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1.
Clin Infect Dis ; 75(2): 269-277, 2022 08 25.
Artículo en Inglés | MEDLINE | ID: mdl-34718456

RESUMEN

BACKGROUND: Bloodstream infections (BSIs) are a leading cause of morbidity and mortality. The Improving Outcomes and Antimicrobial Stewardship study seeks to evaluate the impact of the Accelerate PhenoTest BC Kit (AXDX) on antimicrobial use and clinical outcomes in BSIs. METHODS: This multicenter, quasiexperimental study compared clinical and antimicrobial stewardship metrics, prior to and after implementation of AXDX, to evaluate the impact this technology has on patients with BSIs. Laboratory and clinical data from hospitalized patients with BSIs (excluding contaminants) were compared between 2 arms, 1 that underwent testing on AXDX (post-AXDX) and 1 that underwent alternative organism identification and susceptibility testing (pre-AXDX). The primary outcomes were time to optimal therapy (TTOT) and 30-day mortality. RESULTS: A total of 854 patients with BSIs (435 pre-AXDX, 419 post-AXDX) were included. Median TTOT was 17.2 hours shorter in the post-AXDX arm (23.7 hours) compared with the pre-AXDX arm (40.9 hours; P<.0001). Compared with pre-AXDX, median time to first antimicrobial modification (24.2 vs 13.9 hours; P<.0001) and first antimicrobial deescalation (36.0 vs 27.2 hours; P=.0004) were shorter in the post-AXDX arm. Mortality (8.7% pre-AXDX vs 6.0% post-AXDX), length of stay (7.0 pre-AXDX vs 6.5 days post-AXDX), and adverse drug events were not significantly different between arms. Length of stay was shorter in the post-AXDX arm (5.4 vs 6.4 days; P=.03) among patients with gram-negative bacteremia. CONCLUSIONS: For BSIs, use of AXDX was associated with significant decreases in TTOT, first antimicrobial modification, and time to antimicrobial deescalation.


Asunto(s)
Antiinfecciosos , Programas de Optimización del Uso de los Antimicrobianos , Bacteriemia , Infecciones por Bacterias Gramnegativas , Antibacterianos/uso terapéutico , Antiinfecciosos/uso terapéutico , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Humanos
2.
J Antimicrob Chemother ; 76(9): 2453-2463, 2021 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-34021752

RESUMEN

BACKGROUND: Data from the Improving Outcomes and Antibiotic Stewardship for Patients with Bloodstream Infections: Accelerate PhenoTest™ BC Kit (AXDX) Registry Study were analysed to determine the impact of rapid organism identification and antimicrobial susceptibility testing (AST) for Gram-positive bacteraemia. PATIENTS AND METHODS: This multicentre, quasi-experimental study evaluated clinical and antimicrobial stewardship metrics following the implementation of AXDX. Data from hospitalized patients with bacteraemia were compared between groups, one that underwent testing on AXDX (post-AXDX) and one that underwent traditional identification and AST (pre-AXDX). An analysis of patients with Gram-positive bacteraemia was performed. The primary outcome was time to optimal therapy (TTOT). Secondary outcomes included time to first antibiotic modification (overall and Gram-positive), duration of unnecessary MRSA coverage, incidence of adverse events, length of stay and mortality. RESULTS: A total of 219 (109 pre-AXDX, 110 post-AXDX) patients with Gram-positive bacteraemia were included. Median TTOT was 36.3 h (IQR, 16.9-56.7) in the pre-AXDX group and 20.4 h (IQR, 7.5-36.7) in the post-AXDX group (P = 0.01). Compared with pre-AXDX, median time to first antibiotic modification (29.1 versus 15.9 h; P = 0.002), time to first Gram-positive antibiotic modification (33.2 versus 17.2 h; P = 0.003) and median duration of unnecessary MRSA coverage (58.4 versus 29.7 h; P = 0.04) were reduced post-AXDX. A trend towards decreased acute kidney injury (24% versus 13%; P = 0.06) was observed in the post-AXDX group. Groups did not differ in other secondary outcomes. CONCLUSIONS: Implementation of AXDX testing for patients with Gram-positive bacteraemia shortened the TTOT and reduced unnecessary antibiotic exposure due to faster antibiotic modifications.


