scholarly journals Successful Treatment of Cryptococcal Meningitis and Cryptococcoma with Isavuconazole in a Patient Living with HIV

2021 ◽  
Vol 7 (6) ◽  
pp. 425
Author(s):  
Brendan O’Kelly ◽  
Aia Mohamed ◽  
Colm Bergin ◽  
Fiona Lyons ◽  
Thomas R. Rogers ◽  
...  
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Cryptococcal Meningitis ◽  
Inhibitory Concentration ◽  
Area Under The Curve ◽  
Hiv Positive ◽  
Days Of Therapy ◽  
Daily Dose ◽  
Living With Hiv ◽  
Inflammatory Syndrome ◽  
Modelling Data

We describe the successful use of isavuconazole for treatment of an HIV-positive patient with cryptococcal meningitis following induction therapy with liposomal amphotericin B and flucytosine. Because the Cryptococcus neoformans isolate from cerebrospinal fluid had a borderline minimum inhibitory concentration of 8 mg/L, initial consolidation therapy was given with a daily dose of fluconazole 1200 mg based on area under the curve to minimum inhibitory concentration modelling data. Toxicity, and the radiological emergence of a cryptococcoma in the setting of immune reconstitution inflammatory syndrome, prompted a therapeutic switch to isavuconazole. Subsequent imaging after 19 weeks of isavuconazole shows a significant reduction in cryptococcoma size from 11 mm to complete resolution. The patient remains well after 210 days of therapy with a view to completion of treatment after 1 year.

Prevalence of Asymptomatic Cryptococcal Antigenemia and Association with Follow-up risk of Cryptococcal Meningitis and Mortality among HIV Infected Patients in North West India – A Prospective Cohort Study

2020 ◽  
Vol 18 ◽  
Author(s):  
Rajendra Bhati ◽  
Pramendra Sirohi ◽  
Bharat Sejoo ◽  
Deepak Kumar ◽  
Gopal K Bohra ◽  
...  
Keyword(s):  
Cryptococcal Meningitis ◽  
Morbidity And Mortality ◽  
People Living With Hiv ◽  
Cryptococcal Antigen ◽  
North West ◽  
Cryptococcal Disease ◽  
Increased Risk ◽  
Living With Hiv ◽  
Inflammatory Syndrome

Objective: Cryptococcal meningitis is an important cause of morbidity and mortality in HIV infected individuals. In the era of universal antiretroviral therapy incidence of immune reconstitution inflammatory syndrome (IRIS) related cryptococcal meningitis has increased. Detection of serum cryptococcal antigen in asymptomatic PLHIV (People Living With HIV) and pre-emptive treatment with fluconazole can decrease the burden of cryptococcal disease. We conducted this study to find the prevalence of asymptomatic cryptococcal antigenemia in India and its correlation with mortality in PLHIV. Method and material: This was a prospective observational study. HIV infected ART naïve patients with age of ≥ 18 years who had CD4 counts ≤ 100 /µL were included and serum cryptococcal antigen test was done. These patients were followed for six months to look for the development of Cryptococcal meningitis and mortality. Results: A total of 116 patients were analysed. Asymptomatic cryptococcal antigenemia was detected in 5.17% patients and it correlated with increased risk of cryptococcal meningitis and mortality on follow-up in PLHIV. Conclusion: Serum cryptococcal positivity is correlated with increased risk of Cryptococcal meningitis and mortality in PLHIV. We recommend the screening of asymptomatic PLHIV with CD4 ≤ 100/µL for serum cryptococcal antigen, so that pre-emptive treatment can be initiated to reduce morbidity and mortality.

scholarly journals Minimum Inhibitory Concentration Distribution of Fluconazole Against Cryptococcus Species and the Fluconazole Exposure Prediction Model

2019 ◽  
Vol 6 (10) ◽  
Author(s):  
Supavit Chesdachai ◽  
Radha Rajasingham ◽  
Melanie R Nicol ◽  
David B Meya ◽  
Felix Bongomin ◽  
...  
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Inhibitory Concentration ◽  
Geometric Mean ◽  
Area Under The Curve ◽  
Systemic Review ◽  
Dose Selection ◽  
Treatment And Prevention ◽  
Optimal Dosing ◽  
Cryptococcus Species ◽  
Dosing Strategy

