SARS-CoV-2 intrahost evolution in immunocompromised patients in comparison with immunocompetent populations after treatment.

Many evidence suggests that long-lasting infection can develop with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This occurrence has been widely described in immunocompromised individuals. In these patients, ineffective clearance of virus infection provides an opportunity for developing immune escape mutants. This study aimed to characterize SARS-CoV-2 intrahost evolution in five immunocompromised in comparison with five immunocompetent COVID-19 patients during treatment. We performed next-generation sequencing (NGS) on collected two oropharyngeal samples from immunocompromised and immunocompetent COVID-19 patients before and after treatment. In this study, we detected alpha and delta variants of SARS-CoV-2. The most common substitutions in structural proteins in patients with alpha variant were S-ΔY143-144, A570D, D614G and D1118H, and N-R203K and G204R, and in delta variant S-T19R, G142D, E156G, 157-158del, L452R, T478K, D614G, D950N and N-D63G, R203M and D377Y were dominant. The common variations in nonstructural and accessory proteins including nsp3-A488S, P1228L, nsp6-T77A, nsp12-P323L, G671S, nsp13-P77L, NS3-S26L, and NS7a-T120I were detected. Also some infrequent substitutions were seen in immunocompromised and immunocompetent patients. After treatment, nsp12-V166A was emerged as a remdesivir resistance and S-L452M in a patient with common variable immunodeficiency. S-E484Q was detected in a patient with acute lymphoma leukemia. This study showed the possibility of the genetic diversity and development of some new mutations in immunocompromised patients. Therefore, surveillance of these patients to characterize any new variants is necessary.

Safety of megadose meropenem in the empirical treatment of nosocomial sepsis: a pilot randomized clinical trial.

Objective: To evaluate the safety of megadose meropenem as empirical treatment of nosocomial sepsis. Materials & methods: Critically ill patients diagnosed with sepsis received either high-dose (2 g every 8 h) or megadose (4 g every 8 h) meropenem as an intravenous infusion over 3 h. Results: A total of 23 patients with nosocomial sepsis were eligible and included in the megadose (n = 11) or high-dose (n = 12) group. No treatment-related adverse events were observed during a 14-day follow-up. Clinical response was also comparable between the groups. Conclusion: Megadose meropenem may be considered for empirical treatment of nosocomial sepsis without serious concern regarding its safety.

As resistance to antibiotics is increasing among microbes, rational use of these drugs is important both in the community and in hospitals. Many infections with resistant microorganisms may be fatal. For a long time, carbapenems have been the last resort for treatment of resistant microorganisms. Unfortunately, resistance to these drugs is increasing. It appears that use of higher doses of antibiotics may help in some cases. However, the potential harm caused by higher doses is a problem. In this primary study, higher doses of meropenem, a common carbapenem, were found to be safe.

Antibiotic use during the first 6 months of COVID-19 pandemic in Iran: A large-scale multi-centre study.

WHAT IS KNOWN AND OBJECTIVE: Although antibiotics are ineffective against viral infections, epidemiological studies have revealed that the COVID-19 pandemic resulted in the overuse of antibiotics and disruption of antimicrobial stewardship programmes. We investigated the pattern of antibiotic use during the first 6 months of the COVID-19 pandemic in Iran. METHODS: A multi-centre retrospective study was designed to investigate the use of 16 broad-spectrum antibiotics in 12 medical centres. The rate of antibiotic use was calculated and reported based on the Defined Daily Dose (DDD) per 100 hospital bed-days. The bacterial co-infection rate was also reported. RESULTS AND DISCUSSION: Totally, 43,791 hospitalized COVID-19 patients were recruited in this study. It was found that 121.6 DDD of antibiotics were used per 100 hospital bed-days, which estimated that each patient received approximately 1.21 DDDs of antibiotics every day. However, the bacterial co-infections were detected only in 14.4% of the cases. A direct correlation was observed between the rate of antibiotic use and mortality (r[142] = 0.237, p = 0.004). The rate of antibiotic consumption was not significantly different between the ICU and non-ICU settings (p = 0.15). WHAT IS NEW AND CONCLUSION: In this study, widespread antibiotic use was detected in the absence of the confirmed bacterial coinfection in COVID-19 patients. This over-consumption of broad-spectrum antibiotics may be associated with increased mortality in hospitalized COVID-19 patients, which can be an alarming finding.

Prevalence of cryptococcal antigen positivity among HIV infected patient with CD4 cell count less than 100 of Imam Khomeini Hospital, Tehran, Iran.

