Liposomal amphotericin for secondary prophylaxis: A systematic review and meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to determine the safety of liposomal amphotericin B (L-AMB) compared to other antifungal agents for secondary prophylaxis. METHOD: We conducted a comprehensive search across international databases and reference lists of articles to compile all relevant published evidence evaluating the efficacy and safety of L-AMB versus other antifungals (NLAMB) for secondary prophylaxis against invasive fungal infections. Pooled estimates were calculated after data transformation to evaluate mortality, breakthrough infections, and the frequency of adverse effects, including hypokalemia and nephrotoxicity. Comparisons of breakthrough fungal infection and mortality between the L-AMB and NLAMB groups were performed. RESULT: We identified 10 studies. The cumulative frequency of patients using L-AMB was 148, compared to 341 patients in the NLAMB group. The mortality rates in the L-AMB and NLAMB groups were 10% and 0%, respectively. However, based on the odds ratio, the mortality in the L-AMB group was lower than that in the NLAMB group. No significant difference was observed in breakthrough invasive fungal infections between the L-AMB and NLAMB groups. The frequencies of nephropathy and hypokalemia in the L-AMB group were 36% and 18%, respectively. CONCLUSION: Our findings indicate a lower incidence of mortality in the L-AMB group compared to the NLAMB group. No statistically significant difference was observed in the incidence of breakthrough infection between the two groups. L-AMB administration is associated with nephropathy and hypokalemia. However, the refusal to continue treatment due to adverse effects is not significantly high.

Mucormycosis, New Causative Agents, and New Susceptible Populations: Review of Cases in a Tertiary Care Hospital in Iran (2007-2021).

Background: Mucormycosis is an aggressive opportunistic fungal infection that afflicts patients with severe underlying immunosuppression, uncontrolled hyperglycemia and/or ketoacidosis, iron overload, and occasionally healthy patients who are inoculated with fungal spores through traumatic injuries. The epidemiology of mucormycosis has changed after the COVID-19 pandemic, with mucormycosis becoming the most common and the fatal coinfection. Methods: In a retrospective, cross-sectional study, 82 hospitalized patients with a definite diagnosis of mucormycosis were reported from 2007 to 2021 in a referral, tertiary care center in Tehran, Iran. Results: The number of post-COVID cases increased 4.6 times per year, with 41.5% of patients admitted during the two years of the pandemic. Mucormycosis was more common in women (57.3%), and the most common underlying diseases were diabetes (43.7%), both COVID-19 and diabetes (23.2%), cancer (11%), rheumatic diseases (7.3%), COVID-19 without other underlying diseases (6.1%), and transplantation (4.9%). Rhino-orbito-cerebral Mucormycosis (54.9%) followed by Sino-orbital infection (23.2%) was the most common presentation. There was a significant relationship between the use of immunosuppressive agents and the development of Mucormycosis (P<0.005) The average mortality was 41.5%, but this ratio decreased to 35% during the pandemic era. Conclusion: The COVID-19 pandemic caused a 4.6-fold increase in the number of mucormycosis patients, and there was a significant relationship between hyperglycemia, corticosteroid use, and mucormycosis. The death rate during the COVID-19 pandemic has decreased by 6.5%, and during the COVID period, the interval between the arrival of a patient with mucormycosis and the start of the correct treatment was significantly decreased.

Evaluation of vancomycin pharmacokinetics in patients with augmented renal clearances: A randomized clinical trial.

