Clinical characteristics and prognosis of infections caused by OXA-48 carbapenemase-producing Enterobacteriaceae in patients treated with ceftazidime-avibactam.

BACKGROUND: Ceftazidime-avibactam has in vitro activity against Gram-negative bacilli that produce Class A, C and some D ß-lactamases, and has been successfully used in the treatment of infections caused by cephalosporin and carbapenem-resistant Enterobacteriaceae. However, actual experience in the treatment of OXA-48 carbapenemase-producing Enterobacteriaceae (CPE) is limited. OBJECTIVE: To review the characteristics and prognosis of OXA-48 CPE infections treated with ceftazidime-avibactam since introduction of the drug to the current centre during the period October 2014 to December 2016. METHODS: Retrospective assessment of episodes of infection caused by OXA-48 CPE treated with ceftazidime-avibactam, analysing data collected from infection diagnosis until 90 days after the end of treatment. RESULTS: Twenty-four episodes were analysed. Ceftazidime-avibactam was given as the initial definitive treatment in 15 (62.5%) and as salvage therapy in nine (37.5%). Intraabdominal (seven, 29%), urinary (six, 25%) and respiratory (five, 21%) were the most common sources. The 30-day and 90-day mortality rates were 8.3% and 20.8%, respectively. Clinical cure at 30 days was achieved in 62.5% of episodes. Four (16.7%) patients had adverse events, two of them were related to impaired renal function. Among patients who finished the treatment with ceftazidime-avibactam, seven (35%) were diagnosed with infection recurrence within 90 days of the end of treatment. CONCLUSIONS: From experience, ceftazidime-avibactam is an effective drug for treating infections due to OXA-48 CPE. From these results a better safety profile than the current best available therapy could be expected.

Evaluation of ceftazidime/avibactam for serious infections due to multidrug-resistant and extensively drug-resistant Pseudomonas aeruginosa.

OBJECTIVES: The steady progress in resistance of Pseudomonas aeruginosa (PA) has led to difficulties in treating infections due to multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains. Ceftazidime/avibactam (CAZ/AVI) has in vitro activity against many of these strains, however clinical experience with CAZ/AVI is limited. This study aimed to evaluate the characteristics and outcomes of eight patients with infections due to MDR- or XDR-PA treated with CAZ/AVI, including four strains resistant to ceftolozane/tazobactam. METHODS: This was a retrospective descriptive study of patients admitted to a teaching hospital between January 2016 and May 2017 who received CAZ/AVI as initial or continuation therapy for infection due to MDR- and XDR-PA. RESULTS: The sources of infection were hospital-acquired lower respiratory tract infection in five patients (62.5%) and osteomyelitis, meningitis and catheter-related bacteraemia in one patient each. Clinical cure was achieved in 4 patients (50.0%). The 30-day and 90-day mortality rates were 12.5% and 37.5%, respectively. One patient (12.5%) developed encephalopathy that improved with discontinuation of the drug. CONCLUSIONS: CAZ/AVI may be a valuable option for serious infections due to resistant PA.

Moxifloxacin plus rifampin as an alternative for levofloxacin plus rifampin in the treatment of a prosthetic joint infection with Staphylococcus aureus.

OBJECTIVES: The combination of a fluoroquinolone with rifampin is one of the cornerstones in the treatment of prosthetic joint infections (PJI) caused by staphylococci. Moxifloxacin is highly active against methicillin-susceptible Staphylococcus aureus (MSSA) and, therefore, is an attractive agent to use. However, several studies reported a lowering in serum moxifloxacin levels when combined with rifampin. The clinical relevance remains unclear. We determined the outcome of patients with early acute PJI caused by MSSA treated with either moxifloxacin/rifampin or levofloxacin/rifampin. METHODS: Medical files of patients treated with moxifloxacin/rifampin (University Medical Centre Groningen) or levofloxacin/rifampin (Hospital Clinic Barcelona) were retrospectively reviewed (2005-2015). Treatment failure was defined as the need for revision surgery and/or suppressive therapy, death by infection or a relapse of infection during follow-up. RESULTS: Differences in baseline characteristics between the two cohorts were observed, but prognostic parameters for failure, as defined by the KLIC-score (Kidney failure, Liver cirrhosis, Index surgery, C-reactive protein and Cemented prosthesis), were similar in the two groups (2.9 [1.5 SD] for the moxifloxacin group vs. 2.2 [1.2 SD] for the levofloxacin group [P = 0.16]). With a mean follow-up of 50 months (36 SD) in the moxifloxacin group, and 67 months (50 SD) in the levofloxacin group (P = 0.36), treatment was successful in 89% vs. 87.5%, respectively (P = 0.89). None of the failures in the moxifloxacin group were due to rifampin- or moxifloxacin-resistant S. aureus strains. CONCLUSION: Our data indicate that moxifloxacin combined with rifampin is as clinically effective as levofloxacin/rifampin for early acute PJI caused by MSSA.

