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Management of invasive candidiasis in nonneutropenic ICU patients.

ABSTRACT: Invasive candidiasis (IC) is a leading cause of morbidity and mortality among nonneutropenic ICU patients and these life-threatening nosocomial infections require early diagnosis and prompt treatment. However, none of the predictive tools are sufficiently accurate to identify high-risk patients and the potential interest of IC prophylactic, empirical and preemptive treatment in the nonneutropenic ICU population has not yet been demonstrated. In the case of nosocomial severe sepsis after necrotizing pancreatitis or upper digestive anastomotic leakage, early probabilistic antifungals are probably indicated. In the remaining ICU surgical and medical patients, prophylactic and empirical strategies are highly debated because they may promote antifungal selective pressure through an overuse of these molecules. In this context, non-culture-based methods such as mannan or ?-D glucan or polymerase chain reaction tests are promising. However, none of these tests used alone in ICU patients is sufficiently accurate to avoid overuse of empirical/preemptive treatment. The interest of strategies associating predictive clinical scores and non-culture-based methods still needs to be demonstrated by well-conducted randomized, controlled trials. While awaiting these studies, we consider that probabilist treatment should be stopped earlier if IC is not proven.

SUBMITTER: Weiss E

PROVIDER: S-EPMC4340669 | biostudies-literature | 2014 Oct

REPOSITORIES: biostudies-literature

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Management of invasive candidiasis in nonneutropenic ICU patients.

Weiss Emmanuel E Timsit Jean-François JF

Therapeutic advances in infectious disease 20141001 5-6

Invasive candidiasis (IC) is a leading cause of morbidity and mortality among nonneutropenic ICU patients and these life-threatening nosocomial infections require early diagnosis and prompt treatment. However, none of the predictive tools are sufficiently accurate to identify high-risk patients and the potential interest of IC prophylactic, empirical and preemptive treatment in the nonneutropenic ICU population has not yet been demonstrated. In the case of nosocomial severe sepsis after necrotiz ...[more]

PMID: 25745560

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Project description:Background: The relationship between antibiotic use and the incidence of triazole-resistant phenotypes of invasive candidiasis (IC) in critically ill patients is unclear. Different methodologies on determining this relationship may yield different results. Methods: A retrospective multicenter observational analysis was conducted to investigate exposure to antibiotics and the incidence of non-duplicate clinical isolates of Candida spp. resistant to fluconazole, voriconazole, or both during November 2013 to April 2018, using two different methodologies: group-level (time-series analysis) and individual-patient-level (regression analysis and propensity-score adjusting). Results: Of 393 identified Candida spp. from 388 critically ill patients, there were three phenotypes of IC identified: fluconazole-resistance (FR, 63, 16.0%); voriconazole-resistance (VR, 46, 11.7%); and cross-resistance between fluconazole and voriconazole (CR, 32, 8.1%). Exposure to several antibacterial agents with activity against the anaerobic gastrointestinal flora, especially third-generation cefalosporins (mainly cefoperazone/sulbactam and ceftriaxone), but not triazoles, have an immediate effect (time lag = 0) on subsequent ICU-acquired triazole-resistant IC in the group-level (p < 0.05). When the same patient database was analyzed at the individual-patient-level, we found that exposure to many antifungal agents was significantly associated with triazole-resistance (fluconazole [adjusted odds ratio (aOR) = 2.73] or caspofungin [aOR = 11.32] on FR, voriconazole [aOR = 2.87] on CR). Compared to the mono-triazole-resistant phenotype, CR IC has worse clinical outcomes (14-days mortality) and a higher level of resistance. Conclusion: Group-level and individual-patient-level analyses of antibiotic-use-versus-resistance relations yielded distinct but valuable results. Antibacterials with antianaerobic activity and antifungals might have "indirect" and "direct" effect on triazole-resistant IC, respectively.

Project description:The estimated attributable mortality rate for invasive candidiasis (IC) in the intensive care unit (ICU) setting varies from 30 to 40%. Physiological changes in critically ill patients may affect the distribution and elimination of micafungin, and therefore, dosing adjustments might be mandatory. The objective of this study was to determine the pharmacokinetic parameters of micafungin in critically ill patients and assess the probability of target attainment. Micafungin plasma concentrations were measured to estimate the pharmacokinetic properties of micafungin. MIC values for Candida isolates were determined to assess the probability of target attainment for patients. Data from 19 patients with suspected or proven invasive candidiasis were available for analysis. The median area under the concentration-time curve from 0 to 24 h at steady state (AUC0-24) was 89.6 mg · h/liter (interquartile range [IQR], 75.4 to 113.6 mg · h/liter); this was significantly lower than the median micafungin AUC0-24 values of 152.0 mg · h/liter (IQR, 136.0 to 162.0 mg · h/liter) and 134.0 mg · h/liter (IQR, 118.0 to 148.6 mg · h/liter) in healthy volunteers (P = <0.0001 and P = <0.001, respectively). All Candida isolates were susceptible to micafungin, with a median MIC of 0.016 mg/liter (IQR, 0.012 to 0.023 mg/liter). The median AUC0-24/MIC ratio was 5,684 (IQR, 4,325 to 7,578), and 3 of the 17 evaluable patients (17.6%) diagnosed with proven invasive candidiasis did not meet the AUC/MIC ratio target of 5,000. Micafungin exposure was lower in critically ill patients than in healthy volunteers. The variability in micafungin exposure in this ICU population could be explained by the patients' body weight. Our findings suggest that healthier patients (sequential organ failure assessment [SOFA] score of <10) weighing more than 100 kg and receiving 100 mg micafungin daily are at risk for inappropriate micafungin exposure and potentially inadequate antifungal treatment. (This study has been registered at ClinicalTrials.gov under identifier NCT01716988.).

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Management of invasive candidiasis in nonneutropenic ICU patients.

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Management of invasive candidiasis in nonneutropenic ICU patients.

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