Abstract Background Fluconazole is lifesaving for treatment and prevention of cryptococcosis; however, optimal dosing is unknown. Initial fluconazole doses of 100 mg to 2000 mg/day have been used. Prevalence of fluconazole nonsusceptible Cryptococcus is increasing over time, risking the efficacy of long-established standard dosing. Based on current minimum inhibitory concentration (MIC) distribution, we modeled fluconazole concentrations and area under the curve (AUC) relative to MIC to propose a rational fluconazole dosing strategy. Method We conducted a systematic review using the MEDLINE database for reports of fluconazole MIC distribution against clinical Cryptococcus isolates. Then, we utilized fluconazole concentrations from 92 Ugandans who received fluconazole 800mg/day coupled with fluconazole’s known pharmacokinetics to predict plasma fluconazole concentrations for doses ranging from 100 mg to 2000 mg via linear regression. The fluconazole AUC above MIC ratio were calculated using Monte Carlo simulation and using the MIC distribution elucidated during the systemic review. Results We summarized 21 studies with 11 049 clinical Cryptococcus isolates. Minimum inihibitory concentrations were normally distributed with a geometric mean of 3.4 µg/mL, median (MIC50) of 4 µg/mL, and 90th percentile (MIC90) of 16 µg/mL. The median MIC50 trended upwards from 4 µg/mL in 2000–2012 to 8 µg/mL in 2014–2018. Predicted subtherapeutic fluconazole concentrations (below MIC) would occur in 40% with 100 mg, 21% with 200 mg, and 9% with 400 mg. The AUC:MIC ratio >100 would occur in 53% for 400 mg, 74% for 800 mg, 83% for 1200 mg, and 88% for 1600 mg. Conclusions Currently recommended fluconazole doses may be inadequate for cryptococcosis. Further clinical studies are needed for rational fluconazole dose selection.

Clinical Evaluation of Rectally Administered Ampicillin in Acute Otitis Media

1988 ◽  
Vol 16 (5) ◽  
pp. 376-385 ◽  
Author(s):  
B. K. V. Bergström ◽  
S. O. Bertilson ◽  
G. Movin
Keyword(s):  
Body Weight ◽  
Minimum Inhibitory Concentration ◽  
Clinical Outcome ◽  
Otitis Media ◽  
Inhibitory Concentration ◽  
Plasma Concentrations ◽  
Acute Otitis Media ◽  
Good Alternative ◽  
Respiratory Pathogens ◽  
Daily Dose

An ampicillin suppository was compared with amoxycillin suspension in the treatment of acute otitis media in children. Both antibiotics were given three times daily for 5 days in a daily dose of 25–50 mg/kg body weight. Safety was evaluated in 454 patients in the group given suppository and in 229 given the suspension, and 421 and 229 patients, respectively, were evaluable for efficacy. Ampicillin was rapidly absorbed and produced plasma concentrations well above the minimum inhibitory concentration for common respiratory pathogens. The overall clinical outcome was satisfactory (cured plus improved) in 89% of the patients given the suppository and in 86% given the suspension. Gastro-intestinal disturbances occurred in 28.4% of the patients given the suppository compared with 14.4% of those given the suspension. Perianal irritation was recorded in 12.1% of the patients given the suppository and in 5.2% of those given the suspension. Treatment was interrupted in 9.8% of patients given the suppository and in 0.9% of those given the suspension. In spite of these discomforts rectally administered ampicillin is considered to be a good alternative in children when oral medication is not feasible.

scholarly journals Comparison between conventional dosing versus personalized pharmacokinetic dosing of vancomycin: a pilot study from a Malaysian private hospital

2021 ◽  
Vol 12 (2) ◽  
pp. 1020-1029
Author(s):  
Tsuey Li Yong ◽  
Chee Ping Chong
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Pilot Study ◽  
Private Hospital ◽  
Inhibitory Concentration ◽  
Hospital Setting ◽  
Total Daily Dose ◽  
Pharmacokinetic Parameters ◽  
Efficacy And Safety ◽  
Daily Dose ◽  
Dosing Method

