Utilization of a Meningitis/Encephalitis PCR panel at the University Hospital Basel - a retrospective study to develop a diagnostic decision rule.

Background: The Biofire® FilmArray® Meningitis/Encephalitis (ME) PCR panel covers 14 viral, bacterial, and fungal pathogens and has been implemented in many institutions worldwide. Post-marketing studies indicate a reduced sensitivity and overutilization underscoring the need for a more targeted usage. The aim of our study is to describe the utilization of the ME panel and to develop a diagnostic-stewardship based decision rule. Materials: Adult patients, who underwent CSF analysis with the ME panel between August 2016 and June 2021 at the University Hospital Basel, were included. Demographic, clinical, microbiological, and laboratory data were extracted from the electronic health record. Factors associated with a positive ME panel result were identified, and a decision rule was developed to potentially optimize the diagnostic yield and reduce the number of unnecessary tests. Results: 1,236 adult patients received at least one panel in the observed period, of whom 106 panels tested positive (8.6%). The most frequently observed pathogens were Varicella Zoster Virus (VZV, 27%), Streptococcus pneumoniae (19%), Enterovirus (16%), Herpes simplex Virus 1/2 (16%), and Human Herpesvirus 6 (HHV-6, 13%). Fever, vomiting, headache, and photophobia were more frequently present in test positive patients as were significantly higher CSF leukocytes and protein concentrations. When simulating a decision rule based on CSF leukocytes and protein concentration, only 35% of all patients would have qualified for a ME panel tests, thereby increasing the positivity rate to 22.7%. 10 of 106 positive ME panels would have been missed, only involving HHV-6 and VZV (6 and 4 cases, respectively). As these subjects were either severely immunocompromised or had clinical features of shingles we propose extending the testing algorithm by including those criteria. Conclusion: The ME panel positivity rate at our institution was similar as previously published. Our results highlight the need for diagnostic-stewardship interventions when utilizing this assay by implementing a stepwise approach based on a limited number of clinical and laboratory features. This decision rule may improve the pretest probability of a positive test result, increase the quality of test utilization, and reduce costs.

Switch from a ritonavir to a cobicistat containing antiretroviral regimen and impact on tacrolimus levels in a kidney transplant recipient.

BACKGROUND: Solid-organ transplantation due to end-stage organ disease is increasingly performed in people living with HIV. Despite improved transplant outcomes, management of these patients remains challenging due to higher risk for allograft rejection, infection and drug-drug interactions (DDIs). Complex regimens for multi-drug resistant HIV-viruses may cause DDIs particularly if the regimen contains drugs such as ritonavir or cobicistat. CASE PRESENTATION: Here we report on a case of an HIV-infected renal transplant recipient on long-term immunosuppressive therapy with mycophenolate mofetil and tacrolimus dosed at 0.5 mg every 11 days due to the co-administration of a darunavir/ritonavir containing antiretroviral regimen. In the presented case the pharmacokinetic booster was switched from ritonavir to cobicistat for treatment simplification. A close monitoring of tacrolimus drug levels was performed in order to prevent possible sub- or supratherapeutic tacrolimus trough levels. A progressive decrease in tacrolimus concentrations was observed after switch requiring shortening of tacrolimus dosing interval. This observation was unexpected considering that cobicistat is devoid of inducing properties. CONCLUSIONS: This case highlights the fact that the pharmacokinetic boosters ritonavir and cobicistat are not fully interchangeable. Therapeutic drug monitoring of tacrolimus is warranted to maintain levels within the therapeutic range.

OPAT in Switzerland: single-center experience of a model to treat complicated infections.

