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1.
Diagn Microbiol Infect Dis ; 109(3): 116269, 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38692201

RESUMO

We assessed the performance of GenMark's ePlex® Blood Culture Identification (BCID) Panels for overall agreement of organism identification and resistance mechanism detection with standard microbiologic methods. This study included patients with a positive blood culture from May 2020 to January 2021. The primary outcomes were to assess concordance of ePlex® organism identification with standard identification methods and concordance of ePlex® genotypic resistance mechanism detection with standard phenotypic susceptibility testing. Secondary outcomes included panel specific performance and characterization of antimicrobial stewardship opportunities. The overall identification concordance rate in 1276 positive blood cultures was 98.1%. The overall concordance for the presence of resistance markers was 98.2% and concordance for the absence of resistance markers was 100%. A majority of ePlex® results (69.5%) represented opportunities for potential antimicrobial stewardship intervention. High concordance rates between the ePlex® BCID panels and standard identification and susceptibility methods enable utilization of results to guide rapid antimicrobial optimization.

2.
Surg Infect (Larchmt) ; 25(3): 192-198, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38407831

RESUMO

Background: Appropriate antimicrobial therapy for the management of intra-abdominal infection (IAI) continues to evolve based on available literature. The Study to Optimize Peritoneal Infection Therapy (STOP-IT) trial provided evidence to support four days of antibiotic agents in IAI post-source control but excluded patients with a planned re-laparotomy. This study aimed to determine the short- and long-term recurrent infection risk in this population. Patients and Methods: This is a single-center, retrospective, observational study of adult patients admitted to a quaternary medical center between January 1, 2016, and August 1, 2022, with IAI requiring planned laparotomy. Patients were designated as receiving five or less days of antibiotic agents (short course) or more than five days (long course) after source control. The primary outcome was IAI recurrence within 30 days. Results: Of the 104 patients who met inclusion criteria, 78 were included in analysis. Average age was 57 ± 13.3 years, 56% were male, 94% Caucasian, with a mean Acute Physiology and Chronic Health Evaluation (APACHE) II score of 17 ± 7.09. All other baseline characteristics and clinical severity markers were similar between the two groups. Regarding the primary outcome of IAI recurrence, there was no difference when comparing those who received short course versus those who received long course therapy (41.2% vs. 44.4%; p = 0.781). No differences were found between groups with respect to secondary outcomes. Conclusions: In patients admitted with IAI managed with planned re-laparotomy those who received short course antimicrobial therapy were not found to have an increase in IAI recurrence compared to those with longer courses of therapy.


Assuntos
Anti-Infecciosos , Infecções Intra-Abdominais , Adulto , Humanos , Masculino , Pessoa de Meia-Idade , Idoso , Feminino , Antibacterianos/uso terapêutico , Laparotomia , Estudos Retrospectivos , Infecções Intra-Abdominais/tratamento farmacológico , Infecções Intra-Abdominais/cirurgia
3.
Ther Adv Infect Dis ; 10: 20499361231191877, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37636216

RESUMO

Outpatient parenteral antimicrobial therapy (OPAT) has been widely used in clinical practice for many decades because of its associated cost savings, reductions in inpatient hospital days, and decreases in hospital-associated infections. Despite this long history, evolving practice patterns and new drug delivery devices continue to present challenges as well as opportunities for clinicians when designing appropriate outpatient antimicrobial regimens. One such change is the increasing use of extended and continuous infusion (CI) of antimicrobials to optimize the achievement of pharmacokinetic and pharmacodynamic targets. Elastomeric devices are also becoming increasingly popular in OPAT, including for the delivery of CI. In this article, we review the clinical evidence for CI in OPAT, as well as practical considerations of patient preferences, cost, and antimicrobial stability.

4.
Open Forum Infect Dis ; 10(4): ofad170, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37125229

RESUMO

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.

