Treatment Outcomes for Carbapenem-Resistant and Cephalosporin-Susceptible Pseudomonas aeruginosa Pneumonia.

BACKGROUND: Carbapenem-resistant (Car-R) Pseudomonas aeruginosa is an urgent threat. These isolates may remain susceptible to traditional noncarbapenem antipseudomonal ß-lactams, but it is unclear if carbapenem resistance impacts the effectiveness of these agents. OBJECTIVE: The purpose of this study was to compare clinical outcomes in Car-R and cephalosporin-susceptible (Ceph-S) P. aeruginosa pneumonia treated with cefepime versus other susceptible agents. METHODS: This retrospective cohort study evaluated patients diagnosed with hospital-acquired or ventilator-associated pneumonia who had a respiratory isolate of Car-R Ceph-S P. aeruginosa. Patients were excluded if they had polymicrobial respiratory cultures, other concomitant infections, empyema, death within 3 days of index culture, or received less than 3 days of susceptible therapy. Patients treated with cefepime were compared to other susceptible therapies. The primary endpoint was 30-day in-hospital mortality. RESULTS: Eighty-seven patients were included: cefepime, n = 61; other susceptible therapies, n = 26. There were no differences in 30-day in-hospital mortality between cefepime and other susceptible therapies (19.6% vs. 19.2%, p value = 0.719). In addition, there were no differences between clinical cure rates (cefepime 65.6% vs. other therapies 72 %, p value = 0.47). In multivariate logistic regression, treatment with cefepime (odds ratio [OR], 0.57; 95% confidence interval [CI], 0.11-2.52) was not independently associated with 30-day in-hospital mortality. CONCLUSION AND RELEVANCE: For the treatment of Car-R Ceph-S P. aeruginosa pneumonia, cefepime showed similar rates of 30-day in-hospital mortality and clinical outcomes when compared to other susceptible therapies. Cefepime may be utilized to conserve novel ß-lactam and ß-lactamase inhibitors.

A Quasi-Experiment To Study the Impact of Vancomycin Area under the Concentration-Time Curve-Guided Dosing on Vancomycin-Associated Nephrotoxicity.

Evidence suggests that maintenance of vancomycin trough concentrations at between 15 and 20 mg/liter, as currently recommended, is frequently unnecessary to achieve the daily area under the concentration-time curve (AUC24) target of ≥400 mg · h/liter. Many patients with trough concentrations in this range have AUC24 values in excess of the therapeutic threshold and within the exposure range associated with nephrotoxicity. On the basis of this, the Detroit Medical Center switched from trough concentration-guided dosing to AUC-guided dosing to minimize potentially unnecessary vancomycin exposure. The primary objective of this analysis was to assess the impact of this intervention on vancomycin-associated nephrotoxicity in a single-center, retrospective quasi-experiment of hospitalized adult patients receiving intravenous vancomycin from 2014 to 2015. The primary analysis compared the incidence of nephrotoxicity between patients monitored by assessment of the AUC24 and those monitored by assessment of the trough concentration. Multivariable logistic and Cox proportional hazards regression examined the independent association between the monitoring strategy and nephrotoxicity. Secondary analysis compared vancomycin exposures (total daily dose, AUC, and trough concentrations) between monitoring strategies. Overall, 1,280 patients were included in the analysis. After adjusting for severity of illness, comorbidity, duration of vancomycin therapy, and concomitant receipt of nephrotoxins, AUC-guided dosing was independently associated with lower nephrotoxicity by both logistic regression (odds ratio, 0.52; 95% confidence interval [CI], 0.34 to 0.80; P = 0.003) and Cox proportional hazards regression (hazard ratio, 0.53; 95% CI, 0.35 to 0.78; P = 0.002). AUC-guided dosing was associated with lower total daily vancomycin doses, AUC values, and trough concentrations. Vancomycin AUC-guided dosing was associated with reduced nephrotoxicity, which appeared to be a result of reduced vancomycin exposure.

Risk factors and outcomes for patients with bloodstream infection due to Acinetobacter baumannii-calcoaceticus complex.