Purpose: Vancomycin is a narrow therapeutic window glycopeptide antibiotic that acts against Gram-positive bacteria. As it is renally eliminated, therapeutic drug monitoring is recommended for vancomycin, especially in case of kidney function alteration. Augmented renal clearance (ARC), defined as a creatinine clearance of more than 130 ml/min, is a risk factor for sub-therapeutic concentrations of vancomycin. This study aimed to evaluate the vancomycin pharmacokinetics following the administration of two different regimens in ARC patients. Methods: A randomized clinical trial (IRCT20180802040665N1) was conducted on patients in need of vancomycin therapy. Eight hours of urine was collected and 56 patients divided into two groups with creatinine clearance of more than 130 ml/min were included in the study. The first group received 15 mg/kg of vancomycin every 12 h and the second group 15 mg/kg every 8 h. After four doses, the peak and trough concentrations were measured from two blood samples. The primary outcome was the percentage of patients who attainted AUC more than 400. The occurrence of acute kidney injury also was evaluated after seven days. Results: The mean age of patients in the every 12 h and every 8 h groups was 44.04 ± 16.55 and 42.86 ± 11.83 years, respectively. While neurosurgical issues were the most common causes of hospitalization, central nervous infections were the most common indications for vancomycin initiation. Urinary creatinine clearance was 166.94 ± 41.32 ml/min in the every 12 h group and 171.78 ± 48.56 ml/min in the every 8 h group. 46.42% of patients in the every 12 h group and 82.14% of patients in the every 8 h group attained AUC/MIC of more than 400 mg × hr/L. None of the patients in the every 12 h group reached more than 15 mcg/ml concentration. At the 7-day follow-up, 10.7% patients in the BD group and 28.6% patients in the TDS group developed acute kidney injury (p = 0.089). Conclusion: Administration of vancomycin at a dose of 15 mg/kg every 8 h is associated with higher pharmacokinetic attainment in ARC patients. The occurrence of acute kidney injury also was not significantly higher in this therapeutic regimen. AUC/MIC monitoring is necessary in this population.

Evaluation of the epidemiologic, clinical, radiologic, and treatment methods of patients with subacute and chronic meningitis.

BACKGROUND: Meningitis is known as a meningeal inflammation accompanied by pleocytosis in the cerebrospinal fluid (CSF), and can be classified into acute, subacute, and chronic meningitis based on symptoms duration of ≤ 5 days, ≥ 5 days and ≥ 4 weeks, respectively. Subacute and chronic meningitis are caused mainly by indolent infectious agents and noninfectious causes such as autoimmune, and neoplastic. In this study, we investigated the characteristics, diagnosis, and treatment of subacute and chronic meningitis. METHODS: We extracted the medical records of patients with chronic and subacute meningitis who were referred to three tertiary centers from Jun 2011 to Jun 2021. Initially, 2050 cases of meningitis were screened, and then 79 patients were included in the study. RESULTS: Headache (87.3%), nausea and vomiting (74.7%), fever (56.4%), and visual impairments (55.7%) were the most prevalent symptoms. The most common signs were nuchal rigidity (45.3%), altered mental status (26.9%), and papillary edema (37.5%). Brain computed tomography (CT) was normal in 68.6% of the patients while 22.9% of the cases had hydrocephalus. Brain magnetic resonance imaging (MRI) was normal in 60.0% of the patients. The most common abnormal MRI findings were leptomeningeal enhancement (16.0%) and hydrocephalus (16.0%). We had a 44.3% definite diagnosis with bacterial (n:25, 31.6%) and neoplastic (n:8, 10.1%) being the most prevalent etiologies. Mycobacterium tuberculosis (60%) and Brucella spp. (12%) were the most prevalent bacterial pathogens. CONCLUSIONS: The most common etiologies include infectious, neoplastic, and immunologic. Due to insidious presentation and uncommon etiologies, establishing a proper diagnosis, and providing timely targeted treatment for patients with subacute and chronic meningitis remains a challenge for clinicians.

Meningitis Caused by Cryptococcus neoformans in an Apparently Immunocompetent Patient.

Cryptococcal meningitis (CM), as a life-threatening opportunistic infection, often is among cases with cell-mediated immunodeficiencies, such as AIDS, hematologic malignancies, and solid organ transplant recipients. Cryptococcal meningitis in healthy individuals is uncommon, and its detection in immunocompetent cases may be tricky because the presentation is generally more indolent than the traditional meningitis presentation, leading to late diagnosis and potential sequels. We present a CM case in an immunocompetent Iranian male patient who was treated successfully.