Dalbavancin in the treatment of different gram-positive infections: a real-life experience.

Dalbavancin is a lipoglycopeptide with a very prolonged half-life enabling treatment with a single intravenous administration that has been approved to treat complicated skin and soft-tissue infections. Information on the efficacy and safety of dalbavancin in other situations is very scarce. This retrospective study included adult patients who received at least one dose of dalbavancin between 2016 and 2017 in 29 institutions in Spain. The primary objective was to report the use of dalbavancin in clinical practice, including its efficacy and tolerability. The potential impact of dalbavancin on reducing the length of hospital stay and hospital costs was also evaluated. A total of 69 patients received dalbavancin during the study period (58.0% male; median age 63.5 years). Dalbavancin was used to treat prosthetic joint infection (29.0%), acute bacterial skin and skin-structure infection (21.7%), osteomyelitis (17.4%) and catheter-related bacteraemia (11.6%). These infections were mainly caused by Staphylococcus aureus (27 isolates), coagulase-negative staphylococci (24 isolates) and Enterococcus spp. (11 isolates). All but two patients received previous antibiotics for a median of 18 days. Dalbavancin was administered for a median of 21 days (range 7-168 days), and concomitant antimicrobial therapy was prescribed to 25 patients (36.2%). The overall clinical success rate of dalbavancin was 84.1%. Adverse events, mainly mild in intensity, were reported in nine patients. Overall, dalbavancin was estimated to reduce hospitalisation by 1160 days, with an estimated overall cost reduction of €211 481 (€3064 per patient). Dalbavancin appears to be an effective therapy for many serious Gram-positive infections.

A propensity score analysis shows that empirical treatment with linezolid does not increase the thirty-day mortality rate in patients with Gram-negative bacteremia.

The role of linezolid in empirical therapy of suspected bacteremia remains unclear. The aim of this study was to evaluate the influence of empirical use of linezolid or glycopeptides in addition to other antibiotics on the 30-day mortality rates in patients with Gram-negative bacteremia. For this purpose, 1,126 patients with Gram-negative bacteremia in the Hospital Clinic of Barcelona from 2000 to 2012 were included in this study. In order to compare the mortality rates between patients who received linezolid or glycopeptides, the propensity scores on baseline variables were used to balance the treatment groups, and both propensity score matching and propensity-adjusted logistic regression were used to compare the 30-day mortality rates between the groups. The overall 30-day mortality rate was 16.0% during the study period. Sixty-eight patients received empirical treatment with linezolid, and 1,058 received glycopeptides. The propensity score matching included 64 patients in each treatment group. After matching, the mortality rates were 14.1% (9/64) in patients who received glycopeptides and 21.9% (14/64) in those who received linezolid, and a nonsignificant association between empirical linezolid treatment and mortality rate (odds ratio [OR], 1.63; 95% confidence interval [CI], 0.69 to 3.82; P = 0.275, McNemar's test) was found. This association remained nonsignificant when variables that remained unbalanced after matching were included in a conditional logistic regression model. Further, the stratified propensity score analysis did not show any significant relationship between empirical linezolid treatment and the mortality rate after adjustment by propensity score quintiles or other variables potentially associated with mortality. In conclusion, the propensity score analysis showed that empirical treatment with linezolid compared with that with glycopeptides was not associated with 30-day mortality rates in patients with Gram-negative bacteremia.

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

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 (C(min)) and to determine factors associated with a C(min) < 2 mg/liter and other clinically relevant thresholds. Characteristics of 78 patients receiving 600 mg/12 h of linezolid with a C(min) 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 C(min). A total of 29.5% of patients had a C(min) < 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 C(min) < 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 C(min) 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.