Non-intravenous carbapenem-sparing antibiotics for definitive treatment of bacteraemia due to Enterobacteriaceae producing extended-spectrum ß-lactamase (ESBL) or AmpC ß-lactamase: A propensity score study.

Carbapenems are considered the treatment of choice for extended-spectrum ß-lactamase (ESBL)- or AmpC ß-lactamase-producing Enterobacteriaceae bacteraemia. Data on the effectiveness of non-intravenous carbapenem-sparing antibiotic options are limited. This study compared the 30-day mortality and clinical failure associated with the use of carbapenems versus alternative non-intravenous antibiotics for the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia. This 12-year retrospective study (2004-2015) included all patients with bacteraemia due to ESBL/AmpC-producing Enterobacteriaceae at a Spanish hospital. Given the lack of randomisation of initial therapies, a propensity score for receiving carbapenems was calculated. There were 1115 patients with a first episode of bacteraemia due to Escherichia coli or Klebsiella pneumoniae, of which 123 (11.0%) were ESBL/AmpC-positive. There were 101 eligible patients: 59 in the carbapenem group and 42 in the alternative treatment group (trimethoprim/sulfamethoxazole 59.5%, quinolones 21.4%). The most frequent sources of infection were urinary (63%) and biliary (15%). Compared with the carbapenem group, patients treated with an alternative regimen had a shorter hospital stay [median (IQR) 7 (5-10) days vs. 12 (9-18) days; P < 0.001]. Use of an alternative non-intravenous therapy did not increase mortality (OR = 0.27, 95% CI 0.05-1.61; P = 0.15). After controlling for confounding factors with the propensity score, the adjusted OR of carbapenem treatment was 4.95 (95% CI 0.94-26.01; P = 0.059). Alternative non-intravenous carbapenem-sparing antibiotics could have a role in the definitive treatment of ESBL/AmpC-positive Enterobacteriaceae bacteraemia, allowing a reduction in carbapenem use. Use of trimethoprim/sulfamethoxazole in this series showed favourable results.

Impact on mortality of adherence to evidence-based interventions in patients with catheter-related bloodstream infection due to methicillin-sensitive Staphylococcus aureus.

BACKGROUND: Recent studies have demonstrated improved survival when the management of Staphylococcus aureus bloodstream infection (BSI) is compliant with evidence-based therapeutic interventions. Whether this effect extends to low-risk sources, such as catheter-related BSI, remains unclear. METHODS: We retrospectively included 225 episodes of methicillin-sensitive S. aureus catheter-related BSI diagnosed in our centre during two non-consecutive periods: 2002-2004 (first period (101 episodes)) and 2009-2013 (second period (124 episodes)). We evaluated the adherence (percentage of compliance = (no. of interventions performed/no. of interventions recommended) × 100) to the following bundle: early catheter removal (≤72 hours), early initiation of appropriate antibiotic therapy, adequate sampling of follow-up blood cultures, transthoracic echocardiography (TTE) during hospitalization and adequate duration of therapy. RESULTS: Patients in the second period had a higher burden of comorbidities and more severe underlying conditions. All-cause 30-day mortality was 9.3%, with a significant difference between the first and second periods (13.9% versus 5.6%; p value = .035). Bundle adherence was significantly higher in the second period, particularly for follow-up blood cultures (26.7% versus 48.4%; p value = .001), performance of TTE (45.5% versus 84.7%; p value < .001) and appropriate duration of therapy (34.7% versus 50.0%; p value = .022). Bundle adherence ≥ 55% was associated with lower 30-day mortality (hazard ratio: 0.31; 95% confidence interval: 0.13-0.76). This effect remained significant across propensity score-based models adjusted for septic shock, study period and underlying conditions. CONCLUSIONS: There was a survival benefit in adhering to a bundle of evidence-based interventions in the specific setting of catheter-related BSI due to methicillin-sensitive S. aureus.

Vitamin D deficiency and infection risk in kidney transplant recipients: A single-center cohort study.

