A Prospective Observational Study of the Epidemiology, Management, and Outcomes of Skin and Soft Tissue Infections Due to Carbapenem-Resistant Enterobacteriaceae.
carbapenem-resistant Enterobacteriaceae; Klebsiella pneumoniae; ST258; surgical site infections; wound infection
BACKGROUND: This study was performed to characterize the epidemiology, management, and outcomes of skin and soft tissue infection (SSTI) and colonization due to carbapenem-resistant Enterobacteriaceae (CRE). METHODS: Patients from the Consortium on Resistance Against Carbapenem in Klebsiella and Other Enterobacteriaceae (CRACKLE-1) from December 24, 2011 to October 1, 2014 with wound cultures positive for CRE were included in the study. Predictors of surgical intervention were analyzed. Molecular typing of isolates was performed using repetitive extragenic palindromic polymerase chain reaction (PCR). Carbapenemase genes were detected using PCR. RESULTS: One hundred forty-two patients were included: 62 had SSTI (44%) and 56% were colonized. Mean age was 61 years, and 48% were male: median Charlson score was 3 (interquartile range, 1-5). Forty-eight percent of patients were admitted from long-term care facilities (LTCFs), and 31% were from the community. Two strain types (ST258A and ST258B) were identified (73% of 45 tested). Carbapenemase genes were detected in 40 of 45 isolates (blaKPC-3 [47%], blaKPC-2 [42%]). Sixty-eight patients (48%) underwent surgical intervention, 63% of whom had SSTI. Patients admitted from LTCFs were less likely to undergo surgical intervention (odds ratio [OR], 0.36; 95% confidence interval [CI], 0.18-0.71). In multivariable analysis, among patients with SSTI, those admitted from LTCFs were less likely to undergo debridement (OR, 0.18; 95% CI, 0.04-0.93). CONCLUSIONS: Patients admitted from LTCFs with CRE SSTI were less likely to undergo surgical intervention. Sixteen percent of the patients died, and approximately 50% of survivors required more intensive care upon discharge. These findings suggest a unique, impactful syndrome within the CRE infection spectrum. Further studies are needed to assess the role of surgical debridement in management of CRE-SSTI, particularly among LTCF residents.
Henig Oryan; Cober Eric; Richter Sandra S; Perez Federico; Salata Robert A; Kalayjian Robert C; Watkins Richard R; Marshall Steve; Rudin Susan D; Domitrovic T Nicholas; Hujer Andrea M; Hujer Kristine M; Doi Yohei; Evans Scott; Fowler Vance G Jr; Bonomo Robert A; van Duin David; Kaye Keith S
Open forum infectious diseases
2017
1905-7
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1093/ofid/ofx157" target="_blank" rel="noreferrer noopener">10.1093/ofid/ofx157</a>
Carbapenem-Resistant Enterobacteriaceae Infections in Patients on Renal Replacement Therapy.
carbapenem-resistant Enterobacteriaceae; Klebsiella pneumoniae; mortality; renal failure; renal replacement therapy
Background: Patients on chronic intermittent renal replacement therapy (RRT) are at risk for infection with carbapenem-resistant Enterobacteriaceae (CRE). However, the impact of RRT on outcomes after CRE infections remains to be defined. Here we perform a comparison of outcomes for CRE-infected patients with preserved renal function compared with CRE-infected patients on RRT. Methods: Cases and controls were defined from a prospective cohort of CRE-infected patients from the Consortium on Resistance against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE). Cases were defined as CRE-infected patients on RRT at hospital admission, while controls were defined as CRE-infected patients with serum creatinine \textless2 mg/dL and not receiving RRT at admission. Risk factors for 28-day in-hospital mortality were assessed using multivariable logistic regression. An ordinal ranking of outcomes by desirability analysis was performed. Results: Patients on RRT were more likely to have diabetes mellitus and cardiac disease than controls. Urinary sources of infection were less common in the RRT group. In RRT patients, 28-day in-hospital mortality was increased as compared with controls: 22/71 (31%) vs 33/295 (11%). RRT remained significantly associated with 28-day in-hospital mortality after adjustment for source of infection, prehospitalization origin, and severity of illness (adjusted odds ratio, 2.27; 95% confidence interval [CI], 1.09-4.68; P = .03). Using univariable desirability of outcome ranking analysis, RRT status was associated with a 68% (95% CI, 61%-74%) chance of a worse disposition outcome. Conclusions: Chronic RRT in CRE-infected patients is associated with increased in-hospital mortality and worse disposition outcomes at 28 days.
