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1.
J Occup Environ Hyg ; 18(sup1): S53-S60, 2021.
Article in English | MEDLINE | ID: mdl-33822695

ABSTRACT

RESUMENCuando se retira el equipo de protección personal (EPP), los patógenos pueden transferirse desde el EPP al cuerpo de los trabajadores de la salud, poniendo en riesgo de exposición e infección tanto a ellos mismos como a sus pacientes. Entre marzo de 2017 y abril de 2018 se observaron las prácticas de retirada del EPP del personal sanitario que atendía pacientes con infecciones respiratorias virales en un hospital de atención de enfermedades agudas. Un observador capacitado registró el desempeño del personal sanitario cuando retiraba el EPP dentro de las habitaciones de los pacientes, utilizando una lista de verificación predefinida basada en las directrices de los Centros para el Control y Prevención de Enfermedades (Centers for Disease Control and Prevention, CDC). Se observaron 162 prácticas de retirada durante el cuidado de 52 pacientes infectados con patógenos virales respiratorios. De estos 52 pacientes, 30 estaban en aislamiento por gota y contacto, 21 en aislamiento por gota y uno en aislamiento de contacto. En general, en 90% de los casos la retirada del EPP observada se realizó de manera incorrecta, ya sea en cuanto a la secuencia de retirada, la técnica de retirada o el uso del EPP apropiado. Los errores más comunes consistieron en quitarse la bata por adelante, retirar la pantalla facial de la mascarilla y tocar superficies y EPP potencialmente contaminados durante el proceso. Las desviaciones del protocolo recomendado para retirar el EPP son comunes y pueden aumentar el potencial de contaminación de la ropa o la piel del personal sanitario después de proporcionar atención. Existe una clara necesidad de cambiar el enfoque utilizado para capacitar al personal en las prácticas de retirada del EPP.

2.
Clin Infect Dis ; 71(11): 2920-2926, 2020 12 31.
Article in English | MEDLINE | ID: mdl-32548628

ABSTRACT

BACKGROUND: Outbreaks of coronavirus disease 2019 (COVID-19) have been reported in nursing homes and assisted living facilities; however, the extent of asymptomatic and presymptomatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in this high-risk population remains unclear. METHODS: We conducted an investigation of the first known outbreak of SARS-CoV-2 at a skilled nursing facility (SNF) in Illinois on 15 March 2020 and followed residents for 30 days. We tested 126/127 residents for SARS-CoV-2 via reverse-transcription polymerase chain reaction and performed symptom assessments. We calculated the point prevalence of SARS-CoV-2 and assessed symptom onset over 30-day follow-up to determine: (1) the proportion of cases who were symptomatic, presymptomatic, and asymptomatic and (2) incidence of symptoms among those who tested negative. We used the Kaplan-Meier method to determine the 30-day probability of death for cases. RESULTS: Of 126 residents tested, 33 had confirmed SARS-CoV-2 on 15 March. Nineteen (58%) had symptoms at the time of testing, 1 (3%) developed symptoms over follow-up, and 13 (39%) remained asymptomatic. Thirty-five residents who tested negative on 15 March developed symptoms over follow-up; of these, 3 were re-tested and 2 were positive. The 30-day probability of death among cases was 29%. CONCLUSIONS: SNFs are particularly vulnerable to SARS-CoV-2, and residents are at risk of severe outcomes. Attention must be paid to preventing outbreaks in these and other congregate care settings. Widespread testing and infection control are key to help prevent COVID-19 morbidity and mortality in these high-risk populations.


