Evaluation of early clinical failure criteria for gram-negative bloodstream infections

ObjectivesThe aim was the development of early clinical failure criteria (ECFC) to predict unfavourable outcomes in patients with Gram-negative bloodstream infections (GN-BSI).MethodsAdults with community-onset GN-BSI who survived hospitalization for ≥72 hr at Prisma Health-Midlands hospitals in Columbia, SC, USA from January 1, 2010 to June 30, 2015 were identified. Multivariable logistic regression was used to examine the association between clinical variables between 72 and 96 hr after GN-BSI and unfavourable outcomes (28-day mortality or hospital length of stay >14 days from GN-BSI onset).ResultsAmong 766 patients, 225 (29%) had unfavourable outcomes. After adjustments for Charlson Comorbidity Index and appropriateness of empirical antimicrobial therapy in multivariable model, predictors of unfavourable outcomes included systolic blood pressure <100 mmHg or vasopressor use (adjusted odds ratio (aOR) 1.8, 95% confidence interval (CI) 1.2–2.9), heart rate >100 beats/minute (aOR 1.7, 95% CI 1.1–2.5), respiratory rate ≥22 breaths/minute or mechanical ventilation (aOR 2.1, 95% CI 1.4–3.3), altered mental status (aOR 4.5, 95% CI 2.8–7.1), and white blood cell count >12 000/mm³ (aOR 2.7, 95% CI 1.8–4.1) between 72 and 96 hr after index GN-BSI. Area under receiver operating characteristic curve of ECFC model in predicting unfavourable outcomes was 0.77 (0.84 and 0.71 in predicting 28-day mortality and prolonged hospitalization, respectively).ConclusionsRisk of 28-day mortality or prolonged hospitalization can be estimated between 72 and 96 hr after GN-BSI using ECFC. These criteria may have clinical utility in management of GN-BSI and may improve methodology of future investigations assessing response to antimicrobial therapy based on a standard evidence-based definition of early clinical failure.     

Risk factors for community-onset bloodstream infection with extended-spectrum β-lactamase-producing Enterobacteriaceae: national population-based case–control study

ObjectivesThe aim was to investigate risk factors for community-onset bloodstream infections with extended-spectrum β-lactamase-producing Enterobacteriaceae (EPE BSI).MethodsIt is mandatory to report EPE BSI to a national register at the Public Health Agency of Sweden. Using this register, we performed a population-based case–control study from 2007 to 2012 of 945 cases and 9390 controls. Exposure data on comorbidity, hospitalization, in- and outpatient antibiotic consumption and socio-economic status were collected from hospital and health registers.ResultsThe overall incidence of EPE BSI was 1.7 per 100 000 person-years. The 30-day mortality was 11.3%. Urological disorders inferred the highest EPE BSI risk, adjusted odds ratio (aOR) 4.32 (95% Confidence Interval (CI) 3.41–5.47), followed by immunological disorders, aOR 3.54 (CI 2.01–6.23), haematological malignancy, aOR 2.77 (CI 1.57–4.87), solid tumours, aOR 2.28 (1.76–2.94) and diabetes, aOR 2.03 (1.58–2.61). Consumption of fluoroquinolones or mostly non-EPE-active antibiotics with selective Gram-negative spectrum of activity within the previous 3 months was associated with EPE BSI, aORs 5.52 (CI 2.8–11.0) and 3.8, CI 1.9–7.7) respectively. There was a dose–response relationship in EPE BSI risk with increasing number of consecutive regimens. Antibiotic consumption >3 months before EPE BSI was not associated with increased risk. Higher age, malignancies and education ≤12 years (aORs >2) were associated with increased 30-day mortality.ConclusionsTargeted interventions should be directed towards improving care for patients with immunosuppression, urological disorders and subjects with lower socio-economic status. Antibiotic stewardship should focus on reduction of fluoroquinolones.     

Community-acquired bacterial meningitis in adults: in-hospital prognosis,long-term disability and determinants of outcome in a multicentre prospective cohort

