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1.
Chemotherapy ; 67(4): 261-268, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36417841

RESUMO

INTRODUCTION: Community-acquired urinary tract infections (UTIs) caused by extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli have limited oral therapeutic options and pose significant clinical challenges. The goal of this study was to evaluate the in vitro synergy between CFM and AMC against ESBL E. coli with aims to identify an oral treatment option for UTIs. METHODS: Minimum inhibitory concentrations (MICs) of CFM in the presence of AMC were determined for 46 clinical isolates by placing a CFM Etest on a plate with AMC impregnated in the agar. Isolates with CFM MIC ≤1 µg/mL in the presence of AMC were considered susceptible to the CFM and AMC combination. Five isolates were then selected for further testing using time-kill analysis in the presence of CFM, AMC, and CFM with AMC. Time-kill curves were plotted to determine synergy over 24 h. RESULTS: AMC improved the activity of CFM against ESBL E. coli isolates by 128-fold in the Etest analysis with 85% of tested isolates being susceptible to the combination. A fourfold or greater reduction in CFM MIC was exhibited in 44 of 46 (96%) isolates when in the presence of AMC. Synergy and bactericidal activity between CFM and AMC were exhibited in each of the five isolates tested by time-kill analysis. DISCUSSION/CONCLUSION: This study found that AMC improves the activity of CFM against ESBL E. coli and that this antibiotic combination has potential as an oral therapeutic option to treat ESBL E. coli UTIs.


Assuntos
Infecções por Escherichia coli , Infecções Urinárias , Humanos , Cefixima/farmacologia , Cefixima/uso terapêutico , Escherichia coli , beta-Lactamases , Combinação Amoxicilina e Clavulanato de Potássio/farmacologia , Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Testes de Sensibilidade Microbiana , Infecções por Escherichia coli/tratamento farmacológico , Infecções Urinárias/tratamento farmacológico
2.
Clin Infect Dis ; 72(10): e675-e681, 2021 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-32898221

RESUMO

Vancomycin is commonly prescribed to hospitalized patients. Decades of pharmacokinetic/pharmacodynamic research culminated in recommendations to monitor the ratio of the area under the concentration-time curve (AUC) to the minimum inhibitory concentration in order to optimize vancomycin exposure and minimize toxicity in the revised 2020 guidelines. These guideline recommendations are based on limited data without high-quality evidence and limitations in strength. Despite considerable effort placed on vancomycin therapeutic drug monitoring (TDM), clinicians should recognize that the majority of vancomycin use is empiric. Most patients prescribed empiric vancomycin do not require it beyond a few days. For these patients, AUC determinations during the initial days of vancomycin exposure are futile. This added workload may detract from high-level patient care activities. Loading doses likely achieve AUC targets, so AUC monitoring after a loading dose is largely unnecessary for broad application. The excessive vancomycin TDM for decades has been propagated with limitations in evidence, and it should raise caution on contemporary vancomycin TDM recommendations.


Assuntos
Preparações Farmacêuticas , Vancomicina , Antibacterianos/efeitos adversos , Monitoramento de Medicamentos , Humanos , Futilidade Médica , Vancomicina/efeitos adversos
3.
Artigo em Inglês | MEDLINE | ID: mdl-32205348

RESUMO

Intensive care unit (ICU) patients may experience ceftriaxone underexposure, but clinical outcomes data are lacking. The objective of this study was to determine the impact of ceftriaxone dosing on clinical outcomes among ICU patients without central nervous system (CNS) infection. A retrospective study of ICU patients receiving intravenous, empirical ceftriaxone for non-CNS infections was conducted. Patients ≥18 years of age who received ≤2 g of ceftriaxone daily for ≥72 h were included and categorized as receiving ceftriaxone 1 g or 2 g daily. The primary, composite outcome was treatment failure, defined as inpatient mortality and/or antibiotic escalation due to clinical worsening. Propensity score matching was performed based on the probability of receiving 2 g of ceftriaxone daily. Multivariable logistic regression determined the association between ceftriaxone dose and treatment failure in a propensity-matched cohort. A total of 212 patients were included in the propensity-matched cohort. The most common diagnoses (83.0%) were pneumonia and urinary tract infection. Treatment failure occurred in 17.0% and 5.7% of patients receiving 1 g and 2 g daily, respectively (P = 0.0156). Overall inpatient mortality was 8.5%. Ceftriaxone 2 g dosing was associated with a reduced likelihood of treatment failure (adjusted odds ratio [aOR] = 0.190; 95% confidence interval [CI] = 0.059 to 0.607). Other independent predictors of treatment failure included sequential organ failure assessment score (aOR = 1.440; 95% CI = 1.254 to 1.653) and creatinine clearance at 72 h from ceftriaxone initiation (aOR = 0.980; 95% CI = 0.971 to 0.999). Therefore, ceftriaxone at 2 g daily, when used as appropriate antimicrobial coverage, may be appropriate for ICU patients with lower mortality risk.