Subject(s)
COVID-19 , SARS-CoV-2 , Disease Outbreaks , Humans , Illinois/epidemiology , Skilled Nursing Facilities
3.
Clin Infect Dis ; 70(8): 1536-1545, 2020 04 10.
Article in English | MEDLINE | ID: mdl-31157370

ABSTRACT

BACKGROUND: Vancomycin is the most commonly administered antibiotic in hospitalized patients, but optimal exposure targets remain controversial. To clarify the therapeutic exposure range, this study evaluated the association between vancomycin exposure and outcomes in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. METHODS: This was a prospective, multicenter (n = 14), observational study of 265 hospitalized adults with MRSA bacteremia treated with vancomycin. The primary outcome was treatment failure (TF), defined as 30-day mortality or persistent bacteremia ≥7 days. Secondary outcomes included acute kidney injury (AKI). The study was powered to compare TF between patients who achieved or did not achieve day 2 area under the curve to minimum inhibitory concentration (AUC/MIC) thresholds previously found to be associated with lower incidences of TF. The thresholds, analyzed separately as co-primary endpoints, were AUC/MIC by broth microdilution ≥650 and AUC/MIC by Etest ≥320. RESULTS: Treatment failure and AKI occurred in 18% and 26% of patients, respectively. Achievement of the prespecified day 2 AUC/MIC thresholds was not associated with less TF. Alternative day 2 AUC/MIC thresholds associated with lower TF risks were not identified. A relationship between the day 2 AUC and AKI was observed. Patients with day 2 AUC ≤515 experienced the best global outcomes (no TF and no AKI). CONCLUSIONS: Higher vancomycin exposures did not confer a lower TF risk but were associated with more AKI. The findings suggest that vancomycin dosing should be guided by the AUC and day 2 AUCs should be ≤515. As few patients had day 2 AUCs <400, further study is needed to define the lower bound of the therapeutic range.


Subject(s)
Bacteremia , Methicillin-Resistant Staphylococcus aureus , Staphylococcal Infections , Adult , Anti-Bacterial Agents/therapeutic use , Bacteremia/drug therapy , Humans , Microbial Sensitivity Tests , Prospective Studies , Retrospective Studies , Staphylococcal Infections/drug therapy , Treatment Outcome , Vancomycin/therapeutic use
4.
MMWR Morb Mortal Wkly Rep ; 69(43): 1591-1594, 2020 Oct 30.
Article in English | MEDLINE | ID: mdl-34463672

ABSTRACT

Data on transmission of SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), among college athletes are limited. In August 2020, the Chicago Department of Public Health (CDPH) was notified of a cluster of COVID-19 cases among a university's men's and women's soccer teams. CDPH initiated an investigation, interviewed members of both teams, and collated laboratory data to understand transmission of SARS-CoV-2 within the teams. Numerous social gatherings with limited mask use or social distancing preceded the outbreak. Transmission resulted in 17 laboratory-confirmed COVID-19 cases across both teams (n = 45), likely from a single source introduction of SARS-CoV-2 (based on whole genome sequencing) and subsequent transmission during multiple gatherings. Colleges and universities are at risk for COVID-19 outbreaks because of shared housing and social gatherings where recommended prevention guidance is not followed. Improved strategies to promote mask use and social distancing among college-aged adults need to be implemented, as well as periodic repeat testing to identify asymptomatic infections and prevent outbreaks among groups at increased risk for infection because of frequent exposure to close contacts in congregate settings on and off campus.


Subject(s)
Athletes/statistics & numerical data , COVID-19/epidemiology , Disease Outbreaks , Soccer , Students/statistics & numerical data , Universities , Adolescent , COVID-19/prevention & control , COVID-19/transmission , COVID-19 Testing , Chicago/epidemiology , Contact Tracing , Disease Outbreaks/prevention & control , Female , Humans , Male , Masks/statistics & numerical data , Physical Distancing , Quarantine , SARS-CoV-2/isolation & purification , Young Adult
5.
Clin Infect Dis ; 69(3): 552-553, 2019 07 18.
Article in English | MEDLINE | ID: mdl-30462184

ABSTRACT

Doernberg and colleagues describe the role and resourcing of the infectious disease (ID) physician for an effective hospital-based antibiotic stewardship program (ASP). There are similar resource requirements for the ID physician leader in an effective infection prevention (IP) program. This ID physician partnership is supported by professional organizations and predates the imperative of ID physician leadership in ASP. There are regulatory requirements for established IP programs, but they do not specify leadership structure to the same degree as ASP regulations. The Centers for Medicare and Medicaid and The Joint Commission have specified the inclusion of an ID-trained physician leader in ASP, and this has led to the development of curriculum to train more ASP physicians. More robust advocacy may ensure a similar regulatory mandate supporting the participation of ID-trained physicians in IP programs. This may encourage the development of a curriculum to meet the workforce.