Identifying patients at risk for bloodstream infection (BSI) due to Acinetobacter baumannii-Acinetobacter calcoaceticus complex (ABC) and providing early appropriate therapy are critical for improving patient outcomes. A retrospective matched case-control study was conducted to investigate the risk factors for BSI due to ABC in patients admitted to the Detroit Medical Center (DMC) between January 2006 and April 2009. The cases were patients with BSI due to ABC; the controls were patients not infected with ABC. Potential risk factors were collected 30 days prior to the ABC-positive culture date for the cases and 30 days prior to admission for the controls. A total of 245 case patients were matched with 245 control patients. Independent risk factors associated with BSI due to ABC included a Charlson's comorbidity score of ≥ 3 (odds ratio [OR], 2.34; P = 0.001), a direct admission from another health care facility (OR, 4.63; P < 0.0001), a prior hospitalization (OR, 3.11; P < 0.0001), the presence of an indwelling central venous line (OR, 2.75; P = 0.011), the receipt of total parenteral nutrition (OR, 21.2; P < 0.0001), the prior receipt of ß-lactams (OR, 3.58; P < 0.0001), the prior receipt of carbapenems (OR, 3.18; P = 0.006), and the prior receipt of chemotherapy (OR, 15.42; P < 0.0001). The median time from the ABC-positive culture date to the initiation of the appropriate antimicrobial therapy was 2 days (interquartile range [IQR], 1 to 3 days). The in-hospital mortality rate was significantly higher among case patients than among control patients (OR, 3.40; P < 0.0001). BSIs due to ABC are more common among critically ill and debilitated institutionalized patients, who are heavily exposed to health care settings and invasive devices.

Eravacycline, the first four years: health outcomes and tolerability data for 19 hospitals in 5 U.S. regions from 2018 to 2022.

IMPORTANCE: The rise of multidrug-resistant (MDR) pathogens, especially MDR Gram-negatives, poses a significant challenge to clinicians and public health. These resilient bacteria have rendered many traditional antibiotics ineffective, underscoring the urgency for innovative therapeutic solutions. Eravacycline, a broad-spectrum fluorocycline tetracycline antibiotic approved by the FDA in 2018, emerges as a promising candidate, exhibiting potential against a diverse array of MDR bacteria, including Gram-negative, Gram-positive, anaerobic strains, and Mycobacterium. However, comprehensive data on its real-world application remain scarce. This retrospective cohort study, one of the largest of its kind, delves into the utilization of eravacycline across various infectious conditions in the USA during its initial 4 years post-FDA approval. Through assessing clinical, microbiological, and tolerability outcomes, the research offers pivotal insights into eravacycline's efficacy in addressing the pressing global challenge of MDR bacterial infections.

Early use of daptomycin versus vancomycin for methicillin-resistant Staphylococcus aureus bacteremia with vancomycin minimum inhibitory concentration >1 mg/L: a matched cohort study.

BACKGROUND: Recent reports have described decreased effectiveness with vancomycin treatment for methicillin-resistant Staphylococcus aureus bacteremia (MRSAB) when the vancomycin minimum inhibitory concentration (MIC) is >1 µg/mL. METHODS: This matched, retrospective cohort study compared the clinical effectiveness of daptomycin with that of vancomycin for the treatment of MRSAB with vancomycin MICs >1 µg/mL. The primary outcome was clinical failure, defined as a composite of 30-day mortality or bacteremia persisting for ≥7 days. RESULTS: One hundred seventy patients were matched 1:1 with respect to the antimicrobial administered. In the daptomycin group, all patients received <72 hours of vancomycin (median, 1.7 days [interquartile range, 1.1-2.3 days]) prior to switching to daptomycin. The rate of clinical failure at 30 days was significantly lower in the daptomycin arm compared to the vancomycin arm (20.0% vs 48.2%; P < 0.001). Both 30-day mortality and persistent bacteremia were significantly lower in the daptomycin group compared to the vancomycin group (3.5% vs 12.9% [P = .047] and 18.8% vs 42.4% [P = .001], respectively). Logistic regression confirmed the association between vancomycin treatment and increased risk of clinical failure (adjusted odds ratio, 4.5; 95% confidence interval, 2.1-9.8). CONCLUSIONS: This is the first matched study comparing early daptomycin versus vancomycin for the treatment of MRSAB when the vancomycin MIC is >1 µg/mL. Treatment with daptomycin resulted in significantly improved outcomes, including decreased 30-day mortality and persistent bacteremia. These results support the practice of switching early from vancomycin to daptomycin for the treatment of MRSAB when the vancomycin MIC is >1 µg/mL.

