: Despite continued reduction in PCV13-VT-IPD, overall IPD was stable during the last two years due to serotype replacement. Yet, the significant decrease in adult IPD, six years post-PCV7/13 implementation emphasizes the importance of indirect protection in achieving overall population impact and should be considered when discussing the potential additional benefits of direct adult PCV vaccination.

A nationwide surveillance of invasive pneumococcal disease in adults in Israel before an expected effect of PCV7.

Pneumococcal infections in adults vary in severity and incidence is affected by childhood vaccination policy. Here, we try to define the host determinants and the interaction with specific serotypes that result in invasive pneumococcal disease (IPD) before an expected effect of pneumococcal conjugate vaccines. A nationwide active surveillance was initiated on July 2009, at the time of national implementation of PCV7 in Israel. The surveillance included all 27 laboratories and medical centers performing blood cultures in Israel, providing all blood and CSF pneumococcal isolates from persons ≥18y. Capture-recapture method assured that >95% of all cases were reported. IPD outcome and medical history were recorded and isolates were serotyped. Four hundred and sixty IPD cases were reported (annual incidence [/100,000] of 9.25). Incidence increased with age, from 2.6 among 18-34y to 66.8 among ≥85y. The most common diagnosis was pneumonia (72.4%), followed by bacteremia with no apparent focus (20.2%). Case fatality rate increased with age and number of comorbidities (34.5% for ≥75y or those with ≥3 comorbidities vs. 9.2-11.2% among <65y or those with no comorbidities; p=0.015). Variables independently associated with mortality were: age ≥75, chronic renal failure, malignancy, neurosurgery, alcohol abuse, multi-lobar pneumonia and sepsis with no apparent focus. The predominant serotypes in patients 18-49y were 1, 5, 8, 7F and 9V (constituting 56.3% in this age-group vs. 11.9% in ≥75y; p<0.01). The predominant serotypes among patients ≥75y were 3, 19A, 23F and 14 (40.3% of this age-group vs. 12.9% of 18-49y; p<0.01). Overall, PCV7 and PCV13 covered 25.6% and 63.7% of isolates, respectively, and 30.9% and 67.9% of isolates in mortality cases respectively. This nationwide active surveillance provides the baseline incidence, mortality rates and risk group distributions of IPD in adults before expected PCV effect.

[Vaccinations for travelers--a review of current recommendations].

The number of travelers abroad rises every year. Concurrently, the age and health conditions of the travelers are becoming increasingly varied as are their destinations and the degree of risk involved. In the face of this complexity, it is recommended that travelers seek medical advice at specializing travel medicine clinics before leaving for their trip. The object of the consultation is to fit the general guidelines regarding preventative behavior and vaccinations to the specific traveler. Several sources of information are available for receiving updated vaccination recommendations for travelers. Usually these sources provide similar recommendations but occasionally different instructions can be found. In this review, the authors discuss vaccination recommendations for travelers while pointing out the similarities and differences among the various information sources. The different recommendations for travelers groups and types are noted. The available vaccinations are reviewed, detailing the indications and contraindications as well as side effects.

Prevalence of the K65R resistance reverse transcriptase mutation in different HIV-1 subtypes in Israel.

The K65R mutation in HIV-1 reverse transcriptase (RT) can be selected by the RT inhibitors tenofovir (TDF), abacavir (ABC), and didanosine (DDI). Recently, in vitro studies have shown that K65R is selected in tissue culture more rapidly with subtype C than subtype B viruses. The prevalence of K65R in viruses sequenced at the Tel-Aviv AIDS Center was evaluated. This study analyzed retrospectively sequences from 1999 to 2007 in patients treated with TDF, ABC, and/or DDI and compared rates of mutational prevalence between subtypes. Fisher's exact test was used to determine statistical significance. Forty-four sequences from patients treated with the three above-cited drugs were analyzed. Subtypes A (n = 1), CRF01_AE (n = 4), CRF02_AG (n = 2), B (n = 21), C (n = 11), D (n = 1), F (n = 3), and G (n = 1) were represented. Seven non-B viruses had the K65R mutation, which was only found in one subtype B virus. Of these seven samples four were subtype C, one was subtype CRF01_AE, and two were subtype CRF02_AG. None of the eight viruses with K65R harbored thymidine analogue mutations. In this study, non-subtype B viruses possessed the K65R mutation at higher incidence than subtype B viruses. Subtype C viruses may be especially prone to develop this mutation. Larger studies are needed to confirm these data. Efforts should be intensified to understand better differences in drug resistance between various HIV subtypes.

Corynebacterium striatum--a classic pathogen eluding diagnosis.

We report one case of infective endocarditis and two cases of arthritis due to Corynebacterium striatum. After reviewing all previously reported cases, we illustrate the clinical features typical of infection, including nosocomial risk factors and prominent embolic phenomena in the cases of endocarditis. Our cases underscore the importance of prompt diagnosis when confronted with positive blood and synovial cultures. This ubiquitous organism and common contaminant is a rare yet deadly pathogen.

