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A 55-year-old man sought treatment for an uncomplicated febrile illness after returning to Canada from the Philippines. A suspected diagnosis of Plasmodium knowlesi infection was confirmed by PCR, and treatment with atovaquone/proguanil brought successful recovery. We review the evolving epidemiology of P. knowlesi malaria in the Philippines, specifically within Palawan Island.
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Malária , Plasmodium knowlesi , Masculino , Humanos , Pessoa de Meia-Idade , Filipinas/epidemiologia , Plasmodium knowlesi/genética , Malária/diagnóstico , Malária/tratamento farmacológico , Malária/epidemiologia , Canadá/epidemiologia , Reação em Cadeia da PolimeraseRESUMO
BACKGROUND: WHO identifies pregnant women to be at increased risk for severe outcomes from influenza virus infections and recommends that they be prioritized for influenza vaccination. The evidence supporting this, however, is inconsistent. Ecologic studies in particular suggest more severe outcomes from influenza infection during pregnancy than studies based on individual patient data. Individual studies however may be underpowered and, as reported in a previous systematic review, confounding factors could not be adjusted for. We therefore conducted an individual participant data meta-analysis to assess the risk for severe outcomes of influenza infection in pregnant women while adjusting for other prognostic factors. METHODS: We contacted authors of studies included in a recently published systematic review. We pooled the individual participant data of women of reproductive age and laboratory confirmation of influenza virus infection. We used a generalized linear mixed model and reported odds ratios (OR) and 95% confidence intervals (CI). RESULTS: A total of 33 datasets with data on 186,656 individuals were available, including 36,498 eligible women of reproductive age and known pregnancy status. In the multivariable model, pregnancy was associated with a 7 times higher risk of hospital admission (OR 6.80, 95%CI 6.02-7.68), among patients receiving medical care as in- or outpatients, pregnancy was associated with a lower risk of admission to intensive care units (ICU; OR 0.57, 95%CI 0.48-0.69), and was not significantly associated with death (OR 1.00, 95%CI 0.75-1.34). CONCLUSIONS: Our study found a higher risk of influenza associated hospitalization among pregnant women as compared to non-pregnant women. We did not find a higher mortality rate or higher likelihood of ICU admission among pregnant women who sought medical care. However, this study did not address whether a true community based cohort of pregnant women is at higher risk of influenza associated complications.
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Influenza Humana/mortalidade , Complicações Infecciosas na Gravidez/mortalidade , Complicações Infecciosas na Gravidez/virologia , Adolescente , Adulto , Estudos de Coortes , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Vacinas contra Influenza/uso terapêutico , Influenza Humana/complicações , Influenza Humana/tratamento farmacológico , Unidades de Terapia Intensiva/estatística & dados numéricos , Pessoa de Meia-Idade , Razão de Chances , Gravidez , Gestantes , Fatores de RiscoRESUMO
BACKGROUND: Antibiotics can disturb gastrointestinal microbiota which may lead to reduced resistance to pathogens such as Clostridium difficile (C. difficile). Probiotics are live microbial preparations that, when administered in adequate amounts, may confer a health benefit to the host, and are a potential C. difficile prevention strategy. Recent clinical practice guidelines do not recommend probiotic prophylaxis, even though probiotics have the highest quality evidence among cited prophylactic therapies. OBJECTIVES: To assess the efficacy and safety of probiotics for preventing C.difficile-associated diarrhea (CDAD) in adults and children. SEARCH METHODS: We searched PubMed, EMBASE, CENTRAL, and the Cochrane IBD Group Specialized Register from inception to 21 March 2017. Additionally, we conducted an extensive grey literature search. SELECTION CRITERIA: Randomized controlled (placebo, alternative prophylaxis, or no treatment control) trials investigating probiotics (any strain, any dose) for prevention of CDAD, or C. difficile infection were considered for inclusion. DATA COLLECTION AND ANALYSIS: Two authors (independently and in duplicate) extracted data and assessed risk of bias. The primary outcome was the incidence of CDAD. Secondary outcomes included detection of C. difficile infection in stool, adverse events, antibiotic-associated diarrhea (AAD) and