BACKGROUND: Recent studies have reported an increased susceptibility to infection among vitamin D-deficient kidney transplant (KT) recipients, although methodological concerns remain. METHODS: Serum 25-hydroxyvitamin D (25(OH)D) levels were measured in 246 KT recipients at post-transplant months 1, 3, 6 and 12. Vitamin D status was analysed in terms of deficiency (Endocrine Society [<20 ng/mL] and Institute of Medicine [IoM, <12 ng/mL] criteria) and as a continuous variable. Cox models for overall, bacterial and opportunistic infection were adjusted for nutritional status and immunosuppression-related covariates. RESULTS: Median serum 25(OH)D increased from month 1 (10.5 ng/mL) to month 6 (16.3 ng/mL; P-value = 0.001). Prevalence of vitamin D deficiency at month 1 ranged from 87.0% to 61.0% (depending on the diagnostic criteria) and significantly decreased over the next months. After adjustment for age and nutritional status, vitamin D deficiency (serum 25(OH)D < 12 ng/mL) at month 1 was an independent risk factor for overall (hazard ratio [HR]: 1.70; 95% confidence interval [CI]: 1.08-2.69; P-value = 0.023) and opportunistic infection (HR: 4.05; 95% CI: 1.57-10.46; P-value = 0.004), but not for bacterial infection. A protective effect for overall (adjusted HR: 0.76; 95% CI: 0.63-0.93; P-value = 0.007) and opportunistic infection (adjusted HR: 0.62; 95% CI: 0.45-0.86; P-value = 0.004) was observed when 25(OH)D levels were analyzed per one-quartile increases. CONCLUSIONS: Vitamin D status influences the risk of infection among KT recipients, with the association being particularly evident for opportunistic events and mainly restricted to the early post-transplant period.

Risk factors for bacteremia in urinary tract infections attended in the emergency department.

Urinary tract infections (UTI) are common in emergency departments (ED), and at least 15% of them are bacteremic. However, there are few data on how to predict which patients are at high risk of developing bacteremic UTI (b-UTI). We performed a retrospective observational cohort study including patients diagnosed with UTI who were admitted to the ED of a tertiary-care hospital in Spain. We included only those patients in whom blood cultures were performed. A nomogram for b-UTI was developed as visualizations of a logistic regression model. Two hundred and thirteen patients with UTI were finally included, 108 of them developed b-UTI (50.7%). The mean age was 60.5 ± 21.4 years. A previous urologic disease was present in 45.5%, 12 out of 213 patients (5.6%) had a urologic tumor (10.2% in b-UTI group vs. 1% in non b-UTI, p = 0.003), and 4.2% were kidney transplant recipients. In a multivariate analysis, variables associated with b-UTI were: solid organ malignancy (OR 3.19; CI 95% 1.01-10.03, p = 0.04), elevated neutrophil count (more than 80% of neutrophils) (OR 5.84; CI 95% 2.13-15.99, p = 0.0006), elevated C reactive protein (OR 1.046; CI 95% 1.006-1.087, p = 0.022), and pyuria (presence of ≥50 white cells per high-power field of urine) (OR 4.43; CI 95% 1.94-10.11, p = 0.0004). The presence of solid tumor, elevated neutrophil count, elevated C reactive protein, and pyuria are independent risk factors that could be useful in anticipating the development of bacteremia in patients with UTI seen in the ED.

High MICs for Vancomycin and Daptomycin and Complicated Catheter-Related Bloodstream Infections with Methicillin-Sensitive Staphylococcus aureus.

We investigated the prognostic role of high MICs for antistaphylococcal agents in patients with methicillin-sensitive Staphylococcus aureus catheter-related bloodstream infection (MSSA CRBSI). We prospectively reviewed 83 episodes from 5 centers in Spain during April 2011-June 2014 that had optimized clinical management and analyzed the relationship between E-test MICs for vancomycin, daptomycin, oxacillin, and linezolid and development of complicated bacteremia by using multivariate analysis. Complicated MSSA CRBSI occurred in 26 (31.3%) patients; MICs for vancomycin and daptomycin were higher in these patients (optimal cutoff values for predictive accuracy = 1.5 µg/mL and 0.5 µg/mL). High MICs for vancomycin (hazard ratio 2.4, 95% CI 1.2-5.5) and daptomycin (hazard ratio 2.4, 95% CI 1.1-5.9) were independent risk factors for development of complicated MSSA CRBSI. Our data suggest that patients with MSSA CRBSI caused by strains that have high MICs for vancomycin or daptomycin are at increased risk for complications.

[Cloxacillin-susceptible Staphylococcus aureus with high MIC to glycopeptides. Ever we use cloxacillin?]. / Staphylococcus aureus sensible a cloxacilina con CMI elevada a glucopéptidos. ¿Ponemos siempre cloxacilina?

Staphylococcus aureus infections are yet an important cause of morbidity and mortality despite of numerous effective anti-staphylococcal antibiotics available. There has been an increasing incidence of methicillin-resistant strains which might have led to a wider use of vancomycin. This seems to ride alongside a covert progressive increase of S. aureus vancomycin minimum inhibitory concentration. In this way, the emergence of vancomycin-intermediate S. aureus (VISA) strains and heteroresistant-VISA has raised concern for the scarcity of alternative treatment options. Equally alarming, though fortunately less frequent, is the emergence of vancomycin-resistant S. aureus. Ultimately, various debate issues have arisen regarding the emergence of S. aureus strains with decreased vancomycin susceptibility, within the range still considered sensitive. These strains have shown a different clinical behaviour regardless of vancomycin use, both in methicillin resistant and sensitive S. aureus. The emergence of increasing vancomycin-resistance in S. aureus isolates, has stirred up the basis of therapeutic approach in staphylococcal infections. There is yet much to explore to better define the impact of higher vancomycin minimum inhibitory concentration in staphylococcal infections.

