Implementation considerations for a point-of-care Neisseria gonorrhoeae rapid diagnostic test at primary healthcare level in South Africa: a qualitative study.

BACKGROUND: South Africa maintains an integrated health system where syndromic management of sexually transmitted infections (STI) is the standard of care. An estimated 2 million cases of Neisseria gonorrhoeae (N. gonorrhoeae) occur in South Africa every year. Point-of-care diagnostic tests (POCT) may address existing STI control limitations such as overtreatment and missed cases. Subsequently, a rapid lateral flow assay with fluorescence-based detection (NG-LFA) with a prototype reader was developed for N. gonorrhoeae detection showing excellent performance and high usability; however, a better understanding is needed for device implementation and integration into clinics. METHODS: A qualitative, time-series assessment using 66 in-depth interviews was conducted among 25 trained healthcare workers involved in the implementation of the NG-LFA. Findings were informed by the Normalization Process Theory (NPT) as per relevant contextual (strategic intentions, adaptive execution, and negotiation capacity) and procedural constructs (coherence, cognitive participation, collective action, reflexive monitoring) to examine device implementation within primary healthcare levels. Interviews were audio-recorded, transcribed, and then analyzed using a thematic approach guided by NPT to interpret results. RESULTS: Overall, healthcare workers agreed that STI POCT could guide better STI clinical decision-making, with consideration for clinic integration such as space constraints, patient flow, and workload. Perceived NG-LFA benefits included enhanced patient receptivity and STI knowledge. Further, healthcare workers reflected on the suitability of the NG-LFA given current limitations with integrated primary care. Recommendations included sufficient STI education, and appropriate departments for first points of entry for STI screening. CONCLUSIONS: The collective action and participation by healthcare workers in the implementation of the NG-LFA revealed adaptive execution within the current facility environment including team compositions, facility-staff receptivity, and STI management experiences. User experiences support future clinic service integration, highlighting the importance of further assessing patient-provider communication for STI care, organizational readiness, and identification of relevant departments for STI screening.

Significant increase in azithromycin "resistance" and susceptibility to ceftriaxone and cefixime in Neisseria gonorrhoeae isolates in 26 European countries, 2019.

BACKGROUND: The European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) performs annual sentinel surveillance of Neisseria gonorrhoeae susceptibility to therapeutically relevant antimicrobials across the European Union/European Economic Area (EU/EEA). We present the Euro-GASP results from 2019 (26 countries), linked to patient epidemiological data, and compared with data from previous years. METHODS: Agar dilution and minimum inhibitory concentration (MIC) gradient strip methodologies were used to determine the antimicrobial susceptibility (using EUCAST clinical breakpoints, where available) of 3239 N. gonorrhoeae isolates from 26 countries across the EU/EEA. Significance of differences compared with Euro-GASP results in previous years was analysed using Z-test and the Pearson's χ2 test was used to assess significance of odds ratios for associations between patient epidemiological data and antimicrobial resistance. RESULTS: European N. gonorrhoeae isolates collected between 2016 and 2019 displayed shifting MIC distributions for; ceftriaxone, with highly susceptible isolates increasing over time and occasional resistant isolates each year; cefixime, with highly-susceptible isolates becoming increasingly common; azithromycin, with a shift away from lower MICs towards higher MICs above the EUCAST epidemiological cut-off (ECOFF); and ciprofloxacin which is displaying a similar shift in MICs as observed for azithromycin. In 2019, two isolates displayed ceftriaxone resistance, but both isolates had MICs below the azithromycin ECOFF. Cefixime resistance (0.8%) was associated with patient sex, with resistance higher in females compared with male heterosexuals and men-who-have-sex-with-men (MSM). The number of countries reporting isolates with azithromycin MICs above the ECOFF increased from 76.9% (20/26) in 2016 to 92.3% (24/26) in 2019. Isolates with azithromycin MICs above the ECOFF (9.0%) were associated with pharyngeal infection sites. Following multivariable analysis, ciprofloxacin resistance remained associated with isolates from MSM and heterosexual males compared with females, the absence of a concurrent chlamydial infection, pharyngeal infection sites and patients ≥ 25 years of age. CONCLUSIONS: Resistance to ceftriaxone and cefixime remained uncommon in EU/EEA countries in 2019 with a significant decrease in cefixime resistance observed between 2016 and 2019. The significant increase in azithromycin "resistance" (azithromycin MICs above the ECOFF) threatens the effectiveness of the dual therapy (ceftriaxone + azithromycin), i.e., for ceftriaxone-resistant cases, currently recommended in many countries internationally and requires close monitoring.

Enterococcus faecalis bloodstream infection: does infectious disease specialist consultation make a difference?

