Lowering the Acquisition of Multi-drug Resistant Organism (MDROs) with Pulsed-xenon (LAMP) Study: a cluster randomized controlled, double-blinded, interventional crossover trial.

BACKGROUND: Environmental disinfection is essential for reducing spread of healthcare associated infections (HAIs). Previous studies report conflicting results regarding the effects of ultraviolet light (UV) in reducing infections. This trial evaluated the impact of adding pulsed xenon UV (PX-UV) to standard terminal cleaning in reducing environmentally-implicated HAIs (eiHAIs). METHODS: The LAMP trial was conducted in 2 hospitals (15 inpatient wards) utilizing a cluster randomized controlled, double-blinded, interventional crossover trial comparing standard terminal cleaning followed by either pulsed xenon ultraviolet (PX-UV) disinfection (intervention arm) or sham disinfection (control arm). The primary outcome was incidence of eiHAIs from clinical microbiology tests on the 4th day of stay or later or within 3 days after discharge from the study unit. EiHAIs included clinical cultures positive for vancomycin-resistant enterococci (VRE), extended spectrum beta-lactamase-producing Escherichia coli or Klebsiella pneumonia, methicillin-resistant Staphylococcus aureus (MRSA), and Acinetobacter baumannii, and stool PCR positive for Clostridiodes difficile. FINDINGS: Between May 18, 2017 to Jan 7, 2020, 25,732 patients were included, with an incidence of 601 eiHAI and 180,954 patient days. There was no difference in the rate of eiHAIs in the intervention and sham arms (3.49 vs 3.17 infections/1000 patient days respectively, RR 1.10 CI (0.94, 1.29, p= 0.23)). Study results were similar when stratified by eiHAI type, hospital, and unit type. CONCLUSION: The LAMP study failed to demonstrate an effect of the addition of UV light disinfection following terminal cleaning on reductions in rates of eiHAIs. Further investigations targeting hospital environmental surfaces and the role of no touch technology to reduce HAIs are needed.

Clinical Outcomes and Bacterial Characteristics of Carbapenem-resistant Acinetobacter baumannii Among Patients From Different Global Regions.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAb) is 1 of the most problematic antimicrobial-resistant bacteria. We sought to elucidate the international epidemiology and clinical impact of CRAb. METHODS: In a prospective observational cohort study, 842 hospitalized patients with a clinical CRAb culture were enrolled at 46 hospitals in five global regions between 2017 and 2019. The primary outcome was all-cause mortality at 30 days from the index culture. The strains underwent whole-genome analysis. RESULTS: Of 842 cases, 536 (64%) represented infection. By 30 days, 128 (24%) of the infected patients died, ranging from 1 (6%) of 18 in Australia-Singapore to 54 (25%) of 216 in the United States and 24 (49%) of 49 in South-Central America, whereas 42 (14%) of non-infected patients died. Bacteremia was associated with a higher risk of death compared with other types of infection (40 [42%] of 96 vs 88 [20%] of 440). In a multivariable logistic regression analysis, bloodstream infection and higher age-adjusted Charlson comorbidity index were independently associated with 30-day mortality. Clonal group 2 (CG2) strains predominated except in South-Central America, ranging from 216 (59%) of 369 in the United States to 282 (97%) of 291 in China. Acquired carbapenemase genes were carried by 769 (91%) of the 842 isolates. CG2 strains were significantly associated with higher levels of meropenem resistance, yet non-CG2 cases were over-represented among the deaths compared with CG2 cases. CONCLUSIONS: CRAb infection types and clinical outcomes differed significantly across regions. Although CG2 strains remained predominant, non-CG2 strains were associated with higher mortality. Clinical Trials Registration. NCT03646227.

Prolonged impacts of COVID-19-associated cystitis: A study on long-term consequences.