Staphylococcus aureus sensible a cloxacilina con CMI elevada a glucopéptidos. ¿Ponemos siempre cloxacilina? / Cloxacillin-susceptible Staphylococcus aureus with high MIC to glycopeptides. Ever we use cloxacillin?

Las infecciones por Staphylococcus aureus constituyen una causa de morbi-mortalidad importante tanto en el medio hospitalario como en la comunidad, a pesar de la gran cantidad de antibióticos antiestafilocócicos disponibles. El aumento creciente en los últimos años de la incidencia de S. aureus resistente a meticilina ha conducido a un uso más extenso de la vancomicina, y este hecho ha ido en paralelo de un incremento progresivo de la concentración mínima inhibitoria a vancomicina. La aparición de cepas con sensibilidad intermedia (VISA y hVISA) o resistentes a vancomicina (VRSA) suponen un reto en cuanto a la escasez de opciones terapéuticas disponibles. En los últimos años se ha observado la aparición infecciones estafilocócicas por cepas con una concentración mínima inhibitoria elevada a vancomicina, aún dentro de los límites de sensibilidad, que se han visto asociadas a un peor pronóstico clínico tanto en cepas sensibles como resistentes a meticilina. Hacen falta más estudios para determinar el impacto real de la disminución de la sensibilidad a vancomicina en infecciones por S. aureus en cuanto al pronóstico clínico y al mejor abordaje terapéutico (AU)

Staphylococcus aureus infections are yet an important cause of morbidity and mortality despite of numerous effective anti-staphylococcal antibiotics available. There has been an increasing incidence of methicillin-resistant strains which might have led to a wider use of vancomycin. This seems to ride alongside a covert progressive increase of s. aureus vancomycin minimum inhibitory concentration. In this way, the emergence of vancomycin-intermediate S. aureus (VISA) strains and heteroresistant-VISA has raised concern for the scarcity of alternative treatment options. Equally alarming, though fortunately less frequent, is the emergence of vancomycin-resistant S. aureus. Ultimately, various debate issues have arisen regarding the emergence of S. aureus strains with decreased vancomycin susceptibility, within the range still considered sensitive. These strains have shown a different clinical behaviour regardless of vancomycin use, both in methicillin resistant and sensitive S. aureus. The emergence of increasing vancomycin-resistance in S. aureus isolates, has stirred up the basis of therapeutic approach in staphylococcal infections. There is yet much to explore to better define the impact of higher vancomycin minimum inhibitory concentration in staphylococcal infections (AU)

Implementation challenges of a TB programme in rural northern mozambique: evaluation of 2012-2013 outcomes.

BACKGROUND: We aimed to identify challenges and to propose solutions for the implementation of tuberculosis (TB) programmes in rural Sub-Saharan Africa (SSA) by evaluating the outcomes of the TB programme in the Ancuabe district in rural Northern Mozambique. METHODS: Retrospective descriptive study of the patients included in the TB programme in 2012-2013. Follow-up was continued till June 2014. RESULTS: Three hundred nineteen patients were registered, 62.1% male, mean age 36.3 (SD 14.4), estimated case detection rate (eCDR) of 24.24%. Two hundred seventy-two were new cases, 21 transferred-in, 11 back after lost to follow-up (LTFU), 10 relapsing TB, 5 previous treatment failures. 94.4% were tested for Human immunodeficiency virus (HIV), 41.9% HIV-positive. 87.5% of the new cases were pulmonary TB (PTB), 43.4% were HIV co-infected. Initial sputum results were available in 207 cases, with 145 smear-positive (SP) cases. Outcomes of new cases: 122 (44.9%) LTFU, 55 (20.2%) cured, 43 (15.8%) treatment completed (98-36%-treatment success), 31 (11.4%) died, 19 (7%) transferred out and 2 (0.7%) failures. CONCLUSIONS: A low eCDR and high proportion of LTFU demonstrate that few patients were identified and had a low probability of complete treatment, suggesting a fragile health system. This raises the hypothesis that, probably, to improve TB health care in rural SSA, interventions should aim at improving health systems. Special attention should be given to social protection and compensation of the financial burden associated with TB.