Eilertson Brandon; Cober Eric; Richter Sandra S; Perez Federico; Salata Robert A; Kalayjian Robert C; Watkins Richard R; Doi Yohei; Kaye Keith S; Evans Scott; Fowler Vance G Jr; Bonomo Robert A; DeHovitz Jack; Kreiswirth Barry; van Duin David
Open forum infectious diseases
2017
1905-07
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1093/ofid/ofx216" target="_blank" rel="noreferrer noopener">10.1093/ofid/ofx216</a>
Colistin Resistance in Carbapenem-Resistant Klebsiella pneumoniae: Laboratory Detection and Impact on Mortality.
*beta-Lactam Resistance; *carbapenem-resistant Enterobacteriaceae; *colistin; *Klebsiella pneumoniae; *mortality; *ST258; Aged; Anti-Bacterial Agents/pharmacology/*therapeutic use; beta-Lactamases/genetics; Carbapenems/pharmacology/therapeutic use; Colistin/pharmacology/*therapeutic use; Comorbidity; Female; Humans; Kaplan-Meier Estimate; Klebsiella Infections/diagnosis/*drug therapy/*microbiology/mortality; Klebsiella pneumoniae/classification/*drug effects/genetics; Male; Microbial Sensitivity Tests; Middle Aged; Phylogeny; Proportional Hazards Models
Background: Polymyxins including colistin are an important "last-line" treatment for infections caused by carbapenem-resistant Klebsiella pneumoniae (CRKp). Increasing use of colistin has led to resistance to this cationic antimicrobial peptide. Methods: A cohort nested within the Consortium on Resistance against Carbapenems in Klebsiella pneumoniae (CRACKLE) was constructed of patients with infection, or colonization with CRKp isolates tested for colistin susceptibility during the study period of December, 2011 to October, 2014. Reference colistin resistance determination as performed by broth macrodilution was compared to results from clinical microbiology laboratories (Etest) and to polymyxin resistance testing. Each patient was included once, at the time of their first colistin-tested CRKp positive culture. Time to 30-day in-hospital all-cause mortality was evaluated by Kaplan-Meier curves and Cox proportional hazard modeling. Results: In 246 patients with CRKp, 13% possessed ColR CRKp. ColR was underestimated by Etest (very major error rate = 35%, major error rate = 0.4%). A variety of rep-PCR strain types were encountered in both the ColS and the ColR groups. Carbapenem resistance was mediated primarily by blaKPC-2 (46%) and blaKPC-3 (50%). ColR was associated with increased hazard for in-hospital mortality (aHR 3.48; 95% confidence interval, 1.73-6.57; P \textless .001). The plasmid-associated ColR genes, mcr-1 and mcr-2 were not detected in any of the ColR CRKp. Conclusions: In this cohort, 13% of patients with CRKp presented with ColR CRKp. The apparent polyclonal nature of the isolates suggests de novo emergence of ColR in this cohort as the primary factor driving ColR. Importantly, mortality was increased in patients with ColR isolates.
