Etiology,clinical features,management, and outcomes of skin and soft tissue infections in hospitalized children: A 10-year review

PurposeThis study aimed to describe the etiology, clinical features, hospital course, and outcomes of hospitalized children with skin and soft tissue infections (SSTIs) and to test if clinical and laboratory variables at admission could differentiate between community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-acquired methicillin-sensitive S. aureus (CA-MSSA).MethodsWe reviewed the clinical, laboratory, treatment, and outcome data for children hospitalized with SSTIs, aged 0–18 years at MacKay Children's Hospital between 2010 and 2019. Multivariable logistic regression was used to identify independent predictors of CA-MRSA and CA-MSSA SSTIs.ResultsA total of 1631 patients were enrolled. Erysipelas/cellulitis (73.8%) was the most common pediatric SSTI type, followed by acute lymphadenitis (13.6%) and abscess/furuncle/carbuncle (8.6%). Among the 639 culture-positive isolates (purulent SSTIs), 142 (22.2%) were CA-MSSA and 363 (56.8%) were CA-MRSA. The age group 0–1 month (OR, 6.52; 95% CI 1.09–38.92; P = 0.04) and local lymph node reaction (OR, 2.47; 95% CI 1.004–6.08; P = 0.049) were independent factors for differentiating children with CA-MSSA from those with CA-MRSA SSTIs. MRSA isolates in our cohort were highly susceptible to glycopeptides (100%), linezolid (100%), daptomycin (100%), and sulfamethoxazole/trimethoprim (98.6%) but were significantly less susceptible to clindamycin compared with MSSA (34.2% vs. 78.2%, P < 0.001).ConclusionS. aureus is the leading pathogen of culture-proven SSTIs in hospitalized children with MRSA accounting for more than half. Determining the optimal empirical antibiotics in CA-SSTIs may rely on the patient's age, disease severity, and local epidemiologic data.     

Clostridioides difficile colonization among very young children in resource-limited settings

ObjectivesTo describe the epidemiology and risk factors for Clostridioides difficile (C. difficile) colonization among young children in eight low-resource settings.MethodsWe tested 41 354 monthly non-diarrhoeal and diarrhoeal stools for C. difficile toxin genes (TcdA and TcdB) using quantitative PCR (qPCR) in 1715 children from birth to age two years in a multisite birth cohort study. We estimated the prevalence, cumulative incidence, and seasonality of C. difficile colonization and investigated the associations of C. difficile detection with risk factors of infection, markers of enteropathy, and growth.ResultsThe prevalence of C. difficile detection was lower in diarrhoeal (2.2%; n = 151/6731) compared to non-diarrhoeal stools (6.1%; n = 2106/34 623). By 24 months of age, the cumulative incidence of C. difficile varied widely by site, with 17.9% (n = 44; Pakistan) to 76.3% (n = 148; Peru) of children having at least one positive stool. Only Bangladesh and Pakistan had seasonal differences in C. difficile detection. Female sex (adjusted risk ratio (aRR): 1.18; 95% CI: 1.02–1.35), cephalosporin use in the past 15 days (aRR: 1.73; 95% CI: 1.39–2.16), and treated water (aRR: 1.24; 95% CI: 1.02–1.50) were risk factors for C. difficile positivity. The presence of C. difficile was significantly associated with elevated faecal myeloperoxidase, neopterin, and α-1-antitrypsin, but no associations were found between C. difficile and child growth at 24 months of age.DiscussionC. difficile colonization among children ages 0–2 years was variable across low-resource settings. Significant elevation of intestinal inflammation and barrier disruption markers associated with C. difficile detection suggests a subclinical impact of colonization.     