Asunto(s)
Programas de Optimización del Uso de los Antimicrobianos , Bacteriemia , Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Bacteriemia/tratamiento farmacológico , Humanos
3.
Infect Control Hosp Epidemiol ; 42(6): 688-693, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33504376

RESUMEN

OBJECTIVE: To determine the usefulness of adjusting antibiotic use (AU) by prevalence of bacterial isolates as an alternative method for risk adjustment beyond hospital characteristics. DESIGN: Retrospective, observational, cross-sectional study. SETTING: Hospitals in the southeastern United States. METHODS: AU in days of therapy per 1,000 patient days and microbiologic data from 2015 and 2016 were collected from 26 hospitals. The prevalences of Pseudomonas aeruginosa, extended-spectrum ß-lactamase (ESBL)-producing bacteria, methicillin-resistant Staphylococcus aureus (MRSA), and vancomycin-resistant enterococci (VRE) were calculated and compared to the average prevalence of all hospitals in the network. This proportion was used to calculate the adjusted AU (a-AU) for various categories of antimicrobials. For example, a-AU of antipseudomonal ß-lactams (APBL) was the AU of APBL divided by (prevalence of P. aeruginosa at that hospital divided by the average prevalence of P. aeruginosa). Hospitals were categorized by bed size and ranked by AU and a-AU, and the rankings were compared. RESULTS: Most hospitals in 2015 and 2016, respectively, moved ≥2 positions in the ranking using a-AU of APBL (15 of 24, 63%; 22 of 26, 85%), carbapenems (14 of 23, 61%; 22 of 25; 88%), anti-MRSA agents (13 of 23, 57%; 18 of 26, 69%), and anti-VRE agents (18 of 24, 75%; 15 of 26, 58%). Use of a-AU resulted in a shift in quartile of hospital ranking for 50% of APBL agents, 57% of carbapenems, 35% of anti-MRSA agents, and 75% of anti-VRE agents in 2015 and 50% of APBL agents, 28% of carbapenems, 50% of anti-MRSA agents, and 58% of anti-VRE agents in 2016. CONCLUSIONS: The a-AU considerably changes how hospitals compare among each other within a network. Adjusting AU by microbiological burden allows for a more balanced comparison among hospitals with variable baseline rates of resistant bacteria.


Asunto(s)
Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Enterococos Resistentes a la Vancomicina , Antibacterianos/uso terapéutico , Estudios Transversales , Humanos , Estudios Retrospectivos , Infecciones Estafilocócicas/tratamiento farmacológico
4.
J Clin Microbiol ; 58(11)2020 10 21.
Artículo en Inglés | MEDLINE | ID: mdl-32878953

RESUMEN

Identification (ID) and antimicrobial susceptibility testing (AST) of respiratory pathogens are critical to the management of patients with pneumonia to facilitate optimal antibiotic therapy selection. Few studies have examined the time to results (TTR) for this critical specimen, and such data can be valuable for benchmarking the current paradigm of diagnostic approaches. TTR for bronchoalveolar lavage (BAL) and endotracheal aspirate (ETA) specimens from hospitalized patients was evaluated using the Premier Healthcare Database, a comprehensive database of 194 U.S. hospitals. Times from specimen collection to reporting of organism ID/AST were evaluated and compared by specimen types and characteristics. A total of 79,662 (43,129 BAL; 36,533 ETA) specimens were included, of which 19.3% harbored no growth, 47.1% contained normal respiratory flora alone (including yeast), and 0.6% contained mycobacteria/molds. Potential bacterial pathogens (PBP) were recovered from 33.0%. ETA specimens had a higher proportion of specimens with isolation of PBP (39.2% versus 27.7%) and with normal respiratory flora (52.0% versus 43.0%) and were less likely to be negative (8.2% versus 28.6%) than BAL specimens (all P < 0.0001). Staphylococcus aureus and Pseudomonas aeruginosa were isolated in 10.5 and 6.4% of the specimens, respectively, and were the most common organisms identified. Median (interquartile range) TTR were 37.0 h (21.8 to 51.7 h) and 60.5 h (46.6 to 72.4 h) for ID and AST, respectively. Median TTR for major respiratory pathogens by organism ranged from 29.2 to 43.9 h for ID and from 47.9 to 73.9 h for AST. Organism type, specimen collection time, and hospital teaching status influenced TTR. Mechanically vented patients and ETA specimens were more likely to recover PBP.