Pharmacist led vancomycin dosing is not a common practice in private hospital settings of the Malaysian healthcare system. The lack of this pharmacist led system has led to conventional vancomycin dosing without considering the differences in patients pharmacokinetic parameters. This study aims to compare the differences in vancomycin doses between conventional dosing and pharmacist-led personalized pharmacokinetic dosing. A retrospective pilot study was conducted on inpatient adults who were prescribed with intravenous vancomycin in a private hospital. Personalized vancomycin doses were retrospectively calculated by using the pharmacokinetic parameters and was then compared with the actual conventional doses used in the patients. The area under concentration curve over 24 hours/minimum inhibitory concentration (AUC24/MIC) ratio achieved by the doses was also compared. The targeted AUC24/MIC ratio was 400-600 to ensure efficacy and safety of the therapy. A total of 24 patients with a median age of 55.50 years were conveniently sampled. The patients were mostly male (58.3%) and were admitted to the neurosurgical ward (33.3%). Vancomycin was mainly prescribed as empirical treatment (58.3%) for a median treatment period of 5.00 days (IQR 4.00 – 7.00 days). The conventional doses had significant (p < 0.001) lower median total daily dose (2000 mg versus 2500 mg) and lower AUC24/MIC ratio (385 versus 495) as compared to personalized doses. In conclusion, the personalized pharmacokinetic dosing method was significantly more able to achieve the targeted AUC24/MIC ratio. Vancomycin personalized dosing should be considered in the Malaysian private hospital setting.

Treatment of tricuspid valve endocarditis with daptomycin and linezolid therapy

2019 ◽  
Vol 76 (14) ◽  
pp. 1033-1036 ◽  
Author(s):  
Kayla M Galanter ◽  
Jackie Ho
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Tricuspid Valve ◽  
Inhibitory Concentration ◽  
Synergistic Effects ◽  
Skilled Nursing Facility ◽  
Stable Condition ◽  
Multidrug Resistant ◽  
Replacement Procedure ◽  
Days Of Therapy ◽  
Tricuspid Valve Endocarditis

Abstract Purpose A case report of the use of linezolid and daptomycin for the treatment of multidrug-resistant right-sided infective endocarditis is presented. Summary A 36-year-old patient with a history of intravenous drug use was hospitalized for treatment of native tricuspid valve endocarditis resulting in persistent methicillin-resistant Staphylococcus aureus bacteremia. During the admission the patient was unsuccessfully treated with vancomycin monotherapy (final E-test minimum inhibitory concentration, 4 μg/mL). The patient’s treatment was switched to daptomycin and gentamicin, with no improvement in blood culture results over 4 days. Gentamicin was discontinued, and linezolid was administered in combination with daptomycin; bacteremia was cleared after 13 days of linezolid and daptomycin combination therapy. Due to daptomycin resistance (minimum inhibitory concentration, 4 μg/mL), gentamicin was substituted for daptomycin due to the former agent’s synergistic effects with linezolid. After 23 days of therapy the patient was transferred to another facility for a tricuspid valve replacement procedure, which was completed without complications. The patient was transferred in stable condition to a skilled nursing facility to continue antibiotic therapy lasting 6 weeks from the date of surgery. The patient’s blood cultures remained negative. Conclusion A 36-year-old woman with resistant tricuspid valve endocarditis was successfully treated with linezolid in combination with daptomycin.

Evaluation of the Association between Trough and Area Under the Curve to Minimum Inhibitory Concentration Ratio (AUC24/MIC) of Vancomycin in Infected Patients with Methicillin Resistant Staphylococcus aureus (MRSA)

2020 ◽  
Vol 27 (2) ◽  
pp. 201-208
Author(s):  
Ayda Esmaeili ◽  
Mohammadreza Salehi ◽  
Nava Makhdoomi ◽  
Yalda H. Ardakani ◽  
Mehdi Rajabi ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Minimum Inhibitory Concentration ◽  
Strong Correlation ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Inhibitory Concentration ◽  
Trough Level ◽  
Area Under The Curve ◽  
Methicillin Resistant ◽  
Fourth Dose ◽  
Trough Levels

