Laura Morata

Influence of Multidrug Resistance and Appropriate Empirical Therapy on the 30-Day Mortality Rate of Pseudomonas aeruginosa Bacteremia

ABSTRACT Infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa are increasing. The aim of our study was to evaluate the influences of appropriate empirical antibiotic therapy and multidrug resistance on mortality in patients with bacteremia due to P. aeruginosa (PAB). Episodes of PAB were prospectively registered from 2000 to 2008. MDR was considered when the strain was resistant to ≥3 antipseudomonal antibiotics. Univariate and multivariate analyses were performed. A total of 709 episodes of PAB were studied. MDR PAB (n = 127 [17.9%]) was more frequently nosocomial and associated with longer hospitalization, bladder catheter use, steroid and antibiotic therapy, receipt of inappropriate empirical antibiotic therapy, and a higher mortality. Factors independently associated with mortality were age (odds ratio [OR], 1.02; 95% confidence interval [CI], 1.002 to 1.033), shock (OR, 6.6; 95% CI, 4 to 10.8), cirrhosis (OR, 3.3; 95% CI, 1.4 to 7.6), intermediate-risk sources (OR, 2.5; 95% CI, 1.4 to 4.3) or high-risk sources (OR, 7.3; 95% CI, 4.1 to 12.9), and inappropriate empirical therapy (OR, 2.1; 95% CI, 1.3 to 3.5). To analyze the interaction between empirical therapy and MDR, a variable combining both was introduced in the multivariate analysis. Inappropriate therapy was significantly associated with higher mortality regardless of the susceptibility pattern, and there was a trend toward higher mortality in patients receiving appropriate therapy for MDR than in those appropriately treated for non-MDR strains (OR, 2.2; 95% CI, 0.9 to 5.4). In 47.9% of MDR PAB episodes, appropriate therapy consisted of monotherapy with amikacin. In conclusion, MDR PAB is associated with a higher mortality than non-MDR PAB. This may be related to a higher rate of inappropriate empirical therapy and probably also to amikacin as frequently the only appropriate empirical therapy given to patients with MDR PAB.

Risk factors for a low linezolid trough plasma concentration in acute infections.

ABSTRACT Linezolid is an antibiotic with time-dependent activity, and both the percentage of time that plasma concentrations exceed the MIC and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC24/MIC ratio) are associated with clinical response. The aim of this study was to analyze the linezolid trough plasma concentration (Cmin) and to determine factors associated with a Cmin < 2 mg/liter and other clinically relevant thresholds. Characteristics of 78 patients receiving 600 mg/12 h of linezolid with a Cmin determination at the steady state and within the first 10 days of treatment were retrospectively reviewed. Concentrations were measured using high-pressure liquid chromatography. Univariate and multivariate analysis were performed to identify risk factors of low Cmin. A total of 29.5% of patients had a Cmin < 2 mg/liter. The percentage was significantly higher in patients with an estimated glomerular filtration (eGF) > 80 ml/min, in intensive care unit (ICU) patients, and in patients with an infection due to Staphylococcus aureus. The independent predictors of Cmin < 2 mg/liter were an eGF > 80 ml/min (odds ratio [OR], 10; 95% confidence interval [CI], 2.732 to 37.037; P = 0.001) and infection due to S. aureus (OR, 5.906; 95% CI, 1.651 to 21.126; P = 0.006). A linezolid Cmin of <2 mg/liter was found in 29.5% of cases, and the risk was significantly higher among those with an eGF > 80 ml/min and in infections due to S. aureus. In patients with severe sepsis, a loading dose or continuous infusion and drug monitoring could improve the pharmacodynamic parameters associated with linezolid efficacy.