length of hospital stay. Dichotomous outcomes (e.g. incidence of CDAD) were pooled using a random-effects model to calculate the risk ratio (RR) and corresponding 95% confidence interval (95% CI). We calculated the number needed to treat for an additional beneficial outcome (NNTB) where appropriate. Continuous outcomes (e.g. length of hospital stay) were pooled using a random-effects model to calculate the mean difference and corresponding 95% CI. Sensitivity analyses were conducted to explore the impact of missing data on efficacy and safety outcomes. For the sensitivity analyses, we assumed that the event rate for those participants in the control group who had missing data was the same as the event rate for those participants in the control group who were successfully followed. For the probiotic group, we calculated effects using the following assumed ratios of event rates in those with missing data in comparison to those successfully followed: 1.5:1, 2:1, 3:1, and 5:1. To explore possible explanations for heterogeneity, a priori subgroup analyses were conducted on probiotic species, dose, adult versus pediatric population, and risk of bias as well as a post hoc subgroup analysis on baseline risk of CDAD (low 0% to 2%; moderate 3% to 5%; high > 5%). The overall quality of the evidence supporting each outcome was independently assessed using the GRADE criteria. MAIN RESULTS: Thirty-nine studies (9955 participants) met the eligibility requirements for our review. Overall, 27 studies were rated as either high or unclear risk of bias. A complete case analysis (i.e. participants who completed the study) among trials investigating CDAD (31 trials, 8672 participants) suggests that probiotics reduce the risk of CDAD by 60%. The incidence of CDAD was 1.5% (70/4525) in the probiotic group compared to 4.0% (164/4147) in the placebo or no treatment control group (RR 0.40, 95% CI 0.30 to 0.52; GRADE = moderate). Twenty-two of 31 trials had missing CDAD data ranging from 2% to 45%. Our complete case CDAD results proved robust to sensitivity analyses of plausible and worst-plausible assumptions regarding missing outcome data and results were similar whether considering subgroups of trials in adults versus children, inpatients versus outpatients, different probiotic species, lower versus higher doses of probiotics, or studies at high versus low risk of bias. However, in a post hoc analysis, we did observe a subgroup effect with respect to baseline risk of developing CDAD. Trials with a baseline CDAD risk of 0% to 2% and 3% to 5% did not show any difference in risk but trials enrolling participants with a baseline risk of > 5% for developing CDAD demonstrated a large 70% risk reduction (interaction P value = 0.01). Among studies with a baseline risk > 5%, the incidence of CDAD in the probiotic group was 3.1% (43/1370) compared to 11.6% (126/1084) in the control group (13 trials, 2454 participants; RR 0.30, 95% CI 0.21 to 0.42; GRADE = moderate). With respect to detection of C. difficile in the stool pooled complete case results from 15 trials (1214 participants) did not show a reduction in infection rates. C. difficile infection was 15.5% (98/633) in the probiotics group compared to 17.0% (99/581) in the placebo or no treatment control group (RR 0.86, 95% CI 0.67 to 1.10; GRADE = moderate). Adverse events were assessed in 32 studies (8305 participants) and our pooled complete case analysis indicates probiotics reduce the risk of adverse events by 17% (RR 0.83, 95% CI 0.71 to 0.97; GRADE = very low). In both treatment and control groups the most common adverse events included abdominal cramping, nausea, fever, soft stools, flatulence, and taste disturbance. AUTHORS' CONCLUSIONS: Based on this systematic review and meta-analysis of 31 randomized controlled trials including 8672 patients, moderate certainty evidence suggests that probiotics are effective for preventing CDAD (NNTB = 42 patients, 95% CI 32 to 58). Our post hoc subgroup analyses to explore heterogeneity indicated that probiotics are effective among trials with a CDAD baseline risk >5% (NNTB = 12; moderate certainty evidence), but not among trials with a baseline risk ≤5% (low to moderate certainty evidence). Although adverse effects were reported among 32 included trials, there were more adverse events among patients in the control groups. The short-term use of probiotics appears to be safe and effective when used along with antibiotics in patients who are not immunocompromised or severely debilitated. Despite the need for further research, hospitalized patients, particularly those at high risk of CDAD, should be informed of the potential benefits and harms of probiotics.