ObjectivesTo identify factors associated with unfavourable in-hospital outcome (death or disability) in adults with community-acquired bacterial meningitis (CABM).MethodsIn a prospective multicentre cohort study (COMBAT; February 2013 to July 2015), all consecutive cases of CABM in the 69 participating centres in France were enrolled and followed up for 12 months. Factors associated with unfavourable outcome were identified by logistic regression and long-term disability was analysed.ResultsAmong the 533 individuals enrolled, (Streptococcus pneumoniae 53.8% (280/520 isolates identified), Neisseria meningitidis 21.3% (111/520), others 24.9% (129/520)), case fatality rate was 16.9% (90/533) and unfavourable outcome occurred in 45.0% (225/500). Factors independently associated with unfavourable outcome were: age >70 years (adjusted odds ratio (aOR) 4.64; 95% CI 1.93–11.15), male gender (aOR 2.11; 95% CI 1.25–3.57), chronic renal failure (aOR 6.65; 95% CI 1.57–28.12), purpura fulminans (aOR 4.37; 95% CI 1.38–13.81), localized neurological signs (aOR 3.72; 95% CI 2.29–6.05), disseminated intravascular coagulation (aOR 3.19; 95% CI 1.16–8.79), cerebrospinal fluid (CSF) white-cell count <1500 cells/μL (aOR 2.40; 95% CI 1.42–4.03), CSF glucose concentration (0.1–2.5 g/L: aOR 1.92; 95% CI 1.01–3.67; <0.1 g/L: aOR 2.24; 95% CI 1.01–4.97), elevated CSF protein concentration (aOR 1.09; 95% CI 1.03–1.17), time interval between hospitalization and lumbar puncture >1 day (aOR 2.94; 95% CI 1.32–6.54), and S. pneumoniae meningitis (aOR 4.99; 95% CI 1.98–12.56), or meningitis other than N. meningitidis (aOR 4.54; 95% CI 1.68–12.27). At 12 months, 26.7% (74/277) had hearing loss, 32.8% (87/265) depressive symptoms, 31.0% (86/277) persistent headache, and 53.4% had a physical health-related quality of life (142/266) <25th centile of the distribution of the score in the general French population (p < 0.0001).ConclusionsThe burden of CABM (death, disability, depression, impaired quality of life and hearing loss) is high. Identification of cases from the first symptoms may improve prognosis.ClinicalTrialGov identification number: NCT01730690.     

Chlorhexidine and octenidine use,carriage of qac genes,and reduced antiseptic susceptibility in methicillin-resistant Staphylococcus aureus isolates from a healthcare network

ObjectivesWith the widespread use of antiseptics in healthcare facilities for the prevention of methicillin-resistant Staphylococcus aureus (MRSA) transmission, there are concerns for antiseptic tolerance and resistance. We sought to understand the use of chlorhexidine and octenidine, carriage of qac genes, and reduced antiseptic susceptibilities.MethodsA serial cross-sectional study was conducted in an acute care hospital and three extended-care facilities of a healthcare network in June–July, 2014–2016. Two of the extended-care facilities were exposed to intranasal octenidine and universal daily chlorhexidine/octenidine bathing. The minimum inhibitory concentration (MIC) levels and qac genes were determined by broth microdilution tests and whole genome sequencing respectively. Multivariable logistic regression was used to assess for the independent associations between antiseptic exposures, qac genes, and reduced antiseptic susceptibilities.ResultsA total of 878 MRSA isolates were obtained. There were associations between qacA/B carriage and chlorhexidine (adjusted odds ratio (aOR) 7.80; 95% confidence interval (CI) 3.25–18.71) and octenidine (aOR 11.79; 95% CI 5.14–27.04) exposures. Chlorhexidine exposure was associated with reduced chlorhexidine susceptibility (MIC ≥4 mg/L) (aOR 3.15; 95% CI 1.14–8.74). Carriage of qacA/B (aOR 10.65; 95% CI 4.14–27.40) or qacC (aOR 2.55; 95% CI 1.22–5.32) had an association with reduced chlorhexidine susceptibility; while MRSA sequence type modified the association. However, we found no direct association between (i) antiseptics use and qacC carriage, (ii) octenidine exposure and reduced susceptibility, and (iii) reduced octenidine susceptibility and qacA/B or qacC carriage.ConclusionsAntiseptic exposures were associated with carriage of qac genes. Chlorhexidine exposure was associated with reduced chlorhexidine susceptibility, requiring continued surveillance for the emergence of resistance.     

Colistin plus meropenem for carbapenem-resistant Gram-negative infections: in vitro synergism is not associated with better clinical outcomes

