Bacterial Patterns and Empiric Antibiotic Use in COPD Patients With Community-Acquired Pneumonia.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) is strongly associated with the development of community-acquired pneumonia (CAP). Limited data are available on risk factors for difficult to manage bacteria such as Pseudomonas aeruginosa in COPD patients with CAP. Our objective was to assess the microbiological patterns associated with risk factors that determine empiric antibiotic therapy in hospitalized COPD patients with CAP. METHODS: We performed a secondary data analysis of an international, multicenter, observational, point-prevalence study involving hospitalized COPD patients with CAP from March to June 2015. After identifying the risk factors associated with different microorganisms, we developed a scoring system to guide decision-making about empiric anti-pseudomonal antibiotic therapy in this population. RESULTS: We enrolled 689 hospitalized COPD patients with CAP with documented microbiological testing. The most frequent microorganisms isolated were Streptococcus pneumoniae (8%) and Gram-negative bacteria (8%), P. aeruginosa (7%) and Haemophilus influenzae (3%). We developed a scoring system incorporating the variables independently associated with P. aeruginosa that include a previous P. aeruginosa isolation or infection (OR 14.2 [95%CI 5.7-35.2]), hospitalization in the past 12 months (OR 3.7 [1.5-9.2]), and bronchiectasis (OR 3.2 [1.4-7.2]). Empiric anti-pseudomonal antibiotics were overutilized in COPD patients with CAP. The new scoring system has the potential to reduce empiric anti-pseudomonal antibiotic use from 54.1% to 6.2%. CONCLUSIONS: COPD patients with CAP present different microbiological profiles associated with unique risk factors. Anti-pseudomonal treatment is a critical decision when selecting empiric antibiotic therapy. We developed a COPD scoring system to guide decision-making about empiric anti-pseudomonal antibiotic therapy.

Transmission, start of symptom and morbidity among Danish COVID-19 patients admitted to hospital.

INTRODUCTION: We explored transmission of the coronavirus disease 2019 (COVID-19) in severely ill patients and analysed the relationship between co-morbidity and mortality or the need for intensive care unit (ICU) care. METHODS: Clinical data, treatment and outcome were analysed in this retrospective study of 101 consecutive patients with COVID-19 admitted to a regional Danish hospital from 2 March 2020, based on data from electronic medical records. RESULTS: The mean age was 71.8 years, 33% were never smokers and 82% had one or more predefined chronic diseases. In-hospital mortality was 30%, and 20% of the patients were offered ICU care. In ICU patients, we found a male preponderance (88% versus 44%, p = 0.006), but death (50% versus 25%, p = 0.053) and other pre-defined co-morbidities did not differ significantly from non-ICU patients. The source of infection was unknown in 74% of patients, related to endemic travel in 10%, hospital acquired in 6% and related to close acquaintances in 11%. COVID-19-related symptoms were initially observed from February 21 (week 8 and week 9) in the first three patients who had no known source of infection. We found that 7% of cases had an increased risk of in-hospital transmission, based on a 7-16 days delay in coronavirus testing. CONCLUSIONS: The frequency of co-morbidity in hospital-admitted COVID-19 patients and the correlation to death and ICU attendance were analysed. In all, 74% of the infection cases were of unknown source during the first weeks of the epidemic, which points to considerable community transmission and possibly pre- or asymptomatic transmission, also several weeks before 21 February 2020. FUNDING: none. TRIAL REGISTRATION: not relevant after correspondence with the Ethics Committee of Region Zealand. Furthermore, permission was granted from The Danish Data Protection Agency, Region Zealand (REG-070-2020).

Outcome and clinical characteristics in pleural empyema: a retrospective study.

BACKGROUND: Pleural empyema is a serious condition with a considerable mortality rate and morbidity. This study evaluated the correlations between several potential prognostic factors (age, predisposing diseases, early drainage, insufficient initial antimicrobial therapy, thoracic surgical treatment, intrapleural fibrinolysis, and nosocomial status) and outcome. METHODS: Danish patients with positive pleural cultures attending 3 hospitals over a 9-y period, were identified in the laboratory databases. Clinical details and outcome were evaluated retrospectively by audit of the medical records. RESULTS: We included 158 patients in this study. The overall mortality was 27% and the median length of stay was 29 days. Mortality correlated independently with several factors: nosocomial infection (odds ratio (OR) 2.62, 95% confidence interval (CI) 1.71-4.16), predisposing conditions (OR 2.17, 95% CI 1.50-3.14), and also with the possibly interventional factors of sufficient initial antimicrobial therapy (OR 0.45, 95% CI 0.31-0.65), thoracic surgery treatment (OR 0.27, 95% CI 0.14-0.52) and local fibrinolytic therapy (OR 0.13, 95% CI 0.06-0.28). Delay in chest tube drainage more than 2 days was not independently correlated with mortality. The initial biochemical diagnostics of non-purulent pleural effusions (63%) did not follow the current international guidelines. CONCLUSION: Factors correlating independently with survival included the possible interventional parameters of fibrinolytic therapy, insufficient initial antimicrobial therapy, and having thoracic surgery treatment.