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Antibacterianos/efeitos adversos , Clostridioides difficile , Diarreia/prevenção & controle , Enterocolite Pseudomembranosa/complicações , Probióticos/uso terapêutico , Adulto , Criança , Diarreia/microbiologia , Enterocolite Pseudomembranosa/epidemiologia , Humanos , Incidência , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Background: The cefazolin inoculum effect (CzIE) is a phenomenon whereby some MSSA isolates demonstrate resistance to cefazolin when a high bacterial inoculum is used for susceptibility testing. The clinical significance of this phenotypic phenomenon remains unclear. We conducted a systematic review to answer the following question: In patients with serious MSSA infection treated with cefazolin, does infection due to CzIE-positive MSSA isolates result in worse clinical outcomes than infection due to CzIE-negative MSSA isolates? Methods: Ovid MEDLINE, Embase, Cochrane CENTRAL, medRxiv and bioRxiv were searched from inception until 12 April 2023. Studies were included if they tested for CzIE in clinical isolates from MSSA infections in humans. Two independent reviewers extracted data and conducted risk-of-bias assessment. Main outcomes were treatment failure and mortality. Pooling of study estimates was not performed given the heterogeneity of patient populations and outcome definitions. Results: Twenty-three observational studies were included. CzIE presence amidst MSSA isolates ranged from 0% to 55%. There was no statistically significant mortality difference in two studies that compared MSSA infections with and without CzIE, with ORs ranging from 0.72 to 19.78. Of four studies comparing treatment failure, ORs ranged from 0.26 to 13.00. One study showed a significantly higher treatment failure for the CzIE group, but it did not adjust for potential confounders. Conclusions: The evidence on CzIE is limited by small observational studies. In these studies, CzIE did not predict higher mortality in MSSA infections treated with cefazolin. Our findings do not support CzIE testing in clinical practice currently.
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Colistin resistance testing methods such as broth microdilution (BMD) are time-consuming and labour intensive for clinical laboratories. MBT Lipid Xtract Kit on MALDI Biotyper Sirius System (Bruker, Billerica, MA, USA) utilizes lipidomic analysis to identify specific cell wall modifications associated with colistin resistance. We compared MBT to BMD (ComASP Colistin, Liofilchem) across 36 Gram-negative isolates (non-resistant MIC ≤2 µg ml-1, resistant MIC ≥4 µg ml-1). All samples were tested twice on MBT with discrepant results repeated before assessing categorical agreement between MBT and BMD. 44.4% (16/36) of isolates were colistin resistant via BMD. MBT Lipid Xtract had 80.6% agreement (29/36) with BMD, with 5/7 discrepancies corrected to match upon repeat testing. There was 100% agreement for Escherichia coli isolates (n=16). The whole-genome sequencing was completed on the two discrepant Klebsiella pneumoniae isolates, with variants within colistin resistance-associated loci identified (MIC 0.5 µg ml-1: arnC S30T, pmrB T246A, lapB N212T, lpxM S253G, crrB Q287K and MIC >16 µg ml-1: arnC S30T, pmrB R90insRN, pmrB T246A, pmrA E57G, lpxM S253G). Further evaluation, particularly for non-E. coli, of MBT is required prior to implementation in clinical laboratories.
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Antibacterianos , Colistina , Farmacorresistência Bacteriana , Testes de Sensibilidade Microbiana , Colistina/farmacologia , Antibacterianos/farmacologia , Humanos , Bactérias Gram-Negativas/efeitos dos fármacos , Sequenciamento Completo do Genoma , Escherichia coli/efeitos dos fármacos , Escherichia coli/genéticaRESUMO
Introduction: Although rare, human infections caused by Gordonia spp. have been reported, especially within the immunocompromised population and those with long-term indwelling devices. We report a case of Gordonia spp. bacteraemia in a renal transplant patient and present a literature review on microbiological identification methods of this organism. Case Presentation: A 62-year-old female renal transplant recipient admitted to hospital with a 2-month history of dry cough and fevers occurring weekly when receiving electrolyte replacement infusions via a Groshong line. Over 2 weeks, blood cultures repeatedly isolated a Gram-positive bacillus solely in aerobic bottles, and this was initially reported as Rhodococcus spp. by the local microbiology laboratory. Chest computed tomography (CT) showed multiple ground-glass lung opacities suggestive of septic pulmonary emboli. As central line-associated bloodstream infection was suspected, empirical antibiotics were initiated and the Groshong line was removed. The Gram-positive bacillus was later confirmed by the reference laboratory as Gordonia sputi via 16S rRNA sequencing. Vancomycin and ciprofloxacin for a duration of 6 weeks were completed as targeted antimicrobial therapy. After treatment, the patient remained symptom-free with marked improvement on repeat CT chest imaging. Conclusion: This case illustrates the challenges surrounding identification of Gordonia spp. and other aerobic actinomycetes. 16S rRNA gene sequencing may be a preferred identification method, especially when initial workup of a weakly acid-fast organism fails to make an identification or shows discrepant results using traditional diagnostic modalities.