Impact of Staphylococcus aureus phenotype and genotype on the clinical characteristics and outcome of infective endocarditis. A multicentre,longitudinal, prospective,observational study

ObjectiveWe aimed to evaluate the impact of Staphylococcus aureus phenotype (vancomycin MIC) and genotype (agr group, clonal complex CC) on the prognosis and clinical characteristics of infective endocarditis (IE).MethodsWe performed a multicentre, longitudinal, prospective, observational study (June 2013 to March 2016) in 15 Spanish hospitals. Two hundred and thirteen consecutive adults (≥18 years) with a definite diagnosis of S. aureus IE were included. Primary outcome was death during hospital stay. Main secondary end points were persistent bacteraemia, sepsis/septic shock, peripheral embolism and osteoarticular involvement.ResultsOverall in-hospital mortality was 37% (n = 72). Independent risk factors for death were age-adjusted Charlson co-morbidity index (OR 1.20; 95% CI 1.08–1.34), congestive heart failure (OR 3.60; 95% CI 1.72–7.50), symptomatic central nervous system complication (OR 3.17; 95% CI 1.41–7.11) and severe sepsis/septic shock (OR 4.41; 95% CI 2.18–8.96). In the subgroup of methicillin-susceptible S. aureus IE (n = 173), independent risk factors for death were the age-adjusted Charlson co-morbidity index (OR 1.17; 95% CI 1.03–1.31), congestive heart failure (OR 3.39; 95% CI 1.51–7.64), new conduction abnormality (OR 4.42; 95% CI 1.27–15.34), severe sepsis/septic shock (OR 5.76; 95% CI 2.57–12.89) and agr group III (OR 0.27; 0.10–0.75). Vancomycin MIC ≥1.5 mg/L was not independently associated with death during hospital nor was it related to secondary end points. No other genotype variables were independently associated with in-hospital death.ConclusionsThis is the first prospective study to assess the impact of S. aureus phenotype and genotype. Phenotype and genotype provided no additional predictive value beyond conventional clinical characteristics. No evidence was found to justify therapeutic decisions based on vancomycin MIC for either methicillin-resistant or methicillin-susceptible S. aureus.     

Excess length of stay and readmission following hospital-acquired bacteraemia: a population-based cohort study applying a multi-state model approach

ObjectivesPopulation-based estimates of excess length of stay after hospital-acquired bacteraemia (HAB) are few and prone to time-dependent bias. We investigated the excess length of stay and readmission after HAB.MethodsThis population-based cohort study included the North Denmark Region adult population hospitalized for ≥48 hours, from 2006 to 2018. Using a multi-state model with 45 days of follow-up, we estimated adjusted hazard ratios (aHRs) for end of stay and discharge alive. The excess length of stay was defined as the difference in residual length of stay between infected and uninfected patients, estimated using a non-parametric approach with HAB as time-dependent exposure. Confounder effects were estimated using pseudo-value regression. Readmission after HAB was investigated using the Cox regression.ResultsWe identified 3457 episodes of HAB in 484 291 admissions in 205 962 unique patients. Following HAB, excess length of stay was 6.6 days (95% CI, 6.2–7.1 days) compared with patients at risk. HAB was associated with decreased probability of end of hospital stay (aHR, 0.60; 95% CI, 0.57–0.62) driven by the decreased hazard for discharge alive; the aHRs ranged from 0.30 (95% CI, 0.23–0.40) for bacteraemia stemming from ‘heart and vascular’ source to 0.72 (95% CI, 0.69–0.82) for the ‘urinary tract’. Despite increased post-discharge mortality (aHR, 2.76; 95% CI, 2.38–3.21), HAB was associated with readmission (aHR, 1.42; 95% CI, 1.31–1.53).ConclusionHAB was associated with considerably excess length of hospital stay compared with hospitalized patients without bacteraemia. Among patients discharged alive, HAB was associated with increased readmission rates.     

Clostridioides difficile infection in patients with hematological malignancy: A multicenter study in Taiwan