PURPOSE: Outpatient parenteral antimicrobial therapy (OPAT) programmes are established in the minority of Swiss hospitals. We aimed to study the OPAT programme at the University Hospital Basel during a 3-year period to evaluate safety and outcome. METHODS: All patients treated in the OPAT programme between 2015 and 2017 were included in the study. Demographic, clinical and OPAT outcome data were extracted from the hospital information system. Differences between treatment periods were analysed and risk factors for readmission and adverse events identified. RESULTS: In total, 462 patients were enrolled from 2015 to 2017. Patient numbers and total treatment days increased by 68% and 116%, respectively. Indications included many complicated infections such as bone and joint (23%) and intravascular infections (13%). Of the identified Gram-negative bacteria, 25% produced extended spectrum beta-lactamases. The percentage of antibiotics administrated with an elastomeric device increased from 11% in 2015 to 29% in 2017, whereas the use of once-daily antimicrobials (such as ceftriaxone) declined. Adverse events were rare (n = 67; 14.6%) including only two severe catheter-related events. Cure was noted in 98% of patients. 30-day unplanned readmission occurred in 46 (10.0%) patients, and intravascular infections and a higher Charlson comorbidity index were identified as independent predictors. CONCLUSION: This study demonstrates the successful implementation of a formal OPAT programme in a Swiss tertiary care hospital. Careful selection of patients and monitoring during treatment are crucial to avoid frequent readmissions. Hence, our data call for an expansion of OPAT services in Switzerland in the near future.

Appropriateness of antimicrobial prescribing in a Swiss tertiary care hospital: a repeated point prevalence survey.

AIMS OF THE STUDY: Inappropriate use of antimicrobials is associated with the emergence of antimicrobial resistance and adverse events. Antimicrobial stewardship programmes may both optimise treatment of infections and reduce antimicrobial resistance but are implemented in only a minority of Swiss hospitals. In addition, data on prescribing patterns and quality are scarce. We conducted a repeated point prevalence survey to evaluate the quality of antimicrobial prescribing in a single tertiary care centre. METHODS: Antimicrobial use was audited twice (summer 2017 and winter 2018) among all patients admitted to the University Hospital Basel, Switzerland. Data were collected from the electronic health record. Appropriateness of antimicrobial use was evaluated according to previously published rules and local national guidelines. RESULTS: We evaluated 1112 patients of whom 378 (34%) received 548 prescriptions in total (30% for prophylaxis). Penicillins with β-lactamase inhibitors were most commonly used (30%), followed by cotrimoxazole (12%) and ceftriaxone (7%). Intravenous administration was chosen in 56% of patients. Prior to antimicrobial therapy, blood cultures were collected in 69% of patients. Overall, 182 (33%) prescriptions were not appropriate; reasons included lack of indication (11%), incorrect dosing (7%), delay in intravenous to oral switch (9%) or non-adherence to local guidelines (15%). A minority of patients received antimicrobials despite documented allergies (2%). Almost 38% of empirical prescriptions were inappropriate, compared with only 19% of prophylactic and 20% of targeted prescriptions. Penicillins with β-lactamase inhibitors and cephalosporins were most commonly involved in inappropriate prescribing (>50%) followed by carbapenems (30%), narrow-spectrum penicillins (17%) and cotrimoxazole (6%), with oral administration being involved less frequently than intravenous administration (15 vs 37%). Infectious diseases consultation and presence of immunosuppression were associated with reduced odds (odds ratio [OR] 0.38, 95% confidence interval [CI] 0.21–0.70 and OR 0.31, 95% CI 0.17–0.54, respectively) of inappropriate prescription in the per-patient multivariable analysis, whereas being admitted to a surgical or intensive care unit was associated with increased odds (OR 1.83 and 5.67) compared with a medical unit. CONCLUSION: Almost one third of prescriptions were inappropriate in our tertiary care centre despite local guidelines and an on-demand infectious diseases consultation service. Our results underscore the need for expanding current antimicrobial stewardship efforts, including national initiatives such as stewardship and prescribing guidelines, repeated surveys and identification of areas for improvement including timely intravenous to oral switches in order to reduce the consequences of inappropriate prescribing and of multidrug resistant organisms.