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Background/Objectives: Yee Hong Play Intervention for Dementia (PID) is a community program strengthening East Asians >65 years with dementia in their daily functional activities. We analyzed how PID activities align with Hong Kong Montreal Cognitive Assessment. Methods: Utilizing observation sheets procured from documentation notes from the twice-weekly PID sessions, cognitive domains were identified. Mean time duration and activity frequencies were compared between high and low competency client groups. Results: Independent of competency group, activities predominantly targeted attention/concentration (23.8% HC, 16.4% LC), and hand-eye coordination (19.1% HC, 28.7% LC). Less focused domains were delayed recall (3.1-4.7%) and naming (1.3-1.5%). Conclusions: Yee Hong PID tested innovative cognitive domains not currently covered in HK-MoCA screening assessment, emphasizing attention/concentration-oriented activities and none assessing orientation and language domains. Additionally, presence of new domains such as hand-eye coordination and fine motor dexterity suggested that strict adherence with standardized screening tools (e.g., MoCA) may not be ideal. Likely, facilitators have developed innovative measures to assess individual competency to strengthen resilience in our geriatric population.
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The objective of this study was to assess whether use of matrix assisted laser desorption ionization-time of flight (MALDI-TOF), through improvements in identification time, reduces time to directed antibiotic coverage. We therefore conducted a retrospective review of 377 blood cultures from hospitalized patients with gram negative bacteremia that underwent testing by MALDI-TOF compared to standard identification methods (VITEK 2) for blood cultures from January 2016 to December 2017. We found that MALDI significantly reduced time between blood culture collection to reach pathogen identification and was associated with a significantly reduced time to initiate more specific therapy, with a mean difference of 16.37 hours, 95% CI 10.05 to 22.69 (mean time 50.34 hours (+/- 21.21) vs VITEK: 66.71 hrs (+/- 27.12), p<0.001 as well as a reduced time to discontinue previous therapy (p = 0.004). In conclusion, in reducing time to identification of gram negative bacteremia, MALDI-TOF led to improvements in antibiotic coverage.
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Bacteriemia/diagnóstico , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Hemocultura/métodos , Humanos , Estudos RetrospectivosRESUMO
OBJECTIVETo determine whether probiotic prophylaxes reduce the odds of Clostridium difficile infection (CDI) in adults and children.DESIGNIndividual participant data (IPD) meta-analysis of randomized controlled trials (RCTs), adjusting for risk factors.METHODSWe searched 6 databases and 11 grey literature sources from inception to April 2016. We identified 32 RCTs (n=8,713); among them, 18 RCTs provided IPD (n=6,851 participants) comparing probiotic prophylaxis to placebo or no treatment (standard care). One reviewer prepared the IPD, and 2 reviewers extracted data, rated study quality, and graded evidence quality.RESULTSProbiotics reduced CDI odds in the unadjusted model (n=6,645; odds ratio [OR] 0.37; 95% confidence interval [CI], 0.25-0.55) and the adjusted model (n=5,074; OR, 0.35; 95% CI, 0.23-0.55). Using 2 or more antibiotics increased the odds of CDI (OR, 2.20; 95% CI, 1.11-4.37), whereas age, sex, hospitalization status, and high-risk antibiotic exposure did not. Adjusted subgroup analyses suggested that, compared to no probiotics, multispecies probiotics were more beneficial than single-species probiotics, as was using probiotics in clinical settings where the CDI risk is ≥5%. Of 18 studies, 14 reported adverse events. In 11 of these 14 studies, the adverse events were retained in the adjusted model. Odds for serious adverse events were similar for both groups in the unadjusted analyses (n=4,990; OR, 1.06; 95% CI, 0.89-1.26) and adjusted analyses (n=4,718; OR, 1.06; 95% CI, 0.89-1.28). Missing outcome data for CDI ranged from 0% to 25.8%. Our analyses were robust to a sensitivity analysis for missingness.CONCLUSIONSModerate quality (ie, certainty) evidence suggests that probiotic prophylaxis may be a useful and safe CDI prevention strategy, particularly among participants taking 2 or more antibiotics and in hospital settings where the risk of CDI is ≥5%.TRIAL REGISTRATIONPROSPERO 2015 identifier: CRD42015015701Infect Control Hosp Epidemiol 2018;771-781.