Asunto(s)
Antibacterianos , Bacterias , Antibacterianos/uso terapéutico , Lavado Broncoalveolar , Líquido del Lavado Bronquioalveolar , Hospitales , Humanos
5.
Antibiotics (Basel) ; 9(5)2020 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-32423104

RESUMEN

OBJECTIVES: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species. METHODS: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection. RESULTS: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51-1.72) in multivariable Cox proportional hazards regression analysis. CONCLUSIONS: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents.

6.
Eur J Clin Microbiol Infect Dis ; 38(8): 1471-1479, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31079314

RESUMEN

For patients with a single-positive blood culture growing gram-positive cocci, organism identification can provide supportive information for differentiating contamination from infection. We investigated the effect of a rapid blood culture identification panel (BCID) on vancomycin-prescribing patterns and patient outcomes for single positive blood culture (PBC) growing gram-positive cocci. Adult patients with single-positive blood culture growing gram-positive cocci with conventional organism identification (pre-BCID) were compared with organism identification by BCID (post-BCID). Antimicrobial Stewardship Program (ASP) review of PBC was performed in both study groups. Vancomycin prescribing patterns were studied. Secondary endpoints were the incidence of nephrotoxicity, length of stay (LOS), readmission rate, mortality, and hospital costs. A total of 188 patients (86 pre-BCID, 102 post-BCID) were included. Organism identification was known 21 h sooner in the post-BCID group (P < 0.001). Coagulase-negative staphylococci were the most commonly isolated organisms (73%). In patients where vancomycin was deemed unnecessary (n = 133), vancomycin use (51% pre-BCID vs 36% post-BCID; P = 0.09) and time from culture positivity to vancomycin discontinuation (1.5 vs. 1.7 days; P = 0.92) did not differ between groups. We found no differences in the development of nephrotoxicity, LOS, readmission, mortality, or hospital costs. Earlier identification of single positive blood culture growing gram-positive cocci did not significantly influence prescribing patterns of vancomycin. However, baseline antimicrobial stewardship review of single positive blood culture growing gram-positive cocci may have lessened the opportunity for detectable differences. Larger studies, accounting for the impact of ASP intervention, should be performed to determine the value of each individual component.


Asunto(s)
Bacteriemia/diagnóstico , Cultivo de Sangre , Cocos Grampositivos/genética , Cocos Grampositivos/aislamiento & purificación , Reacción en Cadena de la Polimerasa , Adulto , Anciano , Programas de Optimización del Uso de los Antimicrobianos , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Femenino , Humanos , Masculino , Staphylococcus aureus Resistente a Meticilina/aislamiento & purificación , Persona de Mediana Edad , Pautas de la Práctica en Medicina , Staphylococcus/aislamiento & purificación , Factores de Tiempo , Estados Unidos , Vancomicina/uso terapéutico
8.
mSphere ; 3(5)2018 09 26.
Artículo en Inglés | MEDLINE | ID: mdl-30258039

RESUMEN

A blaKPC-2-carrying Citrobacter freundii isolate developed ceftazidime-avibactam resistance during treatment with this agent. The initial and follow-up isolates exhibited ceftazidime-avibactam MICs of 4 and 64 µg/ml, respectively. Overexpression of AcrAB-TolC and porin alterations were detected in both isolates, but no other resistance mechanism was observed. After passaging the initial clinical isolate in ceftazidime-avibactam at a fixed concentration of 4 µg/ml and a 4:1 ratio, resistance to all ß-lactams was noted, and a percentage of the blaKPC-2 sequencing reads had mutations leading to the alterations D176Y (blaKPC-2-D176Y [78%]) or R164S plus P147L (blaKPC-2-R164S + P147L [82%]). Further investigation of the follow-up isolate showed that 11% of the blaKPC-2 reads had mutations leading to D179Y substitution (blaKPC-2-D179Y). In the absence of selective pressure, ceftazidime-avibactam MICs of the passaged and follow-up isolates revealed that 7 or 8 out of 20 screened colonies reverted to susceptible and possessed blaKPC-2 wild-type sequences. Recombinant plasmids carrying the blaKPC-2 alterations observed were transformed in Escherichia coli, and MIC values for ceftazidime ± avibactam were elevated. Lower MICs for ceftriaxone, cefepime, aztreonam, meropenem, and imipenem for the mutated KPC-2-producing isolates were observed compared to those of the isolates producing a wild-type KPC-2. Avibactam at a fixed concentration of 4 µg/ml restored the activity of all ß-lactams tested for the recombinant strains. The heterogenous population of wild-type and mutated blaKPC-2 and the reversibility of the genotypes observed suggest a significant challenge for managing KPC-producing isolates that develop ceftazidime-avibactam resistance during therapy.IMPORTANCE The development of ceftazidime-avibactam resistance among KPC-producing isolates during treatment with this agent has been reported. Usually isolates that become resistant have a mutated blaKPC gene that confers resistance to ceftazidime-avibactam and susceptibility to meropenem. We report a Citrobacter freundii isolate that developed ceftazidime-avibactam resistance due to mutations within the coding region of the blaKPC-2 Ω-loop previously reported; however, in this case, only 11% of the whole-genome sequencing reads had mutations, making this alteration difficult to detect and the treatment of these isolates more challenging. In addition to blaKPC, the initial and the follow-up patient isolates displayed hyperexpression of the AcrAB-TolC efflux system and disruption of the outer membrane protein (OMP) OmpF, which contribute to carbapenem resistance. Experiments performed to confirm our findings included generating mutant isolates from the initial patient isolate, passaging the isolates for purity in drug-free medium, resulting in a reversible phenotype, and cloning the mutations to demonstrate the resistance conferred.


