Number, type and cost of microbiological tests during HIV Pre-Exposure Prophylaxis: The experience of a French hospital.

BACKGROUND: Microbiological tests are required for individuals on HIV Pre-Exposure Prophylaxis (PrEP), but their real-life numbers, types and cost are poorly described. METHODS: Number, type, and results of microbiological tests performed in a Besançon Hospital-associated laboratory, France, from 2016 to 2019, in the setting of PrEP consultations were retrospectively collected. Costs were estimated by the current reimbursement rate set by the French national protection system. RESULTS: 756 consultations for PrEP initiation or follow-up of 135 persons were performed over 4 years. Among 3434 tests performed in the institution-associated laboratory, 1083 and 2351 were virological and bacteriological tests, respectively. Serology was predominant in virology (98% of virological tests), with HIV, HCV, and HBV screening as the 3 more frequent assays, whereas molecular biology was predominant in bacteriology (63.1% of bacteriological tests) with N. gonorrhoeae and C. trachomatis screening as leader assays. Agar-based culture accounted for 1% of bacterial tests. The global cost of microbiological tests was 45,983.20 euros, corresponding to a mean cost of 60.80 euros per consultation. Virological and bacteriological tests accounted for 37.7% and 62.3% of this budget, respectively. No seroconversion was observed for HIV or HCV. N. gonorrhoeae and C. trachomatis were detected at least once in 39.3% and 22.4% of individuals, respectively, with 15% of symptomatic episodes in both cases. Active syphilis infection was detected in 15.4% of individuals. CONCLUSIONS: Since numerous microbiological tests are required during PrEP, the availability of specific technical platforms should not be neglected by centers wishing to set up PrEP consultations.

A Feasible Laboratory-Strengthening Intervention Yielding a Sustainable Clinical Bacteriology Sector to Support Antimicrobial Stewardship in a Large Referral Hospital in Ethiopia.

Background: Access to clinical bacteriology in low resource settings (LRS) is a key bottleneck preventing individual patient management of treatable severe infections, detection of antimicrobial resistance (AMR), and implementation of effective stewardship interventions. We sought to demonstrate the feasibility of a practical bundle of interventions aimed at implementing sustainable clinical bacteriology services at Tikur Anbessa Specialized Hospital in Addis Ababa, Ethiopia, and report on cost and intensity of supervision. Methods: Starting in Dec 2015, an intervention based on the CLSI QMS01-A guideline was established, consisting of (i) an initial needs assessment, (ii) development of key standard operating procedures, (iii) adaptation of processes for LRS, (iv) training and supervision of laboratory staff via consultant visits and existing online resources, and (v) implementation of a practical quality systems approach. A guiding principle of the bundle was sustainability of all interventions post implementation. Outcomes and challenges: An initial investment of ~US$ 26,200 for laboratory reagents, and a total of 50 visit-days per year from three Canadian and Norwegian microbiologists were committed. Twelve SOPs, including antimicrobial susceptibility testing, were adapted, and an automated blood culture platform was donated (bioMerieux). In the first 18 months of implementation of the intervention, the average volume of specimens analyzed in the lab went from 15/day to 75/day. The number of blood cultures tested increased from an average of 2/day to over 45/day. Antimicrobial susceptibility testing was introduced and cumulative antibiograms were generated for the institution. Quality control was implemented for all procedures and quality assurance tools implemented included external quality assurance and proficiency testing of six technologists with longitudinal follow-up. The laboratory is on the path toward SLIPTA accreditation by the African Society for Laboratory Medicine. Reagent costs, staff training and retention, and engagement of clinical personnel with the lab proved to be manageable challenges. Key external challenges include in-country supply-chain management issues, lack of competition among distributors, and foreign-currency exchange distortions. Conclusions: Using a relatively low-intensity intervention based on existing training tools and accreditation schemes, we demonstrate that establishment of reasonable-quality clinical bacteriology is not only within reach but also a critical step toward assessing the burden of AMR in settings like this one and implementing effective stewardship strategies.

Validation and Measurement Uncertainty Assessment of a Microbiological Method Using Generalized Pivotal Quantity Procedure and Monte-Carlo Simulation.