Bacteriological aetiology and antimicrobial treatment of pleural empyema.

BACKGROUND: Our aims were to describe the aetiologies of culture-positive pleural infections and to evaluate the choice of empiric antimicrobial treatment regimens according to antimicrobial sensitivity, and to evaluate the possible influence of this on outcome. METHODS: All cases over a 9-y period were identified from 3 hospitals using the laboratory databases of the clinical microbiology departments, and were verified by evaluating the medical records. RESULTS: We identified 291 isolates in pleural fluid cultures from 158 patients. These included viridans streptococci (25%), Staphylococcus aureus (18%), anaerobic bacteria (17%), Enterobacteriaceae (12%), Staphylococcus epidermidis (10%), and Streptococcus pneumoniae (7%), with differences between nosocomial and community-acquired infections. The mortality (overall 27%) was highest among the patients with Enterobacteriaceae (50%) and S. aureus (36%) infections, and in patients with mixed infections (34%). The actual empiric treatment or the recommended penicillin plus metronidazole had low antimicrobial coverage (49%) compared to the proposed cefuroxime plus metronidazole (78%). Thoracentesis was often delayed (median 2 days). The adequacy of empiric antimicrobial therapy was independently correlated with mortality (odds ratio 0.43, 95% confidence interval 0.30-0.62). CONCLUSIONS: The early diagnosis of pleural infection could be optimized. In this North-European patient population, we suggest that the recommended empiric antimicrobial treatment be changed to cefuroxime plus metronidazole for community-acquired and nosocomial infections.

Antibiotic treatment delay and outcome in acute bacterial meningitis.

OBJECTIVES: To identify to what degree in-hospital delay of antibiotic therapy correlated to outcome in community acquired bacterial meningitis. METHODS: All cases of culture-positive cerebrospinal fluids in east Denmark from 2002 to 2004 were included. Medical records were collected retrospectively with 98.4% case completeness. Glasgow Outcome Scale was used. Multiple regression outcome analyses included the hypothesised factors: delay of therapy, age, bacterial aetiology, adjuvant steroid therapy, coma at admission and the presence of risk factors. RESULTS: One hundred and eighty seven cases were included. Adult mortality was 33% and the proportion of unfavourable outcome in adults was 52%, which differed significantly from that of children (<18 years) with a mortality of 3% (OR=15.8, 95% confidence interval: 3.7-67.6) and an unfavourable outcome of 14% (OR=12.7, CI: 4.3-37.2). Delay of antibiotic therapy correlated independently to unfavourable outcome (OR=1.09/h, CI: 1.01-1.19) among the 125 adult cases. In the group of adults receiving adequate antibiotic therapy within 12h (n=109), the independent correlation between antibiotic delay and unfavourable outcome was even more prominent (OR=1.30/h, CI: 1.08-1.57). The median delay to the first dose of adequate antibiotics was 1h and 39min (1h and 14min in children vs. 2h in adults, p<0.01), and treatment delay exceeded 2h in 21-37% of the cases with clinically evident meningitis. CONCLUSION: The delay in antibiotic therapy correlated independently to unfavourable outcome. The odds for unfavourable outcome may increase by up to 30% per hour of treatment delay.

Adjunctive steroid treatment: local guidelines and patient outcome in adult bacterial meningitis.

Our objective was to evaluate local guidelines regarding early steroid treatment in adult community acquired bacterial meningitis, and assess the actual treatment given and its correlation to clinical outcome. Patient outcome was obtained retrospectively from the medical records of 210 adults admitted to 47 hospitals in Denmark during 2002-2004 (population 5.4 million) and was combined with results from a questionnaire regarding treatment guidelines in these hospitals. In 36 of 47 departments responding to the questionnaire, 21 recommended early steroid treatment, but none did so initially during 2002. Early steroid treatment was given to 15% of patients and was given more often when recommended locally (41% vs 11%, OR=5.7 (2.4-13.5)). Unfavourable outcome was demonstrated rarely in patients treated with early steroids compared to the non-steroid group (17% vs 42%, p<0.05). In the 32 cases with petechial skin lesions, these were caused by pneumococci (15), meningococci (15), Staphylococcus aureus (1) and enterococci (1), and thus the presence of such lesions should not make the clinician abstain from early steroid treatment of bacterial meningitis. In conclusion, concordance with the new consensus of early steroid treatment was poor on a national basis, and better (41%) when adequate local guidelines were available. Early steroid treatment was associated with favourable outcome, and improved implementation of adequate guidelines may contribute to better patient outcome in bacterial meningitis.