5.
Pharmacotherapy ; 42(4): 284-291, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35134264

RESUMO

INTRODUCTION: Consensus guidelines recommend targeting a vancomycin area under the curve to minimum inhibitory concentration (AUC24 :MIC) ratio of 400-600 to improve therapeutic success and reduce nephrotoxicity. Although guidelines specify either Bayesian software or first-order equations may be used to estimate AUC24 , there are currently no large studies directly comparing these methods. OBJECTIVE: To compare calculated vancomycin AUC24 using first-order equations with two-drug concentrations at steady state to Bayesian two- and one-concentration estimations. METHODS: This was a single-center, retrospective cohort study of 978 adult hospitalized patients receiving intravenous vancomycin between 2017 and 2019. Patients were included if they received at least 72 h of vancomycin and had two-serum drug concentrations obtained. AUC24 was calculated using first-order analytic (linear), Bayesian two-concentration, and Bayesian one-concentration methods for each patient. The InsightRx™ software platform was used to calculate Bayesian AUC24 . Pearson's correlation and clinical agreement (based on AUC24  classified as subtherapeutic, therapeutic, or supratherapeutic) were used to assess agreement between methods. Bland-Altman plots were used to assess mean difference (MD) and 95% limits of agreement (LOA). RESULTS: Excellent agreement was observed between linear and Bayesian two-concentration methods (r = 0.963, clinical agreement = 87.4%) and Bayesian two-concentration and one-concentration methods (r = 0.931, clinical agreement = 88.5%); however, a degree of variability was noted with 95% LOA -99 to 76 (MD = -11.5 mg*h/L) and -92 to 113 (MD = -10.4 mg*h/L), for the respective comparisons. The agreement between linear and Bayesian one-concentration approaches was less than prior comparisons (r = 0.823, clinical agreement = 76.8%) and demonstrated the greatest amount of variability with 95% LOA -197 to 153 (MD = -21.9 mg*h/L). CONCLUSIONS: Linear and Bayesian two-concentration methods demonstrated high-level agreement with acceptable variability and may be considered comparable to estimate vancomycin AUC24 . As linear and Bayesian one-concentration methods demonstrated significant variability and suboptimal agreement, concerns exist surrounding the interchangeability of these methods in clinical practice, particularly at higher extremes of AUC24 .


Assuntos
Infecções Estafilocócicas , Vancomicina , Adulto , Antibacterianos/uso terapêutico , Área Sob a Curva , Teorema de Bayes , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/uso terapêutico
7.
Open Forum Infect Dis ; 7(8): ofaa278, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32875001

RESUMO

BACKGROUND: Bloodstream infections (BSIs) due to ceftriaxone (CRO)-resistant Enterobacteriaceae are associated with delays in time to appropriate therapy and worse outcomes compared with infections due to susceptible isolates. However, treating all at-risk patients with empiric carbapenem therapy risks overexposure. Strategies are needed to appropriately balance these competing interests. The purpose of this study was to compare 4 methods for achieving this balance. METHODS: This was a retrospective hypothetical observational study of patients at the Detroit Medical Center with monomicrobial BSIs due to E. coli, K. oxytoca, K. pneumoniae, or P. mirabilis. This study compared the effectiveness of 4 methods to predict CRO resistance at the time of organism isolation. Three methods were based on applying published extended-spectrum beta-lactamase (ESBL) scoring tools. The fourth method was based on the presence or absence of the CTX-M marker from Verigene. RESULTS: Four hundred fifty-one Enterobacteriaceae BSIs were included, 73 (16%) of which were CRO-resistant. Verigene accurately predicted ceftriaxone susceptibility for 97% of isolates, compared with 70%-81% using the scoring tools (P < .001). Verigene was associated with fewer cases of treatment with CRO when the isolate was CRO-resistant (15% vs 63%-71% with scoring tools) and fewer cases of overtreatment with a carbapenem for CRO-susceptible strains (0.3% vs 10%-12%). CONCLUSIONS: Verigene significantly outperformed published ESBL scoring tools for identifying CRO-resistant Enterobacteriaceae BSI. Institutions should validate scoring tools before implementation. Stewardship programs should consider adoption of rapid diagnostic tests to optimize early therapy.