Recently, a novel and effective statistical tool called the uncertainty profile has been developed with the purpose of graphically assessing the validity and estimating the measurement uncertainty of analytical procedures. One way to construct the uncertainty profile is to compute the ß-content, γ-confidence tolerance interval. In this study, we propose a tolerance interval based on the combination of the generalized pivotal quantity procedure and Monte-Carlo simulation. The uncertainty profile has been applied successfully in several fields. However, in order to further confirm its universality, this newer approach has been applied to assess the performance of an alternative procedure versus a reference procedure for counting of Escherichia coli bacteria in drinking water. Hence, the aims of this research were to expose how the uncertainty profile can be powerfully applied pursuant to ISO 16140 standards in the frame of interlaboratory study and how to easily make a decision concerning the validity of the procedure. The analysis of the results shows that after the introduction of a correction factor, the alternative procedure is deemed valid over the studied range because the uncertainty limits lie within the acceptability limits set at ±-0.3 log unit/100 ml for a ß = 66.7% and γ = 90%.

Epidemiology of Meningitis in Oman-Implications for Future Surveillance.

OBJECTIVES: This study aimed to understand the epidemiology of meningitis cases admitted to hospitals in Oman and to identify any changing microbial patterns from the introduction of the new vaccines. METHODS: A retrospective analysis of all cases of meningitis reported through a national surveillance system. Meningitis is a notifiable disease. RESULTS: Of a total of 581 cases of meningitis from the period between January 1, 2005 and December 31, 2013, 15% (88) were confirmed to be bacterial in origin and 7.2% (42/581) viral. In 50.9% (296) of patients with suspected pyogenic meningitis, no specific bacterial pathogen were identified, and in 26% of cases (151) a cerebrospinal fluid study could not be undertaken. Among 88 cases with confirmed bacterial pathogens the organisms identified were Streptococcus pneumoniae (65.9%), Neisseria meningitides (18.2%), Haemophilus influenzae (6.8%), and other organisms (9.1%). The peak incidence was in children <2 years of age (39.4%). It showed notable decline in H. influenzae cases as well as pneumococcal meningitis cases, possibly indicative of the successful immunization program. CONCLUSION: A drop in H. Influenzae and pneumococcal meningitis cases was possibly the effect of the introduction of vaccines. It shows the need for improving diagnostic accuracy, laboratory capacities, and quality of surveillance reporting.

Laboratory Focus on Improving the Culture of Biosafety: Statewide Risk Assessment of Clinical Laboratories That Process Specimens for Microbiologic Analysis.

The Wisconsin State Laboratory of Hygiene challenged Wisconsin laboratories to examine their biosafety practices and improve their culture of biosafety. One hundred three clinical and public health laboratories completed a questionnaire-based, microbiology-focused biosafety risk assessment. Greater than 96% of the respondents performed activities related to specimen processing, direct microscopic examination, and rapid nonmolecular testing, while approximately 60% performed culture interpretation. Although they are important to the assessment of risk, data specific to patient occupation, symptoms, and travel history were often unavailable to the laboratory and, therefore, less contributory to a microbiology-focused biosafety risk assessment than information on the specimen source and test requisition. Over 88% of the respondents complied with more than three-quarters of the mitigation control measures listed in the survey. Facility assessment revealed that subsets of laboratories that claim biosafety level 1, 2, or 3 status did not possess all of the biosafety elements considered minimally standard for their respective classifications. Many laboratories reported being able to quickly correct the minor deficiencies identified. Task assessment identified deficiencies that trended higher within the general (not microbiology-specific) laboratory for core activities, such as packaging and shipping, direct microscopic examination, and culture modalities solely involving screens for organism growth. For traditional microbiology departments, opportunities for improvement in the cultivation and management of highly infectious agents, such as acid-fast bacilli and systemic fungi, were revealed. These results derived from a survey of a large cohort of small- and large-scale laboratories suggest the necessity for continued microbiology-based understanding of biosafety practices, vigilance toward biosafety, and enforcement of biosafety practices throughout the laboratory setting.

A cost-effective interdisciplinary approach to microbiologic send-out test use.

CONTEXT: Use of reference laboratories for selected laboratory testing (send-out tests) represents a significant source of laboratory costs. As the use of more complex molecular analyses becomes common in the United States, strategies to reduce costs in the clinical laboratory must evolve in order to provide high-value, cost-effective medicine. OBJECTIVE: To report a strategy that employs clinical pathology house staff and key hospital clinicians in the effective use of microbiologic send-out testing. DESIGN: The George Washington University Hospital is a 370-bed academic hospital in Washington, DC. In 2012 all requisitions for microbiologic send-out tests were screened by the clinical pathology house staff prior to final dispensation. Tests with questionable utility were brought to the attention of ordering clinicians through the use of interdisciplinary rounds and direct face-to-face consultation. RESULTS: Screening resulted in a cancellation rate of 38% of send-out tests, with proportional cost savings. Nucleic acid tests represented most of the tests screened and the largest percentage of cost saved through screening. Following consultation, requested send-out tests were most often canceled because of a lack of clinical indication. CONCLUSIONS: Direct face-to-face consultation with ordering physicians is an effective, interdisciplinary approach to managing the use of send-out testing in the microbiology laboratory.