Prosthetic joint infections due to Staphylococcus aureus and coagulase-negative staphylococci

Purposes To evaluate the specific characteristics, outcome, and predictors of failure of prosthetic joint infections (PJI) due to S. aureus and coagulase-negative staphylococci (CNS) treated with open debridement and retention of the implant. Methods PJI due to S. aureus or CNS prospectively registered in a database from 1999 to 2009 were retrospectively reviewed. During the study period, 106 patients met the inclusion criteria. The mean follow-up period was 3.8 years and for at least 2 years in all patients. The failure rate was 23.6% (25 out of 106). The only variable significantly associated with failure in the global cohort was polymicrobial infection (38.7% vs. 17.3%, p = 0.024). Fifty-seven (53.8%) patients had an infection due to S. aureus and 49 (46.2%) due to CNS. Among S. aureus infections, 95% corresponded to primary arthroplasties while 98% of PJIs due to CNS were after revision arthroplasties (p<0.001). C-reactive protein was significantly higher in PJI due to S. aureus (9.5 mg/dl vs. 4.9 mg/dl, p = 0.007). The rate of methicillin-resistance (8.8% vs. 59.2%, p<0.001) and fluoroquinolone-resistance (15.8% vs. 34.7%, p = 0.005) was significantly higher in CNS infections. The global failure rate was higher in S. aureus infections (28% vs. 18.3. p = 0.26). In S. aureus infections, patients diagnosed within the first 15 days after joint arthroplasty (p = 0.031) and with bacteremia (p = 0.046) had poor prognosis. In CNS infections only the location of the prosthesis (knee 27.6% vs. hip 5%, p = 0.045) was associated with failure. Conclusions PJIs due to S. aureus were mainly in primary arthroplasties; they had a higher inflammatory response; and the strains were more susceptible to fluoroquinolones and methicillin than CNS infections. S. aureus infections had a higher failure rate than CNS infections, however, the difference was not statistically significant. There were few factors associated with failure and they were different in S. aureus and CNS infections.

Clinical characteristics and outcome of elderly patients with community-onset bacteremia.

OBJECTIVES To evaluate characteristics and prognostic factors of community-onset bloodstream infection (Co-BSI) in elderly patients (≥65 years). METHODS Analysis of a prospective series of Co-BSI at a tertiary hospital (2005-2011). Predictors of 30-day mortality were established by logistic regression analysis. RESULTS A total of 2605 episodes of Co-BSI were identified and empirical antibiotic treatment was inappropriate in 404 (15.5%). Thirty-day mortality was 11.4% and was independently associated with age (75-84 years OR 1.9, 1.37-2.67; ≥85 OR 2.85, 1.93-4.21), previous hospitalization (OR 1.45, 1.05-2.00), a fatal underlying disease (OR 2.81, 2.10-3.76), neutropenia (OR 2.62, 1.54-4.43), absence of fever (OR 1.99, 1.26-3.12), shock (OR 7.96, 5.83-10.89), inappropriate empirical treatment (OR 1.49, 1.03-2.16), isolation of Staphylococcus aureus (methicillin-resistant OR 2.83, 1.38-5.78; methicillin-susceptible OR 3.24, 1.98-5.32), enterococci (OR 2.02, 1.14-3.59) or Enterobacteriaceae resistant to third-generation cephalosporin (3GCR-E) (OR 1.96, 1.16-3.32) and having endovascular non-catheter (OR 4.64, 2.51-8.59), abdominal (OR 3.65, 2.12-6.27), skin/soft tissue (OR 3.48, 1.90-6.37), respiratory (OR 2.80, 1.75-4.50) or unknown (OR 1.83, 1.17-2.87) source. CONCLUSIONS Age is a prognostic factor and appropriateness of empirical treatment is the only modifiable variable. S. aureus, enterococci and 3GCR-E may be the microorganisms with major prognostic significance; hence efforts should be made to improve their management.

New antibiotics against gram-positives: present and future indications.

Gram-positive cocci are the most frequent aetiology of community and nosocomially bacterial acquired infections. The prevalence of multidrug-resistant gram-positive bacteria is increasing and is associated with high morbidity and mortality. New antibiotics will be available in the European market during the next months. This revision is focused on lipoglycopeptides, new cephalosporins active against methicillin-resistant Staphylococcus aureus (MRSA) and the new oxazolidinone, tedizolid. The purpose of this review is to describe their in vitro activity, pharmacokinetic and pharmacodynamic characteristics, and experience from clinical trials.