Subject(s)
Antimicrobial Stewardship , Infections , Physicians , Aged , Health Resources , Humans , Medicare , United States
6.
Clin Infect Dis ; 69(Suppl 3): S178-S184, 2019 09 13.
Article in English | MEDLINE | ID: mdl-31517975

ABSTRACT

BACKGROUND: Respiratory viruses on fomites can be transferred to sites susceptible to infection via contact by hands or other fomites. METHODS: Care for hospitalized patients with viral respiratory infections was observed in the patient room for 3-hour periods at an acute care academic medical center for over a 2 year period. One trained observer recorded the healthcare activities performed, contacts with fomites, and self-contacts made by healthcare workers (HCWs), while another observer recorded fomite contacts of patients during the encounter using predefined checklists. RESULTS: The surface contacted by HCWs during the majority of visits was the patient (90%). Environmental surfaces contacted by HCWs frequently during healthcare activities included the tray table (48%), bed surface (41%), bed rail (41%), computer station (37%), and intravenous pole (32%). HCWs touched their own torso and mask in 32% and 29% of the visits, respectively. HCWs' self-contacts differed significantly among HCW job roles, with providers and respiratory therapists contacting themselves significantly more times than nurses and nurse technicians (P < .05). When HCWs performed only 1 care activity, there were significant differences in the number of patient contacts and self-contacts that HCWs made during performance of multiple care activities (P < .05). CONCLUSIONS: HCWs regularly contact environmental surfaces, patients, and themselves while providing care to patients with infectious diseases, varying among care activities and HCW job roles. These contacts may facilitate the transmission of infection to HCWs and susceptible patients.


Subject(s)
Fomites/virology , Health Facility Environment , Health Personnel , Infection Control/methods , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/transmission , Cross Infection/prevention & control , Cross Infection/virology , Hand/virology , Hospitals/statistics & numerical data , Humans , Intensive Care Units/statistics & numerical data , Patient Isolation , Patients , Patients' Rooms/statistics & numerical data , Respiratory Tract Infections/virology
7.
Clin Infect Dis ; 68(10): 1777-1782, 2019 05 02.
Article in English | MEDLINE | ID: mdl-30239608

ABSTRACT

Antimicrobial stewardship programs (ASPs) are recommended by the Centers for Disease Control and Prevention and World Health Organization and mandated by the Joint Commission to curb antimicrobial resistance. However, <50% of institutions have optimal ASPs in place. Building on its experience of antimicrobial stewardship (AMS) advocacy, the Infectious Diseases Society of America (IDSA) developed the AMS Centers of Excellence (CoE) program, which will serve as a conduit to share best practices and highlight the standards for other hospitals to achieve in order to advance the field of AMS. A designation of CoE signifies that these institutions deliver high-quality care consistently, serve as the "gold" standard for executing novel AMS principles, and demonstrate commitment to their ASP. Here, we describe the process and purpose of designating institutions as AMS CoEs, provide awareness to clinicians on opportunities available through IDSA with this CoE designation, and discuss the evolution of the program.


Subject(s)
Antimicrobial Stewardship/standards , Health Facilities , Societies , Antimicrobial Stewardship/statistics & numerical data , Centers for Disease Control and Prevention, U.S. , Communicable Disease Control , Communicable Diseases/microbiology , Health Facilities/classification , Health Facilities/standards , Humans , United States , World Health Organization
8.
Clin Infect Dis ; 68(2): 239-246, 2019 01 07.
Article in English | MEDLINE | ID: mdl-29901775

