Diagnostic stewardship aiming at expectorated or induced sputum promotes microbial diagnosis in community-acquired pneumonia.

PURPOSE: Studies on aetiology of community-acquired pneumonia (CAP) vary in terms of microbial sampling methods, anatomical locations, and laboratory analyses, since no gold standard exists. In this large, multicentre, retrospective, regional study from Norway, our primary objective was to report the results of a strategic diagnostic stewardship intervention, targeting diagnostic yield from lower respiratory tract sampling. The secondary objective was to report hospitalized CAP aetiology and the diagnostic yield of various anatomical sampling locations. METHODS: Medical records from cases diagnosed with hospitalized CAP were collected retrospectively from March throughout May for three consecutive years at six hospitals. Between year one and two, we launched a diagnostic stewardship intervention at the emergency room level for the university teaching hospital only. The intervention was multifaceted aiming at upscaling specimen collection and enhancing collection techniques. Year one at the interventional hospital and every year at the five other emergency hospitals were used for comparison. RESULTS: Of the 1280 included cases of hospitalized CAP, a microbiological diagnosis was established for 29.1% among 1128 blood cultures and 1444 respiratory tract specimens. Blood cultures were positive for a pathogenic respiratory tract microbe in 4.9% of samples, whereas upper and lower respiratory tract samples overall provided a probable microbiological diagnosis in 21.3% and 47.5%, respectively. Expectorated or induced sputum overall provided aetiology in 51.7% of the samples. At the interventional hospital, the number of expectorated or induced sputum samples were significantly increased, and diagnostic yield from expectorated or induced sputum was significantly enhanced from 41.2 to 62.0% after the intervention (p = 0.049). There was an over-representation of samples from the interventional hospital during the study period. Non-typeable Haemophilus influenza and Streptococcus pneumoniae accounted for 25.3% and 24.7% of microbiologically confirmed cases, respectively. CONCLUSION: Expectorated or induced sputum outperformed other sampling methods in providing a reliable microbiological diagnosis for hospitalized CAP. A diagnostic stewardship intervention significantly improved diagnostic yield of lower respiratory tract sampling.

Antimicrobial therapy of community-acquired pneumonia during stewardship efforts and a coronavirus pandemic: an observational study.

BACKGROUND: Community-acquired pneumonia (CAP) is the most frequent infection diagnosis in hospitals. Antimicrobial therapy for CAP is depicted in clinical practice guidelines, but adherence data and effect of antibiotic stewardship measures are lacking. METHODS: A dedicated antibiotic team pointed out CAP as a potential target for antimicrobial stewardship (AMS) measures at a 1.000-bed, tertiary care, teaching university hospital in Norway from March until May for the years 2016 throughout 2021. The aim of the AMS program was to increase diagnostic and antimicrobial therapy adherence to national clinical practice guideline recommendations through multiple and continuous AMS efforts. Descriptive statistics were retrospectively used to delineate antimicrobial therapy for CAP. The primary outcomes were proportions that received narrow-spectrum beta-lactams, and broad-spectrum antimicrobial therapy. RESULTS: 1.112 CAP episodes were identified. The annual proportion that received narrow-spectrum beta-lactams increased from 56.1 to 74.4% (p = 0.045). Correspondingly, the annual proportion that received broad-spectrum antimicrobial therapy decreased from 34.1 to 17.1% (p = 0.002). Trends were affected by the coronavirus pandemic. Mortality and 30-day readmission rates remained unchanged. De-escalation strategies were frequently unutilized, and overall therapy duration exceeded clinical practice guideline recommendations substantially. Microbiologically confirmed CAP episodes increased from 33.7 to 56.2% during the study period. CONCLUSION: CAP is a suitable model condition that is sensitive to AMS measures. A continuous focus on improved microbiological diagnostics and antimicrobial therapy initiation is efficient in increasing adherence to guideline recommendations. There is an unmet need for better antimicrobial de-escalation strategies.