Epidemiology of bloodstream infections caused by Acinetobacter baumannii and impact of drug resistance to both carbapenems and ampicillin-sulbactam on clinical outcomes.

Acinetobacter baumannii has become a leading cause of bloodstream infections (BSI) in health care settings. Although the incidence of infection with carbapenem- and ampicillin-sulbactam-resistant (CASR) A. baumannii has increased, there is a scarcity of studies which investigate BSI caused by CASR A. baumannii. A retrospective cohort study was conducted on adult patients with BSI caused by A. baumannii and who were admitted to the Detroit Medical Center between January 2006 and April 2009. Medical records were queried for patients' demographics, antimicrobial exposures, comorbidities, hospital stay, and clinical outcomes. Bivariate analyses and logistic regression were employed in the study. Two hundred seventy-four patients with BSI caused by A. baumannii were included in the study: 68 (25%) caused by CASR A. baumannii and 206 (75%) caused by non-CASR A. baumannii. In multivariate analysis, factors associated with BSI caused by CASR A. baumannii included admission with a rapidly fatal condition (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.27 to 6.32, P value = 0.01) and prior use of antimicrobials (OR = 2.83, 95% CI = 1.18 to 6.78, P value = 0.02). In-hospital mortality rates for BSI caused by CASR A. baumannii were significantly higher than those for non-CASR A. baumannii-induced BSI (43% versus 20%; OR = 3.0, 95% CI = 1.60 to 5.23, P value < 0.001). However, after adjusting for potential confounders, the association between BSI caused by CASR A. baumannii and increased risk of in-hospital mortality was not significant (OR = 1.15, 95% CI = 0.51 to 2.63, P value = 0.74). This study demonstrated that CASR A. baumannii had a distinct epidemiology compared to more susceptible A. baumannii strains; however, clinical outcomes were similar for the two groups. Admission with a rapidly fatal condition was an independent predictor for both CASR A. baumannii and in-hospital mortality.

Multicenter study of high-dose daptomycin for treatment of enterococcal infections.

Enterococci are among the leading pathogens isolated in hospital-acquired infections. Current antimicrobial options for vancomycin-resistant enterococci (VRE) are limited. Prior data suggest that daptomycin at >6 mg/kg of body weight/day may be used to treat enterococcal infections. We retrospectively evaluated the effectiveness and safety of high-dose daptomycin (HD-daptomycin) therapy (>6 mg/kg) in a multicenter cohort of adult patients with enterococcal infections to describe the characteristics and outcomes. Two hundred forty-five patients were evaluated. Enterococcus faecium was identified in 175 (71%), followed by Enterococcus faecalis in 49 (20%) and Enterococcus spp. in 21 (9%); overall, 204 (83%) isolates were VRE. Enterococcal infections included bacteremia (173, 71%) and intra-abdominal (35, 14%) and bone and joint (25, 10%) infections. The median dosage and duration of HD-daptomycin were 8.2 mg/kg/day (interquartile range [IQR], 7.7 to 9.7) and 10 days (IQR, 6 to 15), respectively. The overall clinical success rate was 89% (193/218), and microbiological eradication was observed in 93% (177/191) of patients. The median time to clearance of blood cultures on HD-daptomycin was 3 days (IQR, 2 to 5). The 30-day all-cause mortality rate was 27%, and 5 (2%) patients developed daptomycin-nonsusceptible enterococcal strains while on HD-daptomycin. Seven patients (3%) had creatine phosphokinase (CPK) elevation, yet no HD-daptomycin regimen was discontinued due to an elevated CPK and all patients were asymptomatic. Overall, there was a high frequency of clinical success and microbiological eradication in patients treated with HD-daptomycin for enterococcal infections, even in patients with complicated and difficult-to-treat infections. No adverse event-related discontinuation of HD-daptomycin was noted. HD-daptomycin may be an option for the treatment of enterococcal infections.