Posttreatment assessment of women at risk of developing high-grade cervical disease: proposal for new guidelines based on data from the Netherlands.

OBJECTIVE: Women treated for high-grade cervical disease (cervical intraepithelial neoplasia grade 2 or grade 3 [CIN2/3]) face a significant risk of developing post-treatment disease. Therefore, in most European countries, they are monitored by cytologic testing at 6, 12, and 24 months after treatment. Although testing for high-risk types of the human papillomavirus (hrHPV) in the follow-up seems to be a valuable supplementary method, its use is not yet fully explored. METHODS: Besides reviewing the literature, we completed a long-term follow-up study describing the cumulative risk for CIN2/3 or cancer (CIN2+) of different hrHPV and cytology test results after treatment. CONCLUSIONS: High-risk HPV testing improves the sensitivity to detect posttreatment CIN2/3 (relative sensitivity=1.15, 95% confidence interval [CI]=1.06-1.25), but the highest sensitivity (95%, 95% CI=91%-98%) is reached by performing cotesting (both cytology and hrHPV). The CIN2+ risk after a single negative cotesting result taken 6 months after treatments was similar to the risk after 3 consecutive negative cytologic test results (5-y CIN2+ risk being 3.0% [95% CI=1.5%-6.1%] and 2.9% [95% CI=1.2%-7.1%], respectively). Women who test negative for cotesting at both 6 and 24 months after treatment have a minimal risk of developing CIN3+ in the next 5 years (0.0%, 95% CI=0.0%-3.0%). RECOMMENDATIONS: We propose a new posttreatment surveillance protocol, consisting of combined testing with both cytology and hrHPV at 6 and 24 months after treatment. After 2 negative cotesting results, women should be retested after 5 years.

Assessment of microbiological diagnostic procedures for respiratory specimens from cystic fibrosis patients in German laboratories by use of a questionnaire.

Respiratory specimens from cystic fibrosis (CF) patients challenge microbiological laboratories with their complexity of pathogens and atypical variants. We evaluated the diagnostic procedures in German laboratories by use of a questionnaire. Although most laboratories followed guidelines, some of them served only a small number of patients, while others did not use the recommended selective agars to culture the particular CF-relevant species.

[How much diagnostics is required in palliative care? Results from a representative survey and own experiences]. / Wieviel Diagnostik braucht die Palliativmedizin? Ergebnisse einer multizentrischen Studie und Fallserie.

BACKGROUND: Applying diagnostic techniques in palliative care (PC) requires a thorough balance between a physical, psychosocial (and financial) burden and its therapeutic relevance in far advanced diseases. The extent of diagnostic employment in PC, preferred techniques, application problems, its informative value and therapeutic significance still have to be described. METHODS: The Hospice and Palliative Care Evaluation (HOPE) 2007 collected data from the application of microbiological and imaging techniques in German PC institutions. Furthermore, 70 consecutive ultrasound scans in our PC unit have been retrospectively analyzed.In 691 PC patients (from a total of 3184 in HOPE), diagnostic techniques (DIA) were applied and documented. RESULTS: In-patients with DIA (86,1 %) and the HOPE collective showed a comparable age and duration of hospital stay. Microbiological techniques contributed to 26,1 % of all documented in-patient investigations, imaging techniques 69,1 %. Ultrasound was the preferred imaging technique on PC units (67,1 %), whilst radiography, CT or MRI scans were rather employed on oncology wards. Nuclear imaging was rarely documented. In 80,8 %, imaging diagnostics were considered relevant for further treatment decisions (in-patients only); transportation problems and pain during imaging were relevant obstacles. In our own patient cohort, ultrasound was applied rather for general prognostic purposes, less often resulting in immediate therapeutic actions. Transportation problems could be almost entirely avoided by using a mobile ultrasound device. CONCLUSION: DIA in PC are applied independently of age or duration of hospital stay; its therapeutic significance is considered to be high; procedural problems may be resolvable. Therefore, this survey might challenge the tradition of low technology in PC.

