The MORDOR I trial
, conducted in Niger, Malawi and Tanzania, demonstrated that mass azithromycin distribution to preschool children reduced childhood mortality
. However, the large but simple trial ...design precluded determination of the mechanisms involved. Here we examined the gut microbiome of preschool children from 30 Nigerien communities randomized to either biannual azithromycin or placebo. Gut microbiome γ-diversity was not significantly altered (P = 0.08), but the relative abundances of two Campylobacter species, along with another 33 gut bacteria, were significantly reduced in children treated with azithromycin at the 24-month follow-up. Metagenomic analysis revealed functional differences in gut bacteria between treatment groups. Resistome analysis showed an increase in macrolide resistance gene expression in gut microbiota in communities treated with azithromycin (P = 0.004). These results suggest that prolonged mass azithromycin distribution to reduce childhood mortality reduces certain gut bacteria, including known pathogens, while selecting for antibiotic resistance.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Despite numerous studies, the clinical value of sputum cultures in the management of pneumonia remains controversial; therefore, understanding the economic value of sputum cultures may help decision ...makers determine their appropriate use in patient management.
We developed a decision model to determine the economic and clinical value of using sputum cultures in the treatment of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) from the hospital perspective under various conditions.
For both CAP and HCAP patients, obtaining sputum cultures resulted in similar costs compared to no culture, even if cultures cost $0. Given current clinical practices, obtaining cultures cost $539–631 more per CAP patient and $13–170 per HCAP patient compared to no culture use. However, cultures saved $8–202 per HCAP patient with a 40% probability the pathogen was the true cause (75% reduction in adverse outcomes, greater length of hospital stay (LOS) increase) to a 70% probability the pathogen was the true cause (25% reduction in outcomes and greater LOS increase and a 75% reduction in outcomes and all LOS increases). Additionally, obtaining sputum cultures had no impact on the number of adverse outcomes (i.e., adverse drug events, Clostridium difficile infection, pneumonia readmissions, additional hospitalization days). When all patients were treated with antibiotics empirically, obtaining cultures saved $4–342.
Overall, obtaining sputum cultures does not provide significant clinical or economic benefits for CAP or HCAP patients; however, it can reduce costs and shorten overall LOS under some circumstances. Clinicians should consider their local conditions when making decisions about sputum culture use.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Patients with community-onset (CO) methicillin-resistant
(MRSA) infections contribute to MRSA contamination of the home environment and may be reexposed to MRSA strains from this reservoir. This ...study evaluates One Health risk factors, which focus on the relationship between humans, animals, and the environment, for the increased prevalence of multiple antimicrobial-resistant MRSA isolates in the home environment. During a trial of patients with CO-MRSA infection, MRSA was isolated from the household environment at the baseline and 3 months later, following randomization of patients and household members to mupirocin-based decolonization therapy or an education control group. Up to two environmental MRSA isolates collected at each visit were tested. MRSA isolates were identified in 68% (65/95) of homes at the baseline (
= 104 isolates) and 51% (33/65) of homes 3 months later (
= 56 isolates). The rates of multidrug resistance (MDR) were 61% among isolates collected at the baseline and 55% among isolates collected at the visit 3 months later. At the baseline, 100% (14/14) of MRSA isolates from rural homes were MDR. While antimicrobial use by humans or pets was associated with an increased risk for the isolation of MDR MRSA from the environment, clindamycin use was not associated with an increased risk for the isolation of MDR MRSA. Incident low-level mupirocin-resistant MRSA strains were isolated at 3 months from 2 (5%) of 39 homes that were randomized to mupirocin treatment but none of the control homes. Among patients recently treated for a CO-MRSA infection, MRSA and MDR MRSA were common contaminants in the home environment. This study contributes to evidence that occupant use of antimicrobial drugs, except for clindamycin, is associated with MDR MRSA in the home environmental reservoir. (This study has been registered at ClinicalTrials.gov under registration no. NCT00966446.)
MRSA is a common bacterial agent implicated in skin and soft tissue infections (SSTIs) in both community and health care settings. Patients with CO-MRSA infections contribute to environmental MRSA contamination in these settings and may be reexposed to MRSA strains from these reservoirs. People interact with natural and built environments; therefore, understanding the relationships between humans and animals as well as the characteristics of environmental reservoirs is important to advance strategies to combat antimicrobial resistance. Household interactions may influence the frequency and duration of exposure, which in turn may impact the duration of MRSA colonization or the probability for recurrent colonization and infection. Therefore, MRSA contamination of the home environment may contribute to human and animal recolonization and decolonization treatment failure. The aim of this study was to evaluate One Health risk factors that may be amenable to intervention and may influence the recovery of MDR and mupirocin resistance in CO-MRSA isolates.