PURPOSE: To evaluate the relationship between mortality or relapse of bloodstream infection (BSI) due to Enterococcus faecalis and infectious diseases specialist consultation (IDC) and other factors potentially associated with outcomes. METHODS: In a tertiary-care center, consecutive adult patients with E. faecalis BSI between January 1, 2016 and January 31, 2019, were prospectively followed. The management of E. faecalis BSI was evaluated in terms of adherence to evidence-based quality-of-care indicators (QCIs). IDC and other factors potentially associated with 90-day-mortality or relapse of E. faecalis BSI were analyzed by multivariate logistic regression. RESULTS: A total of 151 patients with a median age of 68 years were studied. IDC was performed in 38% of patients with E. faecalis BSI. 30 cases of endocarditis (20%) were diagnosed. All-cause in-hospital mortality was 23%, 90-day mortality was 37%, and 90-day relapsing E. faecalis BSI was 8%. IDC was significantly associated with better adherence to 5 QCIs. Factors significantly associated with 90-day mortality or relapsing EfB in multivariate analysis were severe sepsis or septic shock at onset (HR 4.32, CI 2.36e7.88) and deep-seated focus of infection (superficial focus HR 0.33, CI 0.14e0.76). CONCLUSION: Enterococcus faecalis bacteremia is associated with a high mortality. IDC contributed to improved diagnostic and therapeutic management.

Antimicrobial Susceptibility Patterns and Wild-Type MIC Distributions of Anaerobic Bacteria at a German University Hospital: A Five-Year Retrospective Study (2015-2019).

Local antimicrobial susceptibility surveys are crucial for optimal empirical therapy guidelines and for aiding in antibiotic stewardship and treatment decisions. For many laboratories, a comprehensive overview of local antimicrobial susceptibility patterns of anaerobic bacteria is still lacking due to the long incubation time and effort involved. The present study investigates the antimicrobial susceptibility patterns and related clinical and demographic data of 2856 clinical isolates of anaerobic bacteria that were submitted for analysis to the Institute for Medical Microbiology and Hygiene of the Freiburg University Medical Center (a tertiary university medical center in Southern Germany) between 2015 and 2019. Antimicrobial susceptibility testing has been carried out according to the European Committee on Antimicrobial Susceptibility Testing (EUCAST) guideline. Minimum inhibitory concentration (MIC)50 and MIC90 for penicillin, metronidazole, moxifloxacin, and clindamycin were established for Gram-positive anaerobes and for ampicillin-sulbactam, meropenem, metronidazole, moxifloxacin, and clindamycin for Gram-negative anaerobes. The distribution of MIC-values for various antibiotics against anaerobic bacteria was also established, especially for those having no specific breakpoints according to EUCAST guidelines. Most clinically relevant anaerobic bacteria originated from general surgery, neurological, and orthopedic wards. A high proportion of isolates were resistant to moxifloxacin and clindamycin indicating the importance of their susceptibility testing before administration. Based on our study metronidazole and other ß-lactam/ß-lactamase inhibitor combinations such as ampicillin-sulbactam remain suitable for empirical treatment of infections with anaerobic bacteria.

Protocol for a prospective cohort study: Prevention of Transmissions by Effective Colonisation Tracking in Neonates (PROTECT-Neo).

INTRODUCTION: Transmissions of opportunistic bacterial pathogens between neonates increase the risk of infections with negative repercussions, including higher mortality, morbidity and permanent disabilities. The probability of transmissions between patients is contingent on a set of intrinsic (patient-related) and extrinsic (ward-related) risk factors that are not clearly quantified. It is the dual objective of the Prevention of Transmissions by Effective Colonisation Tracking-Neo study to determine the density of transmission events in a level III neonatal intensive care unit (NICU) and to identify risk factors that may be causally associated with transmission events. METHODS AND ANALYSIS: A full cohort of patients treated in a 17-bed level III NICU will be prospectively followed and transmission events between two or more patients will be documented. A transmission event occurs when isogenic isolates from two different patients can be identified. Isolates will be obtained by routine weekly screening. Isogenicity will be determined by whole-genome sequencing. During the study, relevant intrinsic and extrinsic risk factors will be recorded. Specimen and data will be collected for 1 year. We postulate that transmission density increases during episodes when demand for intensive care cannot be met by existing staff, and that threshold dynamics have a bearing on cohorting and hand hygiene performance. Poisson logistic regression, proportional hazard and multilevel competing risk models will be used to estimate the effect of explanatory variables. ETHICS AND DISSEMINATION: This study has been approved by the local ethics committee (study ID 287/18). The results will be published in peer-reviewed medical journals, communicated to participants, the general public and all relevant stakeholders. TRIAL REGISTRATION NUMBER: The German Clinical Trials Registry (DRKS00017733); Pre-results.