Asunto(s)
Compuestos de Azabiciclo/farmacología , Proteínas Bacterianas/genética , Ceftazidima/farmacología , Citrobacter freundii/efectos de los fármacos , Farmacorresistencia Bacteriana Múltiple/genética , beta-Lactamasas/genética , Antibacterianos/farmacología , Citrobacter freundii/genética , Citrobacter freundii/aislamiento & purificación , Combinación de Medicamentos , Humanos , Pruebas de Sensibilidad Microbiana , Plásmidos/genética
9.
Am J Health Syst Pharm ; 75(16): 1191-1202, 2018 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-29970407

RESUMEN

PURPOSE: The implementation and optimization of molecular rapid diagnostic tests (mRDTs) as an antimicrobial stewardship intervention for patients with bloodstream infections (BSIs) are reviewed. SUMMARY: All U.S. acute care hospitals accredited by the Joint Commission are required to implement an antimicrobial stewardship program (ASP). Of the many interventions available to ASPs, mRDTs have demonstrated consistent, meaningful results on antimicrobial optimization and patient outcomes. Even among infectious diseases and antimicrobial stewardship-trained pharmacists, significant knowledge and familiarity gaps exist regarding available mRDTs and how best to implement and optimize them. Given the paucity of infectious diseases and/or antimicrobial stewardship-trained pharmacists, the mandates for establishing ASPs will require non-infectious diseases/antimicrobial stewardship-trained pharmacists to implement stewardship interventions, which may include mRDTs, within their institution. Optimization of mRDTs requires adequate diagnostic stewardship, specifically evaluating how mRDT implementation may decrease costs and assist in meeting antimicrobial stewardship regulatory requirements. Knowledge of how these technologies will augment existing microbiology and antimicrobial stewardship workflow is essential. Finally, selecting the right mRDT necessitates familiarity with the instrument's capabilities and with the institutional antibiogram. CONCLUSION: mRDTs have demonstrated the ability to be one of the most powerful antimicrobial stewardship interventions. Pharmacists required to implement an ASP in their institution should consider mRDTs as standard of care for patients with BSIs.


Asunto(s)
Bacteriemia/diagnóstico , Técnicas de Diagnóstico Molecular , Antibacterianos/uso terapéutico , Programas de Optimización del Uso de los Antimicrobianos , Bacteriemia/economía , Bacteriemia/microbiología , Humanos , Técnicas de Diagnóstico Molecular/economía , Farmacéuticos , Servicio de Farmacia en Hospital/economía , Servicio de Farmacia en Hospital/organización & administración
11.
Transpl Infect Dis ; 20(3): e12878, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29512930

RESUMEN

Previous studies of patients with cystic fibrosis (CF) treated with azole antifungals have shown altered pharmacokinetics relative to healthy patients. Data regarding the pharmacokinetic profile of isavuconazole in patients with CF undergoing lung transplantation are currently not available. Serum trough concentrations assessed in a single CF patient following transplant revealed significantly lower values relative to available literature. Larger studies are required to validate CF population pharmacokinetics of isavuconazole.


