Confounding by indication affects antimicrobial risk factors for methicillin-resistant Staphylococcus aureus but not vancomycin-resistant enterococci acquisition

Background: Observational studies rarely account for confounding by indication, whereby empiric antibiotics initiated for signs and symptoms of infection prior to the diagnosis of infection are then viewed as risk factors for infection. We evaluated whether confounding by indication impacts antimicrobial risk factors for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) acquisition. Findings: We previously reported several predictors of MRSA and VRE acquisition in 967 intensive care unit (ICU) patients with no prior history of MRSA or VRE who had an initial negative screening culture followed by either a subsequent negative screening culture (controls) or positive screening or clinical culture (cases). Within and prior to this acquisition interval, we collected demographic, comorbidity, daily device and antibiotic utilization data. We now re-evaluate all antibiotics by medical record review for evidence of treatment for signs and symptoms ultimately attributable to MRSA or VRE. Generalized linear mixed models are used to assess variables associated with MRSA or VRE acquisition, accounting for clustering by ward. We find that exclusion of empiric antibiotics given for suspected infection affects 17% (113/661) of antibiotic prescriptions in 25% (60/244) of MRSA-positive patients but only 1% (5/491) of antibiotic prescriptions in 1% (3/227) of VRE-positive patients. In multivariate testing, fluoroquinolones are no longer associated with MRSA acquisition, and aminoglycosides are significantly protective (OR = 0.3, CI:0.1-0.7). Conclusions: Neglecting treatment indication may cause common empiric antibiotics to appear spuriously associated with MRSA acquisition. This effect is absent for VRE, likely because empiric therapy is infrequent given the low prevalence of VRE

Colonization with antibiotic-susceptible strains protects against methicillin-resistant Staphylococcus aureus but not vancomycin-resistant enterococci acquisition: a nested case-control study

Introduction: Harboring sensitive strains may prevent acquisition of resistant pathogens by competing for colonization of ecological niches. Competition may be relevant to decolonization strategies that eliminate sensitive strains and may predispose to acquiring resistant strains in high-endemic settings. We evaluated the impact of colonization with methicillin-sensitive Staphylococcus aureus(MSSA) and vancomycin-sensitive enterococci (VSE) on acquisition of methicillin-resistantStaphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE), respectively, when controlling for other risk factors. Methods: We conducted a nested case-control study of patients admitted to eight ICUs performing admission and weekly bilateral nares and rectal screening for MRSA and VRE, respectively. Analyses were identical for both pathogens. For MRSA, patients were identified who had a negative nares screen and no prior history of MRSA. We evaluated predictors of MRSA acquisition, defined as a subsequent MRSA-positive clinical or screening culture, compared to those with a subsequent MRSA-negative nares screen within the same hospitalization. Medical records were reviewed for the presence of MSSA on the initial MRSA-negative nares screen, demographic and comorbidity information, medical devices, procedures, antibiotic utilization, and daily exposure to MRSA-positive patients in the same ward. Generalized linear mixed models were used to assess predictors of acquisition. Results: In multivariate models, MSSA carriage protected against subsequent MRSA acquisition (OR = 0.52, CI: 0.29, 0.95), even when controlling for other risk factors. MRSA predictors included intubation (OR = 4.65, CI: 1.77, 12.26), fluoroquinolone exposure (OR = 1.91, CI: 1.20, 3.04), and increased time from ICU admission to initial negative swab (OR = 15.59, CI: 8.40, 28.94). In contrast, VSE carriage did not protect against VRE acquisition (OR = 1.37, CI: 0.54, 3.48), whereas hemodialysis (OR = 2.60, CI: 1.19, 5.70), low albumin (OR = 2.07, CI: 1.12, 3.83), fluoroquinolones (OR = 1.90, CI: 1.14, 3.17), third-generation cephalosporins (OR = 1.89, CI: 1.15, 3.10), and increased time from ICU admission to initial negative swab (OR = 15.13, CI: 7.86, 29.14) were predictive. Conclusions: MSSA carriage reduced the odds of MRSA acquisition by 50% in ICUs. In contrast, VSE colonization was not protective against VRE acquisition. Studies are needed to evaluate whether decolonization of MSSA ICU carriers increases the risk of acquiring MRSA when discharging patients to high-endemic MRSA healthcare settings. This may be particularly important for populations in whom MRSA infection may be more frequent and severe than MSSA infections, such as ICU patients

Beyond 30 days: Does limiting the duration of surgical site infection follow-up limit detection?

