Santiago Grau

Trough colistin plasma level is an independent risk factor for nephrotoxicity: a prospective observational cohort study

BackgroundData regarding the most efficacious and least toxic schedules for the use of colistin are scarce. The aim of this study was to determine the incidence and the potential risk factors of colistin-associated nephrotoxicity including colistin plasma levels.MethodsA prospective observational cohort study was conducted for over one year in patients receiving intravenous colistin methanesulfonate sodium (CMS). Blood samples for colistin plasma levels were collected immediately before (Cmin) and 30 minutes after CMS infusion (Cmax). Renal function was assessed at baseline, on day 7 and at the end of treatment (EOT). Severity of acute kidney injury (AKI) was defined by the RIFLE (risk, injury, failure, loss, and end-stage kidney disease) criteria.ResultsOne hundred and two patients met the inclusion criteria. AKI related to CMS treatment on day 7 and at the end of treatment (EOT) was observed in 26 (25.5%) and 50 (49.0%) patients, respectively. At day 7, Cmin (OR, 4.63 [2.33-9.20]; P < 0.001) was the only independent predictor of AKI. At EOT, the Charlson score (OR 1.26 [1.01-1.57]; P = 0.036), Cmin (OR 2.14 [1.33-3.42]; P = 0.002), and concomitant treatment with ≥ 2 nephrotoxic drugs (OR 2.61 [1.0-6.8]; P = 0.049) were independent risk factors for AKI. When Cmin was evaluated as a categorical variable, the breakpoints that better predicted AKI were 3.33 mg/L (P < 0.001) on day 7 and 2.42 mg/L (P < 0.001) at EOT.ConclusionsWhen using the RIFLE criteria, colistin-related nephrotoxicity is observed in a high percentage of patients. Cmin levels are predictive of AKI. Patients who receive intravenous colistin should be closely monitored and Cmin might be a new useful tool to predict AKI.

Effectiveness and safety of colistin for the treatment of multidrug-resistant Pseudomonas aeruginosa infections

Purpose:To describe the clinical and microbiological outcomes of patients infected with multidrug-resistant Pseudomonas aeruginosa (MDRP) treated with colistin (colistimethate sodium) and the adverse events observed with this treatment.Methods:Retrospective study of MDRP infections treated with colistin from 1997 to 2006.Results:121 episodes were identified. The median daily intravenous dose was 240 mg/day; 28.9% of patients received intravenous and nebulized colistin. Clinical outcome was favorable in ten cases of bacteremia (62.5%, n = 16), 43 cases of bronchial infection (72.9%, n = 59), 13 cases of pneumonia (65%, n = 20), 11 cases of urinary infection (84.6%, n = 13), eight cases of skin and soft tissues (72.7%, n = 11), and in the one case of arthritis and one case of otitis. Eradication was achieved in 31 (34.8%) of the 89 patients with available bacteriologic data. Factors associated with bacteriological failure were smoking, chronic obstructive pulmonary disease (COPD), and previous infection with P. aeruginosa. Nephrotoxicity occurred in ten cases (8.3%), with the associated factors being previous chronic renal insufficiency, diabetes mellitus, and aminoglycoside use. Crude mortality was 16.5%, and related MDRP was 12.4%, and was higher in patients with pneumonia or bacteremia (36.1%) than in other types of infections (8.2%).Conclusions:Colistin is a safe option for the treatment of MDRP infections, with acceptable clinical outcomes. However, bacteriological eradication is difficult to achieve, especially in COPD patients.

Eosinophil Count and Neutrophil-Lymphocyte Count Ratio as Prognostic Markers in Patients with Bacteremia: A Retrospective Cohort Study

Introduction There is scarce evidence on the use of eosinophil count as a marker of outcome in patients with infection. The aim of this study was to evaluate whether changes in eosinophil count, as well as the neutrophil-lymphocyte count ratio (NLCR), could be used as clinical markers of outcome in patients with bacteremia. Methods We performed a retrospective study of patients with a first episode of community-acquired or healthcare-related bacteremia during hospital admission between 2004 and 2009. A total of 2,311 patients were included. Cox regression was used to analyze the behaviour of eosinophil count and the NLCR in survivors and non-survivors. Results In the adjusted analysis, the main independent risk factor for mortality was persistence of an eosinophil count below 0.0454·103/uL (HR = 4.20; 95% CI 2.66–6.62). An NLCR value >7 was also an independent risk factor but was of lesser importance. The mean eosinophil count in survivors showed a tendency to increase rapidly and to achieve normal values between the second and third day. In these patients, the NLCR was <7 between the second and third day. Conclusion Both sustained eosinopenia and persistence of an NLCR >7 were independent markers of mortality in patients with bacteremia.