The scope of mycoplasma contamination within the biopharmaceutical industry.

Mycoplasma is well recognized as one of the most prevalent and serious microbial contaminants encountered within the manufacturing of biopharmaceuticals from the research phase to clinical development and production. The potential for mycoplasma contamination within cell culture systems was first identified by Robinson et al. in 1956. Presently, contamination rates in established cell cultures have been reported between 15 and 35% with considerably higher occurrence cited in certain selected populations. In the last few years, there has been an expansion of diagnostic approaches for mycoplasma detection with the development and validation of rapid microbiological methods. The objective of this study was to determine current levels of mycoplasma infection of cell cultures, cell substrates and biologicals within a client based population. Retrospective comparison of 40,000 sample results was done to determine total contaminations rates amongst four (4) individual analytical assays. The establishment of reference data, such as existing contamination rates, becomes important in the critical appraisal of rapid microbiological methods for the detection of mycoplasma.

Use and cost-effectiveness of intraoperative acid-fast bacilli and fungal cultures in assessing infection of joint arthroplasties.

The objective of this study is to determine a protocol for collecting acid-fast bacilli (AFB) and fungal intraoperative cultures during orthopedic procedures. An observational study was undertaken. Four hundred forty-six AFB cultures and 486 fungal cultures were processed over a 2-year period. The number of positive cultures was determined. A protocol specific to handling these types of specimens was developed. Cost analysis was completed to determine both the time and money saved if the new protocol was implemented. The infrequency of positive AFB and fungal cultures in this study suggests that it is only necessary to routinely request AFB and fungal cultures on 1 of 5 samples. Implementation of this protocol has potential to lead to substantial cost reduction and resource savings without diminishing patient outcomes.

Evaluation of the Q score and Q234 systems for cost-effective and clinically relevant interpretation of wound cultures.

The Q score and Q234 systems were compared to our current protocol for interpreting wound cultures. The Q score and Q234 systems were more cost effective than our current method, with the Q234 system being considered the most useful protocol for implementation by both the laboratory and our clinicians.

Inequalities of primary care microbiology testing between hospital catchment areas.

AIMS: To compare differences in microbiology testing activity between general practices within and between five hospitals in two National Health Service (NHS) regions in England. METHODS: Retrospective capture of standardised microbiology testing activity from the laboratory computer databases. Six equivalent tests were identified and compared. Data were obtained for 174 general practices in eight primary care groups, served by two NHS hospital trusts and three public health laboratories. The total catchment population was 1,180,000 people. Comparative test activities were displayed graphically and differences in median test activity and the hospital activity distributions were examined by the Wilcoxon signed rank test. RESULTS: Median testing activity differed by 200% (urine) to 800% (wound swabs) between the trusts that performed the highest and the lowest number of tests, and from 300% to 1900% between the top and bottom 10% activity bands of general practices. Large and significant differences were found between the hospitals, irrespective of whether they belonged to the same trust, and irrespective of their geographical location. CONCLUSIONS: Large differences in microbiology testing exist within individual trust catchment areas in primary care, and there are also considerable differences between trusts. These inequalities may also introduce a selection bias into epidemiological and antibiotic resistance surveillance. This indicates a widespread need to examine and deal with the reasons responsible for these differences.

Pathology tests: is the time for demand management ripe at last?

With the ever increasing demands for pathology testing within the National Health Service there is a need to manage the demand for these tests. This review discusses strategies for the demand management of requests made by clinicians in the disciplines of biochemistry, haematology, and microbiology. The various approaches that have been used to manage demand will be described, along with specific clinical strategies for demand management.

Clinical impact of blood cultures taken in the emergency department.

OBJECTIVES: (1) To establish the proportion of blood cultures that yield a positive microbiological culture. (2) To determine what proportion of blood cultures taken in the emergency department impact on patient management. (3) To develop guidelines for the appropriate ordering of blood cultures from patients in the emergency department (ED). METHODS: Retrospective review of all blood cultures taken in the ED of a metropolitan teaching hospital between 26 September 1995 and 30 June 1996. RESULTS: One thousand and sixty two blood cultures were taken from patients in the ED during the study period. Ninety two (9%) returned a positive microbiological culture. Of these, 52 (5%) were "true" positives and 18 (1.6%) resulted in changes in management. CONCLUSIONS: Blood cultures taken in the ED rarely yield positive cultures. Only 1.6% of blood cultures taken in the ED impact on management of patients. Simple strategies could reduce the number of blood cultures ordered with little prospect of patient compromise.