BACKGROUND AND OBJECTIVES: Cryptococcal meningitis is one of the main opportunistic infections associated with human immunodeficiency virus (HIV) infection. Despite the present and increasingly availability of specific treatment for cryptococcosis, the mortality rate of this infection is still high, particularly in patients with advanced immunsupression and advanced cryptococcal diseases. MATERIALS AND METHODS: This Prospective Cohort study was conducted at Imam Khomeini hospital in Tehran, Iran. Serum cryptococcal antigen was detected using the Lateral Flow Assay (LFA) There were 86 HIV-infected patients included in this study. RESULTS: There were 86 HIV-infected patients in this study. The prevalence of positive serum cryptococcal antigen was 0% (0 of 86). CONCLUSION: The prevalence of cryptococcal infection among patients with advanced acquired immunodeficiency syndrome (AIDS) in the Iran is very low (<3%) thus the screening test for cryptococcal antigenemia dose not save lives and is not cost-effective in Iranian population.

Hospitalizations and its related factors in HIV/AIDS patients in Tehran, Iran.

BACKGROUND: HIV/AIDS patients are mainly hospitalized for HIV-related diseases and opportunistic infections.ions. This study was performed to determine the causes of hospitalization and its related factors in HIV/AIDS patients in Tehran's Imam Khomeini Hospital during 2009-2012. METHODS: This study was a descriptive cross-sectional study. HIV patients admitted to the Imam Khomeini Hospital were included in the study through census method, during the study. Demographic variables, hepatitis co-infection, CD4 count, history of receiving anti- retroviral therapy (ART), cause of admission, length of hospitalization and patient's outcome were recorded. Data were analyzed by SPSS software and by means of Chisquare and Mann Whitney U tests. RESULTS: During the study, 555 HIV patients were included in, 84.9% of whom were male, with the mean age of 36.59±8.51 years and the average length of hospitalization for 16.04±18.82 days. Opportunistic infections were the most common cause of hospitalization (46.5%) with prevalent of which was pulmonary tuberculosis being the most prevalent (37.6%). Patients suffering from opportunistic infections had significantly lower CD4 count and longer hospitalization than the other diseases. A significant difference was detected between patients outcome and the history of ART. CONCLUSION: Low CD4 count may contribute to an increase in number and length of hospitalization in HIV/AIDS patients. Accordingly, it appears to affect outcome of their treatment and ART was accompanied by a drop in the death rate of hospitalized patients.

Efavirenz severe hypersensitivity reaction: case report and rapid desensitization protocol development.

OBJECTIVE: Long-term efavirenz desensitization protocols have been reported; however, publication of a rapid desensitization protocol has not been noted to date. We report a case of severe hypersensitivity reaction that was successfully managed using a rapid desensitization protocol. CASE SUMMARY: In a 52-year old HIV-positive woman, antiretroviral therapy was started with lamivudine 150 mg twice daily, zidovudine 300 mg twice daily, and efavirenz 600 mg daily. Nine days after starting antiretroviral therapy, she developed a generalized maculopapular rash. Despite concomitant chlorpheniramine administration, the rash did not improve. With suspicion of efavirenz hypersensitivity reaction, efavirenz was discontinued for 5 days and when the patient's rash resolved, the drug was restarted at 600 mg daily. The patient developed a severe generalized pruritic rash the next day and all antiretroviral agents were discontinued. One week later, lamivudine and zidovudine were restarted and were well tolerated. An OBJECTIVE: 20,000 solution of the target therapeutic dose, was successful. The patient was followed for 6 weeks and had no further signs or symptoms of a hypersensitivity reaction. DISCUSSION: Efavirenz hypersensitivity reactions typically include cutaneous reactions that are observed in the first 2 weeks of treatment, are often mild to moderate without systemic manifestation, and improve with continued therapy. Previously, successful desensitization protocols have been described in patients receiving efavirenz who developed rash without systemic symptoms, but these protocols were carried out over 7 or 14 days. This case report indicates a rapid desensitization protocol that may be an available option for some patients. CONCLUSIONS: Considering that efavirenz can be the cornerstone of many antiretroviral therapy regimens and hypersensitivity reactions can restrict regimen options, effective desensitization protocols are valuable, especially in the developing countries with limited available antiretroviral drugs.

