Impact of De-escalation on Prognosis of Patients With Bacteremia due to Enterobacteriaceae: A Post Hoc Analysis From a Multicenter Prospective Cohort.

BACKGROUND: More data are needed about the safety of antibiotic de-escalation in specific clinical situations as a strategy to reduce exposure to broad-spectrum antibiotics. The aims of this study were to investigate predictors of de-escalation and its impact on the outcome of patients with bloodstream infection due to Enterobacteriaceae (BSI-E). METHODS: A post hoc analysis was performed on a prospective, multicenter cohort of patients with BSI-E initially treated with ertapenem or antipseudomonal ß-lactams. Logistic regression was used to analyze factors associated with early de-escalation (EDE) and Cox regression for the impact of EDE and late de-escalation (LDE) on 30-day all-cause mortality. A propensity score (PS) for EDE vs no de-escalation (NDE) was calculated. Failure at end of treatment and length of hospital stay were also analyzed. RESULTS: Overall, 516 patients were included. EDE was performed in 241 patients (46%), LDE in 95 (18%), and NDE in 180 (35%). Variables independently associated with a lower probability of EDE were multidrug-resistant isolates (odds ratio [OR], 0.50 [95% confidence interval {CI}, .30-.83]) and nosocomial infection empirically treated with imipenem or meropenem (OR, 0.35 [95% CI, .14-.87]). After controlling for confounders, EDE was not associated with increased risk of mortality; hazard ratios (HR) (95% CIs) were as follows: general model, 0.58 (.25-1.31); model with PS, 0.69 (.29-1.65); and PS-based matched pairs, 0.98 (.76-1.26). LDE was not associated with mortality. De-escalation was not associated with clinical failure or length of hospital stay. CONCLUSIONS: De-escalation in patients with monomicrobial bacteremia due to Enterobacteriaceae was not associated with a detrimental impact on clinical outcome.

Characteristics and outcome of spontaneous bacterial meningitis in patients with cancer compared to patients without cancer.

In cancer patients, who are frequently immunocompromised, bacterial meningitis (BM) can be a severe complication, with a different presentation, etiology, and course, compared to patients without cancer. Our objective is to compare the characteristics and outcomes of BM in patients with and without cancer. A single-center, prospective observational cohort study, conducted between 1982 and 2012, in a tertiary university hospital in Barcelona (Spain). The main outcome measure is in-hospital mortality. We evaluated 659 episodes of BM; 97 (15%) had active cancer. Patients with malignancies were older (median 63 (interquartile range [IQR] 24) vs 52 [IQR 42] years, P < .001) and more often had a Charlson comorbidity score of ≥3 (51% vs 11%, P < .001). The classic meningitis triad (35% vs 50%, P = .05), fever (91% vs 96%, P = .03), neck stiffness (58% vs 78%, P < .001), headache (63% vs 77%) P = .003), and rash (7% vs 30%, P < .001) were less frequent. There was a longer interval between admission and antibiotic therapy (median 5 [IQR 14] vs 3 [IQR 6] hours, P < .001). Listeria meningitis was the commonest cause of BM (29%) and was more frequent in cancer than noncancer (8%, P < .001) patients, whereas meningococcal meningitis was much less frequent (4% vs 36%, P < .001). Overall mortality was higher in patients with cancer (31% vs 16%, P < .001), although cancer was not associated with an unfavorable outcome in the multivariate analysis (odds ratio 1.825, P = .07). Patients with meningitis and cancer are older and have more subtle clinical manifestations than patients without cancer. Listeria monocytogenes is the predominant pathogen and mortality is higher in cancer patients.

MIC of amoxicillin/clavulanate according to CLSI and EUCAST: discrepancies and clinical impact in patients with bloodstream infections due to Enterobacteriaceae.