BACKGROUND: The Coronavirus Disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 virus is an international health concern with substantial morbidity and mortality. COVID-associated cystitis (CAC), presents as new onset or exacerbated urinary symptoms, resembling overactive bladder (OAB) symptoms. AIM: To examines the long-term outcomes of patients with CAC in the context of Long COVID. METHODS: A cohort of 350 patients admitted to Detroit Hospitals with COVID-19 between May and December 2020, displaying CAC symptoms following discharge, was prospectively followed. Initial urologic evaluations occurred at 10-14 wk and were repeated at 21-28 mo post-discharge. Symptoms were managed conservatively, employing behavioral modifications and standard OAB medications. Participants completed surveys assessing urinary symptoms and quality of life (QoL) at both time points. The primary outcome was the Urology Care Foundation Overactive Bladder Assessment Tool. RESULTS: 87% of the final cohort (n = 310) reported symptom improvement at 21-28 mo post-discharge. Patients with new onset CAC symptoms showed a median decrease of 9-10 points in OAB and QoL scores, while those with existing symptoms experienced a decrease of 6 points. Overall, 95.4% of patients with new onset symptoms reported symptom improvement at follow-up, contrasting with 60.7% among those with existing symptoms. CONCLUSION: This study presents the first long-term follow-up of adult patients with CAC, revealing a promising prognosis with conservative management measures in the context of Long COVID. These findings provide reassurance to patients regarding symptom resolution and underscore the need for further research into this evolving aspect of COVID-19's impact on urological health.

Colistin Monotherapy versus Combination Therapy for Carbapenem-Resistant Organisms.

BACKGROUND: Pneumonia and bloodstream infections (BSI) due to extensively drug-resistant (XDR) Acinetobacter baumannii, XDR Pseudomonas aeruginosa, and carbapenem-resistant Enterobacterales (CRE) are associated with high mortality rates, and therapeutic options remain limited. This trial assessed whether combination therapy with colistin and meropenem was superior to colistin monotherapy for the treatment of these infections. METHODS: The OVERCOME (Colistin Monotherapy versus Combination Therapy) trial was an international, randomized, double-blind, placebo-controlled trial. We randomly assigned participants to receive colistin (5 mg/kg once followed by 1.67 mg/kg every 8 hours) in combination with either meropenem (1000 mg every 8 hours) or matching placebo for the treatment of pneumonia and/or BSI caused by XDR A. baumannii, XDR P. aeruginosa, or CRE. The primary outcome was 28-day mortality, and secondary outcomes included clinical failure and microbiologic cure. RESULTS: Between 2012 and 2020, a total of 464 participants were randomly assigned to treatment, and 423 eligible patients comprised the modified intention-to-treat population. A. baumannii was the predominant trial pathogen (78%) and pneumonia the most common index infection (70%). Most patients were in the intensive care unit at the time of enrollment (69%). There was no difference in mortality (43 vs. 37%; P=0.17), clinical failure (65 vs. 58%; difference, 6.8 percentage points; 95% confidence interval [CI], -3.1 to 16.6), microbiologic cure (65 vs. 60%; difference, 4.8 percentage points; 95% CI, -5.6 to 15.2), or adverse events (acute kidney injury, 52 vs. 49% [P=0.55]; hypersensitivity reaction, 1 vs. 3% [P=0.22]; and neurotoxicity, 5 vs. 2% [P=0.29]) between patients receiving monotherapy and combination therapy, respectively. CONCLUSIONS: Combination therapy with colistin and meropenem was not superior to colistin monotherapy for the treatment of pneumonia or BSI caused by these pathogens. (Funded by the National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases protocol 10-0065; ClinicalTrials.gov number, NCT01597973.).

Clinical Impact of Ceftriaxone Resistance in Escherichia coli Bloodstream Infections: A Multicenter Prospective Cohort Study.