ABSTRACT

Background: Intervention by infectious diseases (ID) physicians improves outcomes for inpatients in Medicare, but patients with other insurance types could fare differently. We assessed whether ID involvement leads to better outcomes among privately insured patients under age 65 years hospitalized with common infections. Methods: We performed a retrospective analysis of administrative claims data from community hospital and postdischarge ambulatory care. Patients were privately insured individuals less than 65 years old with an acute-care stay in 2014 for selected infections, classed as having early (by day 3) or late (after day 3) ID intervention, or none. Key outcomes were mortality, cost, length of the index stay, readmission rate, mortality, and total cost of care over the first 30 days after discharge. Results: Patients managed with early ID involvement had shorter length of stay, lower spending, and lower mortality in the index stay than those patients managed without ID involvement. Relative to late, early ID involvement was associated with shorter length of stay and lower cost. Individuals with early ID intervention during hospitalization had fewer readmissions and lower healthcare payments after discharge. Relative to late, those with early ID intervention experienced lower readmission, lower spending, and lower mortality. Conclusions: Among privately insured patients less than 65 years old, treated in a hospital, early intervention with an ID physician was associated with lower mortality rate and shorter length of stay. Patients who received early ID intervention during their hospital stay were less likely to be readmitted after discharge and had lower total healthcare spending.


Subject(s)
Health Care Costs , Infectious Disease Medicine , Patient Readmission , Cohort Studies , Female , Hospitals , Humans , Infection Control/methods , Male , Patient Discharge , Retrospective Studies , United States
9.
BMC Health Serv Res ; 19(1): 306, 2019 May 14.
Article in English | MEDLINE | ID: mdl-31088551

ABSTRACT

BACKGROUND: Qualitative research studies are becoming increasingly necessary to understand the complex challenges in the healthcare setting. Successfully integrating interdisciplinary teams of investigators can be challenging, as investigators inherently view data through their disciplinary lens. Thus, new methods, such as focused conservation, are needed to facilitate qualitative data analysis by interdisciplinary teams. The purpose of this manuscript is to provide a clear description of how we implemented the focused conversation method to facilitate an organized data-driven discussion that responded to our study objectives and ensured participation of our interdisciplinary team. The focused conversation method has not, to our knowledge, been utilized for this purpose to date. METHODS: To better understand the experience of healthcare personnel (HCP) during preparations for the 2014-2015 Ebola Virus Disease (EVD) outbreak, we interviewed HCP who participated in decision making about EVD preparations and training of workers in the use of enhanced personal protective equipment ensembles in the metropolitan Chicagoland area of Illinois to attain a priori research objectives. We identified a systematic method - the focused conversation method - that enabled our interdisciplinary team to interactively contribute to the framing, analysis and interpretation of the data that would enable us to focus on our research objectives. RESULTS: The focused conversation developed to support our a priori research objective about the training of HCP in preparations included objective, reflective, interpretive and decisional questions. These questions grounded the conversation in the data, while leveraging discipline-specific lenses and professional experience in the analysis and interpretation. Insights from the conversation were reviewed later against interview transcripts to ensure validity. The conversation identified areas for future research directions and deficiencies in the interview instrument. CONCLUSIONS: The focused conversation is an efficient, organized method for analysis of qualitative data by an interdisciplinary team.


Subject(s)
Health Services Research/organization & administration , Patient Care Team/organization & administration , Public Health , Attitude of Health Personnel , Communication , Focus Groups , Health Personnel , Humans , Illinois , Qualitative Research
10.
J Occup Environ Hyg ; 16(8): 575-581, 2019 08.
Article in English | MEDLINE | ID: mdl-31291152

ABSTRACT

During the doffing of personal protective equipment (PPE), pathogens can be transferred from the PPE to the bodies of healthcare workers (HCWs), putting HCWs and patients at risk of exposure and infection. PPE doffing practices of HCWs who cared for patients with viral respiratory infections were observed at an acute care hospital from March 2017 to April 2018. A trained observer recorded doffing performance of HCWs inside the patient rooms using a pre-defined checklist based on the Centers for Disease Control and Prevention (CDC) guideline. Doffing practices were observed 162 times during care of 52 patients infected with respiratory viral pathogens. Out of the 52 patients, 30 were in droplet and contact isolation, 21 were in droplet isolation, and 1 was in contact isolation. Overall, 90% of observed doffing was incorrect, with respect to the doffing sequence, doffing technique, or use of appropriate PPE. Common errors were doffing gown from the front, removing face shield of the mask, and touching potentially contaminated surfaces and PPE during doffing. Deviations from the recommended PPE doffing protocol are common and can increase potential for contamination of the HCW's clothing or skin after providing care. There is a clear need to change the approach used to training HCWs in PPE doffing practices.