Rapid Diagnosis of Staphylococcal Catheter-Related Bacteraemia in Direct Blood Samples by Real-Time PCR

Catheter-related bacteremia (CRB) is an important cause of morbidity and mortality among hospitalized patients, being staphylococci the main etiologic agents. The objective of this study was to assess the use of a PCR-based assay for detection of staphylococci directly from blood obtained through the catheter to diagnose CRB caused by these microorganisms and to perform a cost-effectiveness analysis. A total of 92 patients with suspected CRB were included in the study. Samples were obtained through the catheter. Paired blood cultures were processed by standard culture methods and 4 ml blood samples were processed by GeneXpert-MRSA assay for the detection of methicillin-susceptible (MSSA) or methicillin-resistant (MRSA) Staphylococcus aureus, and methicillin-resistant coagulase-negative staphylococci (MR-CoNS). Sixteen CRB caused by staphylococci were diagnosed among 92 suspected patients. GeneXpert detected 14 out of 16 cases (87.5%), including 4 MSSA and 10 MR-CoNS in approximately 1 hour after specimen receipt. The sensitivity and specificity of GeneXpert were 87.5% (CI 95%: 60.4–97.8) and 92.1% (CI 95%: 83–96.7), respectively, compared with standard culture methods. The sensitivity of GeneXpert for S. aureus was 100%. Regarding a cost-effectiveness analysis, the incremental cost of using GeneXpert was of 31.1€ per patient while the incremental cost-effectiveness ratio of GeneXpert compared with blood culture alones was about 180€ per life year gained. In conclusion, GeneXpert can be used directly with blood samples obtained through infected catheters to detect S. aureus and MR-CoNS in approximately 1h after sampling. In addition, it is cost-effective especially in areas with high prevalence of staphylococcal CRB.

Importance of selection and duration of antibiotic regimen in prosthetic joint infections treated with debridement and implant retention.

OBJECTIVES Early prosthetic joint infections (PJIs) are managed with debridement, implant retention and antibiotics (DAIR). Our aim was to evaluate risk factors for failure after stopping antibiotic treatment. METHODS From 1999 to 2013, early PJIs managed with DAIR were prospectively collected and retrospectively reviewed. The main variables potentially associated with outcome were gathered, and the minimum follow-up was 2 years. For the present study, only patients who were in remission after one debridement and without long-term antibiotic suppression were included. The primary endpoint was implant removal or the need to reintroduce antibiotic treatment due to failure. RESULTS One-hundred-and-forty-three patients met the inclusion criteria. The failure rate after a median duration of oral antibiotic treatment of 69 days (IQR 45-95 days) was 11.8%. In 92 cases, PJI was due to Gram-positive microorganisms, in 21 cases PJI was due to Gram-negative microorganisms and in 30 cases PJI was due to a polymicrobial infection with both Gram-positive and Gram-negative microorganisms. In Gram-positive infections, rifampicin administered in combination with linezolid, co-trimoxazole or clindamycin was associated with a higher failure rate (27.8%, P = 0.026) than that in patients receiving a combination of rifampicin with levofloxacin, ciprofloxacin or amoxicillin (8.3%) or monotherapy with linezolid or co-trimoxazole (0%). Among patients with a Gram-negative infection, the use of fluoroquinolones was associated with a lower failure rate (7.1% versus 37.5%, P = 0.044). CONCLUSIONS The only factor associated with failure was the oral antibiotic selection, not the duration of treatment. Linezolid, co-trimoxazole and clindamycin, but not levofloxacin, serum concentrations are reduced by rifampicin; a fact that could explain our findings. Further studies monitoring serum concentration could help to improve the efficacy of these antibiotics when administered in combination with rifampicin.

Usefulness of time-to-positivity in aerobic and anaerobic vials to predict the presence of Candida glabrata in patients with candidaemia