ObjectivesIn vitro models showing synergism between polymyxins and carbapenems support combination treatment for carbapenem-resistant Gram-negative (CRGN) infections. We tested the association between the presence of in vitro synergism and clinical outcomes in patients treated with colistin plus meropenem.MethodsThis was a secondary analysis of AIDA, a randomized controlled trial comparing colistin with colistin–meropenem for severe CRGN infections. We tested in vitro synergism using a checkerboard assay. Based on the fractional inhibitory concentration (ΣFIC) index for each colistin–meropenem combination, we categorized results as synergistic, antagonistic or additive/indifferent. The primary outcome was clinical failure at 14 days. Secondary outcomes were 14- and 28-day mortality and microbiological failure.ResultsThe sample included 171 patients with infections caused by carbapenem-resistant Acinetobacter baumannii (n = 131), Enterobacteriaceae (n = 37) and Pseudomonas aeuruginosa (n = 3). In vitro testing showed synergism for 73 isolates, antagonism for 20 and additivism/indifference for 78. In patients who received any colistin plus meropenem, clinical failure at 14 days was 59/78 (75.6%) in the additivism/indifference group (reference category), 54/73 (74.0%) in the synergism group (adjusted odds ratio (aOR) 0.76, 95% CI 0.31–1.83), and 11/20 (55%) in the antagonism group (aOR 0.77, 95% CI 0.22–2.73). There was no significant difference between groups for any secondary outcome. Comparing the synergism group to patients treated with colistin monotherapy, synergism was not protective against 14-day clinical failure (aOR 0.52, 95% CI 0.26–1.04) or 14-day mortality (aOR1.09, 95% CI 0.60–1.96).DiscussionIn vitro synergism between colistin and meropenem via checkerboard method did not translate into clinical benefit.     

Obesity,diabetes, hypertension and severe outcomes among inpatients with coronavirus disease 2019: a nationwide study

ObjectivesInitial studies of individuals with coronavirus disease 2019 (COVID-19) revealed that obesity, diabetes and hypertension were associated with severe outcomes. Subsequently, some authors showed that the risk could vary according to age, gender, co-morbidities and medical history. In a nationwide retrospective cohort, we studied the association between these co-morbidities and patients' requirement for invasive mechanical ventilation (IMV) or their death.MethodsAll French adult inpatients with COVID-19 admitted during the first epidemic wave (February to September 2020) were included. When patients were diagnosed with obesity, diabetes or hypertension for the first time in 2020, these conditions were considered as incident co-morbidities, otherwise they were considered prevalent. We compared outcomes of IMV and in-hospital death according to obesity, diabetes and hypertension, taking age, gender and Charlson's co-morbidity index score (CCIS) into account.ResultsA total of 134 209 adult inpatients with COVID-19 were included, half of them had hypertension (n = 66 613, 49.6%), one in four were diabetic (n = 32 209, 24.0%), and one in four were obese (n = 32 070, 23.9%). Among this cohort, IMV was required for 13 596 inpatients, and 19 969 patients died. IMV and death were more frequent in male patients (adjusted oods ratio (aOR) 2.0, 95% CI 1.9–2.1 and aOR 1.5, 95% CI 1.4–1.5, respectively), IMV in patients with co-morbidities (aOR 2.1, 95% CI 2.0–2.2 for CCIS = 2 and aOR 3.0, 95% CI 2.8–3.1 for CCIS ≥5), and death in patients aged 80 or above (aOR 17.0, 95% CI 15.5–18.6). Adjusted on age, gender and CCIS, death was more frequent among inpatients with obesity (aOR 1.2, 95% CI 1.1–1.2) and diabetes (aOR 1.2, 95% CI 1.1–1.2). IMV was more frequently necessary for inpatients with obesity (aOR 1.9, 95% CI 1.8–2.0), diabetes (aOR 1.4, 95% CI 1.3–1.4) and hypertension (aOR 1.7, 95% CI 1.6–1.8). Comparatively, IMV was more often required for patients with the following incident co-morbidities: obesity (aOR 3.5, 95% CI 3.3–3.7), diabetes (aOR 2.0, 95% CI 1.8–2.1) and hypertension (aOR 2.5, 95% CI 2.4–2.6).ConclusionsAmong 134 209 inpatients with COVID-19, mortality was more frequent among patients with obesity and diabetes. IMV was more frequently necessary for inpatients with obesity, diabetes and hypertension. Patients for whom these were incident co-morbidities were particularly at risk. Specific medical monitoring and vaccination should be priorities for patients with these co-morbidities.     

Comparative outcomes of cefazolin versus antistaphylococcal penicillins in methicillin-susceptible Staphylococcus aureus infective endocarditis: a post hoc analysis of a prospective multicentre French cohort study