Background: Ceftriaxone-resistant (CRO-R) Escherichia coli bloodstream infections (BSIs) are common. Methods: This is a prospective cohort of patients with E coli BSI at 14 United States hospitals between November 2020 and April 2021. For each patient with a CRO-R E coli BSI enrolled, the next consecutive patient with a ceftriaxone-susceptible (CRO-S) E coli BSI was included. Primary outcome was desirability of outcome ranking (DOOR) at day 30, with 50% probability of worse outcomes in the CRO-R group as the null hypothesis. Inverse probability weighting (IPW) was used to reduce confounding. Results: Notable differences between patients infected with CRO-R and CRO-S E coli BSI included the proportion with Pitt bacteremia score ≥4 (23% vs 15%, P = .079) and the median time to active antibiotic therapy (12 hours [interquartile range {IQR}, 1-35 hours] vs 1 hour [IQR, 0-6 hours]; P < .001). Unadjusted DOOR analyses indicated a 58% probability (95% confidence interval [CI], 52%-63%) for a worse clinical outcome in CRO-R versus CRO-S BSI. In the IPW-adjusted cohort, no difference was observed (54% [95% CI, 47%-61%]). Secondary outcomes included unadjusted and adjusted differences in the proportion of 30-day mortality between CRO-R and CRO-S BSIs (-5.3% [95% CI, -10.3% to -.4%] and -1.8 [95% CI, -6.7% to 3.2%], respectively), postculture median length of stay (8 days [IQR, 5-13 days] vs 6 days [IQR, 4-9 days]; P < .001), and incident admission to a long-term care facility (22% vs 12%, P = .045). Conclusions: Patients with CRO-R E coli BSI generally have poorer outcomes compared to patients infected with CRO-S E coli BSI, even after adjusting for important confounders.

Long COVID and COVID-19-associated cystitis (CAC).

PURPOSE: There is scarce literature regarding genitourinary symptoms in COVID-19, especially post-acute disease otherwise known as Long COVID. We identified recovered COVID-19 patients presenting with new or worsening overactive bladder symptoms, known as COVID-19-associated cystitis (CAC). METHODS: We used the American Urological Association Urology Care Foundation Overactive Bladder (OAB) Assessment Tool to screen COVID-19 recovered patients presenting with urological complaints at our urban-located institution from 5/22/2020 to 12/31/2020. Patients 10-14 weeks post-discharge responded to 5 symptom and 4 quality-of-life (QoL) questions. We reported median symptom scores, as well as QoL scores, based on new or worsening urinary symptoms, and by sex. RESULTS: We identified 350 patients with de novo or worsening OAB symptoms 10-14 weeks after hospitalization with COVID-19. The median total OAB symptom score in both men and women was 18. The median total QoL score for both men and women was 19. Patients with worsening OAB symptoms had a median pre-COVID-19 symptom score of 8 (4-10) compared to post-COVID-19 median symptom score of 19 (17-21). Median age was 64.5 (range 47-82). Median hospital length-of-stay was 10 days (range 5-30). CONCLUSION: We report survey-based results of patients suffering from new or worsening OAB symptoms months after their hospitalization from COVID-19. Future studies with larger sample sizes and more extensive testing will hopefully elucidate the specific pathophysiology of OAB symptoms in the context of long COVID so urologists can timely and appropriately treat their patients.

Strategies for Effective Infection Prevention Programs: Structures, Processes, and Funding.

Successful Infection Prevention Programs (IPPs) consist of a multidisciplinary team led by a hospital epidemiologist and managed by infection preventionists. Knowledge of the economics of health care-associated infections (HAIs) and the ability to make a business plan is now essential to the success of programs. Prevention of HAIs is the core function of IPPs with impact on patient outcomes, quality of care, and cost savings for hospitals. This article discusses the structure and responsibilities of an IPP, the regulatory pressures and opportunities that these programs face, and how to build and manage a successful program.

Standardized Treatment and Assessment Pathway Improves Mortality in Adults With Methicillin-resistant Staphylococcus aureus Bacteremia: STAPH Study.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) management remains challenging for clinicians. Numerous in vitro studies report synergy when vancomycin (VAN) and daptomycin (DAP) are combined with beta-lactams (BLs), which has led to clinical implementation of these combinations. While shorter durations of bacteremia have often been reported, there has been no significant impact on mortality. METHODS: The Detroit Medical Center (DMC) developed and implemented a clinical pathway algorithm for MRSA BSI treatment in 2016 that included the early use of BL combination therapy with standard of care (VAN or DAP) and a mandatory Infectious Diseases consultation. This was a retrospective, quasi-experimental study at the DMC between 2013 and 2020. Multivariable logistic regression was used to assess the independent association between pathway implementation and 30-day mortality while adjusting for confounding variables. RESULTS: Overall, 813 adult patients treated for MRSA BSI were evaluated. Compared with prepathway (PRE) patients (n = 379), those treated postpathway (POST; n = 434) had a significant reduction in 30-day and 90-day mortality: 9.7% in POST vs 15.6% in PRE (P = .011) and 12.2% in POST vs 19.0% in PRE (P = .007), respectively.The incidence of acute kidney injury (AKI) was higher in the PRE compared with the POST group: 9.6% vs 7.2% (P = .282), respectively. After adjusting for confounding variables including Infectious Diseases consult, POST was independently associated with a reduction in 30-day mortality (adjusted odds ratio [aOR], 0.608; 95% CI, 0.375-0.986). CONCLUSIONS: Implementation of an MRSA BSI treatment pathway with early use of BL reduced mortality with no increased rate of AKI. Further prospective evaluation of this pathway approach is warranted.