High Prevalence of Extended-spectrum Beta-lactamase-producing Enterobacteriaceae in Bacteremia After Transrectal Ultrasound-guided Prostate Biopsy: A Need for Changing Preventive Protocol

OBJECTIVES To determine whether the incidence of bacteremia after transrectal ultrasound-guided prostate biopsy (TRUSGPB) significantly diminishes with the setting up of a new preventive protocol. This protocol was set up after detecting an augmented incidence of bacteremia after TRUSGPB with a high prevalence of antibiotic-resistant microorganisms. METHODS Retrospective descriptive and prospective intervention study performed at a University Hospital. PARTICIPANTS Patients undergoing TRUSGPB under the old preventive protocol (January 2006-February 2007), that is, amoxicillin-clavulanate 500 mg tid the day before, the day of the procedure, and 1 day after the procedure, and after setting up a new protocol (March 2007-April 2008), that is, 2 g cefoxitin 1 hour before the procedure and ciprofloxacin 750 mg p.o. bid the day before, the day of the procedure, and 3 days after the procedure; dipstick urinalysis was performed before the procedure, and patients with positive results were not biopsied. RESULTS Incidence of bacteremia with old and new protocols: 9 of 204 procedures (4.4%) vs 2 of 207 (0.9%), (P = .03). Four isolates (44.4%) under the old protocol produced extended-spectrum beta-lactamase (ESBL). With the new protocol, 2 (0.9%) cases of non-ESBL Escherichia coli bacteremia were observed. Sixty-five (23.8%) cases were not biopsied because of positive result of dipstick urinalysis, lack of antibiotic prophylaxis adherence, or altered coagulation parameters. CONCLUSIONS Antibiotic prophylaxis for TRUSGPB should take into account local resistance patterns. Cefoxitin could be used as prophylaxis in centers with high prevalence of ESBL enterobacteriaceae. Before TRUSGPB, excluding patients with positive results of dipstick urinalysis is an advisable practice.

Hospital costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition

BackgroundWe aimed to assess the hospital economic costs of nosocomial multi-drug resistant Pseudomonas aeruginosa acquisition.MethodsA retrospective study of all hospital admissions between January 1, 2005, and December 31, 2006 was carried out in a 420-bed, urban, tertiary-care teaching hospital in Barcelona (Spain). All patients with a first positive clinical culture for P. aeruginosa more than 48 h after admission were included. Patient and hospitalization characteristics were collected from hospital and microbiology laboratory computerized records. According to antibiotic susceptibility, isolates were classified as non-resistant, resistant and multi-drug resistant. Cost estimation was based on a full-costing cost accounting system and on the criteria of clinical Activity-Based Costing methods. Multivariate analyses were performed using generalized linear models of log-transformed costs.ResultsCost estimations were available for 402 nosocomial incident P. aeruginosa positive cultures. Their distribution by antibiotic susceptibility pattern was 37.1% non-resistant, 29.6% resistant and 33.3% multi-drug resistant. The total mean economic cost per admission of patients with multi-drug resistant P. aeruginosa strains was higher than that for non-resistant strains (15,265 vs. 4,933 Euros). In multivariate analysis, resistant and multi-drug resistant strains were independently predictive of an increased hospital total cost in compared with non-resistant strains (the incremental increase in total hospital cost was more than 1.37-fold and 1.77-fold that for non-resistant strains, respectively).ConclusionsP. aeruginosa multi-drug resistance independently predicted higher hospital costs with a more than 70% increase per admission compared with non-resistant strains. Prevention of the nosocomial emergence and spread of antimicrobial resistant microorganisms is essential to limit the strong economic impact.