BackgroundAmong the individuals with hematological malignancy (HM) complicated with Clostridioides difficile infection (CDI), the variables associated with in-hospital mortality and recurrence of CDI were investigated.Material and methodsIncluding adults with HM and those without malignancy suffering from CDI from January 2015 to December 2016 in three hospitals in Taiwan.ResultsTotally 314 patients including 77 with HM and 237 patients without malignancy were included. HM patients more often had low leukocyte counts (<500 cells/mL: 28.6% vs. 2.1%) than those without malignancy and more patients without malignancy had severe CDI than patients with HM (31.6% vs. 14.3%, P = .003), according to the severity score of IDSA/SHEA. Patients with HM had a higher recurrence rate of CDI (14.3%, 11/77 vs. 7.2%, 17/237; P = .07) and longer hospital stay (47.2 ± 40.8 days vs. 33.3 ± 37.3 days; P = .006) than those without malignancy. In the multivariate analyses for those with HM and CDI, the in-hospital mortality was associated with vancomycin-resistant Enterococcus (VRE) colonization or infection (odds ratio [OR] 7.72; P = .01), and C. difficile ribotype 078 complex infection (OR 9.22; P = .03). Moreover underlying hematological malignancy (OR 2.74; P = .04) and VRE colonization/infection (OR 2.71; P = .02) were independently associated with CDI recurrence.ConclusionPatients with HM complicated with CDI were often regarded as non-severe infection, but had a similar in-hospital mortality rate as those without malignancy. CDI due to ribotype 078 complex isolates heralded a poor prognosis among HM patients.     

Host factors are more important in predicting recurrent Clostridium difficile infection than ribotype and use of antibiotics

ObjectiveA frequent complication of Clostridium difficile infection (CDI) is recurrent disease. The aim of this study was to determine whether early recurrence risk was higher after infection with ribotype 027 (outbreak strain) compared with infection with endemic strain types of C. difficile.MethodsConsecutive patients diagnosed with CDI between May 2013 and March 2014 were included (outbreak strain, and non-outbreak strains). Patients who developed recurrent CDI within 30 days after completion of CDI treatment, were compared with patients without a recurrence. Medical charts were reviewed for demographic and clinical characteristics. General practitioners were contacted to complete data about the occurrence of recurrent CDI, and the use of medication after hospital discharge.ResultsIn total, 135 patients were at risk for the development of recurrent CDI; 74 patients were infected by ribotype 027, and 61 patients by other ribotypes. Thirty-nine patients (29%) developed recurrent CDI within 30 days after completion of CDI treatment. In multivariable analysis, age ≥70 years (HR 3.05, 95% CI 1.54–6.03), and a duration of CDI treatment ≥11 days (HR 1.92, 95% CI 1.00–3.69) were clearly associated with recurrence; infection with ribotype 027 showed a HR of 1.72 (95% CI 0.88–3.33).ConclusionDuring this outbreak of C. difficile in a tertiary care centre, age and a prolonged duration of CDI therapy (which is most likely a marker of underlying disease severity) were the main risk factors for recurrent CDI. This points to host factors as more important predictors for recurrent CDI than strain type or antibiotic use.     

Role of frailty in prediction of hospitalized older adult patient’s outcomes: a prospective study

Background/aim Frailty is associated with an increased risk of negative short-term and long-term hospital outcomes. This study aimed to evaluate the role of frailty in predicting readmission, length of stay, and quality of life in the hospitalized older adults.Materials and methods This observational study was conducted at Ziaiyan Hospital, Tehran, Iran. In total, 304 participants (65–85 years), were enrolled through the inclusion criteria from August to December 2019. The frailty index (FI) was assessed by the minimum data set-home care. Readmission was obtained through telephone interviews. The length of stay was gathered by the patient’s hospital records, and the EuroQol questionnaire was used for assessing the quality of life. Data were collected by a researcher nurse at the admission time, 30, 60, and 90 days after discharge. The logistic regression model and repeated measures ANOVA were employed to analyze the association between frailty and outcomes.ResultsAccording to FI, 102 (33.55%) participants were pre-frail, whereas 35 (11.51%) were frail. In the fully-adjusted model for readmission, the pre-frail participants had a higher risk of readmission at the hospital in comparison with the nonfrail and frail groups (OR = 1.88, 95% CI = 1.90–3.26), and also for GP visits, frail patients showed nearly significant differences (OR = 2.45, 95% CI = 0.99–6.06) but there were no differences between frail and pre-frail patients in readmissions in the emergency ward. In a fully-adjusted prolonged stay model, pre-frail patients had a higher probability to stay longer in hospital (OR = 2.28, 95% CI: 1.24–4.18). The fully-adjusted model for QoL showed, frail patients were more prone to the declined levels of QoL in comparison with pre-frail patients (OR = 10.77, 95% CI: 3.97–29.18).ConclusionsThe findings indicated that frailty worsened negative outcomes and declined QoL. Early diagnosis in hospital settings could be beneficial for designing optimal care plans for the frail and pre-frail patients.     