Concern over consistency and completeness of surgical site infection (SSI) surveillance has increased due to public reporting of hospital SSI rates and imminent non-payment rules for hospitals that do not meet national benchmarks. Already, hospitals no longer receive additional payment from the Centers for Medicare & Medicaid Services (CMS) for certain infections following coronary artery bypass graft (CABG) surgery, orthopedic procedures, and bariatric surgery. One major concern is incomplete and differential post-discharge surveillance. At present, substantial variation exists in how and whether hospitals identify SSI events after the hospitalization in which the surgery occurred. Parameters used for SSI surveillance such as the duration of the window of time that surveillance takes place following the surgical procedure can impact the completeness of surveillance data. Determination of the optimal surveillance time period involves balancing the potential increased case ascertainment associated with a longer follow-up period with the increased resources that would be required. Currently, the time window for identifying potentially preventable SSIs related to events at the time of surgery is not fully standardized. The Centers for Disease Control and Prevention (CDC) National Healthcare Surveillance Network (NHSN) requires a 365-day postoperative surveillance period for procedures involving implants and a 30-day period for non-implant procedures. In contrast, the National Surgical Quality Improvement Program (NSQIP) and the Society of Thoracic Surgeons (STS) systems employ 30-day post-operative surveillance regardless of implant. As consensus builds towards national quality measures for hospital-specific SSI rates, it will be important to assess the frequency of events beyond the 30-day post-surgical window that may quantify the value of various durations of surveillance, and ultimately inform the choice of specific outcome measures

Metabolic versatility of the nitrite-oxidizing bacterium Nitrospira marina and its proteomic response to oxygen-limited conditions

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Bayer, B., Saito, M. A., McIlvin, M. R., Lucker, S., Moran, D. M., Lankiewicz, T. S., Dupont, C. L., & Santoro, A. E. (2020). Metabolic versatility of the nitrite-oxidizing bacterium Nitrospira marina and its proteomic response to oxygen-limited conditions. Isme Journal, doi:10.1038/s41396-020-00828-3.The genus Nitrospira is the most widespread group of nitrite-oxidizing bacteria and thrives in diverse natural and engineered ecosystems. Nitrospira marina Nb-295T was isolated from the ocean over 30 years ago; however, its genome has not yet been analyzed. Here, we investigated the metabolic potential of N. marina based on its complete genome sequence and performed physiological experiments to test genome-derived hypotheses. Our data confirm that N. marina benefits from additions of undefined organic carbon substrates, has adaptations to resist oxidative, osmotic, and UV light-induced stress and low dissolved pCO2, and requires exogenous vitamin B12. In addition, N. marina is able to grow chemoorganotrophically on formate, and is thus not an obligate chemolithoautotroph. We further investigated the proteomic response of N. marina to low (∼5.6 µM) O2 concentrations. The abundance of a potentially more efficient CO2-fixing pyruvate:ferredoxin oxidoreductase (POR) complex and a high-affinity cbb3-type terminal oxidase increased under O2 limitation, suggesting a role in sustaining nitrite oxidation-driven autotrophy. This putatively more O2-sensitive POR complex might be protected from oxidative damage by Cu/Zn-binding superoxide dismutase, which also increased in abundance under low O2 conditions. Furthermore, the upregulation of proteins involved in alternative energy metabolisms, including Group 3b [NiFe] hydrogenase and formate dehydrogenase, indicate a high metabolic versatility to survive conditions unfavorable for aerobic nitrite oxidation. In summary, the genome and proteome of the first marine Nitrospira isolate identifies adaptations to life in the oxic ocean and provides insights into the metabolic diversity and niche differentiation of NOB in marine environments.We thank John B. Waterbury and Frederica Valois for providing the culture of Nitrospira marina Nb-295T and for continued advice about cultivation. The N. marina genome was sequenced as part of US Department of Energy Joint Genome Institute Community Sequencing Project 1337 to CLD, AES, and MAS in collaboration with the user community. We thank Claus Pelikan for bioinformatic assistance. This research was supported by a Simons Foundation Early Career Investigator in Marine Microbiology and Evolution Award (345889) and US National Science Foundation (NSF) award OCE-1924512 to AES. Proteomics analysis was supported by NSF awards OCE-1924554 and OCE-1850719, and NIH award R01GM135709 to MAS. BB was supported by the Austrian Science Fund (FWF) Project Number: J4426-B (“The influence of nitrifiers on the oceanic carbon cycle”), SL by the Netherlands Organization for Scientific Research (NWO) grant 016.Vidi.189.050, and CLD by NSF award OCE-125999

Enhanced surgical site infection surveillance following hysterectomy, vascular, and colorectal surgery