A "resistance calculator": Simple stewardship intervention for refining empiric practices of antimicrobials in acute-care hospitals.

OBJECTIVE: In the era of widespread resistance, there are 2 time points at which most empiric prescription errors occur among hospitalized adults: (1) upon admission (UA) when treating patients at risk of multidrug-resistant organisms (MDROs) and (2) during hospitalization, when treating patients at risk of extensively drug-resistant organisms (XDROs). These errors adversely influence patient outcomes and the hospital's ecology. DESIGN AND SETTING: Retrospective cohort study, Shamir Medical Center, Israel, 2016. PATIENTS: Adult patients (aged >18 years) hospitalized with sepsis. METHODS: Logistic regressions were used to develop predictive models for (1) MDRO UA and (2) nosocomial XDRO. Their performances on the derivation data sets, and on 7 other validation data sets, were assessed using the area under the receiver operating characteristic curve (ROC AUC). RESULTS: In total, 4,114 patients were included: 2,472 patients with sepsis UA and 1,642 with nosocomial sepsis. The MDRO UA score included 10 parameters, and with a cutoff of ≥22 points, it had an ROC AUC of 0.85. The nosocomial XDRO score included 7 parameters, and with a cutoff of ≥36 points, it had an ROC AUC of 0.87. The range of ROC AUCs for the validation data sets was 0.7-0.88 for the MDRO UA score and was 0.66-0.75 for nosocomial XDRO score. We created a free web calculator (https://assafharofe.azurewebsites.net). CONCLUSIONS: A simple electronic calculator could aid with empiric prescription during an encounter with a septic patient. Future implementation studies are needed to evaluate its utility in improving patient outcomes and in reducing overall resistances.

A Physician-Driven Quality Improvement Stewardship Intervention Using Lean Six Sigma Improves Patient Care for Community-Acquired Pneumonia.

Introduction: The Infectious Diseases Society of America (IDSA) recommends a minimum of 5 days of antibiotic therapy in stable patients who have community-acquired pneumonia (CAP). However, excessive duration of therapy (DOT) is common. Define, measure, analyze, improve, and control (DMAIC) is a Lean Six Sigma methodology used in quality improvement efforts, including infection control; however, the utility of this approach for antimicrobial stewardship initiatives is unknown. To determine the impact of a prospective physician-driven stewardship intervention on excess antibiotic DOT and clinical outcomes of patients hospitalized with CAP. Our specific aim was to reduce excess DOT and to determine why some providers treat beyond the IDSA minimum DOT. Methods: A single-center, quasi-experimental quality improvement study evaluating rates of excess antimicrobial DOT before and after implementing a DMAIC-based antimicrobial stewardship intervention that included education, prospective audit, and feedback from a physician peer, and daily tracking of excess DOT on a Kaizen board. The baseline period included retrospective CAP cases that occurred between October 2018 and February 2019 (control group). The intervention period included CAP cases between October 2019 and February 2020 (intervention group). Results: A total of 123 CAP patients were included (57 control and 66 intervention). Median antibiotic DOT per patient decreased (8 versus 5 days; p < 0.001), and the proportion of patients treated for the IDSA minimum increased (5.3% versus 56%; p < 0.001) after the intervention. No differences in mortality, readmission, length of stay, or incidence of Clostridioides difficile infection were observed between groups. Almost half of the caregivers surveyed were aware that as few as 5 days of antibiotic treatment could be appropriate. Conclusions: A physician-driven antimicrobial quality improvement initiative designed using DMAIC methodology led to reduced DOT and increased compliance with the IDSA treatment guidelines for hospitalized patients with CAP reduced without negatively affecting clinical outcomes.