Hematologic malignancies and COVID-19 infection: A monocenter retrospective study.

Introduction: Hematologic malignancies are risk factors for severe COVID-19 infection. Identification of risk factors correlated with mortality in these groups of patients is important in the assessment strategy. We studied the characteristics of patients with hematologic malignancies and COVID-19 and then analyzed the predictors of mortality. Methods: Eligible for the analysis were hospitalized patients with hematologic malignancies and confirmed COVID-19 infection observed between January 2020 and March 2021. Patients were categorized based on the type of malignancy and phase of the treatment. Results: A total of 194 COVID-19 infected patients with hematologic malignancies were included. The median age was 44 (15-81) years; 135 of them were males and 59 were females. Acute myeloid leukemia was the most frequent cancer type (43.8%). A total of 119 patients had severe COVID-19 and 61 patients were admitted to the intensive care unit. A total of 92 deaths occurred in all cases for an overall case-fatality rate of 47%. Male gender, preinduction and induction phase of the treatment, intensive care admission, low levels of oxygen saturation, Rhesus (RH) factor positivity, and higher fibrinogen level correlated with mortality. Conclusion: This study focuses on the epidemiology, risk factors, outcomes, and predictors of mortality of COVID-19 among patients with hematologic malignancies. Patients with hematologic malignancies are at high risk of mortality.

Delayed post-pneumonectomy empyema necessitans caused by Aspergillus flavus: An unusual report.

Post-pneumonectomy empyema (PPE), with or without bronchopleural fistula, is a challenging and serious entity with significant mortality and morbidity. PPE is usually caused by bacteria such as staphylococci, streptococci and also gram-negative rods. Among fungal pathogens, Aspergillus species is a very rare cause of this entity. Herein, we describe an unusual case of delayed post-pneumonectomy empyema necessitans caused by Aspergillus flavus in a 65-year-old man with favourable clinical outcome by combined surgical and antifungal therapy.

An investigation into the beneficial effects of high-dose interferon beta 1-a, compared to low-dose interferon beta 1-a (the base therapeutic regimen) in moderate to severe COVID-19: A structured summary of a study protocol for a randomized controlled l trial.