ObjectivesCurrent guidelines recommend cefazolin as an alternative to antistaphylococcal penicillins (ASPs) in methicillin-susceptible Staphylococcus aureus (MSSA) infective endocarditis despite the lack of comparative study. The objective of this study was to evaluate the comparative outcomes of cefazolin vs. ASPs in MSSA infective endocarditis.MethodsThis was a retrospective analysis of an observational multicentre cohort study using prospectively collected data from patients with MSSA endocarditis confirmed by endocarditis team and treated either with cefazolin or ASPs between July 2013 and December 2018. Patients were excluded if they received both treatments. The primary outcome was 90-day all-cause mortality.ResultsOf 210 patients included, 53 patients (25.2%) received cefazolin and 157 (74.8%) received ASPs. The overall 90-day mortality rate was 27.6% (58/210 patients), 24.5% (13/53) in the cefazolin group vs. 28.7% (45/157) in the ASP group (p 0.561). Premature antimicrobial discontinuation due to adverse events occurred less frequently with cefazolin than with ASPs (0/53 vs. 13/157 patients; p 0.042). In multivariate analysis, there was no difference in 90-day mortality between cefazolin and ASPs (adjusted odds ratio (aOR), 1.2; 95% confidence interval (CI), 0.49–2.91; p 0.681), while age (aOR, 1.06; 95% CI, 1.03–1.09; p < 0.001), Charlson comorbidity index (aOR, 1.18; 95% CI, 1.02–1.36 p 0.023), cerebral embolism (aOR, 2.83; 95% CI, 1.33–6.14; p 0.007) and intensive care unit admission (aOR, 4.16; 95% CI, 1.89–9.59; p 0.001) were factors significantly associated with higher mortality.ConclusionsCefazolin seems to be a possible alternative to ASPs in MSSA endocarditis. More studies are needed to confirm these results and determine which treatment should be recommended as first-line therapy.     

Predictive and prognostic factors associated with unliquefied pyogenic liver abscesses

IntroductionPoor liquefaction of pyogenic liver abscesses, which makes drainage impossible at the time of diagnosis, is not infrequent. The impact of poor liquefaction and subsequent drainage failure on clinical outcomes is unknown.MethodsWe conducted a retrospective study with all patients diagnosed with liver abscesses from July 2017 through June 2020. Late drainage (LD) was defined as drainage performed ≥48 h after diagnosis due to poor liquefaction. Logistic regression was performed to identify the factors associated with late or non-drainage (LD/ND). The Cox proportional hazard model was used to identify the variables related to abscess recurrence by 90 days after diagnosis.ResultsA total of 153 patients were included. Thirty (19.6%) patients underwent LD and 54 (35.3%) did not undergo drainage. Other than non-cystic appearance, LD/ND was associated with smaller size (adjusted odds ratio [aOR] 0.85, 95% confidence interval [CI] 0.73–0.98, p = 0.031) and culture-negativity (aOR 2.69, 95% CI 1.14–6.67, p = 0.027). Current hepatopancreaticobiliary malignancy was the only significant predictor of 90-day recurrence. Neither LD/ND (OR, 0.56; 95% CI, 0.13–2.41; p = 0.426) nor LD (OR, 1.26; 95% CI, 0.23–5.55; p = 0.719) was associated with recurrence by 90 days. The incidence of late complications was reduced by drainage, without a reduction in the duration of hospitalization.ConclusionSeveral clinical features were associated with undrainable liver abscesses. Neither LD/ND nor ND had an adverse impact on clinical outcomes.     

Non-occupational and occupational factors associated with specific SARS-CoV-2 antibodies among hospital workers – A multicentre cross-sectional study

ObjectivesProtecting healthcare workers (HCWs) from coronavirus disease-19 (COVID-19) is critical to preserve the functioning of healthcare systems. We therefore assessed seroprevalence and identified risk factors for severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) seropositivity in this population.MethodsBetween 22 June 22 and 15 August 2020, HCWs from institutions in northern/eastern Switzerland were screened for SARS-CoV-2 antibodies. We recorded baseline characteristics, non-occupational and occupational risk factors. We used pairwise tests of associations and multivariable logistic regression to identify factors associated with seropositivity.ResultsAmong 4664 HCWs from 23 healthcare facilities, 139 (3%) were seropositive. Non-occupational exposures independently associated with seropositivity were contact with a COVID-19-positive household (adjusted OR 59, 95% CI 33–106), stay in a COVID-19 hotspot (aOR 2.3, 95% CI 1.2–4.2) and male sex (aOR 1.9, 95% CI 1.1–3.1). Blood group 0 vs. non-0 (aOR 0.5, 95% CI 0.3–0.8), active smoking (aOR 0.4, 95% CI 0.2–0.7), living with children <12 years (aOR 0.3, 95% CI 0.2–0.6) and being a physician (aOR 0.2, 95% CI 0.1–0.5) were associated with decreased risk. Other occupational risk factors were close contact to COVID-19 patients (aOR 2.7, 95% CI 1.4–5.4), exposure to COVID-19-positive co-workers (aOR 1.9, 95% CI 1.1–2.9), poor knowledge of standard hygiene precautions (aOR 1.9, 95% CI 1.2–2.9) and frequent visits to the hospital canteen (aOR 2.3, 95% CI 1.4–3.8).DiscussionLiving with COVID-19-positive households showed the strongest association with SARS-CoV-2 seropositivity. We identified several potentially modifiable work-related risk factors, which might allow mitigation of the COVID-19 risk among HCWs. The lower risk among those living with children, even after correction for multiple confounders, is remarkable and merits further study.     

