Background.Previous studies of risk factors for Clostridium difficile—associated disease (CDAD) have been limited by small sample sizes and case-control study designs. Many of these studies were ...performed during outbreaks of CDAD. Colonization pressure and use of fluoroquinolones, vancomycin, and gastric acid suppressors have not been fully evaluated as risk factors for CDAD. The purpose of this study was to determine risk factors for endemic CDAD, including CDAD pressure, a modified version of colonization pressure. Methods.We performed a retrospective cohort study of 36,086 patients admitted to Barnes-Jewish Hospital (St. Louis, MO) during the period from 1 January 2003 through 31 December 2003. Administrative, laboratory, and pharmacy data were collected from electronic hospital databases. Colonization pressure was measured through a surrogate variable (i.e., CDAD pressure). Multivariable pooled logistic regression models were used to evaluate independent risk factors for CDAD. Results.The analysis included 382 CDAD case patient admissions and 35,704 non—case patient admissions. Significant independent risk factors for CDAD included increasing age, admission(s) in the previous 60 days, hypoalbuminemia, leukemia and/or lymphoma, mechanical ventilation, and receipt of antimotility drugs, histamine-2 blockers, proton pump inhibitors, intravenous vancomycin, fluoroquinolones, and first-, third-, or fourth-generation cephalosporins. Increasing CDAD pressure was a strong risk factor for CDAD (for a CDAD pressure >1.4, the odds ratio was 4.0; 95% confidence interval, 2.9–5.6). Receipt of metronidazole was protective against CDAD (odds ratio, 0.5; 95% confidence interval, 0.3–0.6). Conclusions.This study identified the previously underrecognized CDAD risk factors of CDAD pressure and vancomycin. More studies are needed to evaluate the relationship between CDAD, these risk factors, and use of gastric acid suppressors and fluoroquinolones.
Purpose
Clinical applications of quantitative computed tomography (qCT) in patients with pulmonary opacifications are hindered by the radiation exposure and by the arduous manual image processing. We ...hypothesized that extrapolation from only ten thoracic CT sections will provide reliable information on the aeration of the entire lung.
Methods
CTs of 72 patients with normal and 85 patients with opacified lungs were studied retrospectively. Volumes and masses of the lung and its differently aerated compartments were obtained from all CT sections. Then only the most cranial and caudal sections and a further eight evenly spaced sections between them were selected. The results from these ten sections were extrapolated to the entire lung. The agreement between both methods was assessed with Bland–Altman plots.
Results
Median (range) total lung volume and mass were 3,738 (1,311–6,768) ml and 957 (545–3,019) g, the corresponding bias (limits of agreement) were 26 (−42 to 95) ml and 8 (−21 to 38) g, respectively. The median volumes (range) of differently aerated compartments (percentage of total lung volume) were 1 (0–54)% for the nonaerated, 5 (1–44)% for the poorly aerated, 85 (28–98)% for the normally aerated, and 4 (0–48)% for the hyperaerated subvolume. The agreement between the extrapolated results and those from all CT sections was excellent. All bias values were below 1% of the total lung volume or mass, the limits of agreement never exceeded ±2%.
Conclusion
The extrapolation method can reduce radiation exposure and shorten the time required for qCT analysis of lung aeration.
General anaesthesia leads to atelectasis, reduced end-expiratory lung volume (EELV), and diminished arterial oxygenation in obese patients. We hypothesized that a combination of a recruitment ...manoeuvre (RM) and individualized positive end-expiratory pressure (PEEP) can avoid these effects.
Patients with a BMI ≥35 kg m−2 undergoing elective laparoscopic surgery were randomly allocated to mechanical ventilation with a tidal volume of 8 ml kg−1 predicted body weight and (i) an RM followed by individualized PEEP titrated using electrical impedance tomography (PEEPIND) or (ii) no RM and PEEP of 5 cm H2O (PEEP5). Gas exchange, regional ventilation distribution, and EELV (multiple breath nitrogen washout method) were determined before, during, and after anaesthesia. The primary end point was the ratio of arterial partial pressure of oxygen to inspiratory oxygen fraction (PaO2/FiO2).