Assuntos
Antibacterianos , Ceftriaxona , Antibacterianos/uso terapêutico , Ceftriaxona/uso terapêutico , Cuidados Críticos , Humanos , Unidades de Terapia Intensiva , Estudos Retrospectivos
4.
Artigo em Inglês | MEDLINE | ID: mdl-30617094

RESUMO

We analyzed the impact of vancomycin (VAN) combined with adjuvant ß-lactam therapy (Combo) on persistent (≥5 days) methicillin-resistant Staphylococcus aureus bacteremia versus VAN alone by using pooled data from two previously published observational studies (n = 156). Combo was inversely associated with persistent bacteremia (adjusted odds ratio, 0.460; 95% confidence interval, 0.229 to 0.923). Acute kidney injury was more common with Combo than with VAN (18.9% and 7.6%, respectively; P = 0.062).


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/uso terapêutico , beta-Lactamas/uso terapêutico , Injúria Renal Aguda/induzido quimicamente , Antibacterianos/efeitos adversos , Bacteriemia/microbiologia , Quimioterapia Combinada , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Estudos Observacionais como Assunto , Estudos Retrospectivos , Resultado do Tratamento , Vancomicina/efeitos adversos , beta-Lactamas/efeitos adversos
5.
Ther Drug Monit ; 41(4): 483-488, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30817704

RESUMO

BACKGROUND: Investigations of the relationship between vancomycin trough concentrations and area under the concentration time curve (AUC) are growing, but still limited. The authors sought to determine vancomycin exposure among hospitalized adults with presumed or confirmed invasive staphylococcal infections using 2-level pharmacokinetic monitoring to inform changes to an institutional vancomycin dosing protocol. METHODS: This was a retrospective observational study performed in 2 acute care hospitals. Adults prescribed vancomycin (therapeutic trough 15-20 mg/L) for a presumed or documented invasive staphylococcal infection were evaluated. Two steady-state serum vancomycin levels were used to determine each patient's 24-hour AUC to minimum inhibitory concentration ratio (AUC/MIC) using a non-Bayesian, equation-based approach. Patient demographics and crude clinical outcomes were also collected. RESULTS: Thirty-four patients were included in the study, with 2 patients having vancomycin levels drawn twice (36 sets of levels). Most patients were located in an intensive care unit (91.2%), and 85.3% of patients were prescribed vancomycin for bacteremia, pneumonia, or endocarditis. The mean ± SD vancomycin Cmin was 16.6 ± 6.1 mg/L, and the mean AUC/MIC was 588 ± 156 mg/L × hour. The rate of 24-hour vancomycin AUC/MIC target attainment was 91.2% (n = 31/34). Of the patients with a Cmin > 9 mg/L, 100% (n = 33) achieved AUC/MIC values >400 mg/L × hour and 93.9% were >500 mg/L × hour. There was a strong correlation between vancomycin Cmin and AUC24 hr (R = 0.731; P < 0.001). CONCLUSIONS: Targeting a vancomycin trough between 15 and 20 mg/L frequently resulted in an AUC/MIC greater than that thought to be necessary for efficacy optimization. Considering these findings alongside the practical challenges associated with wide-scale implementation of AUC monitoring, reducing the target trough as a means to prevent vancomycin overexposure warrants clinical consideration and further evaluation.