Asunto(s)
Antifúngicos/farmacocinética , Fibrosis Quística/tratamiento farmacológico , Trasplante de Pulmón/efectos adversos , Nitrilos/farmacocinética , Piridinas/farmacocinética , Triazoles/farmacocinética , Adulto , Monitoreo de Drogas , Femenino , Humanos , Inmunosupresores/uso terapéutico , Adulto Joven
12.
Int J Antimicrob Agents ; 51(4): 629-635, 2018 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-29408227

RESUMEN

BACKGROUND: Ceftazidime/avibactam is a newly approved ß-lactam/ß-lactamase inhibitor combination with activity against antibiotic-resistant Gram-negative organisms, including many carbapenem-resistant strains. Although this agent may offer a promising treatment option for serious infections with limited alternatives available, clinical experience with ceftazidime/avibactam in treatment of infections caused by multidrug-resistant Gram-negative organisms other than Klebsiella pneumoniae is limited. METHODS: A retrospective case series was performed to evaluate patients treated with ceftazidime/avibactam for infections caused by organisms other than K. pneumoniae at our institution over a 1-year period. Patients aged at least 18 years who received at least one dose of ceftazidime/avibactam were eligible for inclusion. Clinical and microbiological data were collected, and investigators assessed adverse effects, microbiological cure, clinical success, and 30-day in-hospital mortality following completion of ceftazidime/avibactam therapy. RESULTS: Ten patients were included. The most common index infection was pneumonia (n = 6/13, 46%) and the most frequently isolated organism was Pseudomonas aeruginosa (n = 8/21, 38%). Fifty percent of patients received ceftazidime/avibactam as monotherapy. Microbiological cure was achieved in 67% (n = 6/9) of patients and 70% (n = 7/10) of patients met criteria for clinical success. The 30-day in-hospital mortality rate was 30%. No patients experienced adverse events because of ceftazidime/avibactam therapy. CONCLUSIONS: For infections caused by antibiotic-resistant Gram-negative organisms other than K. pneumoniae, clinical and microbiological success rates for patients treated with ceftazidime/avibactam were similar to those that have been reported for K. pneumoniae. Ceftazidime/avibactam appears to be a promising treatment option for infections caused by a variety of resistant Gram-negative organisms when limited alternatives exist.


Asunto(s)
Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/uso terapéutico , Ceftazidima/uso terapéutico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones por Pseudomonas/tratamiento farmacológico , Inhibidores de beta-Lactamasas/uso terapéutico , Adulto , Anciano , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Enterobacteriaceae Resistentes a los Carbapenémicos/efectos de los fármacos , Enterobacteriaceae Resistentes a los Carbapenémicos/aislamiento & purificación , Combinación de Medicamentos , Farmacorresistencia Bacteriana Múltiple , Infecciones por Enterobacteriaceae/microbiología , Infecciones por Enterobacteriaceae/mortalidad , Femenino , Humanos , Infecciones Intraabdominales/tratamiento farmacológico , Infecciones Intraabdominales/microbiología , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Neumonía/tratamiento farmacológico , Neumonía/microbiología , Infecciones por Pseudomonas/microbiología , Infecciones por Pseudomonas/mortalidad , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/aislamiento & purificación , Estudios Retrospectivos , Infecciones de los Tejidos Blandos/tratamiento farmacológico , Infecciones de los Tejidos Blandos/microbiología
13.
Pharmacotherapy ; 37(11): 1479-1483, 2017 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-28869655

RESUMEN

OBJECTIVES: To characterize antibiotic regimens utilized for bacteremic Enterobacteriaceae urinary tract infections and assess treatment failure associated with intravenous-only compared to intravenous transitioned to oral antibiotic treatment. DESIGN: Retrospective cohort. SETTINGS: Tertiary care academic medical center. PATIENTS: 241 adult patients hospitalized between July 1, 2010, and June 30, 2015, with positive blood and urine cultures with the same Enterobacteriaceae pathogen. MAIN RESULTS: Hospital days on antibiotics as well as length of stay were less in the group treated with any oral antibiotics (intravenous/oral, median 5 [IQR 3-7] days vs intravenous-only antibiotics 6 [4-10] days, p<0.001; length of stay for intravenous/oral 4.6 [3.1-7.8] days vs intravenous-only 7.1 [4.0-17.5] days, p<0.001). No statistically significant difference was found in the composite outcome of treatment failure in patients who received intravenous-only antibiotics versus intravenous/oral antibiotics for the treatment of bacteremic urinary tract infections (intravenous-only 3.8% [95% CI: 1.0-9.4%] failure; intravenous/oral 8.2% [95% CI: 4.1-14.1%] failure; p=0.19). CONCLUSIONS: Intravenous transitioned to oral treatment (intravenous/oral) was associated with a shorter length of stay and fewer hospital antibiotic days compared with intravenous-only therapy. Transitioning from intravenous to oral antibiotic therapy is a viable treatment option to consider for patients with bacteremic Enterobacteriaceae urinary tract infection.