Outpatient convalescent plasma therapy for high-risk patients with early COVID-19: a randomized placebo-controlled trial

ObjectivesThe potential benefit of convalescent plasma (CP) therapy for coronavirus disease 2019 (COVID-19) is highest when administered early after symptom onset. Our objective was to determine the effectiveness of CP therapy in improving the disease course of COVID-19 among high-risk outpatients.MethodsA multicentre, double-blind randomized trial was conducted comparing 300 mL of CP with non-CP. Patients were ≥50 years, were symptomatic for <8 days, had confirmed RT-PCR or antigen test result for COVID-19 and had at least one risk factor for severe COVID-19. The primary endpoint was the highest score on a 5-point ordinal scale ranging from fully recovered (score = 1) or not (score = 2) on day 7, over hospital admission (score = 3), intensive care unit admission (score = 4) and death (score = 5) in the 28 days following randomization. Secondary endpoints were hospital admission, symptom duration and viral RNA excretion.ResultsAfter the enrolment of 421 patients and the transfusion in 416 patients, recruitment was discontinued when the countrywide vaccination uptake in those aged >50 years was 80%. Patients had a median age of 60 years, symptoms for 5 days, and 207 of 416 patients received CP therapy. During the 28 day follow-up, 28 patients were hospitalized and two died. The OR for an improved disease severity score with CP was 0.86 (95% credible interval, 0.59–1.22). The OR was 0.58 (95% CI, 0.33–1.02) for patients with ≤5 days of symptoms. The hazard ratio for hospital admission was 0.61 (95% CI, 0.28–1.34). No difference was found in viral RNA excretion or in the duration of symptoms.ConclusionsIn patients with early COVID-19, CP therapy did not improve the 5-point disease severity score.     

Tocilizumab versus baricitinib in hospitalized patients with severe COVID-19: an open label,randomized controlled trial

ObjectiveRandomized controlled trials comparing tocilizumab and baricitinib in patients with coronavirus disease 2019 (COVID-19) are needed. This was an open-label, randomized controlled trial aiming to address this unmet need.MethodsTo determine whether baricitinib was non-inferior to tocilizumab, we assessed whether the upper boundary of the two-sided 95% CI of the hazard ratio (HR) did not exceed 1.50. The primary outcome was mechanical ventilation or death by day 28. Secondary outcomes included time to hospital discharge by day 28 and change in WHO progression scale at day 10.ResultsWe assigned 251 patients with COVID-19 and a PaO_2/FiO₂ ratio of <200 to receive either tocilizumab (n = 126) or baricitinib (n = 125) plus standard of care. Baricitinib was non-inferior to tocilizumab for the primary composite outcome of mechanical ventilation or death by day 28 (mechanical ventilation or death for patients who received baricitinib, 39.2% [n = 49/125]; mechanical ventilation or death for patients who received tocilizumab, 44.4% [n = 56/126]; HR, 0.83; 95% CI, 0.56–1.21; p 0.001 for non-inferiority). Baricitinib was non-inferior to tocilizumab for the time to hospital discharge within 28 days (patients who received baricitinib- discharged alive: 58.4% [n = 73/125] vs. patients who received tocilizumab- discharged alive: 52.4% [n = 66/126]; HR, 0.85; 95% CI, 0.61–1.18; p < 0.001 for non-inferiority). There was no significant difference between the baricitinib and tocilizumab arms in the change in WHO scale at day 10 (0.0 [95% CI, 0.0–0.0] vs. 0.0 [95% CI, 0.0–1.0]; p 0.83).DiscussionIn the setting of this trial, baricitinib was non-inferior to tocilizumab with regards to the composite outcome of mechanical ventilation or death by day 28 and the time to discharge by day 28 in patients with severe COVID-19.     