A multicentre evaluation of the effectiveness and safety of high-dose daptomycin for the treatment of infective endocarditis.

OBJECTIVES: Despite significant medical advances, infective endocarditis (IE) remains an infection associated with high morbidity and mortality. The objective was to assess the safety and efficacy of high-dose daptomycin, defined as ≥ 8 mg/kg/day, in patients with confirmed or suspected staphylococcal and/or enterococcal IE. METHODS: This was a multicentre, retrospective observational study (2005-11). Adult patients, not undergoing haemodialysis, with blood cultures positive for staphylococci or enterococci and a definitive or possible diagnosis of IE, who received daptomycin ≥ 8 mg/kg/day (based on total body weight) for ≥ 72 h were included. RESULTS: Seventy patients met the inclusion criteria and comprised 33 (47.1%) with right-sided IE (RIE), 35 (50%) with left-sided IE (LIE) and 2 with both RIE and LIE. Several patients had concomitant sites of infection, with bone/joint infection being most prevalent (12.9%). Sixty-five patients received daptomycin as salvage therapy. Pathogens were isolated from 64 patients, with methicillin-resistant Staphylococcus aureus as the most common organism (84.4%), followed by vancomycin-resistant Enterococcus faecium (7.8%). The median (IQR) daptomycin dose was 9.8 mg/kg/day (8.2-10.0 mg/kg/day), and was similar in RIE and LIE patients (9.8 and 9.3 mg/kg/day, respectively). A total of 24 (34.3%) received combination therapy. For those patients with pathogens isolated (n = 64), the organism was eradicated in 57 (89.1%) patients. Among 64 clinically evaluable patients, 55 (85.9%) achieved clinical success. No patients required discontinuation of high-dose daptomycin due to creatine phosphokinase elevations. CONCLUSIONS: Patients with both RIE and LIE had successful outcomes with high-dose daptomycin therapy. Additional clinical trials evaluating high daptomycin dosages in patients with IE are warranted.

Clinical Outcomes With Extended Versus Intermittent Infusion of Anti-Pseudomonal Beta-Lactams in Patients With Gram-Negative Bacteremia.

Background: Administration of doses via an extended infusion (EI) is an important strategy to optimize beta-lactams. Available data on the impact of EI on outcomes largely focus on clinical cure or mortality in critically ill patients or those with resistant pathogens. The potential benefits of EI extend beyond these populations and outcomes, and further study is warranted. Methods: This was a retrospective cohort study of adult patients who received cefepime, piperacillin/tazobactam, or meropenem for Gram-negative bacteremia via EI or intermittent infusion. Patients were matched 1:1 based on study drug, sepsis severity, intensive care unit (ICU) status, bacteremia source, and pathogen. Outcomes assessed included time to clinical stabilization, rates of treatment failure, mortality, recurrence, and length of stay (LOS). Results: Two hundred sixty-eight patients were included. Baseline characteristics were similar between groups. Forty-two percent of patients were in the ICU at infection onset and the most common pathogen was Escherichia coli (41%). After adjusting for residual differences between groups, receipt of EI was independently associated with shorter time to clinical stability (adjusted odds ratio, 0.32; 95% confidence interval, .22-.47), time to defervescence, and time to white blood cell count normalization. Furthermore, EI was associated with a lower incidence of treatment failure, decreased recurrence of bacteremia, and shorter LOS. There was no difference in mortality. These findings were consistent regardless of patient location (ICU vs ward), baseline renal function, source of bacteremia, or study drug received. Conclusions: These findings suggest that EI beta-lactams are an important stewardship strategy to improve clinical outcomes in patients with Gram-negative bacteremia.