To identify risk factors for infection with imipenem-resistant Pseudomonas aeruginosa and determine the impact of imipenem resistance on clinical and economic outcomes among patients infected with P. ...aeruginosa.
An ecologic study, a case-control study, and a retrospective cohort study.
A 625-bed tertiary care medical center.
All patients who had an inpatient clinical culture positive for P. aeruginosa between January 1, 1999, and December 31, 2000.
From 1991 through 2000, the annual prevalence of imipenem resistance among P. aeruginosa isolates increased significantly (P<.001 by the chi (2) test for trend). Among 879 patients infected with P. aeruginosa during 1999-2000, a total of 142 had imipenem-resistant P. aeruginosa infection (the case group), whereas 737 had imipenem-susceptible P. aeruginosa infection (the control group). The only independent risk factor for imipenem-resistant P. aeruginosa infection was prior fluoroquinolone use (adjusted odds ratio, 2.52 95% confidence interval {CI}, 1.61-3.92; P<.001). Compared with patients infected with imipenem-susceptible P. aeruginosa, patients infected with imipenem-resistant P. aeruginosa had longer subsequent hospitalization durations (15.5 days vs 9 days; P=.02) and greater hospital costs (81,330 dollars vs 48,381dollars ; P<.001). The mortality rate among patients infected with imipenem-resistant P. aeruginosa was 31.1%, compared with 16.7% for patients infected with imipenem-susceptible P. aeruginosa (relative risk, 1.86 95% CI, 1.38-2.51; P<.001). In multivariable analyses, there remained an independent association between infection with imipenem-resistant P. aeruginosa and mortality.
The prevalence of imipenem resistance among P. aeruginosa strains has increased markedly in recent years and has had a significant impact on both clinical and economic outcomes. Our results suggest that curtailing use of other antibiotics (particularly fluoroquinolones) may be important in attempts to curb further emergence of imipenem resistance.
Guillain-Barré syndrome (GBS) is an acute, immune-mediated flaccid paralysis frequently associated with Campylobacter infection. Of two predominant GBS subtypes, a demyelinating subtype (acute ...inflammatory demyelinative polyneuropathy AIDP) predominates in the United States and Europe, and axonal subtype (acute motor axonal neuropathy AMAN) is the predominant form in China. Previous clinical studies suggested that AMAN also occurs in Mexican children. The purpose of this study was to describe the subtypes of GBS in children from Mexico City.
We prospectively studied 121 children admitted to two pediatric hospitals in Mexico City from 1996 to 2002. Clinical histories were obtained, electrophysiologic studies were performed to determine GBS subtype, and microbiologic studies were performed.
Of the 121 children, 46 had AMAN and 32 had AIDP. The male to female ratio was 1.3 for AMAN cases (mean age = 6.3) and 3.0 for AIDP cases (mean age = 7.0). There was a strong seasonal distribution of AMAN cases in July to September. Children with AMAN, but not AIDP, had worsening of illness during hospitalization as judged by peak severity scores. Vomiting was more likely in AIDP (28.1%) vs AMAN (6.5%) (p = 0.012) and diarrhea was more common in AMAN (32.6%) than AIDP (12.5%) (p = 0.06). IgG anti-GM1 antibody titers were higher in patients with AMAN vs AIDP (p = 0.067). Anti-GD1a antibodies were equally present in both groups. Anti GQ1b titers were higher in AMAN vs AIDP (p = 0.009). Campylobacter antibody responses were positive in 44.1% of patients with AMAN and 37.0% of patients with AIDP. Twenty patients (14 = AMAN, 6 = AIDP) had positive stool cultures for C jejuni. Two serotypes, HS:19 and HS:41, accounted for 6 of 10 Campylobacter isolates available for serotyping from these cases.
This study confirms that acute motor axonal neuropathy is an important Guillain-Barré syndrome subtype in Mexican children, is associated with diarrhea, and occurs seasonally.