Background: The recent studies emphasized on the correlation of vancomycin antibacterial effect with pharmacokinetics properties such as the area under the curve/minimum inhibitory concentration (AUC24/MIC) ≥400 and serum trough level 15-20 mg /L in the patients with severe infection with methicillin-resistant Staphylococcus aureus (MRSA). The purpose is to assay the vancomycin pharmacokinetic properties in our population and evaluates the correlation between AUC24/MIC and trough serum level of vancomycin in given patients. Methods: The patients with a positive MRSA culture, treated with vancomycin, were enrolled in this cross-sectional study. Three plasma samples were obtained during the study including 30 min before fourth and the fifth dose as trough levels and 1 hour after the fourth dose as peak level to determine AUC24. E-TEST determined the MIC of vancomycin. Results: Thirty-eight patients with an average age of 48.33±16.44 were enrolled in this study. The mean ± SD of MIC was 0.99±0.30 mg/L. Thirty-four patients reached the adequate therapeutic range of AUC24/MIC ≥ 400 due to the standard vancomycin dosing method. In comparison, only 7 and 10 patients had the first and second trough levels in target intervals of 15-20 mg/L, respectively. Due to the receiver operating characteristic curve test (ROC test), the trough level after the fourth dose had a strong correlation with target AUC24/MIC with a sensitivity of 94.1%and specificity of 75.0%. Conclusion: This study concluded using only a trough level is not appropriate for therapeutic drug monitoring (TDM) of vancomycin. In our population, target AUC24/MIC (≥ 400) had a reasonably strong correlation with the trough level before the fifth dose which achieved with trough level ≥10.81 mg/L and MIC< 1 mg/L.

scholarly journals Retrospective Study of Cryptococcal Meningitis With Elevated Minimum Inhibitory Concentration to Fluconazole in Immunocompromised Patients

2016 ◽  
Vol 3 (2) ◽  
Author(s):  
Hashem Nasri ◽  
Sarah Kabbani ◽  
Melhim Bou Alwan ◽  
Yun F. Wang ◽  
Paulina A. Rebolledo ◽  
...  
Keyword(s):  
Minimum Inhibitory Concentration ◽  
Maintenance Therapy ◽  
Cryptococcal Meningitis ◽  
Susceptibility Testing ◽  
Inhibitory Concentration ◽  
Organ Transplant ◽  
Retrospective Chart Review ◽  
High Dose ◽  
Solid Organ ◽  
Immunocompromised Patients

Abstract Background.  Mortality for cryptococcal meningitis remains significant, in spite of available treatment. Resistance to first-line maintenance therapy, particularly fluconazole, has been reported. Methods.  A retrospective chart review was performed on immunocompromised patients with cryptococcal meningitis, who had susceptibility testing performed between January 2001 and December 2011, at 3 hospitals in Atlanta, Georgia. Results.  A total of 35 immunocompromised patients with cryptococcal meningitis were identified, 13 (37.1%) of whom had an elevated minimum inhibitory concentration (MIC) to fluconazole (MIC ≥16 µg/mL). Eighty percent of patients were males with African American predominance, the median age was 37 years, and 80% of the patients were human immunodeficiency virus (HIV) positive. Subsequent recurrence of cryptococcal meningitis was more likely in HIV patients compared with solid organ transplant patients (P = .0366). Overall, there was a statistically significant increase in an elevated MIC to fluconazole in patients who had a history of prior azole use (odds ratio, 10.12; 95% confidence interval, 2.04–50.16). Patients with an elevated MIC to fluconazole and those with a high cerebrospinal fluid cryptococcal antigen load (≥1:512) were more likely to have central nervous system complications (P = .0358 and P = .023, respectively). Although no association was observed between an elevated MIC to fluconazole and mortality, those who received voriconazole or high-dose fluconazole (≥800 mg) for maintenance therapy were more likely to survive (P = .0288). Conclusions.  Additional studies are required to further investigate the morbidity and mortality associated with an elevated MIC to fluconazole in cryptococcal meningitis, to determine when it is appropriate to perform susceptibility testing, and to evaluate its cost effectiveness.

Sign in / Sign up

Export Citation Format

Share Document