OBJECTIVES: We will investigate the effectiveness of high dose Interferon Beta 1a, compared to low dose Interferon Beta 1a (the base therapeutic regimen) in COVID-19 Confirmed Cases (Either RT-PCR or CT Scan Confirmed) with moderate to severe disease TRIAL DESIGN: This is a single center, open label, randomized, controlled, 2-arm parallel group (1:1 ratio), clinical trial. PARTICIPANTS: The eligibility criteria in this study is: age ≥ 18 years, oxygen saturation (SPO2) ≤ 93% or respiratory rate ≥ 24, at least one of the following manifestation: radiation contactless body temperature ≥37.8, Cough, shortness of breath, nasal congestion/ discharge, myalgia/arthralgia, diarrhea/vomiting, headache or fatigue on admission. The onset of the symptoms should be acute (≤ 14 days). The exclusion criteria include refusal to participate, using drugs with potential interaction with lopinavir/ritonavir or interferon-ß 1a, blood ALT/AST levels > 5 times the upper limit of normal on laboratory results, pregnant or lactating women, history of alcohol or drug addiction in the past 5 years, the patients who be intubated less than one hours after admission to hospital. This study will be undertaken at the Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences. INTERVENTION AND COMPARATOR: COVID- 19 confirmed patients (using the RT-PCR test or CT scan) will be randomly assigned to one of two groups. The intervention group (Arms1) will be treated with lopinavir / ritonavir (Kaletra) + high dose Interferon-ß 1a (Recigen) and the control group will be treated with lopinavir / ritonavir (Kaletra) + low dose Interferon-ß 1a (Recigen) (the base therapeutic regimen). Both groups will receive standard care consisting of the necessary oxygen support, non-invasive, or invasive mechanical ventilation. MAIN OUTCOMES: Primary outcome: Time to clinical improvement is our primary outcome measure. This is an improvement of two points on a seven-category ordinal scale (recommended by the World Health Organization: Coronavirus disease (COVID-2019) R&D. Geneva: World Health Organization) or discharge from the hospital, whichever comes first. SECONDARY OUTCOMES: mortality from the date of randomization until the last day of the study which will be the day all of the patients have had at least one of the following outcomes: 1) Improvement of two points on a seven-category ordinal scale. 2) Discharge from the hospital 3) Death. Improvement of SPO2 during the hospitalization, duration of hospitalization from date of randomization until the date of hospital discharge or death, whichever comes first. The incidence of new mechanical ventilation uses from the date of randomization until the last day of the study and the duration of it will be extracted. Please note that we are trying to add further secondary outcomes and this section of the protocol is still evolving. RANDOMIZATION: Eligible patients with confirmed SARS-Cov-2 infections will be randomly assigned in a 1:1 ratio to two therapeutic arms using permuted, block-randomization to balance the number of patients allocated to each group. The permuted block (three or six patients per block) randomization sequence will be generated, using Package 'randomizeR' in R software version 3.6.1. and placed in individual sealed and opaque envelopes by the statistician. The investigator will enroll the patients and only then open envelopes to assign patients to the different treatment groups. This method of allocation concealment will result in minimum selection and confounding biases. BLINDING (MASKING): The present research is open-label (no masking) of patients and health care professionals who are undertaking outcome assessment of the primary outcome - time to clinical improvement. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): Of the 100 patients randomised, 50 patients will be assigned to receive high dose Interferon beta-1a plus lopinavir/ritonavir (Kaletra), 50 patients will be assigned to receive low dose Interferon beta 1a plus lopinavir/ritonavir (Kaletra). TRIAL STATUS: Protocol version 1.2.1. Recruitment is finished, the start date of recruitment was on August 20th 2020, and the end date was on September 4th 2020. Last point of data collection will be the last day on which all of the 100 participants have had an outcome of clinical improvement or death, up to 14th days after hospitalization. TRIAL REGISTRATION: This study was registered with National Institutes of Health Clinical trials ( www.clinicaltrials.gov ; identification number NCT04521400, https://clinicaltrials.gov/ct2/show/NCT04521400 , registered August 18, 2020 and first available online August 20, 2020). FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest in expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Cytarabine and Doxorubicin-Induced Palmoplantar Erythrodysesthesia Syndrome: The Possible Role of Voriconazole Interaction.

Palmoplantar Erythrodysesthesia Syndrome (PPES) caused by chemotherapeutic agents is rarely life threatening and requires a reduction in dose or discontinuation of chemotherapy. The use of cytarabine and doxorubicin in the treatment of acute myeloid leukemia (AML) along with voriconazole can potentially alter the metabolism of the drugs and cause some interactions. In this study, we presented a case of AML who received cytarabine and doxorubicin as a chemotherapy regimen and voriconazole as a prophylactic anti-fungal. In this combination, voriconazole probably inhibits the P-glycoprotein pump, which leads to an increase in the cytarabine concentration. The emphasis of this report is the awareness of clinicians and pharmacotherapists about these interactions.

The microbiome and breast cancer: a review.