Subject(s)
Guideline Adherence/statistics & numerical data , Health Personnel , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Personal Protective Equipment/virology , Adult , Hospitals , Humans , Infection Control/methods , Infection Control/standards , Personnel, Hospital , Respiratory Tract Infections/prevention & control , Respiratory Tract Infections/virology , Virus Diseases/prevention & control
11.
J Occup Environ Hyg ; 16(8): 582-591, 2019 08.
Article in English | MEDLINE | ID: mdl-31283428

ABSTRACT

During the 2014-2015 Ebola Virus Disease (EVD) outbreak, hospitals in the United States selected personal protective equipment (PPE) and trained healthcare personnel (HCP) in anticipation of receiving EVD patients. To improve future preparations for high-consequence infectious diseases, it was important to understand factors that affected PPE selection and training in the context of the EVD outbreak. Semistructured interviews were conducted with HCP involved with decision-making during EVD preparations at acute care hospitals in the Chicago, IL area to gather information about the PPE selection and training process. HCP who received training were surveyed about elements of training and their perceived impact and overall experience by email invitation. A total of 28 HCP from 15 hospitals were interviewed, and 55 HCP completed the survey. Factors affecting PPE selection included: changing guidance, vendor supply, performance evaluations, and perceived risk and comfort for HCP. Cost did not affect selection. PPE acquisition challenges were mitigated by: sharing within hospital networks, reusing PPE during training, and improvising with existing PPE stock. Selected PPE ensembles were similar across sites. Training included hands-on activities with trained observers, instructional videos, and simulations/drills, which were felt to increase HCP confidence. Many felt refresher training would be helpful. Hands-on training was perceived to be effective, but there is a need to establish the appropriate frequency of refresher training frequency to maintain competence. Lacking confidence in the CDC guidance, interviewed trainers described turning to other sources of information and developing independent PPE evaluation and selection. Response to emerging and/or high consequence infectious diseases would be enhanced by transparent, risk-based guidance for PPE selection and training that addresses protection level, ease of use, ensembles, and availability.


Subject(s)
Health Personnel/education , Hemorrhagic Fever, Ebola/prevention & control , Infectious Disease Transmission, Patient-to-Professional/prevention & control , Personal Protective Equipment/standards , Disease Outbreaks/prevention & control , Ebolavirus , Hospital Administration/methods , Hospitals , Humans , Illinois , Personal Protective Equipment/economics , Personal Protective Equipment/supply & distribution , Surveys and Questionnaires
12.
Article in English | MEDLINE | ID: mdl-29311094

ABSTRACT

A recommended total-body-weight (TBW) dosing strategy for telavancin may not be optimal in obese patients. The primary objective of this study was to characterize and compare the pharmacokinetics (PK) of telavancin across four body size groups: normal to overweight and obese classes I, II, and III. Healthy adult subjects (n = 32) received a single, weight-stratified, fixed dose of 500 mg (n = 4), 750 mg (n = 8), or 1,000 mg (n = 20) of telavancin. Noncompartmental PK analyses revealed that subjects with a body mass index (BMI) of ≥40 kg/m2 had a higher volume of distribution (16.24 ± 2.7 liters) than subjects with a BMI of <30 kg/m2 (11.71 ± 2.6 liters). The observed area under the concentration-time curve from time zero to infinity (AUC0-∞) ranged from 338.1 to 867.3 mg · h/liter, with the lowest exposures being in subjects who received 500 mg. AUC0-∞ values were similar among obese subjects who received 1,000 mg. A two-compartment population PK model best described the plasma concentration-time profile of telavancin when adjusted body weight (ABW) was included as a predictive covariate. Fixed doses of 750 mg and 1,000 mg had similar target attainment probabilities for efficacy as doses of 10 mg/kg of body weight based on ABW and TBW, respectively. However, the probability of achieving a target area under the concentration-time curve from time zero to 24 h of ≥763 mg · h/liter in association with acute kidney injury was highest (19.7%) with TBW-simulated dosing and lowest (0.4%) at the 750-mg dose. These results suggest that a fixed dose of 750 mg is a safe and effective alternative to telavancin doses based on TBW or ABW for the treatment of obese patients with normal renal function and Staphylococcus aureus infections. (This study has been registered at ClinicalTrials.gov under identifier NCT02753855.).