Ciprofloxacin usage at a local hospital. / Bruk av ciprofloksacin ved et lokalsykehus.

BACKGROUND: The use of quinolones is subject to strict conditions, in part because of their known tendency to drive antimicrobial resistance. Use of quinolones in Norwegian hospitals increased dramatically from their launch in the 1980s to a peak in 2012. Since then, usage has decreased and had almost halved by 2019. However, little information is available on whether the use of quinolones in hospitals is in accordance with national guidelines. MATERIAL AND METHOD: This study included inpatients over 12 years of age who were prescribed quinolones at a local hospital in the Central Norway Regional Health Authority in the period 1 September-31 December 2018. An expert group of infectious disease specialists evaluated the use of quinolones against the national guidelines for the use of antibiotics in hospitals. RESULTS: The use of ciprofloxacin was considered to have been inconsistent with therapeutic recommendations in 45 out of 49 (92 %) inpatient stays in the medical, surgical and orthopaedic departments. INTERPRETATION: In a local hospital, ciprofloxacin was used all too frequently for indications outside those recommended in the Norwegian guidelines.

Low levels of short- and medium-chain acylcarnitines in HIV-infected patients.

BACKGROUND: Carnitine plays an essential role in fatty acid metabolism, exerts substantial antioxidant action and regulates immune functions. We hypothesized that a disturbed carnitine metabolism could be involved in progression of HIV infection. MATERIALS AND METHODS: Plasma levels of L-carnitine, its precursors, and short-, medium- and long-chain acylcarnitines were analysed with HPLC/mass spectrometry in HIV-infected patients with various disease severities including patients who acquired Mycobacterium avium complex (MAC) infection. In vitro, we examined the MAC-purified protein derivate (PPD)-induced release of TNF-α and IFN-γ in peripheral blood mononuclear cells (PBMCs) from patients with either high or low plasma levels of acylcarnitines. RESULTS: Plasma levels of the short-chain (e.g. propionyl-carnitine) and medium-chain (e.g. octanoyl-carnitine) acylcarnitines were reduced in patients with advanced HIV infection. These acylcarnitines gradually decreased in rapid progressors, while minimal changes were observed in the nonprogressors. Plasma levels of propionyl-carnitine and octanoyl-carnitine significantly increased during antiretroviral therapy (ART). However, ART did not restore levels to those observed in healthy controls. Depletion of propionyl-carnitine and octanoyl-carnitine was observed prior to MAC infection, and the release of TNF-α and IFN-γ from PBMC was decreased after stimulation with MAC-PPD in samples from HIV-infected patients with low levels of propionyl-carnitine or octanoyl-carnitine. CONCLUSIONS: Our findings suggest an association between disturbed acylcarnitine metabolism, immune dysregulation and disease progression in HIV-infected patients. Low levels of propionyl-carnitine and octanoyl-carnitine were associated with increased susceptibility to MAC infection in HIV patients with advanced disease.

Fatty Acids Composition and HIV Infection: Altered Levels of n-6 Polyunsaturated Fatty Acids Are Associated with Disease Progression.

Fatty acids (FAs) are important regulators of immune responses and innate defense mechanisms. We hypothesized that disturbed FA metabolism could contribute to the progression of HIV infection. Plasma levels of 45 FAs were analyzed with gas chromatography in healthy controls and HIV-infected patients with regard to Mycobacterium avium complex (MAC) infection. In vitro, we assessed MAC-PPD-induced release of inflammatory cytokines in peripheral and bone marrow mononuclear cells (PBMC and BMMC) according to levels of n-6 polyunsaturated fatty acids (PUFAs). While plasma saturated FAs were higher in HIV infection, PUFAs, and in particular the n-6 PUFA arachidonic acid (AA), were lower in patients with advanced disease. The ratio between AA and precursor dihomo-γ-linolenic acid, reflecting Δ5-desaturase activity, was markedly lower and inversely correlated with plasma HIV RNA levels in these patients. Depletion of AA was observed prior to MAC infection, and MAC-PPD-induced release of TNF and IL-6 in PBMC and BMMC was lower in patients with low plasma AA. Our findings suggest that dysregulated metabolism of n-6 PUFAs may play a role in the progression of HIV infection. While high AA may contribute to chronic inflammation in asymptomatic HIV-infected patients, low AA seems to increase the susceptibility to MAC infection in patients with advanced disease.