For PEEPIND (n=25) and PEEP5 (n=25) arms together, PaO2/FiO2 and EELV decreased by 15 kPa 95% confidence interval (CI) 11–20 kPa, P<0.001 and 1.2 litres (95% CI 0.9–1.6 litres, P<0.001), respectively, after intubation. Mean (sd) PEEPIND was 18.5 (5.6) cm H2O. In the PEEPIND arm, PaO2/FiO2 before extubation was 23 kPa higher (95% CI 16–29 kPa; P<0.001), EELV was 1.8 litres larger (95% CI 1.5–2.2 litres; P<0.001), driving pressure was 6.7 cm H2O lower (95% CI 5.4–7.9 cm H2O; P<0.001), and regional ventilation was more equally distributed than for PEEP5. After extubation, however, these differences between the arms vanished.
In obese patients, an RM and higher PEEPIND restored EELV, regional ventilation distribution, and oxygenation during anaesthesia, but these differences did not persist after extubation. Therefore, lung protection strategies should include the postoperative period.
German clinical trials register DRKS00004199, www.who.int/ictrp/network/drks2/en/.
Background. The incidence of Clostridium difficile– associated disease (CDAD) is increasing. There are few data on the short-term and long-term attributable costs of CDAD. The objective of this study ...was to determine the acute and 180-day attributable inpatient costs of CDAD. Methods. We performed a retrospective cohort study of all patients without operating room costs who were admitted for ⩾ 48 h to Barnes-Jewish Hospital, a tertiary care hospital in St. Louis, Missouri, 1 January 2003– 31 December 2003 (n=24,691). Attributable costs of CDAD were determined by multivariable linear regression and propensity-score matched-pairs analyses (n=684) for the hospitalization in which CDAD occurred and per patient over a 180-day period, including the initial hospitalization. Results. CDAD was associated with $2454 (95% confidence interval, $2380– $2950; increase in cost, 41%) attributable costs per CDAD episode by linear regression and with $3240 attributable costs (P< .001; increase in cost, 33%) by propensity-score matched-pairs analysis. CDAD was associated with $5042 (95% confidence interval, $3797– $6481; increase in cost, 53%) attributable inpatient costs over 180 days by linear regression and with $7179 attributable costs for inpatient care (P< .001; 48% increase in costs) by propensity-score matched-pairs analysis. Conclusions. CDAD was associated with a significant increase in costs for inpatient care and increased costs at 180 days after the initial hospitalization when the CDAD episode occurred.
Once antibiotic-resistant bacteria become established within the gut microbiota, they can cause infections in the host and be transmitted to other people and the environment. Currently, there are no ...effective modalities for decreasing or preventing colonization by antibiotic-resistant bacteria. Intestinal microbiota restoration can prevent Clostridioides difficile infection (CDI) recurrences. Another potential application of microbiota restoration is suppression of non-C. difficile multidrug-resistant bacteria and overall decrease in the abundance of antibiotic resistance genes (the resistome) within the gut microbiota. This study characterizes the effects of RBX2660, a microbiota-based investigational therapeutic, on the composition and abundance of the gut microbiota and resistome, as well as multidrug-resistant organism carriage, after delivery to patients suffering from recurrent CDI.
An open-label, multi-center clinical trial in 11 centers in the USA for the safety and efficacy of RBX2660 on recurrent CDI was conducted. Fecal specimens from 29 of these subjects with recurrent CDI who received either one (N = 16) or two doses of RBX2660 (N = 13) were analyzed secondarily. Stool samples were collected prior to and at intervals up to 6 months post-therapy and analyzed in three ways: (1) 16S rRNA gene sequencing for microbiota taxonomic composition, (2) whole metagenome shotgun sequencing for functional pathways and antibiotic resistome content, and (3) selective and differential bacterial culturing followed by isolate genome sequencing to longitudinally track multidrug-resistant organisms.