The association of obesity and dengue severity in hospitalized adult patients

BackgroundObesity is associated with unfavorable outcomes for infectious diseases. Most researches exploring the association between nutritional status and dengue severity have focused on pediatric populations, with only few studies assessing adult patients.MethodsAdult patients with laboratory-confirmed dengue admitted to a tertiary hospital in southern Taiwan between 2014 and 2015 were enrolled retrospectively. Demographics, comorbidities, clinical presentation, laboratory findings, and outcomes were obtained from case-record forms. Patients were categorized into obese group and nonobese group. The obese group comprised patients with a body mass index of ≥27.5 kg/m².ResultsA total of 1417 hospitalized patients with dengue were evaluated. The mean age was 57.9 years (range: 18–92 years). The obese and nonobese groups comprised 333 (23.5%) and 1084 (76.5%) patients, respectively. The obese group included more patients with hypertension (85%, p < 0.001), diabetes mellitus (33%, p < 0.001), and congestive heart failure (6.3%, p = 0.049). Multivariate analysis revealed that the obese group had more petechiae (AOR: 1.353, 95% CI: 1.025–1.786, p = 0.033), more dyspnea (AOR: 1.380, 95% CI: 1.015–1.876, p = 0.040), and more severe hepatitis (AOR: 2.061, 95% CI: 1.050–4.048, p = 0.036). The obese group also had higher peak hematocrit values (44.1%, p < 0.001) and lower nadir platelet count (45.3 × 10³/μL, p = 0.049) than the nonobese group.ConclusionIn adult patients with dengue, obese group had more petechiae, dyspnea, severe hepatitis, lower nadir of platelet count, and higher peak hematocrit level. We observed no difference in severe dengue or mortality between obese and nonobese group.     

Metronidazole-sensitive organisms in children with severe acute malnutrition: an evaluation of the indication for empiric metronidazole treatment

ObjectivesChildren with severe acute malnutrition (SAM) are treated with empiric amoxicillin or penicillin and gentamicin because of the high risk of severe infections. Experts have suggested, based on available evidence, adding metronidazole to cover anaerobic bacteraemia and diarrhoea caused by Giardia duodenalis or Clostridium difficile. The objective of this study was to assess the importance of these infections in children with SAM.MethodsChildren from 6 months to 15 years with SAM were enrolled and followed clinically. Aerobic and, when patient weight permitted, anaerobic blood cultures were done using Bactec® system, and isolates identified with matrix-assisted laser desorption ionization–time of flight mass spectrometry. Stool samples were tested for C. difficile, G. duodenalis and Entamoeba histolytica by PCR.ResultsA total of 334 children were enrolled and 174 out of 331 (53%) for which data on this was available had diarrhoea. Of 273 patients tested by blood culture, 11 had bacteraemia (4.0%, 95% CI 2.3–7.1%) but none with strict anaerobic bacteria (0/153, 95% CI 0–2.4%). There was no difference in the prevalence of C. difficile between children with (5/128, 4%) and without (7/87, 8%) diarrhoea (OR 0.47, 95% CI 0.14–1.53), and no difference in the prevalence of Giardia between these groups (78/138, 60% vs. 46/87, 53%; OR 1.34, 95% CI 0.77–2.32). Children with C. difficile had higher mortality than those without this infection (3/11, 27%, vs. 7/186, 4%; OR 43, 95% CI 3.9–483).ConclusionOur results do not provide support for empiric metronidazole to cover for anaerobic bacteraemia. Trials evaluating the effect of empiric treatment and its effect on G. duodenalis and C. difficile are warranted.     

Cessation of screening for intestinal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae in a low-endemicity intensive care unit with universal contact precautions

