RESUMEN
BACKGROUND: Infections caused by carbapenemase-producing Enterobacterales (CPE) are not well represented in pivotal trials with ceftazidime/avibactam. The best strategy for the treatment of these infections is unknown. METHODS: We conducted a multicentre retrospective observational study of patients who received ≥48â h of ceftazidime/avibactam or best available therapy (BAT) for documented CPE infections. The primary outcome was 30â day crude mortality. Secondary outcomes were 21â day clinical response and microbiological response. A multivariate logistic regression model was used to identify factors predictive of 30â day crude mortality. A propensity score to receive treatment with ceftazidime/avibactam was used as a covariate in the analysis. RESULTS: The cohort included 339 patients with CPE infections. Ceftazidime/avibactam treatment was used in 189 (55.8%) patients and 150 (44.2%) received BAT at a median of 2â days after diagnosis of infection. In multivariate analysis, ceftazidime/avibactam treatment was associated with survival (OR 0.41, 95% CI 0.20-0.80; P = 0.01), whereas INCREMENT-CPE scores of >7 points (OR 2.57, 95% CI 1.18-1.5.58; P = 0.01) and SOFA score (OR 1.20, 95% CI 1.08-1.34; P = 0.001) were associated with higher mortality. In patients with INCREMENT-CPE scores of >7 points, ceftazidime/avibactam treatment was associated with lower mortality compared with BAT (16/73, 21.9% versus 23/49, 46.9%; P = 0.004). Ceftazidime/avibactam was also an independent factor of 21â day clinical response (OR 2.43, 95% CI 1.16-5.12; P = 0.02) and microbiological eradication (OR 0.40, 95% CI 0.18-0.85; P = 0.02). CONCLUSIONS: Ceftazidime/avibactam is an effective alternative for the treatment of CPE infections, especially in patients with INCREMENT-CPE scores of >7 points. A randomized controlled trial should confirm these findings.
Asunto(s)
Antibacterianos , Ceftazidima , Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/uso terapéutico , Proteínas Bacterianas , Ceftazidima/uso terapéutico , Combinación de Medicamentos , Humanos , Pruebas de Sensibilidad Microbiana , beta-LactamasasRESUMEN
BACKGROUND: The optimal antibiotic regimen for Pseudomonas aeruginosa bacteremia is controversial. Although ß-lactam monotherapy is common, data to guide the choice between antibiotics are scarce. We aimed to compare ceftazidime, carbapenems, and piperacillin-tazobactam as definitive monotherapy. METHODS: A multinational retrospective study (9 countries, 25 centers) including 767 hospitalized patients with P. aeruginosa bacteremia treated with ß-lactam monotherapy during 2009-2015. The primary outcome was 30-day all-cause mortality. Univariate and multivariate, including propensity-adjusted, analyses were conducted introducing monotherapy type as an independent variable. RESULTS: Thirty-day mortality was 37/213 (17.4%), 42/210 (20%), and 55/344 (16%) in the ceftazidime, carbapenem, and piperacillin-tazobactam groups, respectively. Type of monotherapy was not significantly associated with mortality in either univariate, multivariate, or propensity-adjusted analyses (odds ratio [OR], 1.14; 95% confidence interval [CI], 0.52-2.46, for ceftazidime; OR, 1.3; 95% CI, 0.67-2.51, for piperacillin-tazobactam, with carbapenems as reference in propensity adjusted multivariate analysis; 542 patients). No significant difference between antibiotics was demonstrated for clinical failure, microbiological failure, or adverse events. Isolation of P. aeruginosa with new resistance to antipseudomonal drugs was significantly more frequent with carbapenems (36/206 [17.5%]) versus ceftazidime (25/201 [12.4%]) and piperacillin-tazobactam (28/332 [8.4%] (P = .007). CONCLUSIONS: No significant difference in mortality, clinical, and microbiological outcomes or adverse events was demonstrated between ceftazidime, carbapenems, and piperacillin-tazobactam as definitive treatment of P. aeruginosa bacteremia. Higher rates of resistant P. aeruginosa after patients were treated with carbapenems, along with the general preference for carbapenem-sparing regimens, suggests using ceftazidime or piperacillin-tazobactam for treating susceptible infection.
Asunto(s)
Infecciones por Pseudomonas , Pseudomonas aeruginosa , Antibacterianos/uso terapéutico , Carbapenémicos/uso terapéutico , Ceftazidima/uso terapéutico , Humanos , Pruebas de Sensibilidad Microbiana , Ácido Penicilánico/uso terapéutico , Piperacilina/uso terapéutico , Infecciones por Pseudomonas/tratamiento farmacológico , Estudios RetrospectivosRESUMEN
OBJECTIVES: To describe the case of a patient with infection due to a KPC-producing Klebsiella pneumoniae (K. pneumoniae) isolate developing ceftazidime-avibactam resistance with restored carbapenem susceptibility during ceftazidime-avibactam therapy. To review the clinical/microbiological cure and survival rates using carbapenems in other similar case reports and case series. PATIENTS AND METHODS: A patient with an intra-abdominal infection due to K. pneumoniae producing the KPC-48 variant (L169P-A172T) (resistant to ceftazidime/avibactam and susceptible to carbapenems) who was treated with imipenem-cilastatin in combination with tigecycline and gentamicin. The literature was reviewed in order to summarise the in vivo (clinical/microbiological cure and survival rate) use of carbapenems in this emerging scenario. RESULTS: The patient was successfully treated with the indicated regimen. In other reported cases (mostly with pneumonia) all-cause mortality was 50% and clinical cure was 62.5%. Meropenem-vaborbactam has been successful used in an additional case. CONCLUSIONS: A carbapenem-based regimen of combination therapy seems to be an option for treating patients infected with K. pneumoniae resistant to ceftazidime/avibactam and susceptible to carbapenems, at least when the risk of mortality is low.