Objectives: To compare results of amoxicillin/clavulanate susceptibility testing using CLSI and EUCAST methodologies and to evaluate their impact on outcome in patients with bacteraemia caused by Enterobacteriaceae. Patients and methods: A prospective observational cohort study was conducted in 13 Spanish hospitals. Patients with bacteraemia due to Enterobacteriaceae who received empirical intravenous amoxicillin/clavulanate treatment for at least 48 h were included. MICs were determined following CLSI and EUCAST recommendations. Outcome variables were: failure at the end of treatment with amoxicillin/clavulanate (FEAMC); failure at day 21; and 30 day mortality. Classification and regression tree (CART) analysis and logistic regression were performed. Results: Overall, 264 episodes were included; the urinary tract was the most common source (64.7%) and Escherichia coli the most frequent pathogen (76.5%). Fifty-two isolates (19.7%) showed resistance according to CLSI and 141 (53.4%) according to EUCAST. The kappa index for the concordance between the results of both committees was only 0.24. EUCAST-derived, but not CLSI-derived, MICs were associated with failure when considered as continuous variables. CART analysis suggested a 'resistance' breakpoint of > 8/4 mg/L for CLSI-derived MICs; it predicted FEAMC in adjusted analysis (OR = 1.96; 95% CI: 0.98-3.90). Isolates with EUCAST-derived MICs >16/2 mg/L independently predicted FEAMC (OR = 2.10; 95% CI: 1.05-4.21) and failure at day 21 (OR= 3.01; 95% CI: 0.93-9.67). MICs >32/2 mg/L were only predictive of failure among patients with bacteraemia from urinary or biliary tract sources. Conclusions: CLSI and EUCAST methodologies showed low agreement for determining the MIC of amoxicillin/clavulanate. EUCAST-derived MICs seemed more predictive of failure than CLSI-derived ones. EUCAST-derived MICs >16/2 mg/L were independently associated with therapeutic failure.

Endocarditis in patients with ascending aortic prosthetic graft: a case series from a national multicentre registry.

OBJECTIVES: Endocarditis in patients with ascending aortic prosthetic graft (AAPG) is a life-threatening complication. The purpose of this study was to examine the clinical presentation and prognosis of patients with AAPG endocarditis included in a large prospective infectious endocarditis multicentre study. METHODS: From January 2008 to April 2015, 3200 consecutive patients with infectious endocarditis according to the modified Duke criteria, were prospectively included in the 'Spanish Collaboration on Endocarditis Registry (GAMES)' registry. Twenty-seven definite episodes of endocarditis (0.8%) occurred in patients with AAPG. RESULTS: During the study period, 27 cases of endocarditis were detected in patients with AAPG. The median age of patients was 61 years [interquartile range (IQR) 51-68 years] and 23 (85.2%) patients were male. The median time from AAPG surgery to the episode of AAPG infection was 24 months (IQR 6-108 months). The most frequently isolated micro-organisms were coagulase-negative staphylococci and S. aureus (11 patients, 40.7%). Four patients (14.8%) underwent medical treatment, whereas surgery was performed in 21 (77.7%). Two patients (7.4%) died before surgery could be performed. The median hospital stay prior to surgery was 7 days (IQR 4-21 days). Surgery consisted of replacing previous grafts with a composite aortic graft (10 cases) or aortic homograft (2 patients), and removal of a large vegetation attached to the valve of a composite tube (1 case). Nine patients had an infected aortic valve prosthesis without evidence of involvement of the AAPG. Isolated redo-aortic valve replacement was performed in 8 (88.9%) of these patients. Reinfection occurring during 1 year of follow-up was not detected in any patient. Two patients (7.4%) died while awaiting surgery and 6 did so after surgery (22.2%). A New York Heart Association (NYHA) Class IV was associated with mortality in patients undergoing surgery (P < 0.019). CONCLUSIONS: Most cases of endocarditis in patients with AAPG occur late after initial surgery. Mortality rate of patients with AAPG endocarditis who undergo surgery is acceptable. NYHA Class IV before surgery is associated with an increased postoperative mortality.

Impact of the MIC of piperacillin/tazobactam on the outcome for patients with bacteraemia due to Enterobacteriaceae: the Bacteraemia-MIC project.

OBJECTIVE: Our objective was to evaluate the impact of low versus borderline MIC of piperacillin/tazobactam on the clinical outcomes of patients with bacteraemia caused by Enterobacteriaceae who were treated with that antimicrobial. PATIENTS AND METHODS: A prospective observational multicentre cohort study was conducted in 13 Spanish university hospitals. Patients >17 years old with bacteraemia due to Enterobacteriaceae who received empirical piperacillin/tazobactam treatment for at least 48 h were included. Outcome variables were clinical response at day 21, clinical response at end of treatment with piperacillin/tazobactam and all-cause 30 day mortality. Univariate and multivariate logistic regression analyses were performed. RESULTS: Overall, 275 patients were included in the analysis; 248 (90.2%) in the low MIC group (≤ 4 mg/L) and 27 (9.8%) in the borderline MIC group (8-16 mg/L). The biliary tract was the most common source of infection (48.4%) and Escherichia coli was the most frequent pathogen (63.3%). Crude 30 day mortality rates were 10.5% and 11.1% for the low MIC group and the borderline MIC group, respectively (relative risk = 1.06, 95% CI = 0.34-3.27, P = 1). Multivariate analysis of failure at day 21 and at end of treatment with piperacillin/tazobactam and 30 day mortality showed no trend towards increased clinical failure or mortality with borderline MICs (OR = 0.96, 95% CI = 0.18-4.88, P = 0.96; OR = 0.47, 95% CI = 0.10-2.26, P = 0.35; OR = 1.48, 95% CI = 0.33-6.68, P = 0.6). CONCLUSIONS: We did not find that higher piperacillin/tazobactam MIC within the susceptible or intermediate susceptibility range had a significant influence on the outcome for patients with bacteraemia due to Enterobacteriaceae.