Assuntos
Infecções Estafilocócicas/sangue , Vancomicina/sangue , Vancomicina/farmacocinética , Adulto , Idoso , Área Sob a Curva , Feminino , Humanos , Masculino , Testes de Sensibilidade Microbiana/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/uso terapêutico
6.
Chemotherapy ; 64(5-6): 233-237, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-32396913

RESUMO

Previous studies have demonstrated synergy between piperacillin (PIP)-tazobactam (TAZ) (TZP) and vancomycin (VAN) against methicillin-resistant Staphylococcus aureus (MRSA). However, it is unknown whether PIP and/or TAZ synergizes with VAN against MRSA. We sought to determine whether PIP and/or TAZ synergizes with VAN against MRSA in vitro. The activity of PIP and/or TAZ with and without VAN (1/2 the minimum inhibitory concentration) was tested against 5 clinical MRSA isolates using a 24-h time-kill methodology. Antibiotic susceptibilities, accessory gene regulator (agr) operon functionality, and US strain type were also determined for the isolates. The combination of VAN and TZP was bactericidal against 3/5 isolates and synergistic against 4/5 isolates tested. Neither PIP nor TAZ alone combined with VAN demonstrated a significant reduction in bacterial growth. The combination of TZP and VAN was less active against the lone isolate with agr dysfunction. In summation, the combination of VAN with both PIP and TAZ was required for synergy against MRSA. This antibiotic combination may not be effective against unique MRSA strain types.

7.
Artigo em Inglês | MEDLINE | ID: mdl-29038267

RESUMO

mecA-positive Staphylococcus aureus isolates phenotypically susceptible to cefoxitin (mecA-methicillin-sensitive S. aureus [MSSA]) have been identified. We describe the treatment and outcomes among patients with mecA-MSSA bloodstream infections (BSI) and MRSA BSI matched 1:1 for age, BSI origin, and BSI type (n = 17 per group). Compared to MRSA BSI patients, mecA-MSSA BSI patients more often experienced clinical failure (58.8% and 11.8%, P = 0.010), driven largely by persistent bacteremia (35.3% and 11.8%). mecA-MSSA BSI patients may be at higher risk for poor clinical outcomes.


Assuntos
Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Cefoxitina/uso terapêutico , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Oxacilina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/uso terapêutico , Adulto , Idoso , Bacteriemia/microbiologia , Bacteriemia/mortalidade , Proteínas de Bactérias/genética , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Proteínas de Ligação às Penicilinas/genética , Estudos Retrospectivos , Infecções Estafilocócicas/mortalidade , Resultado do Tratamento , Adulto Jovem
8.
Artigo em Inglês | MEDLINE | ID: mdl-29109159

RESUMO

Candiduria is common in hospitalized patients, and asymptomatic candiduria contributes to antifungal overuse. The guidelines for management of asymptomatic candiduria do not recommend antifungal use, but rather the elimination of predisposing factors. It is unknown whether these recommendations are being followed. The primary objective of this study was to characterize candiduria management among hospitalized patients. This was a retrospective cohort study of a random sample of 305 hospitalized patients with candiduria at four U.S. medical centers from January 2010 to December 2013. Patients were classified as asymptomatic or symptomatic based on established criteria, and data were collected by chart review. Infectious Diseases Society of America (IDSA) treatment guideline adherence and its association with clinical outcomes, including candiduria recurrence (short- and long-term) and 30-day readmission, were assessed. Eighty percent of patients were classified as having asymptomatic candiduria. Overall, 143 (47%) patients were not managed according to recommended guidelines, including 105/243 (43%) in the asymptomatic candiduria group and 38/62 (61%) in the symptomatic group (P = 0.01). Discordance among asymptomatic patients was driven by overtreatment with an antifungal (98/105 [93%]). Thirty-three percent of patients with asymptomatic candiduria not managed according to the guidelines were treated for over 7 days, and 5% received over 14 days of therapy. Fluconazole was the most commonly used empirical antifungal among asymptomatic candiduria patients (96%), followed by micafungin (4%). Asymptomatic candiduria patients not managed according to the guidelines had a trend toward higher 30-day readmission (35% versus 26%, P = 0.27). Inappropriate management of candiduria among hospitalized patients was high, leading to overtreatment with antifungal therapy.