Rojas Laura J; Salim Madiha; Cober Eric; Richter Sandra S; Perez Federico; Salata Robert A; Kalayjian Robert C; Watkins Richard R; Marshall Steve; Rudin Susan D; Domitrovic T Nicholas; Hujer Andrea M; Hujer Kristine M; Doi Yohei; Kaye Keith S; Evans Scott; Fowler Vance G Jr; Bonomo Robert A; van Duin David
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
2017
2017-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1093/cid/ciw805" target="_blank" rel="noreferrer noopener">10.1093/cid/ciw805</a>
Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae.
benefit-risk; carbapenem-resistant Enterobacteriaceae; Carbapenems; Ceftazidime – Therapeutic Use; ceftazidime-avibactam; colistin; Colistin – Therapeutic Use; Comparative Studies; Drug Resistance; Enterobacteriaceae Infections – Drug Therapy; Human; In Vitro Studies; Klebsiella Infections; Klebsiella pneumoniae
Background: The efficacy of ceftazidime-avibactam-a cephalosporin-beta-lactamase inhibitor combination with in vitro activity against Klebsiella pneumoniae carbapenemase-producing carbapenem-resistant Enterobacteriaceae (CRE)-compared with colistin remains unknown. Methods: Patients initially treated with either ceftazidime-avibactam or colistin for CRE infections were selected from the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), a prospective, multicenter, observational study. Efficacy, safety, and benefit-risk analyses were performed using intent-to-treat analyses with partial credit and the desirability of outcome ranking approaches. The ordinal efficacy outcome was based on disposition at day 30 after starting treatment (home vs not home but not observed to die in the hospital vs hospital death). All analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). Results: Thirty-eight patients were treated first with ceftazidime-avibactam and 99 with colistin. Most patients received additional anti-CRE agents as part of their treatment. Bloodstream (n = 63; 46%) and respiratory (n = 30; 22%) infections were most common. In patients treated with ceftazidime-avibactam versus colistin, IPTW-adjusted all-cause hospital mortality 30 days after starting treatment was 9% versus 32%, respectively (difference, 23%; 95% bootstrap confidence interval, 9%-35%; P = .001). In an analysis of disposition at 30 days, patients treated with ceftazidime-avibactam, compared with those treated within colistin, had an IPTW-adjusted probability of a better outcome of 64% (95% confidence interval, 57%-71%). Partial credit analyses indicated uniform superiority of ceftazidime-avibactam to colistin. Conclusions: Ceftazidime-avibactam may be a reasonable alternative to colistin in the treatment of K. pneumoniae carbapenemase-producing CRE infections. These findings require confirmation in a randomized controlled trial.
van Duin David; Lok Judith J; Earley Michelle; Cober Eric; Richter Sandra S; Perez Federico; Salata Robert A; Kalayjian Robert C; Watkins Richard R; Doi Yohei; Kaye Keith S; Fowler Vance G Jr; Paterson David L; Bonomo Robert A; Evans Scott
Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
2018
2018-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1093/cid/cix783" target="_blank" rel="noreferrer noopener">10.1093/cid/cix783</a>
Role of Trimethoprim/Sulfamethoxazole in the Treatment of Infections Caused by Carbapenem-Resistant Enterobacteriaceae.
antimicrobial resistance; carbapenem-resistant enterobacteriaceae; Klebsiella pneumonia; trimethoprim-sulfamethoxazole; urinary tract infection
In the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), trimethoprim-sulfamethoxazole (TMP-SMX) had a limited role in the treatment of less severe carbapenem-resistant Enterobacteriaceae (CRE) infections, especially urinary tract infections. Of tested CRE, only 29% were susceptible to TMP-SMX. Development of resistance further limits the use of TMP-SMX in CRE infections. [ABSTRACT FROM AUTHOR]
Luterbach Courtney L; Boshe Ashley; Henderson Heather I; Cober Eric; Richter Sandra S; Salata Robert A; Kalayjian Robert C; Watkins Richard R; Hujer Andrea M; Hujer Kristine M; Rudin Susan D; Domitrovic T Nicholas; Doi Yohei; Kaye Keith S; Evans Scott; Fowler Vance G; Bonomo Robert A; Duin David van
Open Forum Infectious Diseases
2019
2019-01
Journal Article
<a href="http://doi.org/10.1093/ofid/ofy351" target="_blank" rel="noreferrer noopener">10.1093/ofid/ofy351</a>
The Pitt Bacteremia Score Predicts Mortality in Non-Bacteremic Infections.
