The multi-resistant yeast Candida auris has become a global public health threat because of its ease to persist and spread in clinical environments, especially in intensive care units. One of the most severe manifestations of invasive candidiasis is candidaemia, whose epidemiology has evolved to more resistant non-albicansCandida species, such as C. auris. It is crucial to establish infection control policies in order to control an outbreak due to nosocomial pathogens, including the implementation of screening colonisation studies. We describe here our experience in managing a C. auris outbreak lasting more than two and a half years which, despite our efforts in establishing control measures and surveillance, is still ongoing. A total of 287 colonised patients and 47 blood stream infections (candidaemia) have been detected to date. The epidemiology of those patients with candidaemia and the susceptibility of C. auris isolates are also reported. Thirty-five patients with candidaemia (74.5%) were also previously colonised. Forty-three patients (91.5%) were hospitalised (61.7%) or had been hospitalised (29.8%) in the ICU before developing candidaemia. Antifungal therapy for candidaemia consisted of echinocandins in monotherapy or in combination with amphotericin B or isavuconazole. The most common underlying disease was abdominal surgery (29.8%). The thirty-day mortality rate was 23.4% and two cases of endophtalmitis due to C. auris were found. All isolates were resistant to fluconazole and susceptible to echinocandins and amphotericin B. One isolate became resistant to echinocandins two months after the first isolate. Although there are no established clinical breakpoints, minimum inhibitory concentrations for isavuconazole were low (≤ 1 μg/mL).
Background
Infections caused by carbapenemase-producing Enterobacterales (CPE) are not well represented in pivotal trials with ceftazidime/avibactam. The best strategy for the treatment of these infections is unknown.
Methods
We conducted a multicentre retrospective observational study of patients who received ≥48 h of ceftazidime/avibactam or best available therapy (BAT) for documented CPE infections. The primary outcome was 30 day crude mortality. Secondary outcomes were 21 day clinical response and microbiological response. A multivariate logistic regression model was used to identify factors predictive of 30 day crude mortality. A propensity score to receive treatment with ceftazidime/avibactam was used as a covariate in the analysis.
Results
The cohort included 339 patients with CPE infections. Ceftazidime/avibactam treatment was used in 189 (55.8%) patients and 150 (44.2%) received BAT at a median of 2 days after diagnosis of infection. In multivariate analysis, ceftazidime/avibactam treatment was associated with survival (OR 0.41, 95% CI 0.20–0.80; P = 0.01), whereas INCREMENT-CPE scores of >7 points (OR 2.57, 95% CI 1.18–1.5.58; P = 0.01) and SOFA score (OR 1.20, 95% CI 1.08–1.34; P = 0.001) were associated with higher mortality. In patients with INCREMENT-CPE scores of >7 points, ceftazidime/avibactam treatment was associated with lower mortality compared with BAT (16/73, 21.9% versus 23/49, 46.9%; P = 0.004). Ceftazidime/avibactam was also an independent factor of 21 day clinical response (OR 2.43, 95% CI 1.16–5.12; P = 0.02) and microbiological eradication (OR 0.40, 95% CI 0.18–0.85; P = 0.02).
Conclusions
Ceftazidime/avibactam is an effective alternative for the treatment of CPE infections, especially in patients with INCREMENT-CPE scores of >7 points. A randomized controlled trial should confirm these findings.
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