Assuntos
Antifúngicos/uso terapêutico , Infecções Assintomáticas , Candidíase/tratamento farmacológico , Fluconazol/uso terapêutico , Prescrição Inadequada , Uso Excessivo dos Serviços de Saúde , Micafungina/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Idoso , Candida/efeitos dos fármacos , Candidíase/microbiologia , Feminino , Humanos , Masculino , Estudos Retrospectivos , Infecções Urinárias/microbiologia
9.
Clin Infect Dis ; 73(7): e1778-e1779, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33238309
10.
Antimicrob Agents Chemother ; 58(2): 1028-33, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24277036

RESUMO

Vancomycin with piperacillin-tazobactam is used as empirical therapy for critically ill patients. Studies of this combination against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-intermediate S. aureus (VISA) are limited, but ß-lactams in combination with vancomycin have shown synergistic activity against MRSA and VISA. The goal of this study was to evaluate whether piperacillin-tazobactam and vancomycin were synergistic against MRSA and VISA in vitro. Bloodstream MRSA (n = 20) and VISA (n = 4) strains were selected. In vitro antimicrobial activities of piperacillin-tazobactam and oxacillin were evaluated by disk diffusion, and MICs were determined by Etest using Muller-Hinton agar with and without vancomycin at one-half the MIC. Time-kill studies evaluated 14 MRSA and all 4 VISA isolates using piperacillin-tazobactam at 300/35 mg/liter or oxacillin at 40 mg/liter alone and with vancomycin at one-half the MIC. Mean zones of inhibition for piperacillin-tazobactam and oxacillin increased with vancomycin against MRSA and VISA (P < 0.001 for all), and the MIC90 decreased with vancomycin against MRSA and VISA to values meeting susceptibility criteria for S. aureus (P < 0.001 for both antibiotics against MRSA). In MRSA time-kill studies, the mean 24-h reductions in inoculum for piperacillin-tazobactam, piperacillin-tazobactam with vancomycin, and oxacillin with vancomycin were 3.53, 3.69, and 2.62 log10 CFU/ml, respectively. The mean 24-h reductions in VISA inoculum for piperacillin-tazobactam, piperacillin-tazobactam with vancomycin, and oxacillin with vancomycin were 2.85, 2.93, and 3.45 log10 CFU/ml, respectively. Vancomycin with piperacillin-tazobactam or oxacillin demonstrated synergistic activity against MRSA and VISA. The clinical implications of these combinations against MRSA and VISA should be investigated.


Assuntos
Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Oxacilina/farmacologia , Ácido Penicilânico/análogos & derivados , Staphylococcus aureus/efeitos dos fármacos , Vancomicina/farmacologia , Combinação de Medicamentos , Sinergismo Farmacológico , Humanos , Staphylococcus aureus Resistente à Meticilina/crescimento & desenvolvimento , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Ácido Penicilânico/farmacologia , Piperacilina/farmacologia , Combinação Piperacilina e Tazobactam , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus aureus/isolamento & purificação , Resistência a Vancomicina/efeitos dos fármacos
11.
Antimicrob Agents Chemother ; 58(1): 102-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24145519

RESUMO

Vancomycin (VAN) is often used to treat methicillin-resistant Staphylococcus aureus (MRSA) bacteremia despite a high incidence of microbiological failure. Recent in vitro analyses of ß-lactams in combination with VAN demonstrated synergistic activity against MRSA. The goal of this study was to examine the impact of combination therapy with VAN and a ß-lactam (Combo) on the microbiological eradication of MRSA bacteremia compared to VAN alone. This was a retrospective cohort study of patients with MRSA bacteremia who received Combo therapy or VAN alone. Microbiological eradication of MRSA, defined as a negative blood culture obtained after initiation of therapy, was used to evaluate the efficacy of each regimen. A total of 80 patients were included: 50 patients in the Combo group and 30 patients in the VAN-alone group. Microbiological eradication was achieved in 48 patients (96%) in the Combo group compared to 24 patients (80%) in the VAN-alone group (P = 0.021). In a multivariable model, the Combo treatment had a higher likelihood of achieving microbiological eradication (adjusted odds ratio, 11.24; 95% confidence interval, 1.7 to 144.3; P = 0.01). In patients with infective endocarditis (n = 22), 11/11 (100%) who received Combo therapy achieved microbiological eradication compared to 9/11 (81.8%) treated with VAN alone, but the difference was not statistically significant (P = 0.20). Patients with MRSA bacteremia who received Combo therapy were more likely to experience microbiological eradication of MRSA than patients who received VAN alone.


