Therapeutic drug monitoring guided fluconazole therapy in a patient with cholangitis sepsis

Candida and other fungal species play an increasing role in nosocomial infections, including cholangitis and cholangiosepsis. Early diagnosis and prompt treatment are essential in successful patient outcomes. Fluconazole is an antifungal of choice in fluconazole-sensitive Candida infections. Little information is known about the fluconazole biliary excretion. Decreased tissue penetration may be one of the possible causes of treatment failure. Due to favorable pharmacokinetics, therapeutic drug monitoring of this antifungal has not been recommended routinely. In the presented case we report the successful therapeutic drug monitoring-guided fluconazole treatment in a patient with cholangitis and cholangiosepsis caused by fluconazole-sensitive Candida spp.

Evaluation of the Initial 12 Months of a Routine Cryptococcal Antigen Screening Program in Reduction of HIV-Associated Cryptococcal Meningitis in Uganda

Background: Asymptomatic Cryptococcal Antigenemia (CrAg) patients develop meningitis within a month of testing positive. Pre-emptive antifungal therapy can prevent progression to Cryptococcal meningitis(CM). In April 2016, a national CrAg screening program was initiated in 206 high-volume health facilities that provide antiretroviral therapy in Uganda. We report the evaluation of the CrAg screening cascade focusing on linkage to care, fluconazole therapy for 10 weeks, and ART initiation in a subset of facilities.Methods: We conducted a retrospective, cross-sectional survey of patients with CD4<100 at seven urban and seven rural facilities after one year of program implementation. We quantified the number of patients who transitioned through the steps of the CrAg screening cascade over six-months follow-up. We defined cascade completion as a prophylactic fluconazole prescription. We conducted semi-structured interviews with lab personnel and clinic staff to assess functionality of the CrAg screening program. Data was collected using REDCap.Results:We evaluated 359 patient records; the majority (358/359, 99.7%) were from government owned health facilities and just over half (193/359, 53.8%) had a median baseline CD4 cell count of <50 cell/µL. Overall, CrAg screening had been performed in 255/359 (71.0%, 95% CI, 66.0-75.7) of patients’ records reviewed, with a higher proportion among urban facilities (170/209 (81.3%, 95% CI, 75.4-86.4)) than rural facilities (85/150 (56.7%, 95% CI, 48.3-64.7)). Among those who were CrAg screened, 56/255 (22.0%, 95% CI, 17.0-27.5%) had cryptococcal antigenemia, of whom 47/56 (83.9%, 95% CI, 71.7-92.4%) were initiated on pre-emptive therapy with fluconazole and 8/47 (17.0%, 95% CI, 7.6-30.8%) of these were still receiving antifungal therapy at 6 months follow up. Atleast one CNS symptom was present in 70% (39/56) of those with antigenemia. In patients who had started ART, almost 40% initiated ART prior to CrAg screening. Inadequacy of equipment/supplies was reported by 15/26 (58%) of personnel as a program barrier, while 13/26 (50%) reported a need for training about CM and CrAg screening.Conclusion:There was a critical gap in the follow-up of patients after initiation on fluconazole therapy. ART had been initiated in almost 40% of patients prior to CrAg screening, which predisposes them to unmasking Cryptococcal IRIS. Higher antigenemia patients presenting with CNS symptoms could be related to late presentation. There is need to address these gaps after a more thorough evaluation.

Renal Replacement Therapy and Concurrent Fluconazole Therapy Increase Linezolid-Related Thrombocytopenia Among Adult Patients

Linezolid has been reported to be associated with thrombocytopenia. However, limited information is available on susceptibility to thrombocytopenia after linezolid usage. We aimed to investigate the risk factors for linezolid-associated thrombocytopenia (LAT). We conducted a retrospective cohort study of patients aged ≥ 18 years who received linezolid for ≥ 5 d during hospitalization in 2019. Information was extracted from electronic medical records. Thrombocytopenia was defined as a platelet count of < 100×109/L or a reduction from baseline ≥ 25%. Binary logistic regression and survival analyses were used to evaluate the risk factors for LAT. A total of 98 patients were enrolled. Thrombocytopenia occurred in 53.1% patients, with a median of 9 d after initiation of linezolid. There was no significant difference in the mortality or proportion of platelet transfusions between patients with and without thrombocytopenia. A higher risk of LAT was found in patients who received renal replacement therapy (RRT) (OR 4.8 [1.4–16.4]), concurrent fluconazole (OR 3.5 [1.2–9.8]), or a longer duration of linezolid treatment (OR 1.1 [1.0-1.1]). Patients who received RRT (8 vs. 15 d) or concurrent fluconazole (11 vs. 15 d) had a shorter median time to develop thrombocytopenia. Those who simultaneously received RRT and fluconazole had the shortest median of time (6.5 d) and the highest risk of developing thrombocytopenia (87.5%).