Management of Antimicrobial Use in the Intensive Care Unit

Critically ill patients admitted to the intensive care unit (ICU) are frequently treated with antimicrobials. The appropriate and judicious use of antimicrobial treatment in the ICU setting is a constant clinical challenge for healthcare staff due to the appearance and spread of new multiresistant pathogens and the need to update knowledge of factors involved in the selection of multiresistance and in the patient’s clinical response. In order to optimize the efficacy of empirical antibacterial treatments and to reduce the selection of multiresistant pathogens, different strategies have been advocated, including de-escalation therapy and pre-emptive therapy as well as measurement of pharmacokinetic and pharmacodynamic (pK/pD) parameters for proper dosing adjustment. Although the theoretical arguments of all these strategies are very attractive, evidence of their effectiveness is scarce. The identification of the concentrationdependent and time-dependent activity pattern of antimicrobials allow the classification of drugs into three groups, each group with its own pK/pD characteristics, which are the basis for the identification of new forms of administration of antimicrobials to optimize their efficacy (single dose, loading dose, continuous infusion) and to decrease toxicity. The appearance of new multiresistant pathogens, such as imipenem-resistant Pseudomonas aeruginosa and/or Acinetobacter baumannii, carbapenem-resistant Gram-negative bacteria harbouring carbapenemases, and vancomycin-resistant Enterococcus spp., has determined the use of new antibacterials, the reintroduction of other drugs that have been removed in the past due to toxicity or the use of combinations with in vitro synergy. Finally, pharmacoeconomic aspects should be considered for the choice of appropriate antimicrobials in the care of critically ill patients.

Community-onset healthcare-related urinary tract infections: Comparison with community and hospital-acquired urinary tract infections

OBJECTIVES To analyze the characteristics of infection, adequacy of empirical treatment and outcome of patients with community-onset healthcare-associated (HCA) urinary tract infections (UTI) and compare them with hospital (HA) and community-acquired (CA) UTI. METHODS Prospective observational cohort study performed at a university 600-bed hospital between July 2009 and February 2010. Patients with UTI requiring hospital admission were included. Epidemiological, clinical and outcome data were recorded. RESULTS 251 patients were included. Patients with community-onset HCA UTI were older, had more co-morbidities and had received previous antimicrobial treatment more frequently than CA UTI (p = 0.02, p = 0.01 and p < 0.01). ESBL-Escherichia coli and Pseudomonas aeruginosa infections were more frequent in HCA than in CA UTI (p = 0.03 and p < 0.01). Inadequate empirical treatment was not significantly different between community-onset HCA and CA. Factors related to mortality were P. aeruginosa infection (OR 6.51; 95%CI: 1.01-41.73), diabetes mellitus (OR 22.66; 95%CI: 3.61-142.21), solid neoplasia (OR 22.48; 95%CI: 3.38-149.49) and age (OR 1.15; 95%CI 1.03-1.28). CONCLUSIONS Epidemiological, clinical and microbiological features suggest that community-onset HCA UTI is different from CA and similar to HA UTI. However, in our series inadequate empirical antimicrobial therapy and mortality were not significantly higher in community-onset HCA than in CA UTI.

Comparative effects of olive oil-based and soyabean oil-based emulsions on infection rate and leucocyte count in critically ill patients receiving parenteral nutrition

Soyabean oil-based emulsions high in linoleic acid used in parenteral nutrition (PN) could interfere with immune function and may increase the risk of septic complications. Olive oil-based emulsions, high in oleic acid, could have fewer immune effects. We compared the effects of a soyabean oil-based emulsion v. an olive oil-based emulsion on infection rate, appearance of new infection episodes, leucocyte count (peak and evolution), acute-phase proteins, and major health outcomes in intensive care unit (ICU) adult patients receiving PN. The study was designed as an observational, retrospective, single-centre, cohort study in a general ICU. Patients in the SOYA cohort (n 16) received a soyabean oil-based emulsion and patients in the OLIVE cohort (n 23), an olive oil-based emulsion. Both cohorts had similar basal characteristics and received a similar energy load. The SOYA cohort received an oleic acid:linoleic acid ratio of 0.43 and the OLIVE cohort 2.99 (P < 0.001). No differences were observed in infection rate and appearance, acute-phase proteins, and major health outcomes. At the end of PN, blood leucocyte count decreased by 3.25 x 109 cells/l in the SOYA cohort and increased by 4.51 x 109 cells/l in the OLIVE cohort from baseline values (P = 0.036). Peak leucocyte count presented a trend for a higher value in the OLIVE cohort v. the SOYA cohort (18.86 v. 15.28 x 109 cells/l; P = 0.078). The use of an olive oil-based emulsion in PN had no effect on infection, acute-phase proteins, major health outcomes, and presented higher leucocyte count at the end of PN and a trend to higher peak leucocyte count when compared with soyabean oil-based emulsion in ICU patients.