Staphylococcus aureus bacteraemia mortality: a systematic review and meta-analysis

BackgroundPrecise estimates of mortality in Staphylococcus aureus bacteraemia (SAB) are important to convey prognosis and guide the design of interventional studies.ObjectivesWe performed a systematic review and meta-analysis to estimate all-cause mortality in SAB and explore mortality change over time.Data sourcesThe MEDLINE and Embase databases, as well as the Cochrane Database of Systematic Reviews, were searched from January 1, 1991 to May 7, 2021.Study eligibility criteriaHuman observational studies on patients with S. aureus bloodstream infection were included.ParticipantsThe study analyzed data of patients with a positive blood culture for S. aureus.MethodsTwo independent reviewers extracted study data and assessed risk of bias using the Newcastle–Ottawa Scale. A generalized, linear, mixed random effects model was used to pool estimates.ResultsA total of 341 studies were included, describing a total of 536,791 patients. From 2011 onward, the estimated mortality was 10.4% (95% CI, 9.0%–12.1%) at 7 days, 13.3% (95% CI, 11.1%–15.8%) at 2 weeks, 18.1% (95% CI, 16.3%–20.0%) at 1 month, 27.0% (95% CI, 21.5%–33.3%) at 3 months, and 30.2% (95% CI, 22.4%–39.3%) at 1 year. In a meta-regression model of 1-month mortality, methicillin-resistant S. aureus had a higher mortality rate (adjusted OR (aOR): 1.04; 95% CI, 1.02–1.06 per 10% increase in methicillin-resistant S. aureus proportion). Compared with prior to 2001, more recent time periods had a lower mortality rate (aOR: 0.88; 95% CI, 0.75–1.03 for 2001–2010; aOR: 0.82; 95% CI, 0.69–0.97 for 2011 onward).ConclusionsSAB mortality has decreased over the last 3 decades. However, more than one in four patients will die within 3 months, and continuous improvement in care remains necessary.     

HIV infection and electrocardiogram abnormalities: baseline assessment from the CHART cohort

ObjectivesTo investigate the prevalence of various electrocardiogram (ECG) abnormalities among HIV-positive and HIV-negative individuals.MethodsThis cross-sectional evaluation included 1412 HIV-positive and 2824 HIV-negative participants aged 18 to 75 years and frequency matched by age and sex, derived from the baseline survey of Comparative HIV and Aging Research in Taizhou (CHART), China, between February and December 2017.ResultsHIV-positive individuals had higher prevalence of sinus tachycardia (5.6% (79/1412) vs. 1.3% (36/2824), p < 0.001) and ST/T wave abnormalities (14.9% (211/1412) vs. 9.4% (264/1412), p < 0.001) but lower prevalence of sinus bradycardia (4.8% (68/1412) vs. 7.5% (211/2824), p 0.001); such associations remained statistically significant after adjusting for traditional risk factors (respectively, adjusted odds ratio (aOR) 4.68, 95% confidence interval (CI) 3.06–7.17; aOR 1.89, 95% CI 1.54–2.34; aOR 0.60, 95% CI 0.44–0.80). In adjusted models, being in higher carotid intima–media thickness categories was significantly associated with ST/T abnormalities in HIV-positive individuals only (0.78–1.00 mm: aOR 1.46, 95% CI 1.01–2.12; >1.00 mm: aOR 2.18, 95% CI 1.39–3.42), whereas being in higher blood pressure categories was significantly associated with both sinus tachycardia (prehypertension: aOR 5.61, 95% CI 1.76–17.91; hypertension: aOR 12.62, 95% CI 3.60–44.27) and ST/T abnormalities (hypertension: aOR 2.04, 95% CI 1.41–2.95) in HIV-negative individuals only. Longer duration of known HIV infection was the only HIV-specific factor of ST/T abnormalities (aOR 1.61, 95% CI 1.17–2.22), with none for sinus tachycardia.ConclusionsHIV infection is independently associated with sinus tachycardia and ST/T abnormalities. Further research is needed to investigate specific mechanisms by which HIV infection leads to ECG abnormalities and to evaluate whether inclusion of ECG parameters improves cardiovascular disease prediction. Integrating ECG screening into routine HIV care is recommended in China.     