ObjectivesThe usefulness of screening for carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) with active surveillance cultures (ASC) remains equivocal in low-endemicity intensive care units (ICUs). Our primary objective was to appraise the impact of ceasing ASC on the incidence of ICU-acquired ESBL-E infections in an ICU with universal contact precautions (CP). Patient outcomes and carbapenem consumption were also investigated.MethodsA single-ICU, retrospective, uncontrolled before-and-after study including all patients admitted for ≥3 days during two consecutive 1-year periods with and without ASC.ResultsA total of 524 and 545 patients were included during the ASC and the no-ASC periods, respectively. Twenty-eight patients (5.3%) from the ASC period were ESBL-E carriers. An ICU-acquired ESBL-E infection (median duration of risk exposure, 4 (range 2–9) days for both periods) occurred in 1.1% and 1.5% of patients admitted during the ASC and the no-ASC periods (p = 0.64), with no inter-period variation in incidence after adjustment on competing risks of death and ICU discharge (standardized hazard ratio (SHR) 2.32, 95% CI 0.80–6.73, p = 0.12). An admission during the no-ASC period exerted no independent impact on the hazards of ESBL-E infections (adjusted OR 1.16, 95% CI 0.38–3.50, p = 0.79), in-ICU death (SHR 1.22, 95% CI 0.93–1.59, p = 0.15) and extended length of stay (SHR for discharge 0.89, 95% CI 0.79–1.01, p = 0.08). Carbapenem exposure in patients without ESBL-E infection decreased between the ASC and no-ASC periods (75 versus 61 carbapenem-days per 1000 patient-days, p = 0.01).ConclusionsIn a low-endemicity ICU with universal CP, the withdrawal of routine screening for ESBL-E carriage had no significant effect on the incidence of ICU-acquired ESBL-E infections and patient outcomes. Carbapenem consumption decreased in patients without ESBL-E infection.     

Length of stay and readmission in older adults hospitalized for heart failure

IntroductionHospital length of stay (LoS) and hospital readmissions are metrics of healthcare performance. We examined the association between these two metrics in older patients hospitalized with decompensated heart failure (HF).Material and methodsEight thousand and forty-nine patients hospitalized for HF in 106 U.S. hospitals had a median LoS of 5 days; among them, 3777 had a LoS > 5 days. Using propensity scores for LoS > 5 days, we assembled 2723 pairs of patients with LoS 1–5 vs. > 5 days. The matched cohort of 5446 patients was balanced on 40 baseline characteristics. We repeated the above process in 7045 patients after excluding those with LoS > 10 days, thus assembling a second matched cohort of 2399 pairs of patients with LoS 1–5 vs. 6–10 days. Hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with longer LoS were estimated in matched cohorts.ResultsIn the primary matched cohort (n = 5446), LoS > 5 days was associated with a higher risk of all-cause readmission at 30 days (HR = 1.16; 95% CI: 1.04–1.31; p = 0.010), but not during longer follow-up. A longer LoS was also associated with a higher risk of mortality during 8.8 years of follow-up (HR = 1.13; 95% CI: 1.06–1.21; p < 0.001). LoS had no association with HF readmission. Similar associations were observed among the matched sensitivity cohort (n = 4798) that excluded patients with LoS > 10 days.ConclusionsIn propensity score-matched balanced cohorts of patients with HF, a longer LoS was independently associated with poor outcomes, which persisted when LoS > 10 days were excluded.     

Four-year safety follow-up of the tetravalent dengue vaccine efficacy randomized controlled trials in Asia and Latin America

ObjectiveOur objective was to describe the risk of hospital admission for virologically confirmed dengue (VCD) and the risk of clinically severe hospitalized VCD occurring up to 4 years after the first dose (years 1 to 4) in three randomized clinical trials comparing tetravalent dengue vaccine with placebo.MethodsThe relative risks (RR) for hospitalized VCD from first dose to year 4 were estimated by year and age-group in individual and combined studies.ResultsOverall, from Year 1 to Year 4, 233 and 228 participants had at least one episode of hospitalized VCD in the vaccinated (n = 22 603) and placebo (n = 11 301) groups, respectively (RR = 0.511, 95% CI 0.42–0.62). Among these, 48 and 47 cases, respectively, were classified as clinically severe. In children aged ≥9 years, 88 and 136 participants had at least one episode of hospitalized VCD in the vaccinated (n = 17 629) and placebo (n = 8821) groups, respectively (RR = 0.324; 95% CI 0.24–0.43). In vaccinated participants aged <9 years, particularly in those aged 2–5 years, there were more hospitalized VCD cases compared with the control participants in Year 3 but not in Year 4. The overall RR in those aged <9 years for Year 1 to Year 4 was 0.786 (95% CI 0.60–1.03), with a higher protective effect in the 6–8 year olds than in the 2–5 year olds.ConclusionsThe overall benefit-risk remained positive in those aged ≥9 years up to year 4, although the protective effect was lower in years 3 and 4 than in years 1 and 2.     

