Prior outpatient antibiotic use as predictor for microbial aetiology of community-acquired pneumonia: hospital-based study

Objective: The causative micro-organism in community-acquired pneumonia (CAP) is often difficult to predict. Different studies have examined chronic morbidity and clinical symptoms as predictors for microbial aetiology of pneumonia. The aim of our study was to assess whether prior outpatient antimicrobial treatment is predictive for determining the microbial aetiology of CAP. Methods: This was a hospital-based prospective observational study including all patients admitted with CAP between 1 October 2004 and 1 August 2006. Microbial investigations included sputum, blood culture, sputum PCR, antigen testing and serology. Exposure to antimicrobial drugs prior to hospital admission was ascertained through community pharmacy dispensing records. Multivariate logistic regression analysis was conducted to assess whether prior outpatient antimicrobial treatment is a predictor of microbial aetiology. Patient demographics, co-morbidities and pneumonia severity were considered to be other potential predictors. Results: Overall, 201 patients were included in the study. The microbial aetiology was determined in 64% of the patients. The five most prevalent pathogens were Streptococcus pneumoniae, Heamophilus influenzae, Legionella spp., Mycoplasma pneumoniae and Influenza virus A+B. Forty-seven of the patients (23%) had received initial antimicrobial treatment as outpatients. Multivariate analyses revealed that initial outpatient beta-lactam treatment was associated with a threefold increased chance of finding atypical pathogens and a threefold decreased probability of pneumococcal infection; the corresponding odds ratios were 3.51 (95% CI 1.25-9.99) and 0.30 (95% CI 0.10-0.90), respectively. Patients who received macrolides prior to hospitalisation had an increased probability of viral pneumonia. Conclusion: Prior outpatient antimicrobial therapy has a predictive value in the diagnostic workup aimed at identifying the causative pathogen and planning corresponding antimicrobial treatment in patients hospitalised for pneumonia

Atypical aetiology in patients hospitalised with community-acquired pneumonia is associated with age, gender and season; a data-analysis on four Dutch cohorts

BACKGROUND: Microorganisms causing community-acquired pneumonia (CAP) can be categorised into viral, typical and atypical (Legionella species, Coxiella burnetii, Mycoplasma pneumoniae, and Chlamydia species). Extensive microbiological testing to identify the causative microorganism is not standardly recommended, and empiric treatment does not always cover atypical pathogens. In order to optimize epidemiologic knowledge of CAP and to improve empiric antibiotic choice, we investigated whether atypical microorganisms are associated with a particular season or with the patient characteristics age, gender, or chronic obstructive pulmonary disease (COPD). METHODS: A data-analysis was performed on databases from four prospective studies, which all included adult patients hospitalised with CAP in the Netherlands (N = 980). All studies performed extensive microbiological testing. RESULTS: A main causative agent was identified in 565/980 (57.7 %) patients. Of these, 117 (20.7 %) were atypical microorganisms. This percentage was 40.4 % (57/141) during the non-respiratory season (week 20 to week 39, early May to early October), and 67.2 % (41/61) for patients under the age of 60 during this season. Factors that were associated with atypical causative agents were: CAP acquired in the non-respiratory season (odds ratio (OR) 4.3, 95 % CI 2.68-6.84), age <60 year (OR 2.9, 95 % CI 1.83-4.66), male gender (OR 1.7, 95 % CI 1.06-2.71) and absence of COPD (OR 0.2, 95 % CI 0.12-0.52). CONCLUSIONS: Atypical causative agents in CAP are associated with respectively non-respiratory season, age <60 years, male gender and absence of COPD. Therefore, to maximise its yield, extensive microbiological testing should be considered in patients <60 years old who are admitted with CAP from early May to early October. TRIAL REGISTRATION: NCT00471640 , NCT00170196 (numbers of original studies)

High-sensitivity cardiac troponin T predicts mortality after hospitalization for community-acquired pneumonia