Subject(s)
Aminoglycosides/pharmacokinetics , Anti-Bacterial Agents/pharmacokinetics , Lipoglycopeptides/pharmacokinetics , Body Weight/physiology , Humans , Ideal Body Weight , Models, Theoretical , Obesity/physiopathology , Staphylococcal Infections
13.
Article in English | MEDLINE | ID: mdl-29891606

ABSTRACT

The pharmacokinetics (PK), safety, and tolerability of two repeated dosing regimens of oral fosfomycin tromethamine were evaluated in 18 healthy adult subjects. Subjects received 3 g every other day (QOD) for 3 doses and then every day (QD) for 7 doses, or vice versa, in a phase I, randomized, open-label, two-period-crossover study. Serial blood (n = 11) and urine (n = 4 collection intervals) samples were collected before and up to 24 h after dosing on days 1 and 5, along with predose concentrations on days 3 and 7. PK parameters were similar between days 1 and 5 within and between dosing regimens. The mean (± standard deviation [SD]) PK parameters for fosfomycin in plasma on day 5 during the respective QOD and QD dosing regimens were as follows: maximum concentration of drug in serum (Cmax) = 24.4 ± 6.2 versus 23.8 ± 5.6 µg/ml, time to Cmax (Tmax) = 2.2 ± 0.7 versus 2.0 ± 0.4 h, apparent volume of distribution (V/F) = 141 ± 67.9 versus 147 ± 67.6 liters, apparent clearance (CL/F) = 21.4 ± 8.0 versus 20.4 ± 5.3 liters/h, renal clearance (CLR) = 7.5 ± 4.1 versus 7.3 ± 3.5 liters/h, area under the concentration-time curve from 0 to 24 h (AUC0-24) = 151.6 ± 35.6 versus 156.6 ± 42.5 µg · h/ml, and elimination half-life (t1/2) = 4.5 ± 1.1 versus 5.0 ± 1.7 h. Urine concentrations peaked at approximately 600 µg/ml through the 0- to 8-h urine collection intervals but displayed significant interindividual variability. Roughly 35 to 40% of the 3-g dose was excreted in the urine by 24 h postdose. No new safety concerns were identified during this study. The proportion of diarrhea-free days during the study was significantly lower with the QD regimen than with the QOD regimen (61% versus 77%; P < 0.0001). Further studies to establish the clinical benefit/risk ratio for repeated dosing regimens of oral fosfomycin tromethamine are warranted. (This trial is registered at ClinicalTrials.gov under registration no. NCT02570074.).


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Fosfomycin/pharmacokinetics , Administration, Oral , Adult , Anti-Bacterial Agents/blood , Anti-Bacterial Agents/urine , Area Under Curve , Cross-Over Studies , Drug Administration Schedule , Female , Fosfomycin/blood , Fosfomycin/urine , Half-Life , Healthy Volunteers , Humans , Male , Patient Safety , Random Allocation
14.
JAMA ; 319(8): 788-799, 2018 02 27.
Article in English | MEDLINE | ID: mdl-29486041