Risk factors for candidaemia in hospitalized patients with liver cirrhosis: a multicentre case–control–control study

ObjectivesThe aim of this study was to evaluate the risk factors for candidaemia in patients with liver cirrhosis.MethodsThis was a case–control–control (1:2:2) study performed in four Italian tertiary centres from 2006 to 2015. Cases were patients with liver cirrhosis developing candidaemia. For every case of candidaemia we enrolled two additional patients undergoing blood cultures for suspected infection yielding isolation of a bacterial pathogen (control A) and two additional patients undergoing blood cultures for suspected infection yielding negative results (control B). Patients were matched according to age, sex and model for end stage liver disease at hospital admission.ResultsDuring the study period 90 cases, 180 controls A and 180 controls B were included. At multivariate analysis assessed by means of multinomial conditional regression models, factors independently associated with candidaemia were previous (<30 days) acute-on-chronic liver failure (relative risk ratio (RRR) 2.22 (95% confidence interval (CI) 1.09–4.54), p = 0.046), previous(<30 days) gastrointestinal endoscopy (RRR 2.38 (95% CI 1.19–4.78) p = 0.014), previous(<30 days) antibiotic treatment for at least 7 days (RRR 2.74 (95% CI 1.00–7.48), p = 0.049), presence of central venous catheter (RRR 2.77 (95% CI 1.26–6.09, p = 0.011), total parenteral nutrition (RRR 3.90 (95% CI 1.62–9.40), p = 0.002) at infection onset and length of in-hospital stay >15 days (RRR 4.63 (95% CI 2.11–10.18), p <0.001] Conversely, rifaximin treatment was associated with lower rate of candidaemia (RRR 0.38 (95% CI 0.19–0.77), p = 0.007). Multivariable analysis for 30-day mortality showed that patients with isolation of Candida spp. from blood cultures had worse outcome when compared with controls even though the difference did not reach a statistical significance (hazard ratio 1.64 (95% 0.97–2.75) p = 0.06).ConclusionsWe identified previous antibiotic use, gastrointestinal endoscopy or acute-on-chronic liver failure and presence of central venous catheter especially for parenteral nutrition as independent factors associated with candidaemia. Surprisingly, chronic rifaximin use was a protective factor.     

Stenotrophomonas isolates in a tertiary care centre in South India

PurposeStenotrophomonas maltophilia is an emerging multi-drug resistant pathogen increasingly isolated in India. This study aimed to identify patients from whom Stenotrophomonas maltophilia had been isolated and assess predictors of mortality in this population.MethodsThis was a retrospective cohort study of hospitalized patients with a positive culture for S. maltophilia over a 3-year period. Clinical details and laboratory results were assessed from hospital records. Bivariate and multivariate analysis was used to identify risk factors for mortality.ResultsOne hundred and nineteen patients (mean age 48.6 years) were included in the study. Of these, 111 patients were hospitalized for at least 48 ?hours prior to culture and 98 were admitted in the intensive care unit. Bivariate analysis revealed multiple associations with mortality, including a background of renal, cardiac, autoimmune disease, recent carbapenam use and COVID-19 infection and increasing ventilatory requirement, lower PaO₂/FiO₂ (P/F) ratio, vasopressor use, thrombocytopenia, and hypoalbuminemia at the time of positive isolate. Multivariate analysis showed that autoimmune disease [OR 27.38; 95% CI (1.39–540)], a P/F ratio of less than 300 [OR 7.58; 95% CI (1.52–37.9)], vasopressor requirement [OR 39.50; 95% CI (5.49–284)] and thrombocytopenia [OR 11.5; 95% CI (2.04–65.0)] were statistically significantly associated with increased mortality, while recent surgery and receipt of antibiotics [OR 0.16; 95% CI (0.03–0.8)] targeted against S. maltophilia were associated with decreased mortality.ConclusionStenotrophomonas maltophilia is primarily isolated in patients in the intensive care unit. In our study the need for vasopressors, autoimmune disease, lower P/F ratios and thrombocytopenia were associated with higher mortality. The association of targeted antibiotics with reduced mortality suggests that the pathogenic role of S. maltophilia should not be underestimated. This finding needs to be confirmed with larger, prospective studies.     