Background and objective: Mortality after hospitalization with community-acquired pneumonia (CAP) is high, compared with age-matched controls. Available evidence suggests a strong link with cardiovascular disease. Our aim was to explore the prognostic value of high-sensitivity cardiac troponin T (cTnT) for mortality in patients hospitalized with CAP.   Methods: CTnT level on admission was measured (assay conducted in 2015) in 295 patients hospitalized with CAP who participated in a randomized placebo-controlled double-blind trial on adjunctive dexamethasone treatment. Outcome measures were short- (30-day) and long-term (4.1-year) mortalities.   Results: CTnT levels were elevated (≥14 ng/L) in 132 patients (45%). Pneumonia severity index (PSI) class was 4–5 in 137 patients (46%). Short- and long-term mortality were significantly higher in patients with elevated cTnT levels. cTnT level on admission combined with PSI classification was significantly better in predicting short-term mortality (area under the operating curve (AUC) = 0.903; 95% CI = 0.847–0.960), compared with PSI classification alone (AUC = 0.818; 95% CI = 0.717–0.919). An optimal cTnT cut-off level of 28 ng/L was independently associated with both short- and long-term mortality (OR = 21.9; 95% CI = 4.7–101.4 and 10.7; 95% CI = 5.0–22.8, respectively).   Conclusion: Elevated cTnT level on admission is a strong predictor of short- and long-term mortalities in patients hospitalized with CAP

YKL-40, CCL18 and SP-D predict mortality in patients hospitalized with community-acquired pneumonia

Background and objective: The aim of this study was to investigate the prognostic value of four biomarkers, YKL-40, chemokine (C-C motif) ligand 18 (CCL18), surfactant protein-D (SP-D) and CA 15-3, in patients admitted with community-acquired pneumonia (CAP). These markers have been studied extensively in chronic pulmonary disease, but in acute pulmonary disease their prognostic value is unknown. Methods: A total of 289 adult patients who were hospitalized with CAP and participated in a randomized controlled trial were enrolled. Biomarker levels were measured on the day of admission. Intensive care unit admission, 30-day, 1-year and long-term mortality (median follow-up of 5.4 years, interquartile range (IQR): 4.7–6.1) were recorded as outcomes. Results: Median YKL-40 and CCL18 levels were significantly higher and levels of SP-D were significantly lower in CAP patients compared to healthy controls. Significantly higher YKL-40, CCL18 and SP-D levels were found in patients classified in pneumonia severity index classes 4–5 and with a CURB-65 score ≥2 compared to patients with less severe pneumonia. Furthermore, these three markers were significant predictors for long-term mortality in multivariate analysis and compared with C-reactive protein and procalcitonin level on admission, area under the curves were higher for 30-day, 1-year and long-term mortality. CA 15-3 levels were less predictive. Conclusion: YKL-40, CCL18 and SP-D levels were higher in patients with more severe pneumonia, possibly reflecting the extent of pulmonary inflammation. Of these, YKL-40 most significantly predicts mortality for CAP

Exposure to thioguanine during 117 pregnancies in women with inflammatory bowel disease

BACKGROUND: Safety of thioguanine in pregnant patients with inflammatory bowel disease (IBD) is sparsely recorded. This study was aimed to document the safety of thioguanine during pregnancy and in birth. METHODS: In this multicenter case series, IBD patients treated with thioguanine during pregnancy were included. Data regarding disease and medication history, pregnancy course, obstetric complications and neonatal outcomes were collected. RESULTS: Data on 117 thioguanine-exposed pregnancies in 99 women were collected. Most (78%) had Crohn's disease and the mean age at delivery was 31 years. In eighteen pregnancies (15%) IBD flared. Obstetric and infectious complications were seen in 15% (n=17) and 7% (n=8) of pregnancies, respectively. Ten pregnancies (8.5%) resulted in a first trimester miscarriage and one in a stillbirth at 22 weeks gestational age. Congenital abnormalities were observed in one induced abortion (trisomy 21) and in one of the live-born children (cleft palate) . In total 109 neonates were born from 101 singleton pregnancies and 4 twin pregnancies. In the singleton pregnancies, ten children were born prematurely and ten were born small for gestational age. Screening for myelosuppresion was performed in sixteen neonates (14.7%); two had anemia in umbilical cord blood. All outcomes were comparable to either the general Dutch population or to data from 3 Dutch cohort studies on the use of conventional thiopurines in pregnant IBD patients. CONCLUSION: In this large case series the use of thioguanine during pregnancy is not associated in excess with adverse maternal or neonatal outcomes