Predictors for treatment outcomes among patients with drug-susceptible tuberculosis in the Netherlands: a retrospective cohort study

ObjectivesWe evaluated treatment outcomes and predictors for poor treatment outcomes for tuberculosis (TB) among native- and foreign-born patients with drug-susceptible TB (DSTB) in the Netherlands.MethodsThis retrospective cohort study included adult patients with DSTB treated from 2005 to 2015 from a nationwide exhaustive registry. Predictors for unsuccessful treatment outcomes (default and failure) and TB-associated mortality were analysed using multivariate logistic regression.ResultsAmong 5674 identified cases, the cumulative incidence of unsuccessful treatment and mortality were 2.6% (n/N = 146/5674) and 2.0% (112/5674), respectively. Although most patients were foreign-born (71%; 4042/5674), no significant differences in these outcomes were observed between native- and foreign-born patients (p > 0.05). Significant predictors for unsuccessful treatment were aged 18–24 years (odds ratio (OR), 2.04; 95% CI 1.34–3.10), homelessness (OR, 2.56; 95% CI 1.16–5.63), prisoner status (OR, 5.39; 95% CI 2.90–10.05) and diabetes (OR, 2.02; 95% CI 1.03–3.97). Furthermore, predictors for mortality were aged 74–84 years (OR, 5.58; 95% CI 3.10–10.03) or ≥85 years (OR, 9.35, 95% CI 4.31–20.30), combined pulmonary and extra-pulmonary TB (OR, 4.97; 95% CI 1.42–17.41), central nervous system (OR, 120, 95% CI 34.43–418.54) or miliary TB (OR, 10.73, 95% CI 2.50–46.02), drug addiction (OR, 3.56; 95% CI 1.34–9.47) and renal insufficiency/dialysis (OR, 3.23; 95% CI 1.17–8.96).ConclusionsNative- and foreign-born patients exhibited similar TB treatment outcomes. To further reduce disease transmission and inhibit drug resistance, special attention should be given to high-risk patients.     

Safety of prolonged outpatient courses of intravenous antibiotics: a prospective cohort study

ObjectivesThe perceived need for prolonged intravenous antibiotic courses has become a major driver behind the growth of outpatient parenteral antimicrobial therapy (OPAT) services. Several recent randomized controlled trials demonstrate noninferiority of an early switch to oral therapy and highlight the need to accurately quantify harms associated with OPAT.MethodsWe conducted a 10-year prospective cohort study in a tertiary hospital OPAT service. Adults admitted to the service between 1 June 2009 and 30 June 2019 who received an intravenous antimicrobial agent were included. Adverse events (AEs) attributable to intravenous antibiotics or intravenous access were recorded in a prospectively maintained database and analyzed.ResultsThere were 4160 admissions (median length of stay: 20 days) and a total of 88 432 patient-days of observation; 135 patients (3.3% of admissions) experienced at least one major AE (1.54 per 1000 patient-days; 95% CI, 1.29–1.82). The risk of a major AE peaked in the second week of OPAT admission, with acute kidney injury (43 of 136; 32%) and severe cytopenia (42 of 136; 31%) being the most common. At least one minor AE occurred in 38.3% of admissions (1592 of 4160; 26.4 per 1000 patient-days; 95% CI, 25.4–27.5), with central venous catheter-related complications accounting for 71% of AEs (1658 of 2338).DiscussionThe incidence of major AEs during long courses of intravenous antibiotics is low, peaking in week 2 and tailing off thereafter. These results should inform decisions concerning the choice of intravenous versus oral antimicrobials.     

Predictors of mortality in nursing-home residents with pneumonia: a multicentre study

ObjectivesTo evaluate predictors of mortality in patients residing in nursing-homes (NHs) or long-term care facilities (LTCFs) with diagnosis of NH-acquired pneumonia (NHAP).MethodsWe conducted an observational, prospective study (December 2013-December 2015) of patients residing in nine NHs/LTCFs of Central and Northern Italy with diagnosis of NHAP. Data on demographics, comorbidities, microbiology, and therapies were entered into an electronic database. To identify risk factors associated with 30-day mortality, we performed univariable and multivariable analyses, and predictors were internally validated using a bootstrap resampling procedure. We derived a prediction rule using the coefficients obtained from the multivariable logistic regression. The model obtained was assessed using the area under the receiver operating characteristic curve (AUROC).ResultsOverall, 446 patients with NHAP were included in the final cohort. The median age was 80 (IQR 75–87) years. A definite aetiology was obtained in 120 (26.9%) patients; of these, 66 (55%) had a culture positive for a multidrug-resistant pathogen. The 30-day mortality was 28.7%. On multivariate analysis, malnutrition (OR 7.8; 95% CI 3–20.2, 2 points), bilateral pneumonia (OR 3.7; 95% CI 1.4–9.8, 1 point), acute mental status deterioration (OR 6.2; 95% CI 2.2–17.6, 2 points), hypotension (OR 7.7; 95% CI 2.3–24.9, 2 points), and PaO₂/FiO₂ ratio ≤250 (OR 7.4; 95% CI 2.2–24.2, 2 points) were independently associated with 30-day mortality. The derived prediction rule showed an AUROC of 0.83 (95% CI 0.78–0.87, p <0.001).ConclusionsNH residents with pneumonia have specific risk factors associated with 30-day mortality. Malnutrition and acute mental change appear as major determinants of death in this population.     