Objective.To evaluate the use of inpatient pharmacy and administrative data to detect surgical site infections (SSIs) following hysterectomy and colorectal and vascular surgery.Design.Retrospective cohort study.Setting.Five hospitals affiliated with academic medical centers.Patients.Adults who underwent abdominal or vaginal hysterectomy, colorectal surgery, or vascular surgery procedures between July 1, 2003, and June 30, 2005.Methods.We reviewed the medical records of weighted, random samples drawn from 3,079 abdominal and vaginal hysterectomy, 4,748 colorectal surgery, and 3,332 vascular surgery procedures. We compared routine surveillance with screening of inpatient pharmacy data and diagnosis codes and then performed medical record review to confirm SSI status.Results.Medical records from 823 hysterectomy, 736 colorectal surgery, and 680 vascular surgery procedures were reviewed. SSI rates determined by antimicrobial- and/or diagnosis code-based screening followed by medical record review (enhanced surveillance) were substantially higher than rates determined by routine surveillance (4.3% [95% confidence interval, 3.6%—5.1%] vs 2.7% for hysterectomies, 7.1% [95% confidence interval, 6.7%–8.2%] vs 2.0% for colorectal procedures, and 2.3% [95% confidence interval, 1.9%–2.9%] vs 1.4% for vascular procedures). Enhanced surveillance had substantially higher sensitivity than did routine surveillance to detect SSI (92% vs 59% for hysterectomies, 88% vs 22% for colorectal procedures, and 72% vs 43% for vascular procedures). A review of medical records confirmed SSI for 31% of hysterectomies, 20% of colorectal procedures, and 31% of vascular procedures that met the enhanced screening criteria.Conclusion.Antimicrobial- and diagnosis code-based screening may be a useful method for enhancing and streamlining SSI surveillance for a variety of surgical procedures, including those procedures targeted by the Centers for Medicare and Medicaid Services.</jats:sec

Use of Medicare claims to rank hospitals by surgical site infection risk following coronary artery bypass graft surgery

ObjectiveTo evaluate whether longitudinal insurer claims data allow reliable identification of elevated hospital surgical site infection (SSI) rates.DesignWe conducted a retrospective cohort study of Medicare beneficiaries who underwent coronary artery bypass grafting (CABG) in US hospitals performing at least 80 procedures in 2005. Hospitals were assigned to deciles by using case mix-adjusted probabilities of having an SSI-related inpatient or outpatient claim code within 60 days of surgery. We then reviewed medical records of randomly selected patients to assess whether chart-confirmed SSI risk was higher in hospitals in the worst deciles compared with the best deciles.ParticipantsFee-for-service Medicare beneficiaries who underwent CABG in these hospitals in 2005.ResultsWe evaluated 114,673 patients who underwent CABG in 671 hospitals. In the best decile, 7.8% (958/12,307) of patients had an SSI-related code, compared with 24.8% (2,747/11,068) in the worst decile ([Formula: see text]). Medical record review confirmed SSI in 40% (388/980) of those with SSI-related codes. In the best decile, the chart-confirmed annual SSI rate was 3.2%, compared with 9.4% in the worst decile, with an adjusted odds ratio of SSI of 2.7 (confidence interval, 2.2-3.3; [Formula: see text]) for CABG performed in a worst-decile hospital compared with a best-decile hospital.ConclusionsClaims data can identify groups of hospitals with unusually high or low post-CABG SSI rates. Assessment of claims is more reproducible and efficient than current surveillance methods. This example of secondary use of routinely recorded electronic health information to assess quality of care can identify hospitals that may benefit from prevention programs

Inhibition of native 5-HT3 receptor-evoked contractions in Guinea pig and mouse ileum by antimalarial drugs

Quinine, Chloroquine and mefloquine are commonly used to treat malaria; however with associated gastrointestinal (GI) side-effects. These drugs act as antagonists at recombinant 5-HT3 receptors and modulate gut peristalsis. These gastrointestinal side effects may be the result of antagonism at intestinal 5-HT3 receptors. Ileum from male C57BL/6 mice and guinea pigs was mounted longitudinally in organ baths. Concentration-response curves for 5-HT and the selective 5-HT3 agonist 2-Me-5-HT were obtained with 5-HT (pEC50=7.57±0.33, 12) more potent (P=0.004) than 2-Me-5-HT (pEC50=5.45±0.58, n=5) in mouse ileum. There was no difference in potency of 5-HT (pEC50=5.42±0.15, n=8) and 2-Me-5-HT (pIC50=5.01±0.55, n=11) in guinea pig ileum (P>0.05). Quinine, Chloroquine or mefloquine was applied for 10 min and inhibitions prior to submaximal agonist application. In mouse ileum, quinine, chloroquine and mefloquine antagonised 5-HT-induced contractions (pIC50=4.9±0.17, n=7; 4.76±0.14,n=5; 6.21±0.2, n=4, respectively) with mefloquine most potent (P<0.05). Quinine, chloroquine and mefloquine antagonised 2-me-5-HT-induced contractions (pIC50=6.35±0.11,n=8; 4.64±0.2, n=7; 5.11± 0.22, n=6, respectively) with quinine most potent (P<0.05). In guinea-pig ileum, quinine, chloroquine and mefloquine antagonised 5-HT-induced contractions (pIC50=5.02±0.15, n=6; 4.54±0.1, n=7; 5.32±0.13, n=5, respectively) and 2-me-5-HT-induced contractions (pIC50=4.62±0.25, n=5; 4.56±0.14, n=6; 5.67±0.12, n=4, respectively) with chloroquine least potent against 5-HT and mefloquine most potent against 2-me-5-HT (P<0.05). These results support previous studies identifying anti-malarial drugs as antagonists at recombinant 5-HT3 receptors and may also demonstrate the ability of these drugs to influence native 5-HT3 receptor-evoked contractile responses which may account for their associated GI side-effects