8.
Infect Dis Ther ; 9(2): 325-339, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32248513

RESUMO

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infections (BSI) are associated with high morbidity and mortality. More in vitro, in vivo, and clinical data suggest that vancomycin (VAN) or daptomycin (DAP) combination therapy with ß-lactams (BL) improves outcomes of MRSA infections. We hypothesize that BL combination with VAN or DAP would reduce the odds of clinical failure compared to VAN or DAP monotherapy. METHODS: A retrospective cohort study of adult patients ≥ 18 years treated with VAN or DAP for MRSA BSI from 2006 to 2019 at Detroit Medical Center. Combination therapy (CT) was defined as VAN or DAP plus any BL for ≥ 24 h within 72 h of index culture. Monotherapy (MT) was defined as ≥ 72 h VAN or DAP within 72 h of index culture and no BL for ≥ 24 h up to 7 days following VAN/DAP initiation. Primary outcome was composite endpoint of clinical failure defined as: (1) 30-day mortality, (2) 60-day recurrence, or (3) persistent bacteremia (PB). PB was defined as bacteremia > 5 days. Multivariable logistic regression was used to evaluate the association between CT and the primary outcome. RESULTS: Overall, 597 patients were included in this analysis, 153 in the MT group and 444 in the CT group. CT was independently associated with reduced odds of clinical failure (adjusted odds ratio, 0.523; 95% confidence interval, 0.348-0.787). The composite endpoint was driven by 60-day recurrence and PB but not 30-day mortality. There were no difference in adverse events including nephrotoxicity between the two study arms. CONCLUSIONS: In hospitalized adults with MRSA BSI, CT with any BL was independently associated with improved clinical outcomes and may ultimately be selected as preferred therapy.

9.
Open Forum Infect Dis ; 7(3): ofaa051, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32161775

RESUMO

Fourty patients were treated with meropenem-vaborbactam (MEV) for serious Gram-negative bacterial (GNB) infections. Carbapenem-resistant Enterobacteriaceae (CRE) comprised 80.0% of all GNB infections. Clinical success occurred in 70.0% of patients. Mortality and recurrence at 30 days were 7.5% and 12.5%, respectively. One patient experienced a probable rash due to MEV.

10.
Clin Infect Dis ; 71(1): 1-10, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-31404468

RESUMO

BACKGROUND: Mounting evidence suggests the addition of a ß-lactam (BL) to daptomycin (DAP) results in synergistic in vitro activity against methicillin-resistant Staphylococcus aureus (MRSA) and bolsters the innate immune response to infection. This study's objective was to provide clinical translation to these experimental data and determine if DAP+BL combination therapy results in improved clinical outcomes compared with treatment with DAP alone in patients with MRSA bloodstream infections (BSIs). METHODS: This was a retrospective, comparative cohort study conducted at 2 academic medical centers between 2008 and 2018. Adults with MRSA BSI treated with DAP for ≥72 hours and initiated ≤5 days of culture collection were included. Patients who received a BL for ≥24 hours and initiated ≤24 hours of DAP comprised the DAP+BL group. The primary outcome was composite clinical failure (60-day all-cause mortality and/or 60-day recurrence). Analyses were adjusted for confounding using inverse probability of treatment weighting (IPTW). RESULTS: A total of 229 patients were included (72 DAP+BL and 157 DAP). In unadjusted and IPTW-adjusted analyses, DAP+BL was associated with significantly reduced odds of clinical failure (odds ratio [OR], 0.362; 95% confidence interval [CI], .164-.801; adjusted OR, 0.386; 95% CI, .175-.853). Adjusted analyses restricted to prespecified subgroups based on infection complexity and baseline health status were consistent with the main analysis. CONCLUSIONS: The addition of a BL to DAP was associated with improved clinical outcomes in patients with MRSA BSI. This study provides support to ongoing and future studies evaluating the impact of combination therapy for invasive MRSA infections.Patients treated with daptomycin plus a ß-lactam for MRSA bloodstream infection had lower odds of composite clinical failure defined as 60-day all-cause mortality and/or 60-day recurrence compared with patients treated with daptomycin monotherapy after adjusting for confounding variables using inverse probability of treatment weighting.


Assuntos
Bacteriemia , Daptomicina , Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Adulto , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Estudos de Coortes , Daptomicina/uso terapêutico , Humanos , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina , beta-Lactamas/uso terapêutico
11.
Infect Dis Ther ; 8(2): 199-208, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30915685