ABSTRACT

Importance: Meropenem-vaborbactam is a combination carbapenem/beta-lactamase inhibitor and a potential treatment for severe drug-resistant gram-negative infections. Objective: To evaluate efficacy and adverse events of meropenem-vaborbactam in complicated urinary tract infection (UTI), including acute pyelonephritis. Design, Setting, and Participants: Phase 3, multicenter, multinational, randomized clinical trial (TANGO I) conducted November 2014 to April 2016 and enrolling patients (≥18 years) with complicated UTI, stratified by infection type and geographic region. Interventions: Eligible patients were randomized 1:1 to receive meropenem-vaborbactam (2g/2g over 3 hours; n = 274) or piperacillin-tazobactam (4g/0.5g over 30 minutes; n = 276) every 8 hours. After 15 or more doses, patients could be switched to oral levofloxacin if they met prespecified criteria for improvement, to complete 10 days of total treatment. Main Outcomes and Measures: Primary end point for FDA criteria was overall success (clinical cure or improvement and microbial eradication composite) at end of intravenous treatment in the microbiologic modified intent-to-treat (ITT) population. Primary end point for European Medicines Agency (EMA) criteria was microbial eradication at test-of-cure visit in the microbiologic modified ITT and microbiologic evaluable populations. Prespecified noninferiority margin was -15%. Because the protocol prespecified superiority testing in the event of noninferiority, 2-sided 95% CIs were calculated. Results: Among 550 patients randomized, 545 received study drug (mean age, 52.8 years; 361 [66.2%] women; 374 [68.6%] in the microbiologic modified ITT population; 347 [63.7%] in the microbiologic evaluable population; 508 [93.2%] completed the trial). For the FDA primary end point, overall success occurred in 189 of 192 (98.4%) with meropenem-vaborbactam vs 171 of 182 (94.0%) with piperacillin-tazobactam (difference, 4.5% [95% CI, 0.7% to 9.1%]; P < .001 for noninferiority). For the EMA primary end point, microbial eradication in the microbiologic modified ITT population occurred in 128 of 192 (66.7%) with meropenem-vaborbactam vs 105 of 182 (57.7%) with piperacillin-tazobactam (difference, 9.0% [95% CI, -0.9% to 18.7%]; P < .001 for noninferiority); microbial eradication in the microbiologic evaluable population occurred in 118 of 178 (66.3%) vs 102 of 169 (60.4%) (difference, 5.9% [95% CI, -4.2% to 16.0%]; P < .001 for noninferiority). Adverse events were reported in 106 of 272 (39.0%) with meropenem-vaborbactam vs 97 of 273 (35.5%) with piperacillin-tazobactam. Conclusions and Relevance: Among patients with complicated UTI, including acute pyelonephritis and growth of a baseline pathogen, meropenem-vaborbactam vs piperacillin-tazobactam resulted in a composite outcome of complete resolution or improvement of symptoms along with microbial eradication that met the noninferiority criterion. Further research is needed to understand the spectrum of patients in whom meropenem-vaborbactam offers a clinical advantage. Trial Registration: clinicaltrials.gov Identifier: NCT02166476.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Boronic Acids/administration & dosage , Penicillanic Acid/analogs & derivatives , Pyelonephritis/drug therapy , Thienamycins/administration & dosage , Urinary Tract Infections/drug therapy , Acute Disease , Adult , Aged , Anti-Bacterial Agents/adverse effects , Boronic Acids/adverse effects , Drug Combinations , Female , Humans , Intention to Treat Analysis , Male , Meropenem , Middle Aged , Penicillanic Acid/administration & dosage , Penicillanic Acid/adverse effects , Piperacillin/administration & dosage , Piperacillin/adverse effects , Piperacillin, Tazobactam Drug Combination , Practice Guidelines as Topic , Thienamycins/adverse effects , Urine/microbiology
15.
Clin Infect Dis ; 65(4): 613-618, 2017 Aug 15.
Article in English | MEDLINE | ID: mdl-28444166