Impact of cefepime therapy on mortality among patients with bloodstream infections caused by extended-spectrum-ß-lactamase-producing Klebsiella pneumoniae and Escherichia coli.

Extended-spectrum-ß-lactamase (ESBL)-producing pathogens are associated with extensive morbidity and mortality and rising health care costs. Scant data exist on the impact of antimicrobial therapy on clinical outcomes in patients with ESBL bloodstream infections (BSI), and no large studies have examined the impact of cefepime therapy. A retrospective 3-year study was performed at the Detroit Medical Center on adult patients with BSI due to ESBL-producing Klebsiella pneumoniae or Escherichia coli. Data were collected from the medical records of study patients at five hospitals between January 2005 and December 2007. Multivariate analysis was performed using logistic regression. One hundred forty-five patients with BSI due to ESBL-producing pathogens, including K. pneumoniae (83%) and E. coli (16.5%), were studied. The mean age of the patients was 66 years. Fifty-one percent of the patients were female, and 79.3% were African-American. Fifty-three patients (37%) died in the hospital, and 92 survived to discharge. In bivariate analysis, the variables associated with mortality (P < 0.05) were presence of a rapidly fatal condition at the time of admission, use of gentamicin as a consolidative therapeutic agent, and presence of one or more of the following prior to culture date: mechanical ventilation, stay in the intensive care unit (ICU), and presence of a central venous catheter. In multivariate analysis, the predictors of in-hospital mortality included stay in the intensive care unit (odds ratio [OR], 2.17; 95% confidence interval [CI], 0.98 to 4.78), presence of a central-line catheter prior to positive culture (OR, 2.33; 95% CI, 0.77 to 7.03), presence of a rapidly fatal condition at the time of admission (OR, 5.13; 95% CI, 2.13 to 12.39), and recent prior hospitalization (OR, 1.92; 95% CI, 0.83 to 4.09). When carbapenems were added as empirical therapy to the predictor model, there was a trend between empirical carbapenem therapy and decreased mortality (OR, 0.61; 95% CI, 0.26 to 1.50). When added to the model, receipt of empirical cefepime alone (n = 43) was associated with increased mortality, although this association did not reach statistical significance (OR, 1.66; 95% CI, 0.71 to 3.87). The median length of hospital stay was shorter for patients receiving empirical cefepime than for those receiving empirical or consolidated carbapenem therapy. In multivariate analysis, empirical therapy with cefepime for BSI due to an ESBL-producing pathogen was associated with a trend toward an increased mortality risk and empirical carbapenem therapy was associated with a trend toward decreased mortality risk.

Novel Combination Therapy for Extensively Drug-Resistant Acinetobacter baumannii Necrotizing Pneumonia Complicated by Empyema: A Case Report.

We report our clinical and laboratory experience treating a 50-year-old patient who was critically ill with extensively drug-resistant Acinetobacter baumannii necrotizing pneumonia complicated by empyema in Detroit, Michigan. A precision medicine approach using whole-genome sequencing, susceptibility testing, and synergy analysis guided the selection of rational combination antimicrobial therapy.

Clinical Outcomes of Eravacycline in Patients Treated Predominately for Carbapenem-Resistant Acinetobacter baumannii.

Forty-six patients were treated with eravacycline (ERV) for Acinetobacter baumannii infections, where 69.5% of isolates were carbapenem resistant (CRAB). Infections were primarily pulmonary (58.3%), and most patients received combination therapy (84.4%). The median (IQR) ERV duration was 6.9 days (5.1 to 11.1). Thirty-day mortality was 23.9% in the cohort and 21.9% in CRAB patients. One patient experienced an ERV-possible adverse event. IMPORTANCE Acinetobacter baumannii, particularly when carbapenem resistant (CRAB), is one of the most challenging pathogens in the health care setting. This is complicated by the fact that there is no consensus guideline regarding management of A. baumannii infections. However, the recent Infectious Diseases Society of America guidelines for treatment of resistant Gram-negative infections provided expert recommendations for CRAB management. The panel suggest using minocycline among tetracycline derivatives rather than eravacycline (ERV) until sufficient clinical data are available. Therefore, we present the largest multicenter real-world cohort in patients treated with ERV for A. baumannii, where the majority of isolates were CRAB (69.5%). Our analysis demonstrate that patients treated with ERV-based regimens achieved a 30-day mortality of 23.9% and had a low incidence of ERV-possible adverse events (2.1%). This study is important as it fills the gap in the literature regarding the use of a novel tetracycline (i.e., ERV) in the treatment of this challenging health care infection.