RESUMO

INTRODUCTION: Acute bacterial skin and skin structure infections (ABSSSIs) remain among the most common infectious processes seen in the clinical setting. For patients with complicated ABSSSIs deemed to require intravenous antibiotics, vancomycin remains the mainstay therapy. Ceftaroline has been shown to be non-inferior to vancomycin and may result in faster resolution of signs of infection. METHODS: Multicenter, prospective, open-label, randomized trial of ceftaroline versus vancomycin for the treatment of adult patients admitted for management of ABSSSIs from April 2012 to May 2016; 166 patients in the clinically evaluable (CE) group were needed to determine a 20% difference in primary outcome of clinical response at day 2 or 3 of antibiotics. Clinical response was defined as cessation of spread of lesion and improvement in systemic signs/symptoms of infection. A secondary outcome was a ≥ 20% reduction in lesion size at day 2 or 3 of antibiotics. RESULTS: One hundred seventy-four patients were enrolled in the intention-to-treat (ITT) group and 108 were CE. Among CE patients, 54 were randomized to ceftaroline and 54 to vancomycin. Baseline characteristics were similar except patients in the ceftaroline arm were older and had a non-significantly higher degree of comorbidities (median Charlson score 2 vs. 4, respectively). Cellulitis was the most common type of ABSSSI (85.2% vs. 79.6%, respectively). Rapid diagnostic testing of available cultures (n = 55) demonstrated high agreement with clinical microbiology for identification of Staphylococcus aureus (100%) and MRSA (100%). There was no significant difference in primary outcome of day 2 or 3 clinical response (50.0% vs. 51.9%). CONCLUSION: Early clinical response between vancomycin- and ceftaroline-treated ABSSSIs was similar. Patients with ABSSSIs rarely remained hospitalized for > 2-3 days, thus limiting our ability to critically assess clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02582203. FUNDING: Allergan plc.

14.
Artigo em Inglês | MEDLINE | ID: mdl-29483115

RESUMO

Rapid diagnostic tests (RDTs) have revolutionized the management of Gram-negative bacteremia by allowing antimicrobial stewardship teams the ability to escalate therapy and improve patient outcomes through timely organism identification and detection of certain resistance determinants. However, given the complex nature of Gram-negative resistance, stewardship teams are left without clear direction for how to respond when resistance determinants are absent, as the safety of de-escalation in this setting is unknown. The primary purpose of this analysis was to determine the negative predictive values (NPVs) of resistance marker absence for predicting susceptibility in target bug-drug scenarios at two geographically distinct institutions. A total of 1,046 Gram-negative bloodstream isolates that were analyzed with the Verigene BC-GN platform were assessed. Except for Pseudomonas aeruginosa, the absence of resistance determinants as reported by the RDT largely predicted susceptibility to target antibiotics at both institutions. NPVs for ceftriaxone susceptibility in Escherichia coli and Klebsiella pneumoniae in the absence of either CTX-M or a carbapenemase gene were 98% and 93 to 94%, respectively. Similar results were seen with other target bug-drug scenarios, with NPVs of 94 to 100% demonstrated at both institutions, with the exception of P. aeruginosa, for which NPVs were poor, likely due to the more complex nature of resistance in this pathogen. The results of this study show that clinicians at both institutions should have confidence in de-escalation in the absence of resistance determinant detection by Verigene BC-GN testing, and the methodology described within this article can serve as a blueprint for other stewardship programs to employ at their institutions to optimize management of Gram-negative bacteremia.


Assuntos
Gestão de Antimicrobianos/métodos , Bacteriemia/microbiologia , Bacteriemia/tratamento farmacológico , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Escherichia coli/efeitos dos fármacos , Escherichia coli/patogenicidade , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Negativas/metabolismo , Bactérias Gram-Negativas/patogenicidade , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Humanos , Pseudomonas aeruginosa/efeitos dos fármacos , Pseudomonas aeruginosa/patogenicidade , beta-Lactamases/genética , beta-Lactamases/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-29084753