Asunto(s)
Antibacterianos/administración & dosificación , Bacteriemia/tratamiento farmacológico , Infecciones por Enterobacteriaceae/tratamiento farmacológico , Infecciones Urinarias/tratamiento farmacológico , Administración Intravenosa , Administración Oral , Anciano , Bacteriemia/microbiología , Estudios de Cohortes , Enterobacteriaceae/efectos de los fármacos , Enterobacteriaceae/aislamiento & purificación , Infecciones por Enterobacteriaceae/microbiología , Femenino , Hospitalización/estadística & datos numéricos , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Insuficiencia del Tratamiento , Resultado del Tratamiento , Infecciones Urinarias/microbiología
14.
Artículo en Inglés | MEDLINE | ID: mdl-28947473

RESUMEN

Ceftolozane-tazobactam is a cephalosporin-ß-lactamase inhibitor combination that exhibits potent in vitro activity against Pseudomonas aeruginosa, including strains that are resistant to other ß-lactams. The emergence of ceftolozane-tazobactam resistance among clinical isolates of P. aeruginosa has rarely been described. Here we characterized ceftolozane-tazobactam-resistant P. aeruginosa strains recovered from a patient who was treated with this agent for 6 weeks for a recurrent wound infection. The results showed that the resistance was mediated by a single AmpC structural mutation.


Asunto(s)
Antibacterianos/uso terapéutico , Proteínas Bacterianas/genética , Cefalosporinas/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Ácido Penicilánico/análogos & derivados , Infecciones por Pseudomonas/tratamiento farmacológico , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/genética , Inhibidores de beta-Lactamasas/uso terapéutico , beta-Lactamasas/genética , Anciano , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Tipificación de Secuencias Multilocus , Ácido Penicilánico/uso terapéutico , Polimorfismo de Nucleótido Simple/genética , Tazobactam , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/microbiología
15.
J Intensive Care Med ; 32(1): 25-37, 2017 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-26772199

RESUMEN

Bacterial infections are a frequent cause of hospitalization, and nosocomial infections are an increasingly common condition, particularly within the acute/critical care setting. Infection control practices and new antimicrobial development have primarily focused on gram-positive bacteria; however, in recent years, the incidence of infections caused by gram-negative bacteria has risen considerably in intensive care units. Infections caused by multidrug-resistant (MDR) gram-negative organisms are associated with high morbidity and mortality, with significant direct and indirect costs resulting from prolonged hospitalizations due to antibiotic treatment failures. Of particular concern is the increasing prevalence of antimicrobial resistance to ß-lactam antibiotics (including carbapenems) among Pseudomonas aeruginosa and Acinetobacter baumannii and, recently, among pathogens of the Enterobacteriaceae family. Treatment options for infections caused by these pathogens are limited. Antimicrobial stewardship programs focus on optimizing the appropriate use of currently available antimicrobial agents with the goals of improving outcomes for patients with infections caused by MDR gram-negative organisms, slowing the progression of antimicrobial resistance, and reducing hospital costs. Newly approved treatment options are available, such as ß-lactam/ß-lactamase inhibitor combinations, which significantly extend the armamentarium against MDR gram-negative bacteria.


Asunto(s)
Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/efectos de los fármacos , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Unidades de Cuidados Intensivos , Inhibidores de beta-Lactamasas/uso terapéutico , Antibacterianos/farmacología , Infección Hospitalaria/microbiología , Infección Hospitalaria/prevención & control , Infecciones por Bacterias Gramnegativas/epidemiología , Infecciones por Bacterias Gramnegativas/prevención & control , Adhesión a Directriz , Humanos , Incidencia , Pruebas de Sensibilidad Microbiana , Guías de Práctica Clínica como Asunto , Estados Unidos/epidemiología , Inhibidores de beta-Lactamasas/farmacología
16.
Open Forum Infect Dis ; 3(4): ofw201, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27975076

RESUMEN

We report the development of a collaborative relationship between antimicrobial stewardship and clinical microbiology that incorporates stewardship practices into daily laboratory rounds. Antimicrobial stewardship involvement on rounds was a welcomed and effective initiative with substantial rates of intervention. New opportunities to positively impact use of antimicrobials and laboratory resources were realized.