The human microbiome plays an integral role in physiology, with most microbes considered benign or beneficial. However, some microbes are known to be detrimental to human health, including organisms linked to cancers and other diseases characterized by aberrant inflammation. Dysbiosis, a state of microbial imbalance with harmful bacteria species outcompeting benign bacteria, can lead to maladies including cancer. The microbial composition varies across body sites, with the gut, urogenital, and skin microbiomes particularly well characterized. However, the microbiome associated with normal breast tissue and breast diseases is poorly understood. Collectively, studies have shown that breast tissue has a distinct microbiome with particular species enriched in the breast tissue itself, as well as the nipple aspirate and gut bacteria of women with breast cancer. More importantly, the breast and associated microbiomes may modulate therapeutic response and serve as potential biomarkers for diagnosing and staging breast cancer.

The study of vitamin D administration effect on CRP and Interleukin-6 as prognostic biomarkers of ventilator associated pneumonia.

PURPOSE: In regard with the effect of immune-stimulants in the treatment of infectious diseases, the effect of vitamin D administration on the outcome of patients with Ventilator-Associated Pneumonia (VAP) with a high rate of mortality, was studied. MATERIAL AND METHOD: In this trial, 46 adult patients suffering from VAP and vitamin D deficiency were enrolled. The first group of patients received single intramuscular injection of vitamin D (300000Unit), while the other group were given the placebo. RESULTS: Administration of vitamin D significantly enhanced its levels (P<0.0001) in the treated patients (12.28±8.26) in comparison with placebo group (1.15±1.50). Serum Interleukin-6 levels were significantly reduced in the treated group compared to placebo (P=0.01). Although C-Reactive protein (CRP) levels showed an improving trend in the vitamin D group, no significant difference between groups (P=0.12) was found. Interestingly, the mortality rate of patients that treated with vitamin D (5/24) was significantly lower (p=0.04) than that of the placebo group (11/22). CONCLUSION: Our results indicate that vitamin D administration can significantly reduce the IL-6 as prognostic marker in VAP patients, and must be considered as adjunct option in the treatment of VAP patients.

Evaluation of Renal Toxicity of Colistin Therapy With Neutrophil Gelatinase-associated Lipocalin: a Biomarker of Renal Tubular Damage.

INTRODUCTION: Nephrotoxicity has been a concern with new dosing regimens of colistin. This study was designed to compare nephrotoxicity of high dose and conventional dose of colistin and the ability of detecting it using neutrophil gelatinase-associated lipocalin (NGAL). MATERIALS AND METHODS: A randomized clinical trial was carried out on 40 patients with multidrug-resistant gram-negative infections assigned into 2 groups to receive high and conventional doses of colistin. Blood samples were taken 4 times for measuring serum NGAL. The incidence of acute kidney injury was also evaluated based on the risk, injury, failure, loss, end-stage renal disease (RIFLE) criteria. RESULTS: Baseline levels of NGAL were not significantly different between the patients on the high dose and conventional dose of colistin. The mean NGAL levels on day 10 were 762.14 ± 415.44 pg/mL and 623.67 ± 272.61 pg/mL, respectively.  However, between-group analysis did not show a significant difference in the NGAL levels. The prevalence of acute kidney injury was 60% and 15% based on the RIFLE criteria, in the high-dose and conventional-dose groups, respectively (P = .003). CONCLUSIONS: Although colistin-induced nephrotoxicity was not confirmed with NGAL levels, our findings, however, showed a higher incidence of acute kidney injury associated with high-dose colistin, defined by the RIFLE criteria. Higher levels of NGAL in the acute kidney injury patients were associated with high-dose regimen of colistin.

Nephrotoxicity of High and Conventional Dosing Regimens of Colistin: A Randomized Clinical Trial.