Successful prevention of CDI recurrence with RBX2660 correlated with taxonomic convergence of patient microbiota to the donor microbiota as measured by weighted UniFrac distance. RBX2660 dramatically reduced the abundance of antibiotic-resistant Enterobacteriaceae in the 2 months after administration. Fecal antibiotic resistance gene carriage decreased in direct relationship to the degree to which donor microbiota engrafted.
Microbiota-based therapeutics reduce resistance gene abundance and resistant organisms in the recipient gut microbiome. This approach could potentially reduce the risk of infections caused by resistant organisms within the patient and the transfer of resistance genes or pathogens to others.
ClinicalTrials.gov, NCT01925417 ; registered on August 19, 2013.
The rise of antimicrobial resistance in uropathogens has complicated the management of urinary tract infections (UTIs), particularly in patients who are afflicted by recurrent episodes of UTIs. ...Antimicrobial-resistant (AR) uropathogens persistently colonizing individuals at asymptomatic time points have been implicated in the pathophysiology of UTIs. The dynamics of uropathogen persistence following the resolution of symptomatic disease are, however, mostly unclear. To further our understanding, we determined longitudinal AR uropathogen carriage and clonal persistence of uropathogenic
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isolates in the intestinal and urinary tracts of patients affected by recurrent and nonrecurrent UTIs. Clonal tracking of isolates in consecutively collected urine and fecal specimens indicated repeated transmission of uropathogens between the urinary tract and their intestinal reservoir. Our results further implicate three independent routes of recurrence of UTIs: (i) following an intestinal bloom of uropathogenic bacteria and subsequent bladder colonization, (ii) reinfection of the urinary tract from an external source, and (iii) bacterial persistence within the urinary tract. Taken together, our observation of clonal persistence following UTIs and uropathogen transmission between the intestinal and urinary tracts warrants further investigations into the connection between the intestinal microbiome and recurrent UTIs.
The increasing antimicrobial resistance of uropathogens is challenging the continued efficacy of empiric antibiotic therapy for UTIs, which are among the most frequent bacterial infections worldwide. It has been suggested that drug-resistant uropathogens could persist in the intestine after the resolution of UTI and cause recurrences following periurethral contamination. A better understanding of the transmission dynamics between the intestinal and urinary tracts, combined with phenotypic characterization of the uropathogen populations in both habitats, could inform prudent therapies designed to overcome the rising resistance of uropathogens. Here, we integrate genomic surveillance with clinical microbiology to show that drug-resistant clones persist within and are readily transmitted between the intestinal and urinary tracts of patients affected by recurrent and nonrecurrent UTIs. Thus, our results advocate for understanding persistent intestinal uropathogen colonization as part of the pathophysiology of UTIs, particularly in patients affected by recurrent episodes of symptomatic disease.
Background & Aims: Clostridium difficile –associated disease (CDAD) rates have been increasing. We sought to determine whether CDAD incidence has increased specifically in hospitalized patients with ...IBD. We also explored possible differences in the risk for and time to presentation of CDAD between IBD and non-IBD patients. Methods: We analyzed hospital admissions from 1998–2004 for demographics, length of stay, C difficile infections, and time from admission to a positive C difficile test. We calculated CDAD incidence for non-IBD, all IBD, CD, and UC admissions and used logistic regression to estimate the risk for CDAD. Results: CDAD incidence increased in each group and was higher in all IBD than non-IBD groups. During the observation period, CDAD rates approximately doubled in CD (9.5 to 22.3/1000 admissions) and tripled in UC (18.4 to 57.6/1000). Length of stay was similar among the groups. For all years combined, the adjusted odds ratios for CDAD in all IBD, CD, and UC admissions were 2.9 (95% confidence interval, 2.1–4.1), 2.1 (1.3–3.4), and 4.0 (2.4–6.6), respectively. The median times from admission to a positive C difficile test result for non-IBD, CD, and UC were 4.0, 0.8, and 0.5 days, respectively. Conclusions: CDAD incidence in IBD has increased and is higher than in the non-IBD population. IBD and UC patients in particular have a higher risk for CDAD. C difficile infections in IBD are confirmed predominantly within 48 hours of admission, suggesting most were acquired before hospitalization.