RESUMO

Evidence supports vancomycin therapeutic-drug monitoring by area under the concentration-time curve (AUC), but data to establish an AUC upper limit are limited and published nephrotoxicity thresholds range widely. The objective of this analysis was to examine the association between initial vancomycin AUC and nephrotoxicity. This was a multicenter, retrospective cohort study of adult patients receiving intravenous vancomycin from 2014 to 2015. Nephrotoxicity was defined as a serum creatinine increase of 0.5 mg/liter and 50% from baseline on consecutive measurements. Vancomycin exposure profile during the initial 48 h of therapy was estimated using maximum a posteriori probability Bayesian estimation. Vancomycin AUC and minimum-concentration (Cmin) thresholds most strongly associated with nephrotoxicity were identified via classification and regression tree (CART) analysis. Predictive performances of CART-derived and other candidate AUC thresholds was assessed through positive and negative predictive value and receiver operating characteristic curves. Poisson regression was used to quantify the association between exposure thresholds and nephrotoxicity while adjusting for confounders. Among 323 patients included, nephrotoxicity was significantly higher in patients with AUCs from 0 to 48 h (AUC0-48) of ≥1,218 mg · h/liter, AUC0-24 of ≥677 mg · h/liter, AUC24-48 of ≥683 mg · h/liter, and day 1 Cmin (Cmin24) of ≥18.8 mg/liter. Vancomycin exposure in excess of these thresholds was associated with a 3- to 4-fold-increased risk of nephrotoxicity in Poisson regression. The predictive performance of AUC for nephrotoxicity was maximized at daily AUC values between 600 and 800 mg · h/liter. Although these data support an AUC range for vancomycin-associated nephrotoxity rather than a single threshold, available evidence suggests that a daily AUC limit of 700 mg · h/liter is reasonable.


Assuntos
Antibacterianos/efeitos adversos , Pacientes Internados , Nefropatias/induzido quimicamente , Nefropatias/epidemiologia , Vancomicina/efeitos adversos , Administração Intravenosa , Antibacterianos/administração & dosagem , Área Sob a Curva , Estudos de Coortes , Creatinina/sangue , Relação Dose-Resposta a Droga , Monitoramento de Medicamentos , Feminino , Hospitalização , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Vancomicina/administração & dosagem
16.
Artigo em Inglês | MEDLINE | ID: mdl-28923869

RESUMO

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.


Assuntos
Injúria Renal Aguda/prevenção & controle , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Monitoramento de Medicamentos/métodos , Vancomicina/efeitos adversos , Vancomicina/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Administração Intravenosa , Área Sob a Curva , Feminino , Humanos , Rim/efeitos dos fármacos , Rim/patologia , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
Clin Infect Dis ; 64(2): 116-123, 2017 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-27986669

RESUMO

BACKGROUND: Recent evidence suggests that among patients receiving vancomycin, receipt of concomitant piperacillin-tazobactam increases the risk of nephrotoxicity. Well-controlled, adequately powered studies comparing rates of acute kidney injury (AKI) among patients receiving vancomycin + piperacillin-tazobactam (VPT) compared to similar patients receiving vancomycin + cefepime (VC) are lacking. In this study we compared the incidence of AKI among patients receiving combination therapy with VPT to a matched group receiving VC. METHODS: A retrospective, matched, cohort study was performed. Patients were eligible if they received combination therapy for ≥48 hours. Patients were excluded if their baseline serum creatinine was >1.2mg/dL or they were receiving renal replacement therapy. Patients receiving VC were matched to patients receiving VPT based on severity of illness, intensive care unit status, duration of combination therapy, vancomycin dose, and number of concomitant nephrotoxins. The primary outcome was the incidence of AKI. Multivariate modeling was performed using Cox proportional hazards. RESULTS: A total of 558 patients were included. AKI rates were significantly higher in the VPT group than the VC group (81/279 [29%] vs 31/279 [11%]). In multivariate analysis, therapy with VPT was an independent predictor for AKI (hazard ratio = 4.27; 95% confidence interval, 2.73-6.68). Among patients who developed AKI, the median onset was more rapid in the VPT group compared to the VC group (3 vs 5 days P =< .0001). CONCLUSION: The VPT combination was associated with both an increased AKI risk and a more rapid onset of AKI compared to the VC combination.


Assuntos
Injúria Renal Aguda/epidemiologia , Injúria Renal Aguda/etiologia , Antibacterianos/efeitos adversos , Cefalosporinas/efeitos adversos , Ácido Penicilânico/análogos & derivados , Vancomicina/efeitos adversos , Injúria Renal Aguda/diagnóstico , Injúria Renal Aguda/terapia , Adulto , Idoso , Antibacterianos/uso terapêutico , Cefepima , Cefalosporinas/uso terapêutico , Terapia Combinada , Quimioterapia Combinada , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Razão de Chances , Ácido Penicilânico/efeitos adversos , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam , Prognóstico , Estudos Retrospectivos , Risco , Índice de Gravidade de Doença , Vancomicina/uso terapêutico
18.
Antimicrob Agents Chemother ; 60(6): 3743-50, 2016 06.
Artigo em Inglês | MEDLINE | ID: mdl-27067325