Adherence to Antiretroviral Therapy Among Iranian HIV/AIDS Patients

PURPOSE: Treatment adherence of 95% or higher is recommended for appropriate therapeutic response and improving the function of immune system in HIV positive patients. To the best of our knowledge, there was report of adherence to HAART regimen from Iran. In the present study, we have reported the HAART adherence rate of Iranian HIV positive patients. METHOD: In a twelve-month period, all patients older than 18 years old who referred to HIV clinic were on HAART regimen enrolled in the study. Beside demographic and clinical characteristics of Iranian HIV positive patients, Adherence to HAART was assessed by self-report and pill count methods at during the three consecutive months of the patients' visits. RESULTS: The mean of patients' adherence to HAART regimen based on the self-report method was 69.4%, 64.6% and 62.8% in the first, second and third month of follow up, respectively. The mean of adherence rates in three months followup assessed by self-report (65.5%) and pill count (60.4%) methods were correlated significantly (r=0.93 and p<0.001). Living with family members, changing the HAART regimen and stage of disease had a significant relationship with adherence rates. CONCLUSION: Although the adherence level of Iranian HIV infected patients is acceptable compared to other countries, the available antiretroviral medications are limited in our country, therefore, encouraging patients to have higher levels of adherence is more important.

Association of N-acetyltransferase-2 genotypes and anti-tuberculosis induced liver injury; first case-controlled study from Iran.

PURPOSE: The goals of this study were to identify the frequency of N-acetyltransferase-2 genotypes and phenotypes in Iranian tuberculosis and healthy subjects and to evaluate correlation of acetylator phenotype and antituberculosis-induced hepatotoxicity in pulmonary tuberculosis patients. METHOD: A total of 50 newly diagnosed pulmonary tuberculosis patients and 50 healthy Iranian subjects were enrolled in the study. A combination of polymerase chain reaction and restriction fragment length polymorphism were used to investigate N-acetyltransferase-2 alleles. The tuberculosis patients were followed for occurrence of antituberculosis induced hepatotoxicity during the treatment course. Correlation between N-acetyltransferase-2 phenotypes and antituberculosis induced hepatotoxicity was evaluated. RESULTS: Frequency of slow, intermediate and fast acetylator genotypes in the healthy group were 32%, 54% and 14% and in the tuberculosis patients were 28%, 64% and 8%, respectively. Hepatotoxicity was detected in 64.3% of slow acetylators, 15.6% of intermediate acetylators and interestingly in none of the fast acetylators. CONCLUSION: There were no significant difference in distribution of various N-acetyltransferase-2 alleles, genotypes and phenotypes between pulmonary TB patients and healthy individuals. Among patients, anti-tuberculosis induced hepatotoxicity was more frequent in slow acetylators in comparison with fast acetylators in Iranian tuberculosis patients.

Antituberculosis Drug-Induced Hepatotoxicity in IranianTuberculosis Patients: Role of Isoniazid Metabolic Polymorphism.

The aim of this study was to determine the association of n-acetyltransferase-2 polymorphisms and anti-tuberculosis drug-induced hepatotoxicity in Iranian pulmonary tuberculosis patients. Acetylating phenotypes was studied in 50 Iranian pulmonary tuberculosis patients using metabolic ratio of plasma acetyl-Isoniazid to Isoniazid. The association between hepatotoxicity and the n-acetyltransferase-2 phenotype was evaluated by using the chi-square (x(2)) test. The metabolic ratio had a bimodal distribution with an antimode value of 1.0. Based on the metabolic ratio of the mentioned patients, 20 (40%) were slow acetylators and 30 (60%) were fast ones. Hepatotoxicity was manifested in 9 of 20 slow acetylators (45%) and only in 5 of 30 rapid acetylators (16.7%). There was a significant difference in the frequency of hepatotoxicity between the slow and fast acetylators (x(2) = 4.778, and p = 0.03). Sex and age were not found to be risk factors for hepatotoxicity. Our findings show that slow acetylation profile is significantly associated with a higher risk of developing hepatotoxicity due to the anti-TB drugs in Iranian pulmonary tuberculosis patients.

Is there any difference between acetylator phenotypes in tuberculosis patients and healthy subjects?

BACKGROUND AND PURPOSE: Many studies have been done to determine the distribution of acetylator phenotypes among populations of different geographic origin. The goal of this study was to investigate the acetylator phenotypes of the Iranian population and compare them between tubercular patients and healthy subjects. METHODS: The study population consisted of two groups; the first group included 100 newly diagnosed tubercular patients and the second group consisted of 100 healthy subjects. Acetylator phenotype was determined from the metabolic ratio of acetyl-isoniazid to isoniazid in the plasma samples. Metabolic ratio was used to classify subjects as slow (= or < 0.70) or fast acetylators (>0.70). RESULTS: In the tubercular patients, the frequencies of slow and fast acetylator phenotypes were 62 and 38%, respectively. Of the healthy individuals, 45% were found to be slow acetylators and the remaining 55% were fast acetylators. CONCLUSION: It seems that tubercular patients metabolize isoniazid more slowly than healthy individuals.