Risk factors and clinical impact of multidrug resistance in healthcare-associated bacteraemic urinary tract infections: a post-hoc analysis of a multicentre prospective cohort in Spain.

BACKGROUND: The global burden associated with antimicrobial resistance is of increasing concern. AIM: To evaluate risk factors associated with multidrug-resistant (MDR) infection and its clinical impact in a cohort of patients with healthcare-associated bacteraemic urinary tract infections (BUTIs). METHODS: This was a prospective, multicentre, post-hoc analysis of patients with healthcare-associated-BUTI (ITUBRAS-2). The primary outcome was MDR profile. Secondary outcomes were clinical response (at 48-72 h and at hospital discharge) and length of hospital stay from onset of BUTI. Logistic regression was used to evaluate variables associated with MDR profile and clinical response. Length of hospital stay was evaluated using multivariate median regression. FINDINGS: In all, 443 episodes were included, of which 271 (61.17%) were classified as expressing an MDR profile. In univariate analysis, MDR profile was associated with E. coli episodes (odds ratio (OR): 3.13; 95% confidence interval (CI): 2.11-4.69, P < 0.001) and the extensively drug-resistant (XDR) pattern with P. aeruginosa aetiology (7.84; 2.37-25.95; P = 0.001). MDR was independently associated with prior use of fluoroquinolones (adjusted OR: 2.43; 95% CI: 1.25-4.69), cephalosporins (2.14; 1.35-3.41), and imipenem or meropenem (2.08; 1.03-4.20) but not with prior ertapenem. In terms of outcomes, MDR profile was not associated with lower frequency of clinical cure, but was associated with longer hospital stay. CONCLUSION: MDR profile was independently associated with prior use of fluoroquinolones, cephalosporins, imipenem, and meropenem, but not with prior ertapenem. MDR-BUTI episodes were not associated with worse clinical cure, although they were independently associated with longer duration of hospital stay.

Ceftolozane-tazobactam: When, how and why using it?

Ceftolozane-tazobactam is currently the most active antipseudomonal agent, including multidrug-resistant extensively drug-resistant strains. Tazobactam provides additional activity against many extended-spectrum beta-lactamases Enterobacterales. Ceftolozane-tazobactam is formally approved for complicated urinary tract infection, complicated intra-abdominal infection, and hospital-acquired and ventilator-associated bacterial pneumonia. The clinical and microbiological success is over 70-80% in many series. However, resistant mutants to ceftolozane-tazobactam have been already described. Combination therapies with colistin or meropenem could be among the strategies to avoid the resistance emergence.

Clinical and economic burden of community-onset multidrug-resistant infections requiring hospitalization.

OBJECTIVES: To analyze the clinical and economic burden of community-acquired (CA) or community-onset healthcare-associated (COHCA) multidrug-resistant (MDR) infections requiring hospitalization. METHODS: Case-control study. Adults admitted with CA or COHCA MDR infections were considered cases, while those admitted in the same period with non-MDR infections were controls. The matching criteria were source of infection and/or microorganism. Primary outcome was 30-day clinical failure. Secondary outcomes were 90-day and 1-year mortality, hospitalization costs and resource consumption. RESULTS: 194 patients (97 cases and 97 controls) were included. Multivariate analysis identified age (odds ratio [OR], 1.07, 95% confidence interval [CI], 1.01-1.14) and SOFA score (OR, 1.45, CI95%, 1.15-1.84) as independent predictors of 30-day clinical failure. Age (hazard ratio [HR] 1.09, 95%CI, 1.03-1.16) was the only factor associated with 90-day mortality, whereas age (HR 1.06, 95%CI, 1.03-1.09) and Charlson Index (HR 1.2, 95%CI, 1.07-1.34) were associated with 1-year mortality. MDR group showed longer hospitalization (p<0.001) and MDR hospitalization costs almost doubled those in the non-MDR group. MDR infections were associated with higher antimicrobial costs. CONCLUSIONS: Worse economic outcomes were identified with community-onset MDR infections. MDR was associated with worse clinical outcomes but mainly due to higher comorbidity of patients in MDR group, rather than multidrug resistance.

Oral and intravenous fosfomycin in complicated urinary tract infections.

Urinary tract infections are one of the most common health problems and entail a high consumption of health system resources. Due to the increase in global antibiotic resistances in recent years, it is increasingly common to find uropathogens with multiple resistance mechanisms, including quinolone-resistant bacteria, broad-spectrum ß-lactamase producers and carbapenemase producers. In this scenario, the role of fosfomycin has gained considerable importance, given its spectrum of activity against multidrug resistant microorganisms (Gram-positive and Gram-negative), becoming an attractive alternative therapy. Regarding the use of fosfomycin in complicated urinary tract infections, there is increasing clinical experience with patients with infections caused by multidrug resistant bacteria, those with recurrent urinary tract infection and special populations such as those with kidney transplants. Randomized comparative studies and series are underway, which will provide greater evidence. Nevertheless, more studies are needed to confirm the enormous potential of fosfomycin in complicated urinary tract infection in the era of multiresistance.

High-dose benznidazole in a 62-year-old Bolivian kidney transplant recipient with Chagas central nervous system involvement.

There is little published data on benznidazole dosing, or levels in cerebrospinal fluid. In this report, we describe the clinical course of an immunosuppressed patient with Chagas central nervous system involvement. He was treated successfully with larger benznidazole doses than are recommended, in order to reach therapeutically effective concentrations in the brain.

Impact of universal access to hepatitis C therapy on HIV-infected patients: implementation of the Spanish national hepatitis C strategy.

In April 2015, the Spanish National Health System (SNHS) developed a national strategic plan for the diagnosis, treatment, and management of hepatitis C virus (HCV). Our aim was to analyze the impact of this on human immunodeficiency virus (HIV)-infected patients included in the HERACLES cohort during the first 6 months of its implementation. The HERACLES cohort (NCT02511496) was set up in March 2015 to evaluate the status and follow-up of chronic HCV infection in patients co-infected with HIV in the south of Spain. In September 2015, the data were analyzed to identify clinical events (death, liver decompensation, and liver fibrosis progression) and rate of treatment implementation in this population. The study population comprised a total of 3474 HIV/HCV co-infected patients. The distribution according to liver fibrosis stage was: 1152 F0-F1 (33.2 %); 513 F2 (14.4 %); 641 F3 (18.2 %); 761 F4 (21.9 %); and 407 whose liver fibrosis was not measured (12.3 %). During follow-up, 248 patients progressed by at least one fibrosis stage [7.1 %; 95 % confidence interval (CI): 6.3-8 %]. Among cirrhotic patients, 52 (6.8 %; 95 % CI: 5.2-8.9 %) developed hepatic decompensation. In the overall population, 50 patients died (1.4 %; 95 % CI: 1.1-1.9 %). Eight hundred and nineteen patients (23.56 %) initiated interferon (IFN)-free treatment during follow-up, of which 47.8 % were cirrhotic. In our study, during 6 months of follow-up, 23.56 % of HIV/HCV co-infected patients included in our cohort received HCV treatment. However, we observed a high incidence of negative short-term outcomes in our population.