Assuntos
Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Staphylococcus aureus Resistente à Meticilina/patogenicidade , Vancomicina/uso terapêutico , beta-Lactamas/uso terapêutico , Adulto , Idoso , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Vancomicina/administração & dosagem , beta-Lactamas/administração & dosagem
12.
Infect Control Hosp Epidemiol ; 44(3): 406-412, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-35702922

RESUMO

OBJECTIVES: To identify characteristics of US health systems and end users that report antimicrobial use and resistance (AUR) data, to determine how NHSN AUR data are used by hospitals and health systems and end users, and to identify barriers to AUR reporting. DESIGN: An anonymous survey was sent to Society of Infectious Diseases Pharmacists (SIDP) and Society for Healthcare Epidemiology of America (SHEA) Research Network members. METHODS: Data were collected via Survey Monkey from January 21 to February 21, 2020. Respondent and hospital data were analyzed using descriptive statistics. RESULTS: We received responses from 238 individuals across 43 US states. Respondents were primarily pharmacists (84%), from urban areas, (44%), from nonprofit medical centers (81%), and from hospitals with >250 beds (72%). Also, 62% reported data to the AU module and 19% reported data to the AR module. Use of software for local AU or AR tracking was associated with increased reporting to the AU module (19% vs 64%) and the AR module (2% vs 30%) (P < .001 each). Only 36% of those reporting data to the AU module used NHSN AUR data analysis tools regularly and only 9% reported data to the AR module regularly. Technical challenges and time and/or salary support were the most common barriers to AUR participation cited by all respondents. Among those not reporting AUR data, increased local expectations to report and better software solutions were the most commonly identified solutions to increase AUR reporting. CONCLUSIONS: Efforts to increase AUR reporting should focus on software solutions and salary support for data-entry activities. Increasing expectations to report may incentivize local resource allocation to improve AUR reporting rates.


Assuntos
Antibacterianos , Anti-Infecciosos , Farmacorresistência Bacteriana , Anti-Infecciosos/uso terapêutico , Inquéritos e Questionários , Atenção à Saúde
13.
Sr Care Pharm ; 38(11): 452-456, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37885096

RESUMO

Senior care pharmacists are well-positioned to lead and drive antimicrobial stewardship (AMS) initiatives, not only through audit and data collection, but also through communication, collaboration, and cooperation with prescribers and nurses to influence prescribing behaviors. Senior care pharmacists are in a unique position to take a leadership role within the interprofessional team to achieve AMS goals. They should engage with the interprofessional team to promote the judicious and appropriate use of antimicrobials at their practice sites. This position statement is an update of the 2017 version by the American Society of Consultant Pharmacists (ASCP) Antimicrobial Stewardship and Infection and Prevention Control Committee and the Society of Infectious Diseases Pharmacists (SIDP).


Assuntos
Anti-Infecciosos , Gestão de Antimicrobianos , Doenças Transmissíveis , Humanos , Estados Unidos , Farmacêuticos , Consultores , Anti-Infecciosos/uso terapêutico , Doenças Transmissíveis/tratamento farmacológico
15.
Open Forum Infect Dis ; 9(5): ofac137, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35493116

RESUMO

Vancomycin was introduced nearly 65 years ago and remains the standard antibiotic for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Staphylococcus aureus remains highly susceptibility to vancomycin (>97%). Despite this, MRSA treatment failure with vancomycin is high in complicated bacteremia. Additionally, vancomycin can cause nephrotoxicity, leading to new therapeutic drug monitoring guidance. This demonstrates how difficult it is to dose vancomycin in a way that is both efficacious and safe, especially during long courses of therapy. Often underappreciated are the cost, resources, and complexity of vancomycin care at a time when alternative antibiotics are becoming cost comparable. This perspective highlights a bigger picture of how the treatment repertoires of many other diseases have changed and advanced since vancomycin's introduction in the 1950s, yet the vancomycin MRSA treatment standard remains. While vancomycin can still have a role, 65 years may be a practical retirement age for vancomycin in highly complex endovascular infections.