[Bacterial meningitis in Denmark 2002-2003. A nation-wide laboratory-based registration]. / Bakteriel meningitis i Danmark 2002 og 2003. Landsdaekkende registrering baseret på laboratoriedata.

UNLABELLED: Notification of bacterial meningitis (BM) is likely to be incomplete, and a recent Danish study indicated that unbalanced notification may bias expected aetiology of BM. Therefore the Danish Bacterial Meningitis Group initiated a national registration of culture-positive BM. METHODS: Laboratory data on all bacterial isolates from cerebrospinal fluid deemed to be clinically relevant were identified on a national basis during 2002 and 2003. Bacterial findings were compared to cases notified during the same period. RESULTS: A total of 404 BM cases were identified. The distribution of bacterial species differed from the national notification data during the same period especially with respect to Staphylococcus aureus (6.7% vs. 0.6%), Escherichia coli (3.5% vs. 0%) and non-Streptococcus pneumoniae streptococci (10% vs. 1.9%). The overall notification-rate was 66%, and was below 20% for S. aureus, E. coli, Enterococcus faecalis, non-S. pneumoniae streptococci and for 13 cases of "other bacteria". Sensitivity to antibiotics in the BM cases was as expected for Northern Europe. Reduced sensitivity to penicillin was found in 2/202 S. pneumoniae, in 2/10 Listeria monocytogenes, and 21/27 S. aureus were penicillin resistant. E. coli was resistant to ampicillin in 5 of 13 cases and to gentamicin in 1 of 11 cases. DISCUSSION: A suboptimal notification rate with an unbalanced species distribution was found. Laboratory based data thus constitute an improved basis for future recommendations for empirical treatment of BM. A continued national collaboration may promote the development of quality indicators for diagnosis and initial treatment of BM.

[Bacterial meningitis in Denmark: treatment with dexamethasone and antibiotics]. / Bakteriel meningitis i Danmark. Dexamethason- og antibiotikabehandling.

INTRODUCTION: Early adjuvant dexamethasone treatment has been internationally recommended for adults with bacterial meningitis (BM) since 2002. We explored the local recommendations in Denmark concerning treatment with dexamethasone and antibiotics for BM. MATERIALS AND METHODS: A questionnaire was sent to all Danish departments of infectious diseases, paediatrics and internal medicine (n = 92) concerning their local treatment recommendations for BM in the period 2002-2004. RESULTS: The overall response rate was 79%: 100%, 100% and 72%, respectively, for the three departmental types. Early treatment of BM with dexamethasone was recommended in 5 of 5 (100%) departments of infectious diseases, in 13 of 17 (76%) departments of paediatrics and in 22 of 35 (63%) departments of internal medicine. Four, five, and nine different empirical antibiotic regimens were recommended in the departments of infectious diseases, paediatrics, and internal medicine, respectively. In this three-year period, six departments changed their empirical antibiotic regimen: three to a broader-spectrum regimen and three to a regimen with unchanged bacteriological coverage. CONCLUSION: A considerable number of departments of internal medicine (37%) did not include early dexamethasone treatment in their recommendations for BM, despite the international consensus to provide this adjunctive treatment when pneumococcal meningitis is suspected. In addition, a great variation in the recommended empirical antibiotic treatment was demonstrated in this geographically small area.

[Initial antibiotic therapy of purulent meningitis in adults. An investigation of practice patterns at Danish hospital department in 2000]. / Antibiotisk initialbehandling ved purulent meningitis hos voksne. En opgørelse ved danske hospitalsafdelinger i år 2000.

INTRODUCTION: A previous report demonstrated profound variation in the recommended empirical antibiotic therapy for adult purulent meningitis in Denmark. At present, the only existing "official" recommendation (from the Danish Medical Association) is penicillin monotherapy for all adults, irrespective of age, as the prevalence of penicillin-resistant pneumococci is less than 3%. MATERIAL AND METHODS: A questionnaire concerning empirical antibiotic therapy and the treatment of specific microorganisms was sent to the 125 departments of internal medicine, infectious diseases, clinical microbiology, neurosurgery, otorhinolaryngology, and neurology in 2001. RESULTS: Consensus was not found in the 93% who replied, neither within or between the medical specialties nor within or between the counties. The departments of medicine and clinical microbiology were evenly distributed between two strategies: 1) a third-generation cephalosporin plus a penicillin, or 2) penicillin monotherapy, in supplemented in few departments with an aminoglycoside. For Haemophilus influenzae meningitis, 20% of the departments used ampicillin, whereas the majority preferred ceftriaxone. DISCUSSION: Consensus on empirical antibiotic treatment of purulent meningitis in adults had still not been reached in Denmark in the year 2000, and regimens other than that recommended by the Danish Medical Association were used. Complete and updated information is lacking on the resistance-patterns of bacteria inducing meningitis, and a complete national clinical microbiological database could form the basis for an evidence-based national consensus.