Incidence of and risk factors for colistin-associated nephrotoxicity in a large academic health system.

BACKGROUND: Colistin, originally abandoned due to high rates of nephrotoxicity, has been recently reintroduced due to activity against carbapenem-resistant Gram-negative organisms. Recent literature, largely obtained from outside the United States, suggests a lower rate of nephrotoxicity than historically reported. METHODS: A retrospective cohort of all patients who received colistin for ≥ 48 hours at the Detroit Medical Center over a 5-year period was performed to determine the rate of colistin-associated nephrotoxicity as defined by the RIFLE criteria. RESULTS: Fifty-four (43%) patients in the cohort developed nephrotoxicity. Patients who experienced nephrotoxicity after colistin administration were in the Risk (13%), Injury (17%), or Failure (13%) categories per RIFLE criteria. Patients who developed nephrotoxicity received significantly higher mean doses than those who did not (5.48 mg/kg per day vs 3.95 mg/kg per day; P < .001), and the toxicity occurred in a dose-dependent fashion. Independent predictors for nephrotoxicity were a colistin dose of ≥ 5.0 mg/kg per day of ideal body weight (odds ratio [OR], 23.41; 95% confidence interval [CI], 5.3-103.55), receipt of concomitant rifampin (OR, 3.81; 95% CI, 1.42-10.2), and coadministration of ≥ 3 concomitant nephrotoxins (OR, 6.80; 95% CI, 1.42-32.49). CONCLUSIONS: In this retrospective cohort, nephrotoxicity (as defined by RIFLE criteria) occurred among 43% of treated patients in a dose-dependent manner. Higher colistin doses, similar to those commonly used in the United States, led to a relatively high rate of nephrotoxicity. These data raise important questions regarding the safe use of colistin in the treatment of multidrug-resistant pathogens.

Authorship and characteristics of articles in pharmacy journals: changes over a 20-year interval.

BACKGROUND: To our knowledge, no studies have evaluated authorship patterns and characteristics of articles in pharmacy journals. OBJECTIVE: To investigate changes over a 20-year period in authorship and characteristics of articles in pharmacy journals. METHODS: All articles published in the American Journal of Health-System Pharmacy, The Annals of Pharmacotherapy, and Pharmacotherapy in 1989, 1999, and 2009 were reviewed. Data collected for each article included article type, number of authors, number of physician authors, whether any author was affiliated with a pharmaceutical company, and source of funding. RESULTS: The number of articles included was 574 in 1989, 659 in 1999, and 589 in 2009. The mean number of authors per article increased from 2.5 in 1989 to 2.8 in 1999 and 3.6 in 2009 (p<0.001). Conversely, the proportion of articles with a single author decreased from 35% in 1989 to 23% in 1999 and 11% in 2009 (p<0.001), while the proportion of multi-authored articles (>6 authors) increased from 2% in 1989 to 3% in 1999 and 9% in 2009 (p<0.001). A physician author was listed on 25% of papers in 1989, which increased to 38% in 1999 and 41% in 2009 (p<0.001). Among research articles with declared funding from industry, there was an increase over time in reported author affiliation with an industry sponsor (10% of articles in 1989, 17% in 1999, and 66% in 2009; p<0.001). CONCLUSIONS: Significant changes in authorship patterns and characteristics of articles were observed from 1989 to 2009. We found an increase in the number of authors per article over time, with fewer single-author papers now published. The explanations for the changes are likely multifactorial, including increased pressure to publish, increased research complexity, and inappropriate authorship. To prevent inappropriate author-number inflation and to preserve authorship's meaning and value, authors should adhere to the criteria for authorship from the International Committee of Medical Journal Editors.