Positive predictive value of the German notification system for infectious diseases: Surveillance data from eight local health departments, Berlin, 2012.

The German Infection Protection Act requires notifying certain cases of infectious diseases to local health departments (LHD) in Germany. LHDs transmit notifications meeting case definitions to the national health authority, where the proportion of discarded notifications is not known. The proportion of discarded cases at the level of LHDs can be expressed as the positive predictive value (PPV) of the notification system. The PPV can be used to assess the efficiency of the system. We quantified the proportion of discarded notifications to calculate the PPV of the German notification system at the level of LHDs using electronic notification data from Berlin LHDs from 2012. We also analysed reasons for discarding notifications by reviewing notification forms. Data was available from eight LHDs (67%) receiving 10,113 notifications in 2012. Overall PPV was 89% (minimum-maximum = 77-97% across LHDs) and ranging from 30% (Hepatitis B) to 99% (Rotavirus). Of 166 individual investigation forms 84% were on hepatitis B or C cases, most of them discarded because of previously diagnosed chronic disease. LHDs investigate many notifications that do not lead to public health action and useful surveillance data leading to inefficient use of resources. Adaptation of case definitions or the legal framework concerning notifications may increase the efficiency of the notification system and lead to better use of data from notified cases.

Retrospective study on outcome of salvage Helicobacter pylori eradication therapies based on molecular genetic susceptibility testing.

BACKGROUND: Antimicrobial susceptibility of Helicobacter (H.) pylori is usually determined by phenotypic methods. When H. pylori cannot be grown owing to contaminations or delay in transport of gastric tissue samples to the microbiological laboratory, molecular genetic testing is a reasonable alternative. The aim of this retrospective study was to assess the outcome of salvage eradication treatments based on molecular genetic susceptibility testing. METHODS: Data on 144 H. pylori PCR-positive gastric tissue samples of patients primarily with prior unsuccessful eradication treatments were retrospectively analyzed. Eradication treatments were recommended based on genotypic clarithromycin and/or levofloxacin susceptibility as tested by real-time PCR or reverse hybridization. Treatment success was assessed by attending physicians using urea breath test; stool-antigen ELISA; and microbiology/histopathology. RESULTS: Overall success rate of molecular genetic testing-guided salvage treatments was low (68%); none of the regimens chosen was significantly better than another. Multivariable logistic regression analysis did not reveal any factors that may predict treatment failure. CONCLUSIONS: Eradication success was poor despite susceptibility testing. Gastroenterologists are advised to prescribe recommended salvage treatments, considering recommended dosages and prolonged treatment duration.

Deletion of cd39/entpd1 results in hepatic insulin resistance.

OBJECTIVE: Extracellular nucleotides are important mediators of inflammatory responses and could also impact metabolic homeostasis. Type 2 purinergic (P2) receptors bind extracellular nucleotides and are expressed by major peripheral tissues responsible for glucose homeostasis. CD39/ENTPD1 is the dominant vascular and immune cell ectoenzyme that hydrolyzes extracellular nucleotides to regulate purinergic signaling. RESEARCH DESIGN AND METHODS: We have studied Cd39/Entpd1-null mice to determine whether any associated changes in extracellular nucleotide concentrations influence glucose homeostasis. RESULTS: Cd39/Entpd1-null mice have impaired glucose tolerance and decreased insulin sensitivity with significantly higher plasma insulin levels. Hyperinsulinemic-euglycemic clamp studies indicate altered hepatic glucose metabolism. These effects are mimicked in vivo by injection into wild-type mice of either exogenous ATP or an ecto-ATPase inhibitor, ARL-67156, and by exposure of hepatocytes to extracellular nucleotides in vitro. Increased serum interleukin-1beta, interleukin-6, interferon-gamma, and tumor necrosis factor-alpha levels are observed in Cd39/Entpd1-null mice in keeping with a proinflammatory phenotype. Impaired insulin sensitivity is accompanied by increased activation of hepatic c-Jun NH(2)-terminal kinase/stress-activated protein kinase in Cd39/Entpd1 mice after injection of ATP in vivo. This results in decreased tyrosine phosphorylation of insulin receptor substrate-2 with impeded insulin signaling. CONCLUSIONS: CD39/Entpd1 is a modulator of extracellular nucleotide signaling and also influences metabolism. Deletion of Cd39/Entpd1 both directly and indirectly impacts insulin regulation and hepatic glucose metabolism. Extracellular nucleotides serve as "metabolokines," indicating further links between inflammation and associated metabolic derangements.