Solid organ transplantation remains the gold standard for the treatment of end-stage organ dysfunction and saves thousands of lives. Besides the progress of surgery, advances in understanding ...transplant physiology, immunology and the development of immunosuppressive drugs lead to improved short- and long-term survival. Transplantation is offered to an increasing number of patients with higher age and comorbidities. Approximately one third of organ recipients require hospital readmission after transplantation because of a multitude of clinical problems related to immunosuppressive therapy. We review the current knowledge on typical complications associated with immunosuppressants with emphasis on the intensivist's perspective.
Intestinal microbiota restoration can be achieved by complementing a subject's perturbed microbiota with that of a healthy donor. Recurrent Clostridioides difficile infection (rCDI) is one key ...application of such treatment. Another emerging application of interest is reducing antibiotic-resistant genes (ARGs) and organisms (AROs). In this study, we investigated fecal specimens from a multicenter, randomized, double-blind, placebo-controlled phase 2b study of microbiota-based investigational drug RBX2660. Patients were administered either placebo, 1 dose of RBX2660 and 1 placebo, or 2 doses of RBX2660 via enema and longitudinally tracked for changes in their microbiome and antibiotic resistome.
All patients exhibited significant recovery of gut microbiome diversity and a decrease of ARG relative abundance during the first 7 days post-treatment. However, the microbiome and resistome shifts toward average configurations from unperturbed individuals were more significant and longer-lasting in RBX2660 recipients compared to placebo. We quantified microbiome and resistome modification by RBX2660 using a novel "transplantation index" metric. We identified taxonomic and metabolic features distinguishing the baseline microbiome of non-transplanted patients and taxa specifically enriched during the process of transplantation. We elucidated the correlation between resistome and taxonomic transplantations and post-treatment dynamics of patient-specific and RBX2660-specific ARGs. Whole genome sequencing of AROs cultured from RBX2660 product and patient samples indicate ARO eradication in patients via RBX2660 administration, but also, to a lesser extent, introduction of RBX2660-derived AROs.
Through shotgun metagenomic sequencing, we elucidated the effects of RBX2660 in the microbiome and resistome. Antibiotic discontinuation alone resulted in significant recovery of gut microbial diversity and reduced ARG relative abundance, but RBX2660 administration more rapidly and completely changed the composition of patients' microbiome, resistome, and ARO colonization by transplanting RBX2660 microbiota into the recipients. Although ARGs and AROs were transmitted through RBX2660, the resistome post-RBX2660 more closely resembled that of the administered product-a proxy for the donor-than an antibiotic perturbed state.
ClinicalTrials.gov, NCT02299570 . Registered 19 November 2014 Video Abstract.
Recent outbreaks of Clostridium difficile infection (CDI) have been difficult to control, and data indicate that the importance of different sources of transmission may have changed. Our objectives ...were to evaluate the contributions of asymptomatic and symptomatic C. difficile carriers to new colonizations and to determine the most important epidemiological factors influencing C. difficile transmission.
Retrospective cohort study of all patients admitted to medical wards at a large tertiary care hospital in the United States in the calendar year 2008.
Data from six medical wards and published literature were used to develop a compartmental model of C. difficile transmission. Patients could be in one of five transition states in the model: resistant to colonization (R), susceptible to colonization (S), asymptomatically colonized without protection against CDI (C(-)), asymptomatically colonized with protection against CDI (C(+)), and diseased (ie, with CDI; D).
The contributions of C(-), C(+), and D patients to new colonizations were similar. The simulated basic reproduction number ranged from 0.55 to 1.99, with a median of 1.04. These values suggest that transmission within the ward alone from patients with CDI cannot sustain new C. difficile colonizations and therefore that the admission of colonized patients plays an important role in sustaining transmission in the ward. The epidemiological parameters that ranked as the most influential were the proportion of admitted C(-) patients and the transmission coefficient for asymptomatic carriers.
Our study underscores the need to further evaluate the role of asymptomatically colonized patients in C. difficile transmission in healthcare settings.
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