Spontaneous gram-negative bacillary meningitis in adult patients: characteristics and outcome.

BACKGROUND: Spontaneous meningitis caused by gram-negative bacilli in adult patients is uncommon and poorly characterized. Our objective is to describe and compare the characteristics and the outcome of adult patients with spontaneous gram-negative bacilli meningitis (GNBM) and spontaneous meningitis due to other pathogens. METHODS: Prospective single hospital-based observational cohort study conducted between 1982 and 2006 in a university tertiary hospital in Barcelona (Spain). The Main Outcome Measure: In-hospital mortality. RESULTS: Gram-negative bacilli meningitis was diagnosed in 40 (7%) of 544 episodes of spontaneous acute bacterial meningitis. The most common pathogens were Escherichia coli and Pseudomonas species. On admission, characteristics associated with spontaneous gram-negative bacilli meningitis by multivariate modeling were advanced age, history of cancer, nosocomial acquisition of infection, urinary tract infection as distant focus of infection, absence of rash, hypotension, and a high cerebrospinal fluid white-cell count. Nine (23%) episodes were acquired in the hospital and they were most commonly caused by Pseudomonas. The in-hospital mortality rate was 53%. The mortality rate was higher among patients with Gram-negative bacillary meningitis than among those with other bacterial meningitis and their risk of death was twenty times higher than among patients infected with Neisseria meningitidis (odds ratio 20.47; 95% confidence interval 4.03-103.93; p<0.001). CONCLUSIONS: Gram-negative bacilli cause 9% of spontaneous bacterial meningitis of known etiology in adults. Characteristics associated with GNBM include advanced age, history of cancer, nosocomial acquisition, and urinary tract infection as distant focus of infection. The mortality rate is higher among patients with gram-negative bacillary meningitis than among those with other bacterial meningitides.

Valganciclovir as pre-emptive therapy for cytomegalovirus infection in allogeneic haematopoietic stem cell transplant recipients.

BACKGROUND: In haematopoietic stem cell transplant (HSCT) recipients, cytomegalovirus (CMV) infection contributes significantly to morbidity and mortality in both the early and late post-transplant period. Ganciclovir (GCV) is the treatment of choice for CMV, but requires intravenous administration, a fact that complicates its long-term use. Oral valganciclovir (VGCV) and intravenous GCV were recently shown to have similar efficacy for pre-emptive CMV treatment in solid organ transplant recipients, but relatively limited data are available in HSCT recipients. The objectives of this study were to compare the efficacy of VGCV versus intravenous GCV or foscarnet (FOS) for pre-emptive therapy of active CMV infection in allogeneic HSCT and to determine the incidence of adverse effects and relapses. METHODS: This was a 2-year prospective, comparative cohort study in which 237 episodes of pre-emptive therapy for active CMV infection were collected in 166 allogeneic HSCT recipients out of 717 included in the Spanish Network for Research on Infection in Transplantation (RESITRA/REIPI) database. Intravenous GCV was the first-line treatment in 112 episodes, intravenous FOS in 38 episodes, and oral VGCV in 87 episodes. RESULTS: VGCV was used as pre-emptive therapy for active CMV infection in 87 episodes. Excluding episodes considered as relapse, VGCV was as successful (91.4% [74/81]) as GCV (83.7% [87/14]) or FOS (75.8% [25/33]). In the VGCV arm, 7 (8.6%) cases were considered treatment failures: 4 (4.9%) because of adverse events, 1 (1.2%) due to persistent viral activity and 2 (2.5%) based on clinical decision. There were also 6 (7.4%) cases of recurrent infection. No statistically significant differences were found when compared to GCV or FOS. CONCLUSIONS: In allogeneic HSCT recipients, VGCV seemed effective and safe in the pre-emptive therapy of active CMV infection.

Diagnostic accuracy of a 16S ribosomal DNA gene-based molecular technique (RT-PCR, microarray, and sequencing) for bacterial meningitis, early-onset neonatal sepsis, and spontaneous bacterial peritonitis.