16.
J Am Board Fam Med ; 35(4): 733-741, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35896475

RESUMO

OBJECTIVE: To assess the impact of geodemographic factors on antibiotic prescribing for adult acute, uncomplicated bronchitis or upper respiratory tract infection. METHODS: A retrospective, observational study of 63,051 single health-system, outpatient discharges with a primary diagnosis of bronchitis or upper respiratory tract infection in 2019. Univariate analyses of prescribing predictors and multivariable stepwise logistic modeling were performed. RESULTS: Patients who were older (aOR 1.02; 95% CI 1.02, 1.02), male (1.10; 1.06, 1.14), black (1.29; 1.22, 1.38), smoked (1.18; 1.14, 1.23), seen in urgent care (1.26; 1.22, 1.31) and living in an area with more owner-occupied housing (1.41; 1.30, 1.53) were more likely to receive antibiotics. Patients who were Asian (0.88; 0.77, 0.99), had Medicare (0.83; 0.78, 0.87), Medicaid (0.84; 0.79, 0.87) or Exchange insurance (0.90; 0.82, 0.98), or seen in the emergency department (0.43; 0.40, 0.46) were less likely to receive antibiotics. Distance from a patient's address and their encounter location did not predict antibiotic prescribing. CONCLUSIONS: Antibiotic prescribing interventions for adult acute bronchitis and upper respiratory tract infections could target patients living in an area with higher socioeconomic status.


Assuntos
Bronquite , Infecções Respiratórias , Adulto , Idoso , Antibacterianos/uso terapêutico , Bronquite/tratamento farmacológico , Humanos , Prescrição Inadequada , Masculino , Medicare , Padrões de Prática Médica , Infecções Respiratórias/tratamento farmacológico , Estudos Retrospectivos , Estados Unidos
17.
Crit Care Explor ; 4(7): e0726, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35815181

RESUMO

OBJECTIVE: ß-lactams are the cornerstone of empiric and targeted antibiotic therapy for critically ill patients. Recently, there have been calls to use ß-lactam therapeutic drug monitoring (TDM) within 24-48 hours after the initiation of therapy in critically ill patients. In this article, we review the dynamic physiology of critically ill patients, ß-lactam dose response in critically ill patients, the impact of pathogen minimum inhibitory concentration (MIC) on ß-lactam TDM, and pharmacokinetics in critically ill patients. Additionally, we highlight available clinical data to better inform ß-lactam TDM for critically ill patients. DATA SOURCES: We retrospectively analyzed patients admitted for sepsis or septic shock at a single academic medical center who were treated with ß-lactam antibiotics. STUDY SELECTION: Indexed studies in PubMed in English language were selected for review on topics relative to critical care physiology, ß-lactams, pharmacokinetics/pharmacodynamics, TDM, and antibiotic susceptibility. DATA EXTRACTION: We reviewed potentially related studies on ß-lactams and TDM and summarized their design, patients, and results. This is a synthetic, nonsystematic, review. DATA SYNTHESIS: In the retrospective analysis of patients treated with ß-lactam antibiotics, approximately one-third of patients received less than 48 hours of ß-lactam therapy. Of those who continued beyond 48 hours, only 13.7% had patient-specific factors (augmented renal clearance, fluid overload, morbid obesity, and/or surgical drain), suggesting a potential benefit of ß-lactam TDM. CONCLUSIONS: These data indicate that a strategy of comprehensive ß-lactam TDM for critically ill patients is unwarranted as it has not been shown yet to improve patient-oriented outcomes. This review demonstrates that ß-lactam TDM in the ICU, while laudable, layers ambiguous ß-lactam exposure thresholds upon uncertain/unknown MIC data within a dynamic, unpredictable patient population for whom TDM results will not be available fast enough to significantly affect care. Judicious, targeted TDM for those with risk factors for ß-lactam over- or underexposure is a better approach but requires further study. Clinically, choosing the correct antibiotic and dosing ß-lactams aggressively, which have a wide therapeutic index, to overcome critical illness factors appears to give critically ill patients the best likelihood of survival.