Antibiotic strategies and clinical outcomes in critically ill patients with pneumonia caused by carbapenem-resistant Acinetobacter baumannii

ObjectivesThis study aimed to investigate antibiotic prescribing patterns and effectiveness of different anti-carbapenem-resistant Acinetobacter baumannii (CRAB) strategies for CRAB pneumonia.MethodsWe conducted a multicentre, retrospective study in three hospitals. During 2010–2015, adult ICU patients with CRAB pneumonia treated with at least one antimicrobial agent covering the CRAB isolate in vitro for more than 2 days were included. We used multivariate logistic regression to analyse the associations of anti-CRAB strategies with ICU mortality and other clinical outcomes.ResultsAmong 238 patients with CRAB pneumonia, tigecycline monotherapy (84, 35.3%) was the most common antibiotic strategy, followed by tigecycline with colistin (43, 18.1%), colistin monotherapy (34, 14.3%), colistin combination without tigecycline (33, 13.9%), tigecycline combination without colistin (32, 13.4%), and sulbactam-based therapy without tigecycline and colistin (12, 5.0%). In multivariate analysis, tigecycline-based therapy was associated with higher ICU mortality than non-tigecycline therapy (adjusted OR 2.30, 95% CI 1.19–4.46). There was no difference between colistin-based therapy and non-colistin therapy. Compared with tigecycline monotherapy, colistin monotherapy was associated with lower ICU mortality (aOR 0.30, 95% CI 0.10–0.88). Treatment failure analyses showed similar trends. Tigecycline-based therapy was associated with higher treatment failure rate than non-tigecycline therapy (aOR 2.51, 95% CI 1.39–4.54), whereas colistin-based therapy was associated with lower treatment failure rate than non-colistin-based therapy (aOR 0.48, 95% CI 0.27–0.86).ConclusionsTigecycline was commonly prescribed for CRAB pneumonia. However, tigecycline-based therapy was associated with higher ICU mortality and treatment failure. Our study suggests that colistin monotherapy may be a better antibiotic strategy for CRAB pneumonia.     

Perinatal influences on the development of asthma and atopy in childhood

BackgroundIn most children with asthma and atopy, onset of disease occurs early in life, indicating a crucial role of in utero and early childhood environment. However, only a small part of this burden of disease established early in life has been explained.ObjectiveTo examine the effects of early environmental exposures on the development of asthma and atopy within the setting of an affluent urban population.MethodsThe authors followed 526 German children from birth to 5 years of age. Parental interviews in pregnancy and then yearly assessed the health of the child and environmental characteristics. Endotoxin and allergens in house dust were measured at 3 months. Atopic sensitization was assessed at 1 and 5 years.ResultsIn atopic mothers, acute atopic symptoms during pregnancy were associated with increased risk of early atopic dermatitis (adjusted odds ratio [aOR] 1.74, 95% confidence interval [CI] 1.00–3.02) and allergic rhinitis at 5 years (aOR 2.11, 95% CI 1.01–4.41). Further, maternal illnesses during pregnancy (ie, repeated common colds) increased the risk of asthma at 5 years (aOR 2.31, 95% CI 1.12–4.78). Endotoxin in the child's mattress was inversely associated with atopic sensitization (aOR 0.79, 95% CI 0.64–0.97) and asthma (aOR 0.71, 95% CI 0.55–0.93). A contrasting effect of early endotoxin and mite exposure was observed for mite sensitization: mite exposure increased the risk of mite sensitization at 5 years (aOR 1.30, 95% CI 1.11–1.53), whereas endotoxin exposure was inversely associated with mite sensitization (aOR 0.73, 95% CI 0.57–0.95).ConclusionFactors affecting the in utero environment, such as maternal atopy and infections, and bacterial exposure in pregnancy or early life may act as immunomodulators enhancing or inhibiting the development of asthma and atopy in childhood.     

Current in-hospital management for patients with tuberculosis in a high-income country: a retrospective cohort study