COVID-19 inflammation results in urine cytokine elevation and causes COVID-19 associated cystitis (CAC).

Coronavirus disease 2019 (COVID-19) causes a wide range of symptoms, including several unexpected symptoms such as loss of taste, skin changes, and eye problems. We recently observed patients with documented COVID-19 develop de novo severe genitourinary symptoms, most notably urinary frequency of ≥ 13 episodes/24 h and nocturia ≥ 4 episodes/night. We call these associated urinary symptoms COVID-19 associate cystitis (CAC). COVID-19 severity is associated with inflammation. We collected urine samples from COVID-19 patients, including patients with CAC, and found elevation of proinflammatory cytokines also in the urine. It has been previously shown that patients with urinary incontinence and ulcerative interstitial cystitis/bladder pain syndrome have elevated urinary inflammatory cytokines compared to normal controls. We therefore hypothesize that CAC, with presentation of de novo severe urinary symptoms, can occur in COVID-19 and is caused by increased inflammatory cytokines that are released into the urine and/or expressed in the bladder. The most important implications of our hypothesis are: 1) Physician caring for COVID-19 patients should be aware of COVID-19 associate cystitis (CAC); 2) De novo urinary symptoms should be included in the symptom complex associated with COVID-19; and 3) COVID-19 inflammation may result in bladder dysfunction.

Molecular and clinical epidemiology of carbapenem-resistant Enterobacterales in the USA (CRACKLE-2): a prospective cohort study.

BACKGROUND: Carbapenem-resistant Enterobacterales (CRE) are a global threat. We aimed to describe the clinical and molecular characteristics of Centers for Disease Control and Prevention (CDC)-defined CRE in the USA. METHODS: CRACKLE-2 is a prospective, multicentre, cohort study. Patients hospitalised in 49 US hospitals, with clinical cultures positive for CDC-defined CRE between April 30, 2016, and Aug 31, 2017, were included. There was no age exclusion. The primary outcome was desirability of outcome ranking (DOOR) at 30 days after index culture. Clinical data and bacteria were collected, and whole genome sequencing was done. This trial is registered with ClinicalTrials.gov, number NCT03646227. FINDINGS: 1040 patients with unique isolates were included, 449 (43%) with infection and 591 (57%) with colonisation. The CDC-defined CRE admission rate was 57 per 100 000 admissions (95% CI 45-71). Three subsets of CDC-defined CRE were identified: carbapenemase-producing Enterobacterales (618 [59%] of 1040), non-carbapenemase-producing Enterobacterales (194 [19%]), and unconfirmed CRE (228 [22%]; initially reported as CRE, but susceptible to carbapenems in two central laboratories). Klebsiella pneumoniae carbapenemase-producing clonal group 258 K pneumoniae was the most common carbapenemase-producing Enterobacterales. In 449 patients with CDC-defined CRE infections, DOOR outcomes were not significantly different in patients with carbapenemase-producing Enterobacterales, non-carbapenemase-producing Enterobacterales, and unconfirmed CRE. At 30 days 107 (24%, 95% CI 20-28) of these patients had died. INTERPRETATION: Among patients with CDC-defined CRE, similar outcomes were observed among three subgroups, including the novel unconfirmed CRE group. CDC-defined CRE represent diverse bacteria, whose spread might not respond to interventions directed to carbapenemase-producing Enterobacterales. FUNDING: National Institutes of Health.

Ceftolozane/Tazobactam vs Polymyxin or Aminoglycoside-based Regimens for the Treatment of Drug-resistant Pseudomonas aeruginosa.