The diagnostic accuracy of a 16S ribosomal DNA (rDNA) gene-based molecular technique for bacterial meningitis (BM), early-onset neonatal sepsis (EONS), and spontaneous bacterial peritonitis (SBP) is evaluated. The molecular approach gave better results for BM diagnosis: sensitivity (S) was 90.6% compared to 78.1% for the bacterial culture. Percentages of cases correctly diagnosed (CCD) were 91.7% and 80.6%, respectively. For EONS diagnosis, S was 60.0% for the molecular approach and 70.0% for the bacterial culture; and CCD was 95.2% and 96.4%, respectively. For SPB diagnosis, the molecular approach gave notably poorer results than the bacterial cultures. S and CCD were 48.4% and 56.4% for the molecular approach and 80.6% and 89.1% for bacterial cultures. Nevertheless, bacterial DNA was detected in 53.3% of culture-negative samples. Accuracy of the 16S rDNA PCR approach differs depending on the sample, the microorganisms involved, the expected bacterial load, and the presence of bacterial DNA other than that from the pathogen implied in the infectious disease.

Situación actual de las infecciones fúngicas invasivas. Las nuevas técnicas diagnósticas y los nuevos antifúngicos / Current status of invasive fungal infections. New diagnostic techniques and antifungal agents

En los últimos años, los grandes avances de la medicina en el tratamiento de los pacientes trasplantados, con enfermedades hematooncológicas o ingresados en la UCI, se han acompañado de un aumento de las infecciones fúngicas clásicas y de la emergencia de algunas poco habituales. A pesar de la aparición de nuevas técnicas de diagnóstico, como la de galactomanano, y de la disponibilidad de nuevos antifúngicos, estas infecciones oportunistas siguen siendo difíciles de diagnosticar, alargan la estancia hospitalaria, aumentan el coste y todavía tienen una mortalidad elevada. En este capítulo se incluye una breve revisión sobre la epidemiología, los avances diagnósticos y los nuevos antifúngicos que han aparecido en los últimos años

In the last few years, major advances in the treatment of transplant recipients, with hemato-oncological diseases or admitted to the intensive care unit, has been accompanied by an increase in classical fungal infections and by the emergence of uncommon fungal infections. Despite the development of new diagnostic techniques such as galactomannan detection and the availability of new antifungal agents, these opportunistic infections continue to pose a diagnostic challenge, prolong length of hospital stay, and increase costs. In addition, mortality from these infections is high. The present chapter provides a brief review of the epidemiology of these infections, diagnostic advances, and the new antifungal agents that have been developed in the last few years

[Current status of invasive fungal infections. New diagnostic techniques and antifungal agents]. / Situación actual de las infecciones fúngicas invasivas. Las nuevas técnicas diagnósticas y los nuevos antifúngicos.

In the last few years, major advances in the treatment of transplant recipients, with hemato-oncological diseases or admitted to the intensive care unit, has been accompanied by an increase in classical fungal infections and by the emergence of uncommon fungal infections. Despite the development of new diagnostic techniques such as galactomannan detection and the availability of new antifungal agents, these opportunistic infections continue to pose a diagnostic challenge, prolong length of hospital stay, and increase costs. In addition, mortality from these infections is high. The present chapter provides a brief review of the epidemiology of these infections, diagnostic advances, and the new antifungal agents that have been developed in the last few years.

A review of critical periods for opportunistic infection in the new transplantation era.

BACKGROUND: The risk of opportunistic infection (OI) is considered to be maximum during the first six months after solid organ transplantation. The aim of this study was to know the incidence and risk factors for OI in the late period (>6 months) compared with the early period (<6 months) after solid organ transplantation. METHODS: We used the online database of the Spanish Network of Infection in Transplantation (RESITRA), which prospectively analyzed 2,702 solid organ transplantation recipients from August 2003 to February 2005. Univariate and multivariate analyses were performed to calculate the risk factors associated with the development of late OI. RESULTS: A total of 131 patients (6%) developed 176 infectious episodes in the late period. Although the incidence of infection and cytomegalovirus disease (0.4 per 1000 transplant days and 0.05 per 1000 transplant days, respectively) was lower than in the early period (3.5 per 1000 transplant days and 0.8 per 1000 transplant days; P<0.0001), the incidence of other OIs was similar in both periods (0.05 per 1000 transplant days versus 0.03 per 1000 transplant-days, P=0.5). Patients with the higher risk for developing late OI were those receiving early cytomegalovirus prophylaxis, patients who developed two or more episodes of acute rejection during the early period, patients with recurrent bacterial infection during the early period, patients with renal failure requiring dialysis, and patients with chronic graft malfunction. CONCLUSIONS: Our data suggest that in some high-risk patients, the critical period of risk for OI must be expanded beyond the first six months after transplant.