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.

Real-world, Multicenter Experience With Meropenem-Vaborbactam for Gram-Negative Bacterial Infections Including Carbapenem-Resistant Enterobacterales and Pseudomonas aeruginosa.

BACKGROUND: We aimed to describe the clinical characteristics and outcomes of patients treated with meropenem-vaborbactam (MEV) for a variety of gram-negative infections (GNIs), primarily including carbapenem-resistant Enterobacterales (CRE). METHODS: This is a real-world, multicenter, retrospective cohort within the United States between 2017 and 2020. Adult patients who received MEV for ≥72 hours were eligible for inclusion. The primary outcome was 30-day mortality. Classification and regression tree analysis (CART) was used to identify the time breakpoint (BP) that delineated the risk of negative clinical outcomes (NCOs) and was examined by multivariable logistic regression analysis (MLR). RESULTS: Overall, 126 patients were evaluated from 13 medical centers in 10 states. The most common infection sources were respiratory tract (38.1%) and intra-abdominal (19.0%) origin, while the most common isolated pathogens were CRE (78.6%). Thirty-day mortality and recurrence occurred in 18.3% and 11.9%, respectively. Adverse events occurred in 4 patients: nephrotoxicity (n = 2), hepatoxicity (n = 1), and rash (n = 1). CART-BP between early and delayed treatment was 48 hours (P = .04). MEV initiation within 48 hours was independently associated with reduced NCO following analysis by MLR (adusted odds ratio, 0.277; 95% CI, 0.081-0.941). CONCLUSIONS: Our results support current evidence establishing positive clinical and safety outcomes of MEV in GNIs, including CRE. We suggest that delaying appropriate therapy for CRE significantly increases the risk of NCOs.

Risk factors for bloodstream infection caused by extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella pneumoniae: A focus on antimicrobials including cefepime.

BACKGROUND: Extended-spectrum ß-lactamase (ESBL)-producing pathogens represent increasing challenges to physicians because of rising prevalence, high mortality, and challenging treatment. Identifying high risks and early appropriate therapy is critical to favorable outcomes. METHODS: This is a 5-year retrospective case-case-control study performed at the Detroit Medical Center on adult patients with bloodstream infection (BSI) caused by ESBL-producing and non-ESBL-producing Escherichia coli or Klebsiella pneumoniae, each compared with uninfected controls. Data were collected from December 2004-August 2009. Multivariate analysis was performed using logistic regression. RESULTS: Participants included 103 patients with BSI caused by ESBL-producing pathogens and 79 patients with BSI caused by pathogens that did not produce ESBLs. The mean age of patients in the ESBL group was 67 years; of the patients, 51% were men, 77% were black, and 38% (n = 39) died in hospital. The mean age of patients in the non-ESBL group was 58 years; of the patients, 51% were men, 92% were black, and 22% (n = 17) died in hospital. On multivariate analysis, predictors of BSI caused by ESBL-producing pathogens included central venous catheter (odds ratio [OR], 29.4; 95% confidence interval [CI], 3.0-288.3), prior ß-lactam-/ß-lactamase-inhibitor therapy (OR, 28.1; 95% CI, 1.99-396.5), and prior cefepime therapy (OR, 22.7; 95% CI, 2.7-192.4). The only risk factor for BSI caused by non-ESBL-producing pathogens was urinary catheter insertion (OR, 18.2; 95% CI, 3.3-100.3). CONCLUSION: Prior antimicrobial therapy, particularly with ß-lactam, was the strongest unique risk factor for BSI caused by ESBL-producing E coli or K pneumoniae.

Automated alerts coupled with antimicrobial stewardship intervention lead to decreases in length of stay in patients with gram-negative bacteremia.