Empirical antimicrobial therapy for bloodstream infections not compliant with guideline was associated with discordant therapy, which predicted poorer outcome even in a low resistance environment.

OBJECTIVES: To characterise all bloodstream infections (BSIs) in a low antimicrobial resistance (AMR) prevalence setting with regard to the appropriateness of empirical antimicrobial therapy, compliance with the national clinical practice guideline, de-escalation practice and outcome. METHODS: A retrospective observational study including patients aged ≥ 18 years admitted to a university hospital in central Norway with positive blood culture in 2019. RESULTS: We included 756 BSI episodes in our analysis. Empirical antimicrobial therapy was in accordance with the national guideline in 534 (70.6%), and not in accordance in 190 (25.1%) of the BSI episodes. There was a statistically significant association between compliance with the national guideline and concordant empirical antimicrobial therapy (p = .001). De-escalation of antimicrobial therapy was possible but not done in 217 (31.1%) of the BSI episodes. Variables identified as independent predictors of discordant empirical antimicrobial therapy included hospital department, type of empirical antimicrobial regimen, bacterial species, and AMR. Independent predictors of intra-hospital case fatality rate were coverage of empirical antimicrobial therapy, CCI-score, SAPS-II score, site of infection, and type of empirical antimicrobial regimen. Furthermore, the intra-hospital and long-term unadjusted all-cause case fatality rates were increased (p < .001, log-rank test for overall difference in survival) for the patients who received discordant empirical antimicrobial therapy. CONCLUSION: Our study shows that empirical antimicrobial therapy initiated in accordance with national guideline recommendations increases the likelihood of receiving concordant therapy. Discordant empirical antimicrobial therapy was associated with poorer outcomes, even in a setting with low AMR prevalence.

High levels of discordant antimicrobial therapy in hospital-acquired bloodstream infections is associated with increased mortality in an intensive care, low antimicrobial resistance setting.

BACKGROUND: Bloodstream infections (BSI) occur frequently and are associated with severe outcomes. In this study we aimed to investigate proportions of patients that received discordant empirical antimicrobial therapy and its association to mortality. METHODS: A retrospective cohort study model was undertaken to outline BSI in an intensive care, single centre, and low antimicrobial resistance prevalence setting. We used descriptive statistics to delineate proportions of patients that received discordant empirical antimicrobial therapy, and a correlation model and a logistic regression model to calculate the association with mortality and predictors of receiving discordant therapy, respectively. RESULTS: From 2014 to 2018 we included 270 BSI episodes, of which one third were hospital-acquired. Gram negative, Gram positive, and anaerobic pathogens were detected in 49.0%, 45.3% and 5.7% respectively. The proportion of isolates that conferred extended-spectrum beta-lactamase (ESBL) properties were 5.9% among enterobactereales, and no methicillin-resistant Staphylococcus aureus isolates were detected. Empirical antimicrobial therapy for community-acquired (CA) and hospital-acquired (HA) BSI were discordant at day 0 in 6.5% and 24.4%, respectively (p<.001). Discordant therapy was significantly associated with mortality at day 28 (p=.041). HA-onset BSI, enterococcal BSI and BSI of intraabdominal origin were statistically significant predictors of receiving discordant therapy. CONCLUSION: A significant proportion of HA-BSI did not receive effective antimicrobial therapy and this was significantly associated with mortality. The results underscore the need for more accurate diagnostic tools, improved communication between the microbiological laboratory and the clinicians, and antimicrobial stewardship measures.