ObjectivesIn Japan, most cases of tuberculosis (TB) occur among individuals aged 65 years or older. However, data on in-hospital adverse events (AEs) associated with TB management, especially in high-income nations with an ageing population, are scarce. The present study aimed to scrutinize the current TB unit practices, incidence of in-hospital AEs and predictors of in-hospital mortality.MethodsThis retrospective cohort study was conducted at a tertiary care centre in Tokyo, Japan from 2012 to 2017. Inpatients with the diagnosis of TB and aged >18 years were included. Quality of in-hospital care and factors associated with in-hospital mortality were investigated using multivariate logistic regression analysis.ResultsIn total, 448 patients were enrolled. The in-hospital mortality rate was 16.7% (75/448). Miliary/disseminated TB was common (59/448, 13.2%), especially in those who died (17/75, 22.7%). Factors independently associated with in-hospital mortality were a low Karnofsky performance status score on admission (score: 40-10, adjusted odds ratio (aOR) 25.65, 95% CI 5.63–116.92 and score: 70-50, aOR 9.47, 95% CI 2.07–43.3), age over 89 years (aOR 3.68, 95% CI 1.08–12.46), Charlson Co-morbidity Index >5 (aOR 3.56, 95% CI 1.37–9.21), development of any health-care-associated infection (aOR 2.95, 95% CI 1.35–6.41), and development of any drug-related AE leading to discontinuation of anti-TB agents (seven patients were unable to resume treatment with anti-TB agents before death) (aOR 2.29, 95% CI 1.02–5.11).ConclusionsIn-hospital AEs (i.e. health-care-associated infection and drug-related AEs), as well as patient-related variables, were associated with in-hospital mortality among TB patients.     

Clinical impact of recreational drug use among people living with HIV in southern Taiwan

BackgroundIt is unclear about the impact of recreational drug use on the adherence, drug–drug interaction and the occurrence of sexual transmitted diseases (STDs) among people living with HIV.Material and methodsA retrospective study was conducted between Dec 2016, and July 2018 to assess the clinical impact of recreational drug consumption in people living with HIV with antiretroviral therapy. We collected data of the demographics, recreational drug use, laboratory results and STDs diagnoses. Potential drug–drug interactions were checked with reference databases. The association between recreational drug use and STDs, HIV viral load suppression and drug interactions were evaluated.ResultsA total of 462 participants were enrolled, included 384 recreational drug users and 78 non-recreational drug users. Younger age (adjusted odds ratio [aOR], 0.94; 95% CI: 0.91–0.98; p = 0.001), longer HIV infection period (aOR, 1.11; 95% CI: 1.03–1.20; p = 0.009) and poor antiretroviral drug adherence (1–2 pills missing per month: aOR, 6.82; 95% CI: 3.50–13.27; p < 0.001; >2 pills missing per month: aOR, 3.50; 95% CI: 1.28–9.61; p = 0.015) were factors associated with recreational drug use. Methamphetamine and nitrites were two most common recreational drugs. Recreational drug use was significantly associated with STDs in one-year follow-up period (aOR, 2.43; 95% CI: 1.11–5.32; p = 0.027) but was not significantly associated with unsuppressed viral load, though a trend was observed (OR, 2.23; 95% CI: 0.92–5.37; p = 0.074). Potential interactions with recreational drugs included 33.1% antiretroviral drugs and 31.3% medications for comorbidities.ConclusionRecreational drug was associated with STDs. A great proportion of the patients consuming recreational drugs had potential interactions with antiretroviral drugs and medications for comorbidities. The association of recreational drug use and unsuppressed viral load warrants further investigation.     

Efficacy of adjunctive nebulized colistin in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial pneumonia: a multi-centre observational study

ObjectivesTo investigate the association between adjunctive nebulized colistin and treatment outcomes in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial (CR-GNB) pneumonia.MethodsThis retrospective, multi-centre, cohort study included individuals admitted to the intensive care unit with nosocomial pneumonia caused by colistin-susceptible CR-GNB. Enrolled patients were divided into groups with/without nebulized colistin as adjunct to at least one effective intravenous antibiotic. Propensity score matching was performed in the original cohort (model 1) and a time-window bias-adjusted cohort (model 2). The association between adjunctive nebulized colistin and treatment outcomes was analysed.ResultsIn total, 181 and 326 patients treated with and without nebulized colistin, respectively, were enrolled for analysis. The day 14 clinical failure rate and mortality rate were 41.4% (75/181) versus 46% (150/326), and 14.9% (27/181) versus 21.8% (71/326), respectively. In the propensity score-matching analysis, patients with nebulized colistin had lower day 14 clinical failure rates (model 1: 41% (68/166) versus 54.2% (90/166), p 0.016; model 2: 35.3% (41/116) versus 56.9% (66/116), p 0.001). On multivariate analysis, nebulized colistin was an independent factor associated with fewer day 14 clinical failures (model 1: adjusted odds ratio (aOR) 0.59, 95% CI 0.37–0.92; model 2: aOR 0.37, 95% CI 0.21–0.65). Nebulized colistin was not associated independently with a lower 14-day mortality rate in the time-dependent analysis in both models 1 and 2.ConclusionsAdjunctive nebulized colistin was associated with lower day 14 clinical failure rate, but not lower 14-day mortality rate, in critically ill patients with nosocomial pneumonia caused by colistin-susceptible CR-GNB.