C-reactive protein velocity to distinguish febrile bacterial infections from non-bacterial febrile illnesses in the emergency department.

INTRODUCTION: C-reactive protein (CRP) is a real-time and low-cost biomarker to distinguish febrile bacterial infections from non-bacterial febrile illnesses. We hypothesised that measuring the velocity of the biomarker instead of its absolute serum concentration could enhance its ability to differentiate between these two conditions. METHODS: We prospectively recruited adult patients (age >or= 18 years) who presented to the emergency department with fever. We recorded their data regarding the onset of fever and accompanying symptoms. CRP measurements were obtained upon admission. CRP velocity (CRPv) was defined as the ratio between CRP on admission and the number of hours since the onset of fever. Patients were diagnosed by clinical symptoms, blood cultures and imaging studies, and the diagnoses were confirmed by an infectious disease specialist. The efficacy of CRPv as a diagnostic marker was evaluated by using receiver operator curves (ROC). Excluded were patients who did not know the time fever started with certainty, patients with malignancy, patients with HIV infection and patients who had been using antibiotics upon presentation. RESULTS: Of 178 eligible patients, 108 (60.7%) had febrile bacterial infections (mean CRP: 63.77 mg/L, mean CRPv: 3.61 mg/L/hour) and 70 (39.3%) had non-bacterial febrile illnesses (mean CRP: 23.2 mg/L, mean CRPv: 0.41 mg/L/hour). The area under the curve for CRP and CRPv were 0.783 (95% confidence interval (CI) = 0.717 to 0.850) and 0.871 (95% CI = 0.817 to 0.924), respectively. In a 122-patient subgroup with a CRP level of less than 100 mg/L, the area under the curve increased from 0.689 (95% CI = 0.0595 to 0.782) to 0.842 (95% CI = 0.77 to 0.914) by using the CRPv measurements. CONCLUSIONS: CRPv improved differentiation between febrile bacterial infections and non-bacterial febrile illnesses compared with CRP alone, and could identify individuals who need prompt therapeutic intervention.

Active surveillance for methicillin-resistant Staphylococcus aureus (MRSA) decreases the incidence of MRSA bacteremia.

OBJECTIVES: To evaluate the influence of performance of active surveillance cultures for methicillin-resistant Staphylococcus aureus (MRSA) on the incidence of nosocomial MRSA bacteremia in an endemic hospital. DESIGN: Before-after trial. SETTING: A 700-bed hospital. PATIENTS: All patients admitted to the hospital who were at high risk for MRSA bacteremia. INTERVENTION: Performance of surveillance cultures for detection of MRSA were recommended for all patients at high risk, and contact isolation was implemented for patients with positive results of culture. Each MRSA-positive patient received one course of eradication treatment. We compared the total number of surveillance cultures, the percentage of surveillance cultures with positive results, and the number of MRSA bacteremia cases before the intervention (from January 2002 through February 2003) after the start of the intervention (from July 2003 through October 2004). RESULTS: The number of surveillance cultures performed increased from a mean of 272.57 cultures/month before the intervention to 865.83 cultures/month after the intervention. The percentage of surveillance cultures with positive results increased from 3.13% before to 5.22% after the intervention (P < .001). The mean number of MRSA bacteremia cases per month decreased from 3.6 cases before the intervention to 1.8 cases after the intervention (P < 0.001). CONCLUSIONS: Active surveillance culture is important for identifying hidden reservoirs of MRSA. Contact isolation can prevent new colonization and infection and lead to a significant reduction of morbidity and healthcare costs.

Comparative performance of the Amplicor HIV-1 Monitor Assay versus NucliSens EasyQ in HIV subtype C-infected patients.

In facing global programs for treating HIV-infected patients in the developing countries, there is a real need for viral load assays that are accurate for the local subtypes. The present study was designed to evaluate viral load measurements using the newer version of the NASBA assay in subtype C-infected patients. The performances of this new version, a real-time nucleic acid sequence-based amplification HIV-1 assay (NucliSens EasyQ), were compared to Amplicor HIV-1 Monitor Assay version 1.5 in 79 samples of subtype C-infected patients originating from Ethiopia. Twenty HIV-1 subtype B-infected patients served as a control group. Blood samples from patients in both groups were tested by both assays. The results were compared by a paired, two-tailed Student's t-test. The disparity between the results of the two viral load assays was highly significant in subtype C samples (P = 0.005), such that in the vast majority, higher values of viral load were obtained by the Amplicor assay. However, no differences between the two assays were found in subtype B samples (P = 0.77). CD4 measurements were available for 78 samples of subtype C-infected patients. Of these, a CD4-to-viral load discrepancy (CD4