OBJECTIVES To determine whether time-to-positivity (TTP) in aerobic and anaerobic blood culture vials is useful to predict the presence of Candida glabrata in patients with candidaemia. METHODS TTP was recorded for both aerobic and anaerobic vials for each blood culture set of monomicrobial candidaemia. We considered TTP as the shortest time registered for any positive vial. Two diagnostic criteria were evaluated: the cut-off TTP value as obtained from a receiver operating characteristic curve and the detection of growth only or with a shorter TTP in anaerobic vials. RESULTS A total of 157 episodes were analysed of which 19 (12.1%) were due to C. glabrata. The TTP for C. glabrata was longer than that for other species. C. glabrata grew more frequently than other species in anaerobic vials [9/19 (47%) versus 19/138 (14%); P = 0.001] and also more often exclusively or earlier in anaerobic vials [7/19 (37%) versus 5/138 (4%); P < 0.0001]. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of a TTP >56.5 h for predicting the presence of C. glabrata were 47%, 88%, 36% and 92%, respectively. Growth detection only or earlier in anaerobic flasks had a sensitivity of 37%, a specificity of 96%, a PPV of 58% and an NPV of 92%. CONCLUSIONS Using the BACTEC 9240 system, a TTP ≤ 56.5 h is useful to rule out C. glabrata. In addition, in settings with an ~12% prevalence of C. glabrata candidaemia, yeast detection exclusively or earlier in anaerobic vials increases the probability of the presence of C. glabrata to 58%, which may be useful for early treatment optimization.

Clinical experience with linezolid for the treatment of orthopaedic implant infections

Gram-positive cocci are commonly isolated in orthopaedic implant infections and their resistance to β-lactams and fluoroquinolones is increasing. The high oral bioavailability of linezolid makes it an attractive oral alternative to glycopeptides and its use has increased in the last decade. To evaluate experience with linezolid in orthopaedic implant infections a systematic review of the literature available in English was undertaken. Only those articles describing series of ≥10 patients with acute or chronic orthopaedic implant infections treated with linezolid and with a clear definition of diagnosis and outcome were selected. A total of 293 patients (79.9% had prosthetic joint infections) were analysed in the 10 articles included. The overall remission rate with at least 3 months of follow-up was 79.9%, depending on whether the implant was removed or not (94% versus 69.9%). The addition of rifampicin was described in only two articles and no significant difference was observed. Adverse events were frequent during prolonged administration of linezolid (34.3%), requiring treatment discontinuation in 12.8%. The most common event was anaemia (13.4%) followed by gastrointestinal symptoms (11.1%). In conclusion, linezolid seems a good oral treatment alternative for orthopaedic implant infections due to Gram-positive cocci resistant to β-lactams and fluoroquinolones. However, close monitoring of adverse events is required.

Prophylaxis with Teicoplanin and Cefuroxime Reduces the Rate of Prosthetic Joint Infection after Primary Arthroplasty

ABSTRACT The aim of this study was to compare the prosthetic joint infection (PJI) rate after total joint arthroplasty in two consecutive periods of treatment with different antibiotic prophylaxes: cefuroxime versus cefuroxime plus teicoplanin. We retrospectively reviewed 1,896 patients who underwent total hip arthroplasty or total knee arthroplasty between March 2010 and February 2013. From March 2010 to August 2011, patients received 1.5 g of cefuroxime during induction of anesthesia and another 1.5 g 2 h later (the C group). From September 2011, 800 mg of teicoplanin was added to cefuroxime (the CT group). Throughout the period studied, there were no variations in pre- or postoperative protocols. Univariate and multivariate analyses were performed to evaluate independent predictors of PJI. There were 995 (55.7%) patients in the C group and 791 (44.3%) in the CT group. Patients in the CT group had a significantly lower PJI rate than patients in the C group (1.26% versus 3.51%, P = 0.002). There were no infections due to Staphylococcus aureus in the CT group (0% versus 1.6% in the C group, P < 0.001). A stepwise forward Cox regression model identified male sex (hazard ratio [HR], 3.85; 95% confidence interval [CI], 2.09 to 7.18), a body mass index of ≥35 kg/m2 (HR, 2.93; 95% CI, 1.37 to 6.27), the presence of lung disease (HR, 2.46; 95% CI, 1.17 to 5.15), and red blood cell transfusion (HR, 3.70; 95% CI, 1.89 to 7.23) to be independent variables associated with a higher risk of PJI. The addition of teicoplanin was associated with a lower risk of infection (HR, 0.35; 95% CI, 0.17 to 0.74). In conclusion, the addition of teicoplanin to cefuroxime during primary arthroplasty was associated with a significant reduction in the global PJI rate due to a reduction of infections caused by Gram-positive bacteria.