Eradication of carriage with methicillin-resistant Staphylococcus aureus: determinants of treatment failure

Background: Using data from an observational study in which the effectiveness of a guideline for eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage was evaluated, we identified variables that were associated with treatment failure. Methods: A multivariate logistic regression model was performed with subgroup analyses for uncomplicated and complicated MRSA carriage (the latter including MRSA infection, skin lesions, foreign-body material, mupirocin resistance and/or exclusive extranasal carriage) and for those treated according to the guideline (i.e. mupirocin nasal ointment and chlorhexidine soap solution for uncomplicated carriage, in combination with two oral antibiotics for complicated carriage). Results: Six hundred and thirteen MRSA carriers were included, of whom 333 (54%) had complicated carriage; 327 of 530 patients (62%) with known complexity of carriage were treated according to the guideline with an absolute increase in treatment success of 20% (95% confidence interval 12%-28%). Among those with uncomplicated carriage, guideline adherence [adjusted odds ratio (OR alpha) 7.4 (1.7-31.7)], chronic pulmonary disease [OR alpha 44 (2.9-668)], throat carriage [OR alpha 2.9 (1.4-6.1)], perineal carriage [OR alpha 2.2 (1.1-4.4)] and carriage among household contacts [OR alpha 5.6 (1.2-26)] were associated with treatment failure. Among those with complicated carriage, guideline adherence was associated with treatment success [OR alpha 0.2 (0.1-0.3)], whereas throat carriage [OR alpha 4.4 (2.3-8.3)] and dependence in activities of daily living [OR alpha 3.6 (1.4-8.9)] were associated with failure. Conclusions: Guideline adherence, especially among those with complicated MRSA carriage, was associated with treatment success. Adding patients with extranasal carriage or dependence in daily self-care activities to the definition of complicated carriage, and treating them likewise, may further increase treatment success.Antimicrobial treatment and prevention of infection

Eradication of carriage with methicillin-resistant Staphylococcus aureus: effectiveness of a national guideline

We evaluated the effectiveness of eradication of methicillin-resistant Staphylococcus aureus (MRSA) carriage in the Netherlands after the introduction of a guideline in 2006. The guideline distinguishes complicated (defined as the presence of MRSA infection, skin lesions, foreign-body material, mupirocin resistance and/or exclusive extranasal carriage) and uncomplicated carriage (not meeting criteria for complicated carriage). Mupirocin nasal ointment and chlorhexidine soap solution are recommended for uncomplicated carriers and the same treatment in combination with two oral antibiotics for complicated carriage. A prospective cohort study was performed in 18 Dutch centres from 1 October 2006 until 1 October 2008. Six hundred and thirteen MRSA carriers underwent one or more decolonization treatments during the study period, mostly after hospital discharge. Decolonization was achieved in 367 (60%) patients with one eradication attempt and ultimately 493 (80%) patients were decolonized, with a median time until decolonization of 10 days (interquartile range 7-43 days). Three hundred and twenty-seven (62%) carriers were treated according to the guideline, which was associated with an absolute increase in treatment success of 20% [from 45% (91/203) to 65% (214/327)]. Sixty percent of MRSA carriers were successfully decolonized after the first eradication attempt and 62% were treated according to the guideline, which was associated with an increased treatment succes