[Young girl with abscesses in the face]. / Ung jente med abscesser i ansiktet.

Skin and soft tissue infections are most often caused by Staphylococcus aureus or various species of streptococcus. This case report summarizes the clinical features, diagnosis, treatment and clinical outcome of a facial infection presenting as multiple abscesses in a young and otherwise healthy girl. Nocardia brasiliensis was recovered from abscess aspiration, and treatment failure was eventually recognized for the recommended empirical antibiotic treatment, broad-spectrum antibiotics and surgery.

Results of faecal donor instillation therapy for recurrent Clostridium difficile-associated diarrhoea.

We report a success rate of 83% with faecal donor instillation therapy (FDIT) in this retrospective study of 40 patients with recurrent Clostridium difficile-associated diarrhoea (CDAD), treated at a medium sized Norwegian hospital from 1994 through 2008. The stool transplant was instilled either in the duodenum through a gastroscope or in the colon through a colonoscope with next of kin or other household member as donor. In 29 cases (73%) the first treatment was successful, with no documented recurrence of diarrhoeal disease within 80 days. Of the 11 patients failing to respond to the first instillation treatment, 6 patients received a second instillation, 4 of which were successful. A total of 33 patients (83%) were successfully treated with FDIT. Of the 7 non-responders, 5 were seriously ill due to long lasting diarrhoeal disease and co-morbidity and died within 80 days after the procedure, and 2 were believed to have inflammatory bowel disease with response to corticosteroid treatment. No adverse effects of FDIT were observed. In our experience the procedure is easy to perform, well tolerated, effective, and may be a valuable treatment option in selected cases.

Treatment results with debridement and retention of infected hip prostheses.

A retrospective systematic review of the management of a periprosthetic joint infection (PJI) cohort of 78 cases was conducted at a single-centre, middle-sized Norwegian hospital from 1997 to 2007. We analysed 40 cases that were managed by surgical debridement with hip prosthesis retention followed by long-lasting pathogen-directed antibiotic therapy. A follow-up time of 58 to 510 weeks free from PJI relapse occurred in 27 of 40 PJI cases (67.5%). The need for a more advanced secondary orthopaedic procedure was recognized in 13 cases. The pathogen responsible for PJI was recovered in only 80% of cases, hence 20% were managed as culture-negative PJI. In cases without prior hip infection or hip surgery, success rate reached 96.3%. Multiple risk factors were found in most cases undergoing PJI relapse. Debridement with hip prosthesis retention should be restricted to only current management guidelines.

Reduction of unnecessary i.v. antibiotic days using general criteria for antibiotic switch.

This study was designed to help physicians consider change from intravenous to oral antibiotic therapy for any infection from d 3 of hospital stay, by implementing guidelines for antibiotic switch. A 2-centre intervention study was conducted at Sorlandet Hospital HF Kristiansand and Arendal. All patients admitted to the Medical Clinic at these hospitals prescribed with intravenous antibiotics at hospitalization, were included. After collecting data in an observation period, antibiotic switch guidelines were launched in the respective departments of both hospitals. The length of unnecessary intravenous d, duration of hospital stay and outcome of treatment were compared before (observation group) and after (intervention group) the guidelines were implemented. Antibiotic switch was considered from d 3 and onward. The effect of switch guidelines implementation was measured as a reduction of unnecessary intravenous d. Duration of unnecessary intravenous antibiotic therapy was significantly reduced from 3.4 d in the observation group to 1.4 d in the intervention group. Unnecessary intravenous d were found to constitute 83% of total intravenous therapy duration in the observation group and 48% in the intervention group. Duration of hospital stay was significantly reduced from 7.0 to 6.3 d. There was no statistically significant difference in mortality rate, re-prescription of intravenous antibiotic therapy or re-admittance to the hospital. In conclusion, implementing antibiotic switch guidelines significantly reduces the duration of unnecessary intravenous antibiotic therapy. The switch guidelines were based on general criteria for antibiotic switch for any infection.