18.
Open Forum Infect Dis ; 9(11): ofac542, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36340739

RESUMO

Given the complexity of antimicrobial resistance and the dire implications of misusing antimicrobials, it is imperative to identify accurate and meaningful ways to understand and communicate the realities, challenges, and opportunities associated with antimicrobial utilization and measurement in all sectors, including in animal agriculture. The objectives of this article are to (i) describe how antimicrobials are regulated and used in US animal agriculture and (ii) highlight realities, challenges, and opportunities to foster multidisciplinary understanding of the common goal of responsible antimicrobial use. Recognition of the realities of medicine, practice, and policy in the agricultural setting is critical to identify realistic opportunities for improvement and collaboration.

19.
J Clin Pharmacol ; 62(4): 472-478, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34564865

RESUMO

Oritavancin and dalbavancin are long-acting lipoglycopeptides with activity against susceptible gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. Though similar in structure to traditional glycopeptide antibiotics like vancomycin, these antibiotics have terminal half-lives >10 days, and, as a result, there is potential for administration of vancomycin to a patient while oritavancin or dalbavancin are still appreciably present in serum. Given the structural similarities, this creates an opportunity for lab assay interference when performing therapeutic drug monitoring for vancomycin. Following higher-than-expected serum vancomycin concentrations in a patient who received both oritavancin and vancomycin within a short time frame, we evaluated the potential for lipoglycopeptide interference with clinical vancomycin assays. Five platforms covering 3 immunoassay technologies were used to quantify vancomycin concentrations in serum spiked with oritavancin or dalbavancin. Oritavancin generated spurious vancomycin concentrations (20%-84% increase) in both enzyme-multiplied immunoassay technique and a particle-enhanced turbidimetric inhibition immunoassay. However, the improper detection of oritavancin was not consistent across all particle-enhanced turbidimetric inhibition immunoassay platforms. Dalbavancin interference was not detected on any of the platforms tested. The interference from oritavancin may result in falsely elevated vancomycin concentrations and, subsequently, inappropriately adjusted vancomycin doses.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Vancomicina , Antibacterianos/uso terapêutico , Monitoramento de Medicamentos , Humanos , Lipoglicopeptídeos , Testes de Sensibilidade Microbiana , Vancomicina/farmacologia
20.
J Pharm Pract ; 35(3): 388-395, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33353452

RESUMO

INTRODUCTION: Antibiotic time-outs (ATO) are a recommended antimicrobial stewardship action, but data assessing their impact are lacking. This study investigated the impact of a systematic, pharmacist initiated ATO intervention. METHODS: This pre-post study included inpatients on hospitalist and intensivist services receiving empiric antibiotics for ≥48 hours. The ATO was initiated by pharmacists after 48 hours of empiric therapy and the outcome was documented including antibiotic indication, plan, and duration. An electronic medical record (EMR) alert facilitated ATO completion and pharmacists and prescribers received education prior to implementation. The primary outcome was EMR documentation of an antibiotic plan by 72 hours. Secondary outcomes included antibiotic utilization and antibiotic therapy modifications by 2 hours. RESULTS: 399 patients were included, 199 pre- and 200 post-intervention. The most common indications were pneumonia (32%), intra-abdominal infection (20%) and urinary tract infection (19%), with no between-group differences. EMR documentation of an antibiotic plan significantly improved in the post-intervention group (19% vs. 79%, p<0.0001) as did modifications to antibiotic therapy. The median duration of in-hospital antibiotic therapy was similar between groups (4.0 vs. 4.0 days, p = 0.2499). Approximately 45% of patients in each group received discharge antibiotics and median duration of discharge antibiotic therapy prescribed was reduced (7 vs. 5 days in the pre- and post-intervention groups, respectively; p = 0.0140). DISCUSSION: Implementation of pharmacist initiated ATO was associated with improvements in supporting EMR documentation and antibiotic therapy modifications. These findings highlight an important role in which pharmacists can serve as part of a collaborative antibiotic stewardship team.


Assuntos
Gestão de Antimicrobianos , Farmacêuticos , Adulto , Antibacterianos/uso terapêutico , Hospitalização , Humanos , Estudos Retrospectivos
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