17.
J Clin Microbiol ; 54(10): 2455-63, 2016 10.
Artículo en Inglés | MEDLINE | ID: mdl-27487951

RESUMEN

Studies have demonstrated that the combination of antimicrobial stewardship programs (ASP) and rapid organism identification improves outcomes in bloodstream infections (BSI) but have not controlled for the incremental contribution of the individual components. Hospitalized adult patients with blood culture pathogens on a rapid, multiplex PCR-based blood culture identification panel (BCID) that included 19 bacterial species, 5 Candida spp., and 4 antimicrobial resistance genes were studied over sequential time periods in a pre-post quasiexperimental study in 3 groups in the following categories: conventional organism identification (controls), conventional organism identification with ASP (AS), and BCID with ASP (BCID). Clinical and economic outcomes were compared between groups. There were 783 patients with positive blood cultures; of those patients, 364 (115 control, 104 AS, and 145 BCID) met inclusion criteria. The time from blood culture collection to organism identification was shorter in the BCID group (17 h; P < 0.001) than in the control group (57 h) or the AS group (54 h). The BCID group had a shorter time to effective therapy (5 h; P < 0.001) than the control group (15 h) or AS group (13 h). The AS (57%) and BCID (52%) groups had higher rates of antimicrobial de-escalation than the control group (34%), with de-escalation occurring sooner in the BCID group (48 h; P = 0.034) than in the AS group (61 h) or the control group (63 h). No difference between the control group, AS group, and BCID group was seen with respect to mortality, 30-day readmission, intensive care unit length of stay (LOS), postculture LOS, or costs. In patients with BSI, ASP alone improved antimicrobial utilization. Addition of BCID to an established ASP shortened the time to effective therapy and further improved antimicrobial use compared to ASP alone, even in a setting of low antimicrobial resistance rates.


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Cultivo de Sangre/métodos , Candidemia/diagnóstico , Utilización de Medicamentos/normas , Pruebas de Sensibilidad Microbiana/métodos , Reacción en Cadena de la Polimerasa/métodos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados no Aleatorios como Asunto , Factores de Tiempo , Resultado del Tratamiento , Adulto Joven
18.
Infect Dis (Lond) ; 48(10): 732-7, 2016 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-27196015

RESUMEN

BACKGROUND: Early appropriate antibiotic selection is associated with favorable clinical outcomes. We evaluated the clinical impact of rapid detection of vancomycin-resistant Enterococcal bacteremia (VREB) by the FilmArray blood culture identification (BCID) panel coupled with antimicrobial stewardship program (ASP) interventions. METHODS: Hospitalized adult patients with VREB identified by conventional methods (CM) were compared to patients with VREB identified by BCID. Real time alerts of BCID results were provided to the ASP for intervention. Outcomes were compared between groups. RESULTS: Sixty-eight patients with VREB were included (CM, n = 45; BCID, n = 23). No significant differences in demographics, pre-existing conditions, or clinical characteristics were observed. Significant reductions were demonstrated between CM and BCID groups in median hours to organism identification (47.7 versus 18.2, p < 0.001), to identification of vancomycin resistance from time of culture positivity (50.1 versus 1.2, p < 0.001), and time to effective therapy (50.3 versus 20.8, p < 0.001). Differences between CM and BCID did not reach statistical significance for mortality (35.6% versus 26.1%), 30-day readmission rate (31.0% versus 17.6%), intensive care length of stay [LOS] (8.0 versus 7.0 days), post-culture LOS (14.6 versus 14.1 days) or median hospital costs per patient ($95,826 versus $53,195). CONCLUSIONS: In patients with VREB, rapid organism and resistance detection by the BCID panel with ASP intervention significantly reduced time to initiation of effective therapy by over 24 hours. Non-significant improvements in clinical outcomes were observed. Additional studies are needed to determine the full implications of BCID technology on patient outcome.