Nephrotoxicity has been a major long-standing concern about colistin.This study was designed to compare nephrotoxicity of high dose and conventional dose of colistin. A randomized open-labeled clinical trial on 40 patients with multi-drug resistant gram negative infections was designed. Patients were allocated into two equal-size groups receiving high (a loading dose of 9 million international units (MIU) and maintenance doses of 4.5 MIU every 12 h) and conventional dose (2 MIU every 8 h) of colistin. Blood samples were taken on day 1, 3, 5, 7 and 10 of treatment for measuring serum cystatin C (Cys C) levels. Incidence of acute kidney injury (AKI) was also evaluated based on RIFLE criteria. Mean ± sd of the difference between baseline and day 10 Cys C levels in high dose and conventional dose groups were 1.61 ± 0.90 and 1.32 ± 0.48, respectively (P = 0.30). Within group analysis showed increase in Cys C levels in both groups (P = 0.001),however, no significant difference in Cys C levels was seen in between groups analysis (P = 0.13). Prevalence of AKI based on RIFLE criteria was 60% and 15% in high dose and conventional dose groups, respectively (P = 0.003). Comparison of Cys C between AKI (mean ± sd) and non-AKI (mean ± sd) patients, irrespective of colistin dosage regimens, confirmed a significant difference (P < 0.0001). Although, colistin-induced nephrotoxicity, determined by Cys C levels, was not confirmed by our findings, however, higher incidence of AKI in high-dose group, defined by RIFLE criteria, along with higher levels of Cys C in AKI patients are supportive of the higher risk of renal toxicity associated with high-dose regimen of colistin. More RCTs with a larger sample size are recommended.

Mixed Pulmonary Infection with Penicillium notatum and Pneumocystis jiroveci in a Patient with Acute Myeloid Leukemia.

UNLABELLED: Penicillium notatum is a fungus that widely exists in the environment and is often non-pathogenic to humans. However, in immunocompromised hosts it may be recognized as a cause of systemic mycosis. A 44-year-old man with acute myeloid leukemia (AML) was admitted to our hospital with fever and neutropenia. Due to no improvement after initial treatment, he underwent bronchoscopy. The patient was found to have P. notatum and Pneumocystis jiroveci infection, and therefore was given voriconazole, primaquine and clindamycin. The patient was successfully treated and suffered no complications. CONCLUSION: This case highlights P. notatum as a cause of infection in immunocompromised patients. To the best of our knowledge, mixed lung infection with P. notatum and P. jiroveci in a patient with AML has not been previously reported.

Statins and postoperative infections: a randomized clinical trial.

BACKGROUND: Observational studies, rather than randomized trials, revealed that statins might be associated with other benefits. OBJECTIVES: The present study aimed at evaluating the preventive effects of lovastatin when used as a prophylactic agent for early and late infective complications after surgery. PATIENTS AND METHODS: A total of 149 patients undergoing elective intracranial and spinal surgeries, were enrolled in a double- blind randomized clinical trial in the department of neurosurgery of a teaching hospital. An amount of 20 mg lovastatin and the same dose of placebo, one day before the operation and three days after the surgery, were used for cases and controls, respectively. The patients were evaluated for local and systemic infections during hospitalization and 10, 30, 60 and 90 days after discharge. RESULTS: A total of 149 patients, 78 men and 71 women with a mean age of 40.3 ± 16.5, were assigned to prophylactic protocols. 46 and 103 patients were in the case and control groups, respectively. Eight episodes of infection were detected, including six bacterial meningitis and two episodes of hospital- acquired pneumonia. All of the patients with documented postoperative infections were part of the placebo group, however, there were no significant statistical differences between the groups (P = 0.059). CONCLUSIONS: In spite of the differences between the two groups, the results did not significantly support the preventive effect of statins in postoperative infections.

Tuberculous liver abscess in an immunocompetent patient: a case report.

INTRODUCTION: Tuberculous or tubercular liver abscess (TLA) is a rare manifestation of extrapulmonary tuberculosis (TB) and it should be considered in the differential diagnosis of mass or cystic lesions of the liver especially in a high TB prevalence country like Iran. CASE PRESENTATION: We report an immunocompetent 48 year-old woman with TLA and peritoneal infection. Although hepatic TLA is very rare, it should be considered in the differential diagnosis of mass or cystic lesions of the liver especially in a high TB prevalence country.