Background: Predicting mortality risk in patients is important in research settings. The Pitt bacteremia score (PBS) is commonly used as a predictor of early mortality risk in patients with bloodstream infections (BSI). Here, we determined whether the PBS predicts 14-day inpatient mortality in non-bacteremia carbapenem-resistant Enterobacteriaceae (CRE) infections.; Methods: Patients were selected from the Consortium on resistance against carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE-1), a prospective, multicenter, observational study. We estimated risk ratios to analyze the predictive ability of the PBS overall and each of its components individually. We analyzed each component of the PBS in the prediction of mortality, assessed the appropriate cutoff value for the dichotomized score, and compared the predictive ability of the qPitt score to that of the PBS.; Results: In a cohort of 475 patients with CRE infections, a PBS ≥ 4 was associated with mortality in patients with non-bacteremia infections (RR=21.9 [95% CI: 7.0, 68.8]) and with BSI (RR=6.0 [95% CI: 2.5, 14.4]). In multivariable analysis, the hypotension, mechanical ventilation, mental status, and cardiac arrest parameters of the PBS were independent risk factors for 14-day all-cause inpatient mortality. The temperature parameter as originally calculated for the PBS was not independently associated with mortality. However, a temperature < 36.0ᴼ C versus ≥ 36ᴼ C was independently associated with mortality. A qPitt score ≥ 2 had similar discrimination as a PBS ≥ 4 in non-bacteremia infections.; Conclusion: Here, we validated that the PBS and qPitt score can be used as reliable predictors of mortality in non-bacteremia CRE infections.; © The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.
Henderson Heather; Luterbach Courtney L; Cober Eric; Richter Sandra S; Salata Robert A; Kalayjian Robert C; Watkins Richard R; Doi Yohei; Kaye Keith S; Evans Scott; Fowler Vance G; Bonomo Robert A; Harris Anthony; Napravnik Sonia; van Duin David
Clinical Infectious Diseases: An Official Publication Of The Infectious Diseases Society Of America
2019
2019-06
<a href="http://doi.org/10.1093/cid/ciz528" target="_blank" rel="noreferrer noopener">10.1093/cid/ciz528</a>
The Role of Trimethoprim/Sulfamethoxazole in the Treatment of Infections Caused by Carbapenem-Resistant Enterobacteriaceae.
antimicrobial resistance; carbapenem-resistant Enterobacteriaceae; Klebsiella pneumonia; trimethoprim-sulfamethoxazole; urinary tract infection
In the Consortium on Resistance Against Carbapenems in Klebsiella and other Enterobacteriaceae (CRACKLE), trimethoprim-sulfamethoxazole (TMP-SMX) had a limited role in the treatment of less severe carbapenem-resistant Enterobacteriaceae (CRE) infections, especially urinary tract infections. Of tested CRE, only 29% were susceptible to TMP-SMX. Development of resistance further limits the use of TMP-SMX in CRE infections.
Luterbach Courtney L; Boshe Ashley; Henderson Heather I; Cober Eric; Richter Sandra S; Salata Robert A; Kalayjian Robert C; Watkins Richard R; Hujer Andrea M; Hujer Kristine M; Rudin Susan D; Domitrovic T Nicholas; Doi Yohei; Kaye Keith S; Evans Scott; Fowler Vance G Jr; Bonomo Robert A; van Duin David
Open forum infectious diseases
2019
2019-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1093/ofid/ofy351" target="_blank" rel="noreferrer noopener">10.1093/ofid/ofy351</a>