Cytomegalovirus Infection in Patients Who Underwent Allogeneic Hematopoietic Stem Cell Transplantation in Portugal: A Five-Year Retrospective Review

Cytomegalovirus (CMV) infection is 1 of the leading causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (aHSCT), mainly within the first 100 days after transplantation. We aimed to characterize CMV infection in a cohort of 305 patients with different malignancies undergoing aHSCT at the Portuguese Institute of Oncology of Porto between January 2008 and December 2012. In total, 184 patients (60.3%) developed CMV infection, mainly viral reactivations rather than primary infections (96.2% versus 3.8%, respectively). The majority of patients (166 of 184) developed CMV infection ≤100 days after transplantation, with median time to infection of 29 days (range, 0 to 1285) and median duration of infection of 10 days (range, 2 to 372). Multivariate analysis revealed that CMV infection was increased in donor (D)-/recipient (R)+ and D+/R+ (odds ratio [OR], 10.5; 95% confidence interval [CI], 4.35 to 25.4; P < .001) and in patients with mismatched or unrelated donors (OR, 2.54; 95% CI, 1.34 to 4.80; P = .004). Cox regression model showed that the risk of death was significantly increased in patients >38 years old (OR, 1.89; 95% CI, 1.14 to 3.12; P = .0137), who underwent transplantation with peripheral blood (OR, 3.02; 95% CI, 1.33 to 6.86; P = .008), with mismatched or unrelated donor (OR, 2.16; 95% CI, 1.48 to 3.13; P < .001), and who developed CMV infection (OR, 1.76; 95% CI, 1.07 to 2.90; P = .025). Moreover, patients who developed CMV infection had a significantly reduced median post-transplantation survival (16 versus 36 months; P = .002).     

Susceptibilities of clinical Clostridium difficile isolates to antimicrobials: a systematic review and meta-analysis of studies since 1970

ObjectivesAlthough exposure to antibiotics can cause Clostridium difficile infection, certain antibiotics are used to treat C. difficile. Measurements of antimicrobial C. difficile activity could help to identify antibiotic risk and emergent resistance. Here, we describe publication patterns relating to C. difficile susceptibilities and estimate minimum inhibitory concentrations (MIC) for antibiotic classes in the published literature between January 1970 and June 2014.MethodsWe queried PUBMED and EMBASE for studies reporting antibiotic C. difficile MIC in English or French. We used mixed-effects models to obtain pooled estimates of antibiotic class median MIC (MIC₅₀), 90th percentile of MIC (MIC₉₀), and MIC₉₀:MIC₅₀ ratio.ResultsOur search identified 182 articles that met our inclusion criteria, of which 27 were retained for meta-analysis. Aminoglycosides (MIC₅₀ 120 mg/L, 95% CI 62–250), 3rd (MIC₅₀ 75 mg/L, 95% CI 39–130) and 2nd generation cephalosporins (MIC₅₀ 64 mg/L, 95% CI 27–140) had the least C. difficile activity. Rifamycins (MIC₅₀ 0.034 mg/L, 95% CI 0.012–0.099) and tetracyclines (MIC₅₀ 0.29 mg/L, 95% CI 0.054–1.7) had the highest level of activity. The activity of 3rd generation cephalosporins was more than three times lower than that of 1st generation agents (MIC₅₀ 19 mg/L, 95% CI 7.0–54). Time-trends in MIC₅₀ were increasing for carbapenems (70% increase per 10 years) while decreasing for tetracyclines (51% decrease per 10 years).ConclusionsWe found a 3500-fold variation in antibiotic C. difficile MIC₅₀, with aminoglycosides as the least active agents and rifamycins as the most active. Further research is needed to determine how in vitro measures can help assess patient C. difficile risk and guide antimicrobial stewardship.