We conducted a prospective cohort study between 1 January 2010 and 31 December 2012 at five adult and paediatric academic medical centres to identify factors associated with persistent ...methicillin-resistant Staphylococcus aureus (MRSA) colonisation. Adults and children presenting to ambulatory settings with a MRSA skin and soft tissue infection (i.e. index cases), along with household members, performed self-sampling for MRSA colonisation every 2 weeks for 6 months. Clearance of colonisation was defined as two consecutive negative sampling periods. Subjects without clearance by the end of the study were considered persistently colonised and compared with those who cleared colonisation. Of 243 index cases, 48 (19·8%) had persistent colonisation and 110 (45·3%) cleared colonisation without recurrence. Persistent colonisation was associated with white race (odds ratio (OR), 4·90; 95% confidence interval (CI), 1·38–17·40), prior MRSA infection (OR 3·59; 95% CI 1·05–12·35), colonisation of multiple sites (OR 32·7; 95% CI 6·7–159·3). Conversely, subjects with persistent colonisation were less likely to have been treated with clindamycin (OR 0·28; 95% CI 0·08–0·99). Colonisation at multiple sites is a risk factor for persistent colonisation and may require more targeted decolonisation efforts. The specific effect of clindamycin on MRSA colonisation needs to be elucidated.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Background. We conducted a case-control study to identify risk factors for efflux overexpression, an important mechanism of fluoroquinolone resistance, among patients with fluoroquinolone-resistant ...Escherichia coli (FQREC) gastrointestinal tract colonization. Methods. Three annual fecal surveillance surveys were performed hospital-wide, and all patients colonized with FQREC (levofloxacin minimum inhibitory concentration, >8 µg/mL) were included in the study. Cases and controls were defined on the basis of overexpression of the AcrAB efflux pump, as measured by the organic solvent tolerance (OST) assay. A multivariable logistic regression model was developed to identify risk factors for OST positivity among patients with FQREC colonization. Results. Eighty-nine patients were colonized with FQREC: 44 (49.4%) and 45 (50.6%) patients had isolates that were OST-positive and OST-negative, respectively. On multivariable analyses, location on the surgical service was significantly associated with recovery of an OST-positive isolate (odds ratio, 7.36; 95% confidence interval, 1.82-29.7; P = .005). Furthermore, patients who had received a first-generation cephalosporin in the 30 days prior to sampling were less likely to have an OST-positive isolate (odds ratio, 0.20; 95% confidence interval, .04-.94; P = .04). Conclusions. Among phenotypically identical FQREC isolates, different factors may drive the emergence of different resistance mechanisms. Further studies are needed to elucidate the relationship between antimicrobial use and specific resistance mechanisms.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
We identified eight consecutive patients who presented with a skin or soft tissue infection due to MRSA. Of seven household members of these cases, three were colonized with MRSA. The mean duration ...of MRSA colonization in index cases was 33 days (range 14–104), while mean duration of colonization in household cases was 54 days (range 12–95). There was a borderline significant association between having a concurrent colonized household member and a longer duration of colonization (mean 44 days vs. 26 days, P=0·08).
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
Immunopathological studies suggest that the target of immune attack is different in the subtypes of Guillain‐Barré syndrome (GBS). In acute motor axonal neuropathy (AMAN), the attack appears directed ...against the axolemma and nodes of Ranvier. In acute inflammatory demyelinating polyneuropathy (AIDP), the attack appears directed against a component of the Schwann cell. However, the nature of the antigenic targets is still not clear. We prospectively studied 138 Chinese GBS patients and found that IgG anti‐GD1a antibodies were closely associated with AMAN but not AIDP. With a cutoff titer of greater than 1:100, 60% of AMAN versus 4% of AIDP patients had IgG anti‐GD1a antibodies; with a cutoff titer of greater than 1:1,000, 24% of AMAN patients and none of the AIDP patients had IgG anti‐GD1a antibodies. In contrast, low levels of IgG anti‐GM1 antibodies (>1:100) were detected in both the AMAN and the AIDP forms (57% vs 35%, NS). High titers of IgG anti‐GM1 (>1:1,000) were more common in the AMAN form (24% vs 8%, NS). Serological evidence of recent Campylobacter infection was detected in 81% of AMAN and 50% of AIDP patients, and anti‐ganglioside antibodies were common in both Campylobacter‐infected and noninfected patients. Our results suggest that IgG anti‐GD1a antibodies may be involved in the pathogenesis of AMAN. Ann Neurol 1999;45:168–173
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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