Cost of bacteraemia caused by methicillin-resistant vs. methicillin-susceptible Staphylococcus aureus in Spain: a retrospective cohort study

The aim of this study was to determine the impact on healthcare resource utilization and associated costs of bacteraemia due to methicillin-resistant Staphylococcus aureus (MRSA) vs. methicillin-susceptible S. aureus (MSSA) strains in Spain. An observational, retrospective, cohort multicentre study was conducted during 2005. The target population comprised Spanish patients with S. aureus bacteraemia (five and ten cases per hospital for resistant and susceptible strains, respectively). The resources used were obtained from the hospital patient records. The unit costs were obtained from the participating hospitals and from Spanish databases; the costs of a bacteraemic episode were estimated from resource utilization results and expressed in euros (euro). Univariate sensitivity analyses were performed. The clinical records of 366 valid patients with S. aureus bacteraemia (121 MRSA and 245 MSSA) from 27 Spanish hospitals were reviewed. Resource use per bacteraemic episode was higher for MRSA cases than for MSSA cases, with longer antibiotic treatment (3.1 additional days) and greater length of hospital stay (LOS) (2.2 additional days), more diagnostic tests, and higher rates of admission to the intensive-care unit (ICU) (7.6%). As a consequence, a higher cost per episode was incurred, with an additional euro1205 in episodes of MRSA infections (1.12-fold increase). The main drivers of the cost difference were the higher rates of ICU admission and hospital re-admission and increased LOS. The analysis confirmed that there were additional costs due to resistant strains, ranging from euro293 to euro5188. Overall, MRSA was associated with higher costs in bacteraemic patients, and this was attributable mainly to the greater rate of ICU admissions and increased LOS.

Plasma and peritoneal fluid population pharmacokinetics of micafungin in post-surgical patients with severe peritonitis

OBJECTIVES Limited information about the pharmacokinetics of micafungin in the peritoneal cavity is available. The aim of this study was to explore the pharmacokinetics/pharmacodynamics of micafungin in plasma and peritoneal fluid in post-surgical critically ill patients with proven or suspected intra-abdominal fungal infection. METHODS Patients were administered 100 mg/day micafungin. Serial blood and peritoneal fluid samples were collected on day 1 and day 3 (steady-state) of treatment. Concentrations were determined by validated chromatography and were subject to a population pharmacokinetic analysis with Pmetrics(®). Monte Carlo simulations were performed for AUC0-24/MIC ratios in plasma. The PTA was calculated using AUC0-24/MIC cut-offs: 285 for Candida parapsilosis and 3000 for non-parapsilosis Candida spp. RESULTS Ten patients were included; six were male. The median (range) age, APACHE II score and Mannheim peritonitis index were 72 (43-85) years, 15 (11-36) and 26 (8-37), respectively. On day 1, median (SD) penetration of micafungin into the peritoneal cavity was 30% (30%-40%). A three-compartment model adequately described the data. The mean (SD) estimates for clearance and volume of distribution of the central compartment were 1.27 (0.75) L/h and 9.26 (1.11) L, respectively. In most patients, the PTA in plasma was ≥ 90% for MICs of 0.008-0.016 mg/L for Candida spp. and 0.125-0.25 mg/L for C. parapsilosis. CONCLUSIONS After the first dose, micafungin at 100 mg/day achieves pharmacokinetic/pharmacodynamic targets in plasma for Candida spp. and C. parapsilosis MICs of 0.008-0.016 and 0.125-0.25 mg/L, respectively.