BACKGROUND: Ceftolozane/tazobactam is a novel cephalosporin/beta-lactamase inhibitor combination that often retains activity against resistant Pseudomonas aeruginosa. The comparative safety and efficacy vs polymyxins or aminoglycosides in this setting remains unknown. METHODS: A retrospective, multicenter, observational cohort study was performed. Patients who received ceftolozane/tazobactam were compared with those treated with either polymyxin or aminoglycoside-based regimens for infections due to drug-resistant P. aeruginosa. Multivariate logistic regression was performed controlling for factors associated with treatment to assess the independent impact of ceftolozane/tazobactam on clinical cure, acute kidney injury (AKI), and in-hospital mortality. RESULTS: A total of 200 patients were included (100 in each treatment arm). The cohort represented an ill population with 69% in the intensive care unit, 63% mechanically ventilated, and 42% in severe sepsis or septic shock at infection onset. The most common infection type was ventilator-associated pneumonia (52%); 7% of patients were bacteremic. Combination therapy was more commonly used in polymyxin/aminoglycoside patients than those who received ceftolozane/tazobactam (72% vs 15%, P < .001). After adjusting for differences between groups, receipt of ceftolozane/tazobactam was independently associated with clinical cure (adjusted odds ratio [aOR], 2.63; 95% confidence interval [CI], 1.31-5.30) and protective against AKI (aOR, 0.08; 95% CI, 0.03-0.22). There was no difference in in-hospital mortality. The number needed to treat for a clinical cure with ceftolozane/tazobactam was 5, and the number needed to harm with AKI with a polymyxin/aminoglycoside was 4. CONCLUSIONS: These data support the preferential use of ceftolozane/tazobactam over polymyxins or aminoglycosides for drug-resistant P. aeruginosa infections.

Epidemiology of Diabetic Foot Infection in the Metro-Detroit Area With a Focus on Independent Predictors for Pathogens Resistant to Recommended Empiric Antimicrobial Therapy.

BACKGROUND: The polymicrobial nature of diabetic foot infection (DFI) and the emergence of antimicrobial resistance have complicated DFI treatment. Current treatment guidelines for deep DFI recommend coverage of methicillin-resistant Staphylococcus aureus (MRSA) and susceptible Enterobacteriaceae. This study aimed to describe the epidemiology of DFI and to identify predictors for DFI associated with multidrug-resistant organisms (MDROs) and pathogens resistant to recommended treatment (PRRT). METHODS: Adult patients admitted to Detroit Medical Center from January 2012 to December 2015 with DFI and positive cultures were included. Demographics, comorbidities, microbiological history, sepsis severity, and antimicrobial use within 3 months before DFI were obtained retrospectively. DFI-PRRT was defined as a DFI associated with a pathogen resistant to both vancomycin and ceftriaxone. DFI-MDRO pathogens included MRSA in addition to PRRT. RESULTS: Six-hundred forty-eight unique patients were included, with a mean age of 58.4 ± 13.7 years. DFI-MDRO accounted for 364 (56%) of the cohort, and 194 (30%) patients had DFI-PRRT. Independent predictors for DFI-PRRT included history of PRRT in a diabetic foot ulcer, antimicrobial exposure in the prior 90 days, peripheral vascular disease, and chronic kidney disease. Long-term care facility residence was independently associated with DFI due to ceftriaxone-resistant Enterobacteriaceae, and recent hospitalization was an independent predictor of DFI due to vancomycin-resistant Enterococcus. CONCLUSIONS: An unexpectedly high prevalence of DFI-PRRT pathogens was identified. History of the same pathogen in a prior diabetic foot ulcer and recent antimicrobial exposure were independent predictors of DFI-PRRT and should be considered when selecting empiric DFI therapy.

A Rare Case of Mediastinal Bronchogenic Cyst Infected by Salmonella enteritidis.

Bronchogenic cysts are rare congenital malformations which arise from abnormal budding of the primitive tracheobronchial tube and can localize to either the mediastinum or lung parenchyma. They remain clinically silent in most adults unless they become infected or are large enough to compress adjacent structures. Infections involving bronchogenic cysts are often polymicrobial. Gram-positive, Gram-negative, and mycobacterial infections have been reported, though frequently a pathogen is not identified. We present the case of a 46-year-old female with known history of bronchogenic cyst who presented with suspected postobstructive pneumonia. She underwent cyst excision with culture positive for Salmonella enteritidis, an extremely rare finding on review of the literature. The patient recovered following a three-week course of antibiotics for extraintestinal salmonellosis.