Asunto(s)
Ceftazidima , Neumonía , Antibacterianos/uso terapéutico , Compuestos de Azabiciclo , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Ceftazidima/uso terapéutico , Combinación de Medicamentos , Humanos , Klebsiella pneumoniae , Pruebas de Sensibilidad Microbiana , Neumonía/tratamiento farmacológicoRESUMEN
INTRODUCTION: There is scarce information on the prognosis of urinary tract infections (UTI) caused by KPC carbapenemase-producing Klebsiella pneumoniae (KPC-Kp). OBJETIVE: To investigate the association between KPC-Kp aetiology and clinical failure and all cause mortality and to explore the impact of inappropriate empirical treatment. MATERIAL AND METHODS: This is a retrospective observational study of hospitalized patients with UTI due to K. pneumoniae. We explored clinical failure at day 21 and 30-day all-cause mortality using different models of adjusted analysis. RESULTS: We analyzed 142 episodes of UTI; 46 episodes (32.4%) were due to KPC-Kp and 96 episodes (67.6%) were due to non-KPC-Kp strains (62 wild type and 34 EBSL producer). Clinical failure was more frequent in the KPC-Kp group (41.3% vs. 15.6%, pâ¯=â¯0.001). KPC-Kp aetiology and inappropriate empirical therapy were associated in the non-adjusted analysis with clinical failure. When analysed in separate adjusted models, both were found to be associated; inappropriate empirical treatment (OR 2.51; 95% CI, 1.03-6.12; pâ¯=â¯0.04) and KPC-Kp (OR 2.73; 95% CI, 1.03-7.22; pâ¯=â¯0.04) were associated with increased risk of failure. All-cause 30-day mortality was higher in patients with KPC-Kp UTI (39.1% vs. 15.6%, pâ¯=â¯0.002). Bacteraemia was more frequent in patients with KPC-Kp etiology (23.9% vs. 10.4%; pâ¯=â¯0.034). In both cases, the association was not confirmed in the adjusted analysis. CONCLUSION: KPC-Kp UTI is associated with higher clinical failure and may be due to an increase in inappropriate empirical treatment.
Asunto(s)
Proteínas Bacterianas/genética , Infecciones por Klebsiella/microbiología , Infecciones por Klebsiella/mortalidad , Klebsiella pneumoniae/genética , Infecciones Urinarias/microbiología , Infecciones Urinarias/mortalidad , beta-Lactamasas/genética , Anciano , Anciano de 80 o más Años , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Proteínas Bacterianas/biosíntesis , Causas de Muerte , Femenino , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae/efectos de los fármacos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Vigilancia de la Población , Pronóstico , Curva ROC , Estudios Retrospectivos , Infecciones Urinarias/tratamiento farmacológico , beta-Lactamasas/biosíntesisRESUMEN
Combination therapy including colistin and a carbapenem has been found to be associated with lower mortality in the treatment of bloodstream infections (BSI) due to KPC-producing Klebsiella pneumoniae when the isolates show a meropenem or imipenem MIC of <16 mg/liter. However, the optimal treatment of BSI caused by colistin- and high-level carbapenem-resistant KPC-producing K. pneumoniae is unknown. A prospective cohort study including episodes of bacteremia caused by colistin-resistant and high-level meropenem-resistant (MIC ≥ 64 mg/liter) KPC-producing K. pneumoniae diagnosed from July 2012 to February 2016 was performed. The impact of combination therapy on crude 30-day mortality was analyzed by Cox regression using a propensity score as a covariate to control for indication bias and in an inverse probability of treatment weighting (IPTW) cohort. The study sample comprised 104 patients, of which 32 (30.8%) received targeted monotherapy and 72 (69.2%) received targeted combination therapy; none of them received either colistin or a carbapenem. The 30-day crude mortality rate was 30.8% (43.8% in patients treated with monotherapy and 25% in patients receiving combination therapy). In the Cox regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (hazard ratio [HR], 6.03; 95% confidence interval [CI], 1.65 to 21.9; P = 0.006) and admission to the critical care unit (HR, 2.87; 95% CI, 0.99 to 8.27; P = 0.05). Targeted combination therapy was associated with lower mortality only in patients with septic shock (HR, 0.14; 95% CI, 0.03 to 0.67; P = 0.01). These results were confirmed in the Cox regression analysis of the IPTW cohort. Combination therapy is associated with reduced mortality in patients with bacteremia due to colistin-resistant KPC-producing K. pneumoniae with high-level carbapenem resistance in patients with septic shock.