Asunto(s)
Antibacterianos/uso terapéutico , Bacteriemia/diagnóstico , Cultivo de Sangre/métodos , Infecciones por Bacterias Grampositivas/diagnóstico , Reacción en Cadena de la Polimerasa Multiplex/métodos , Enterococos Resistentes a la Vancomicina/aislamiento & purificación , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Bacteriemia/tratamiento farmacológico , Bacteriemia/microbiología , Femenino , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Humanos , Masculino , Persona de Mediana Edad , Ensayos Clínicos Controlados no Aleatorios como Asunto , Factores de Tiempo , Resultado del Tratamiento , Enterococos Resistentes a la Vancomicina/genética , Enterococos Resistentes a la Vancomicina/crecimiento & desarrollo , Adulto Joven
19.
Am J Health Syst Pharm ; 73(5 Suppl 1): S14-21, 2016 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-26896521

RESUMEN

PURPOSE: Results of a study of the relationship among voriconazole dosages, serum concentrations, adverse effects, and clinical outcomes are presented. METHODS: A retrospective chart review was conducted that included all patients who had at least one voriconazole concentration drawn between July 1, 2009, and August 15, 2014, at a single academic medical center. The primary outcome was the proportion of patients with initial voriconazole concentrations in the target range. RESULTS: Forty-seven of 88 patients (53%) had an initial voriconazole concentration within the target range, 27% (24 of 88) of patients had a concentration above the range, and 19% (17 of 88) had a concentration below the range. Sixty-seven percent of patients with above-target concentrations had adverse effects. Voriconazole was discontinued in 9% of patients, and dosages were reduced in 11% of patients because of adverse effects. Voriconazole for treatment versus prophylaxis was analyzed in a subgroup, as was obesity and nonobesity. Twenty-four percent of patients died during their hospital admission, and 14% were not discharged on voriconazole therapy. The within-target group had the highest proportion of patients discharged on voriconazole and the lowest proportion of deaths. CONCLUSION: A retrospective study in one institution revealed that the first measured voriconazole concentration was within the target range in 53% of patients and that dosage was modified in only 51% of patients whose concentration was outside of that range. The majority of patients with above-target concentrations had an adverse effect, and this result was particularly common in patients with a body mass index of ≥35 kg/m(2).


Asunto(s)
Centros Médicos Académicos/métodos , Antifúngicos/sangre , Monitoreo de Drogas/métodos , Voriconazol/sangre , Adulto , Anciano , Antifúngicos/efectos adversos , Encefalopatías/sangre , Encefalopatías/inducido químicamente , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Masculino , Persona de Mediana Edad , Obesidad/sangre , Estudios Retrospectivos , Voriconazol/efectos adversos
20.
J Microbiol Immunol Infect ; 48(5): 517-24, 2015 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-24863498

RESUMEN

BACKGROUND: Urinary tract infection (UTI) is one of the most prevalent admission diagnoses in hospital-based clinical practice. Despite its frequency, few data are available regarding its demographics and economic implications. PURPOSE: To describe the demography, epidemiology, and burden of care of patients admitted to hospital with UTI and compare these characteristics depending on admission status. METHODS: A retrospective cohort study using an administrative database of patients admitted to Hartford Hospital (September 2011-August 2012) with UTI. Patient demographics, hospital characteristics, and total costs of care were examined. RESULTS: A total of 2345 unique patients were included. The mean age of the patients was 78 years and 71% were female. Median length of stay and total cost were 5 days and $8326 (interquartile range $5388-$14,179), respectively. A total of 359 patients (16.4%) were readmitted within 30 days, of which 111 patients (5.1%) had UTI on readmission. Only 16.3% of readmitted patients were infected with the same causative pathogen. A significant increase in the incidence of Enterococcus faecalis (1.2% vs. 9.3%; p = 0.046) occurred upon readmission, whereas occurrence of Enterobacteriaceae infection decreased in the readmission group (50.0% vs. 25.6%; p = 0.006), including a lower proportion of Escherichia coli (32.5% vs. 11.6%; p < 0.001). A higher proportion of readmission pathogens were nonsusceptible, including significant changes to cefazolin (24.4% vs. 63.6%; p = 0.004) and cefepime (8.7% vs. 27.6; p = 0.05). CONCLUSION: UTI is highly prevalent and is associated with significant utilization of health-care resources among hospitalized patients. These findings, coupled with considerable rates of 30-day readmission, stress the importance of proper diagnosis and treatment.


Asunto(s)
Costos de la Atención en Salud , Readmisión del Paciente/economía , Infecciones Urinarias/economía , Infecciones Urinarias/epidemiología , Anciano , Anciano de 80 o más Años , Demografía , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Recurrencia , Estudios Retrospectivos
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