OBJECTIVE: To assess the impact of active alerting of positive blood culture data coupled with stewardship intervention on time to appropriate therapy, length of stay, and mortality in patients with gram-negative bacteremia. DESIGN: Quasi-experimental retrospective cohort study in patients with gram-negative bacteremia at the Detroit Medical Center from 2009 to 2011. SETTING: Three hospitals (1 community, 2 academic) with active antimicrobial stewardship programs within the Detroit Medical Center. PATIENTS: All patients with monomicrobial gram-negative bacteremia during the study period. INTERVENTION: Active alerting of positive blood culture data coupled with stewardship intervention (2010-2011) compared with patients who received no formalized stewardship intervention (2009). RESULTS: Active alerting and intervention led to a decreased time to appropriate therapy (8 [interquartile range (IQR), 2-24] vs 14 [IQR, 2-35] hours; P = .014) in patients with gram-negative bacteremia. After controlling for differences between groups, being in the intervention arm was associated with an independent reduction in length of stay (odds ratio [OR], 0.73 [95% confidence interval (CI), 0.62-0.86]), correlating to a median attributable decrease in length of stay of 2.2 days. Additionally, multivariate modeling of patients who were not on appropriate antimicrobial therapy at the time of initial culture positivity showed that patients in the intervention group had a significant reduction in both length of stay (OR, 0.76 [95% CI, 0.66-0.86]) and infection-related mortality (OR, 0.24 [95% CI, 0.08-0.76]). CONCLUSIONS: Active alerting coupled with stewardship intervention in patients with gram-negative bacteremia positively impacted time to appropriate therapy, length of stay, and mortality and should be a target of antimicrobial stewardship programs.

Surgical site infections in genital reconstruction surgery for gender reassignment, Detroit: 1984-2008.

BACKGROUND: Gender reassignment surgery (i.e., male-to-female or female-to-male) entails a series of complex surgical procedures. We conducted a study to explore epidemiologic characteristics of patients who underwent genital reconstruction operations as components of gender reassignment and to analyze risk factors for surgical-site infections (SSIs) following these operations. METHODS: The study was a retrospective cohort study conducted from 1984-2008 at Harper University Hospital, a tertiary hospital with 625 beds in Detroit, Michigan. Surgical site infection was defined according to established criteria. RESULTS: Records were available for 82 patients who underwent a total of 1,383 operations as part of genital-reconstruction processes. Thirty-nine (47.6%) of the patients underwent female-to-male reassignment (FTM) and 43 (52.4%) underwent male-to-female reassignment (MTF). The average age of the study cohort was 39.5±9.8 y. Of the patients in the cohort, 56 (68.3%) were Caucasian and 67 (81.7%) were single. The average number of operative encounters per patient was 11.8±4.6 for FTM and 4.9±2.4 for MTF. Forty-three (52.4%) patients developed an SSI at least once during their genital reconstruction process, of whom 34 (87%) were in the FTM group and nine (21%) in the MTF group (p<0.001). Staphylococci were the most common pathogens (61%) isolated in these infections, followed by Enterobacteriaceae (50%), Enterococcus (39%), and Pseudomonas aeruginosa (33.3%). Surgical site infection was associated independently with an increased frequency of operative procedures and operating room encounters. CONCLUSIONS: More than 50% of patients who underwent genital reconstruction operations developed an SSI at some point during the genital reconstruction process. Surgical site infections are more common in FTM than in MTF reconstruction operations, and for both FTM and MTF, SSIs are associated independently with an increased frequency of total operative procedures and encounters.

The role of antimicrobials in Crohn's disease.

This review summarizes literature regarding the role of antimicrobials for induction and maintenance of Crohn's disease (CD) remission. PubMed was searched (1966 to October 2012) for controlled trials involving adults and written in English. Five of the 13 identified studies showed benefit with the use of ciprofloxacin, metronidazole and rifaximin for induction of remission. Eight studies showed no benefit using ciprofloxacin, metronidazole, combination of metronidazole and ciprofloxacin or clarithromycin and rifaximin. Four of the five studies showed benefit based on colonic location. Perianal CD with draining fistulas responded in one of two studies. Two studies in postileocolonic resection demonstrated benefit of metronidazole or ornidazole in reducing CD recurrence. Antimicrobials, especially metronidazole, are promising for inducing remission in patients with colonic CD and preventing recurrence in postileocolonic resection.