piperacillin--tazobactam-drug-combination and Candidiasis--Invasive

Use of antibiotics in critically ill patients may increase the risk of invasive Candida infection. The objective of this study was to determine whether increased exposure to antibiotics is associated with increased prevalence of invasive Candida infection.. Substudy using data from a randomized controlled trial, the Procalcitonin And Survival Study 2006-2010.. Nine multidisciplinary ICUs across Denmark.. A total of 1,200 critically ill patients.. Patients were randomly allocated to either a "high exposure" antibiotic therapy (intervention arm, n = 604) or a "standard exposure" guided by current guidelines (n = 596).. Seventy-four patients met the endpoint, "invasive Candida infection," 40 in the high exposure arm and 34 in standard exposure arm (relative risk = 1.2; 95% CI, 0.7-1.8; p = 0.52). Among medical patients in the high exposure arm, the use of ciprofloxacin and piperacillin/tazobactam was 51% and 75% higher than in the standard exposure arm; no difference in antibiotic exposure was observed between the randomized arms in surgical patients. Among medical intensive care patients, invasive Candida infection was more frequent in the high exposure arm (6.2%; 27/437) than in standard exposure arm (3.3%; 14/424) (hazard ratio = 1.9; 95% CI, 1.0-3.6; p = 0.05). Ciprofloxacin used at study entry independently predicted invasive Candida infection (adjusted hazard ratio = 2.1 [1.1-4.1]); the risk gradually increased with duration of ciprofloxacin therapy: six of 384 in patients not exposed (1.6%), eight of 212 (3.8%) when used for 1-2 days (hazard ratio = 2.5; 95% CI, 0.9-7.3), and 31 of 493 (6.3%) when used for 3 days (hazard ratio = 3.8; 95% CI, 1.6-9.3; p = 0.002). Patients with any ciprofloxacin-containing antibiotic regimen the first 3 days in the trial had a higher risk of invasive Candida infection than did patients on any antibiotic regimen not containing ciprofloxacin (unadjusted hazard ratio = 3.7; 95% CI, 1.6-8.7; p = 0.003; adjusted hazard ratio, 3.4; 95% CI, 1.4-8.0; p = 0.006).. High exposure to antibiotics is associated to increased risk of invasive Candida infection in medical intensive care patients. Patients with ciprofloxacin-containing regimens had higher risk of invasive Candida infection. Other antibiotics, such as meropenem, piperacillin/tazobactam, and cefuroxime, were not associated with such a risk.

Topics: Age Factors; Aged; Anti-Bacterial Agents; APACHE; Candidiasis, Invasive; Cefuroxime; Ciprofloxacin; Critical Illness; Denmark; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Humans; Intensive Care Units; Male; Meropenem; Middle Aged; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Single-Blind Method; Thienamycins

False positivity of antigen immunoassays used as an early diagnostic tool to detect invasive fungal infections is known. Interpretation of the assay needs the identification of sources which could affect the specificity of the test. We focused on the influence of parenteral nutrition (PN) and piperacillin-tazobactam (TZP) on fungal immunoassays. Measurable amounts of Candida antigen mannan were detected in several compounds of PN and TZP in a previous in vitro study. In the current study, 84 patients undergoing allogeneic haematopoietic cell transplantation receiving either TZP, PN or both were monitored with Aspergillus and Candida antigen assay. Six patients were analysed closer in a kinetic analysis with more frequent blood sampling to detect mannan. PN in diverse compositions as well as TZP did not increase significantly the amount of mannan and the Aspergillus antigen in serum. We could not confirm the positive results of the in vitro study. Physicians should be aware that mannan antigenemia due to drug infusion could be a transient issue and should be considered in the interpretation of fungal immunoassays, although we could not find clinically relevant effects on mannan levels.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antigens, Fungal; beta-Lactamase Inhibitors; Candidiasis, Invasive; False Positive Reactions; Female; Hematopoietic Stem Cell Transplantation; Humans; Invasive Pulmonary Aspergillosis; Male; Middle Aged; Parenteral Nutrition; Piperacillin, Tazobactam Drug Combination; Prospective Studies; Transplantation, Homologous; Young Adult

Screening for Aspergillus (Asp-AG) and Candida antigen (Ca-AG) with immunoassays is established for stem cell recipients at high risk for invasive fungal infections (IFI). While parenteral nutrition (PN) will be applied in case of complications leading to insufficient alimentation, piperacillin-tazobactam (TZP) is started at the onset of febrile neutropenia.. The aim of this study was to investigate drug-laboratory interactions between PN and TZP and both immunoassays which could affect the specificity of the assays and lead to the false assumption of an IFI.. Batches of TZP and PN were tested with both assays in vitro. In total, 380 samples of 83 batches were analysed.. None of the examined preparations were tested positive with Asp-AG assay. Measurable amounts of Ca-AG were detected in a lipid emulsion, two different trace element supplements, a fat-soluble vitamin preparation and all tested brands of TZP.. We conclude that false positivity of Asp-AG assay due to TZP and PN does not occur. Cross reactions with Ca-AG assay have been detected in some preparations. The in vivo relevance of Ca-AG positivity has to be reviewed in further studies considering an effect of dilution. Physicians should be aware of a possible cross reaction with Ca-AG assays which could lead to false-positive results.

Topics: Anti-Bacterial Agents; Antigens, Fungal; Aspergillus; beta-Lactamase Inhibitors; Candida; Candidiasis, Invasive; False Positive Reactions; Humans; Invasive Pulmonary Aspergillosis; Parenteral Nutrition Solutions; Piperacillin, Tazobactam Drug Combination; Serologic Tests

Topics: Acetamides; Amikacin; Anti-Bacterial Agents; Antifungal Agents; Candidiasis, Invasive; Drug Therapy, Combination; Humans; Hypokalemia; Linezolid; Lung Diseases, Fungal; Male; Middle Aged; Oxazolidinones; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Potassium Chloride; Pyrimidines; Triazoles; Voriconazole