ABSTRACT

BACKGROUND: Anti-infective shortages are a pervasive problem in the United States. The objective of this study was to identify any associations between changes in prescribing of antibiotics that have a high risk for CDI during a piperacillin/tazobactam (PIP/TAZO) shortage and hospital-onset Clostridium difficile infection (HO-CDI) risk in 88 US medical centers. METHODS: We analyzed electronically captured microbiology and antibiotic use data from a network of US hospitals from July 2014 through June 2016. The primary outcome was HO-CDI rate and the secondary outcome was changes in antibiotic usage. We fit a Poisson model to estimate the risk of HO-CDI associated with PIP/TAZO shortage that were associated with increased high-risk antibiotic use while controlling for hospital characteristics. RESULTS: A total of 88 hospitals experienced PIP/TAZO shortage and 72 of them experienced a shift toward increased use of high-risk antibiotics during the shortage period. The adjusted relative risk (RR) of HO-CDI for hospitals experiencing a PIP/TAZO shortage was 1.03 (95% confidence interval [CI], .85-1.26; P = .73). The adjusted RR of HO-CDI for hospitals that both experienced a shortage and also showed a shift toward increased use of high-risk antibiotics was 1.30 (95% CI, 1.03-1.64; P < .05). CONCLUSIONS: Hospitals that experienced a PIP/TAZO shortage and responded to that shortage by shifting antibiotic usage toward antibiotics traditionally known to place patients at greater risk for CDI experienced greater HO-CDI rates; this highlights an important adverse effect of the PIP/TAZO shortage and the importance of antibiotic stewardship when mitigating drug shortages.


Subject(s)
Anti-Bacterial Agents/supply & distribution , Clostridium Infections/drug therapy , Drug Prescriptions/statistics & numerical data , Penicillanic Acid/analogs & derivatives , Anti-Bacterial Agents/therapeutic use , Clostridioides difficile , Clostridium Infections/epidemiology , Humans , Penicillanic Acid/supply & distribution , Penicillanic Acid/therapeutic use , Piperacillin/supply & distribution , Piperacillin/therapeutic use , Piperacillin, Tazobactam Drug Combination , Treatment Outcome , United States/epidemiology
16.
Article in English | MEDLINE | ID: mdl-28416553

ABSTRACT

Ceftazidime-avibactam administered at 1.25 g every 8 h was used to treat multidrug-resistant Pseudomonas aeruginosa bacteremia in a critically ill patient on continuous venovenous hemofiltration (CVVH). Prefiltration plasma drug concentrations of ceftazidime and avibactam were measured at 0, 1, 2, 4, 6, and 8 h along with postfiltration and ultrafiltrate concentrations at h 2 and h 6. Plasma pharmacokinetic parameters of ceftazidime and avibactam, respectively, were as follows: maximum plasma concentration (Cmax), 61.10 and 14.54 mg/liter; minimum plasma concentration (Cmin), 31.96 and 8.45 mg/liter; half-life (t1/2), 6.07 and 6.78 h; apparent volume of distribution at the steady state (Vss), 27.23 and 30.81 liters; total clearance at the steady state (CLss), 2.87 and 2.95 liters/h; area under the concentration-time curve from 0 to 8 h (AUC0-8), 347.87 and 85.69 mg · h/liter. Concentrations of ceftazidime in plasma exceeded the ceftazidime-avibactam MIC (6 mg/liter) throughout the 8-h dosing interval. Mean CVVH extraction ratios for ceftazidime and avibactam were 14.44% and 11.53%, respectively, and mean sieving coefficients were 0.96 and 0.93, respectively. The calculated mean clearance of ceftazidime by CVVH was 1.64 liters/h and for avibactam was 1.59 liters/h, representing 57.1% of the total clearance of ceftazidime and 54.3% of the total clearance of avibactam. Further data that include multiple patients and dialysis modes are needed to verify the optimal ceftazidime-avibactam dosing strategy during critical illness and CVVH.


Subject(s)
Anti-Bacterial Agents/pharmacokinetics , Azabicyclo Compounds/pharmacokinetics , Ceftazidime/pharmacokinetics , Anti-Bacterial Agents/pharmacology , Azabicyclo Compounds/pharmacology , Ceftazidime/pharmacology , Critical Illness , Drug Combinations , Hemofiltration , Microbial Sensitivity Tests , Pseudomonas aeruginosa/drug effects
20.
Article in English | MEDLINE | ID: mdl-38415079

ABSTRACT

Cultures from urinary catheters are often ordered without indication, leading to possible misdiagnosis of catheter-associated urinary tract infections (CAUTI), increasing antimicrobial use, and C difficile. We implemented a diagnostic stewardship intervention for urine cultures from catheters in a community hospital that led to a reduction in cultures and CAUTIs.

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