Case Report: A Great Mimicker of Neoplasm: Pulmonary Cryptococcosis in an Immunocompetent Host After High-Altitude Descent

Cryptococcus exposure in certain global regions is common and yet virulence in the immunocompetent host remains rare. Radiological findings of pulmonary cryptococcosis may include nonspecific lung nodules or masses indistinguishable from lung cancer or pulmonary tuberculosis. We present a case of an immunocompetent diabetic female who presented with progressively worsening pleuritic chest pain and cough with travel between Tibet and New York 2 months earlier. Chest imaging demonstrated a large lobulated mass, acid-fast bacillus smears were negative, and our patient underwent pulmonary biopsy, which grew rare budding yeast later confirmed by mucicarmine staining as Cryptococcus. Our patient was successfully treated with fluconazole therapy. We hypothesize that the high altitude of Tibet may allow for clinical latency followed by symptomatic reactivation on descent. A raised index of suspicion for pulmonary cryptococcosis with careful attention to travel history is expected to facilitate timely diagnosis.

Renal Replacement Therapy and Concurrent Fluconazole Therapy Increase Linezolid-Related Thrombocytopenia Among Adult Patients

Background: Linezolid, an antibiotic used against gram-positive pathogens, has been reported to be associated with thrombocytopenia. However, limited information is available on susceptibility to thrombocytopenia after linezolid usage. We aimed to investigate the risk factors for linezolid-associated thrombocytopenia. Methods: We conducted a retrospective cohort study of patients aged ≥ 18 years who received linezolid for ≥ 5 d during hospitalization in 2019. Demographic information, hospitalized information and laboratory data were extracted from electronic medical records. Thrombocytopenia was defined as a platelet count of <100,000 cells/mm3 or a reduction from baseline ≥ 25%. Binary logistic regression and survival analyses were used to evaluate the risk factors for linezolid-associated thrombocytopenia.Results: A total of 98 patients were enrolled. Thrombocytopenia occurred in 52 patients (53.1%), with a median first presentation 9 d after initiation of linezolid. There was no significant difference in the mortality or proportion of platelet transfusions between patients with and without thrombocytopenia. A higher risk of linezolid-associated thrombocytopenia was found in patients who received renal replacement therapy (RRT) (OR 4.8 [1.4-16.4]), concurrent fluconazole (OR 3.5 [1.2-9.8]), or a longer duration of linezolid treatment (OR 1.1 [1.0-1.1]). Patients who received RRT or concurrent fluconazole therapy had a shorter median time to develop thrombocytopenia (with vs. without RRT: 8 vs. 15 d; with vs. without fluconazole: 11 vs. 15 d). Those who simultaneously received RRT and fluconazole had the shortest median of time (6.5 d) and the highest risk of developing thrombocytopenia (87.5%).Conclusions: Patients who received RRT, concurrent fluconazole treatment, or a longer-duration linezolid had a higher risk of developing linezolid-associated thrombocytopenia.

Candida pelliculosa sepsis in a neonate: a case report

Candida pelliculosa is a rare fungal cause of neonatal sepsis. Premature and very low birthweight infants are at especially high risk of neonatal fungal infections. There have been no reports of C. pelliculosa infection in Anhui Province, China. Here, we report a case of C. pelliculosa fungemia in a newborn boy admitted 30 minutes after delivery with grunting, cyanosis, and asphyxia. C. pelliculosa was identified as the causative organism using blood culture, DNA sequencing, and mass spectrometric analysis. After 20 days of fluconazole therapy, the patient’s symptoms stabilized. Together with other relevant literature, this report provides evidence that premature neonates are at increased risk of fungal infections and that C. pelliculosa fungemia should be diagnosed early using blood cultures to enable effective treatment. Fluconazole may be effective for treating neonates with C. pelliculosa infection.

Epidemiology and Antifungal Susceptibility in Patients with Candidemia in a University Hospital, Thailand

Background: Candidemia is the most common nosocomial invasive fungal infection that causes high mortality. Emergence of drug-resistant Candida is reported worldwide but there are few studies in Thailand. Objective: To determine the epidemiology, antifungal susceptibility of Candida, and outcomes among adult patients with candidemia. Materials and Methods: A prospective, observational study in adult patients with candidemia was conducted in 2015 at a university hospital. Demographic, microbiological, and outcome data were recorded. Results: Fifty-two patients with candidemia were identified, of whom 76.9% had an underlying disease and 69.2% had risks for candidemia. Sixty-four percent of candidemia patients contracted non-albicans Candida and 36% had Candida albicans. C. tropicalis was the most common non-albicans Candida species isolated (35%), followed by C. parapsilosis (19%), and C. glabrata (10%). Fluconazole resistance was found in 12.5% of C. albicans and in 11.1% of C. parapsilosis isolates. Reduced fluconazole susceptibility or high-level fluconazole resistance was found in 68.7% of C. tropicalis isolates. All except C. parapsilosis had excellent susceptibility to echinocandins. Seventy-three percent (38/52) of patients received antifungal treatment, of whom, 78.9% received empiric fluconazole therapy, and 89.7% were started on antifungal treatment 24 hours after the isolation of Candida. The overall mortality rate was 51.9%. Conclusion: Fluconazole-resistant Candida became more prevalent particularly in C. tropicalis, which was the predominant species among non-albicans Candida causing candidemia. Empiric treatment with either amphotericin B or echinocandins would be appropriate in high-risk patients with suspected candidemia. Trial registration: Thai Clinical Trials Registry, TCTR20150605001 Keywords: Candida, Fluconazole, Resistant, Thailand