RESUMO

Despite their common use as an empirical combination therapy for the better part of a decade, there has been a recent association between combination therapy with vancomycin and piperacillin-tazobactam and high rates of acute kidney injury (AKI). The reasons for this increased association are unclear, and this analysis was designed to investigate the association. Retrospective cohort and case-control studies were performed. The primary objective was to assess if there is an association between extended-infusion piperacillin-tazobactam in combination with vancomycin and development of AKI. The secondary objectives were to identify risk factors for AKI in patients on the combination, regardless of infusion strategy, and to evaluate the impact of AKI on clinical outcomes. AKI occurred in 105/320 (33%) patients from the cohort receiving combination therapy with vancomycin and piperacillin-tazobactam, with similar rates seen in those receiving intermittent (53/160 [33.1%]) and extended infusions (52/160 [32.5%]) of piperacillin-tazobactam. Independent risk factors for AKI in the cohort included having a documented Gram-positive infection, the presence of sepsis, receipt of a vancomycin loading dose (odds ratio [OR], 2.22; 95% confidence interval [CI], 1.05 to 4.71), and receipt of any concomitant nephrotoxin (OR, 2.44; 95% CI, 1.41 to 4.22). For at-risk patients remaining on combination therapy, the highest rates of AKI occurred on days 4 (10.7%) and 5 (19.3%). The incidence of AKI in patients on combination therapy with vancomycin and piperacillin-tazobactam is high, occurring in 33% of patients. Receipt of piperacillin-tazobactam as an extended infusion did not increase this risk. Modifiable risk factors for AKI include receipt of a vancomycin loading dose, concomitant nephrotoxins, and longer durations of therapy.


Assuntos
Injúria Renal Aguda/epidemiologia , Antibacterianos/efeitos adversos , Infecções por Bactérias Gram-Negativas/epidemiologia , Infecções por Bactérias Gram-Positivas/epidemiologia , Ácido Penicilânico/análogos & derivados , Vancomicina/efeitos adversos , Injúria Renal Aguda/induzido quimicamente , Injúria Renal Aguda/patologia , Adulto , Idoso , Antibacterianos/administração & dosagem , Estudos de Casos e Controles , Quimioterapia Combinada/efeitos adversos , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/patologia , Infecções por Bactérias Gram-Positivas/tratamento farmacológico , Infecções por Bactérias Gram-Positivas/microbiologia , Infecções por Bactérias Gram-Positivas/patologia , Humanos , Modelos Logísticos , Masculino , Michigan/epidemiologia , Pessoa de Meia-Idade , Ácido Penicilânico/administração & dosagem , Ácido Penicilânico/efeitos adversos , Piperacilina/administração & dosagem , Piperacilina/efeitos adversos , Combinação Piperacilina e Tazobactam , Estudos Retrospectivos , Vancomicina/administração & dosagem
19.
Infect Dis Ther ; 4(4): 519-28, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-26541469

RESUMO

A 48-year-old female, who was found unresponsive and suffered inhalation injury secondary to a house fire, was transferred to our burn center for definitive treatment. Post tracheostomy, the patient became febrile and tachycardic. On hospital day (HD) 5, the patient expressed thick yellow secretions during suctioning and diffuse rhonchi was noted on physical exam. Blood cultures and a culture from the broncheo-alvelolar lavage grew Gram-positive cocci in clusters and the patient was started on empiric vancomycin. Despite aggressive vancomycin dosing (1750 mg intravenously every 6 h), the patient's status continued to deteriorate. The organism was identified as methicillin-resistant Staphylococcus aureus (MRSA) with a vancomycin minimum inhibitory concentration (MIC) of 2 mg/L. Based on the potential for drug-drug interactions with linezolid, the patient was started on ceftaroline fosamil (MIC = 0.5 mg/L) 600 mg intravenously every 8 h with a prolonged 2-h infusion to anticipate suboptimal concentrations secondary to thermal burn injury. Post change in antibiotic therapy, a rapid clinical improvement was observed with the patient becoming afebrile at 48 h after initiation of ceftaroline. The patient completed a total of 14 days of ceftaroline therapy and was subsequently weaned from the ventilator on HD 22 and decannulated 2 days later. To our knowledge, this is the first report of the use of ceftaroline for the treatment of MRSA pneumonia in a patient with thermal injury.

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