Modulation of host epigenome by coronavirus infections and developing treatment modalities for COVID-19 beyond genetics.

The recent Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) outbreak has resulted in coronavirus disease 2019 (COVID-19) pandemic worldwide, affecting millions of lives. Although vaccines are presently made available, and vaccination drive is in progress to immunize a larger population; still the risk of SARS-CoV-2 infection and related mortality is persistent amid threats of the third wave of the ongoing pandemic. In the scenario of unavailability of robust and efficient treatment modalities, it becomes essential to understand the mechanism of action of the virus and deeply study the molecular mechanisms (both at the virus level and the host level) underlying the infection processes. Recent studies have shown that coronaviruses (CoVs) cause-specific epigenetic changes in the host cells to create a conducive microenvironment for replicating, assembling, and spreading. Epigenetic mechanisms can contribute to various aspects of the SARS-CoV-2 multiplication cycle, like expressing cytokine genes, viral receptor ACE2, and implicating different histone modifications. For SARS-CoV-2 infection, viral proteins are physically associated with various host proteins resulting in numerous interactions between epigenetic enzymes (i.e., histone deacetylases, bromodomain-containing proteins). The involvement of epigenetic mechanisms in the virus life cycle and the host immune responses to control infection result in epigenetic factors recognized as emerging prognostic COVID-19 biomarkers and epigenetic modulators as robust therapeutic targets to curb COVID-19. Therefore, this narrative review aimed to summarize and discuss the various epigenetic mechanisms that control gene expression and how these mechanisms are altered in the host cells during coronavirus infection. We also discuss the opportunities to exploit these epigenetic changes as therapeutic targets for SARS-CoV-2 infection. Epigenetic alterations and regulation play a pivotal role at various levels of coronavirus infection: entry, replication/transcription, and the process of maturation of viral proteins. Coronaviruses modulate the host epigenome to escape the host immune mechanisms. Therefore, host epigenetic alterations induced by CoVs can be considered to develop targeted therapies for COVID-19.

Molecular detection of carbapenem resistance genes in rectal swabs from patients in Gulf Cooperation Council hospitals.

BACKGROUND: Gram-negative organisms harbouring carbapenem resistance genes (CRGs) are spreading globally, including in Gulf Cooperation Council (GCC) countries. However, relatively few data are available about carriage of CRGs in hospitalized patients in this region. AIM: To determine prevalence of CRG carriage and risk factors for colonization among patients in GCC hospitals. METHODS: Rectal swabs were obtained from ∼50 intensive care unit (ICU) patients from each of 11 hospitals in five GCC countries between March and November 2019. The swabs were tested for the presence of blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48 CRG using a commercial polymerase chain reaction test. Data on risk factors for colonization were collected and analysed. FINDINGS: Of 529 specimens screened, 138 (26.1%) were positive for one or more CRGs. The positivity rates among the hospitals ranged from 8.0% to 67.3%; ∼20% of the positive specimens harboured ≥2 CRGs. The most common CRG detected was blaOXA-48, which was present in 82 specimens (15.5%). Additional CRGs included blaNDM, blaVIM, blaKPC, and blaIMP either alone or in combination. Overall, 31.1% of patients on antibiotics on admission to the ICU were positive for CRGs compared to 16.5% not on antibiotic therapy (P < 0.001). CRG detection was also more common among patients aged >65 years (P = 0.027) and increased with hospital length of stay (P = 0.025). CONCLUSION: The rate of CRGs detected in hospitalized patients in GCC countries varied considerably. Prior antibiotic exposure, increasing age, and prolonged length of stay were associated with CRG detection.

Surgical site infection following cesarean section in a general hospital in Kuwait: trends and risk factors.

Surgical site infections (SSI) are a significant cause of post-surgical morbidity and mortality. The objectives of this study were to determine the prevalence of SSI and identify risk factors for infections following cesarean section (CS). A prospective study of SSI after CS was carried out from January 2014 to December 2016 using the methodology of the American National Nosocomial Infection Surveillance System. Suspected SSIs were confirmed clinically by the surgeon, and or, by culture. Seven thousand two hundred thirty five CS were performed with an overall SSI prevalence of 2.1%, increasing from 1.7% in 2014 to 2.95% in 2016 (P = 0.010). Of 152 cases of SSI, the prevalence of infection was 46.7% in women ⩽30 years and 53.3% in women >30 years (P = 0.119). Of 148 culture samples from as many women, 112 (75.7%) yielded growth of microorganisms with 42 (37.5%) of isolates being multi-drug resistant (MDR). Women who did not receive prophylactic antibiotics (35.5%) developed SSI more often than those who did (P < 0.0001). These findings suggest that emergency CS and inappropriate antibiotic prophylaxis are risk factors for developing SSI. In the light of the emergence of MDR bacteria there is a need to implement revised prophylactic antibiotic policy as part of antimicrobial stewardship to decrease SSI rates.

First isolation of Ascotricha chartarum from bronchoalveolar lavage of two patients with pulmonary infections.

Ascotricha chartarum is a rare human pathogen. We describe the isolation and characterization of A. chartarum from bronchoalveolar lavage samples of two patients with underlying pulmonary infections. The identity of both isolates was established by typical phenotypic characteristics and by sequencing of the internal transcribed spacer region and D1/D2 domains of recombinant DNA and ß-tubulin gene fragment. The demonstration of branched, septate hyphae in direct microscopic examination of both the specimens and isolation of the fungus in pure cultures suggest its aetiologic role in the disease process. Because of phenotypic similarities of A. chartarum with Chaetomium spp. and other Chaetomium-like fungi, the application of molecular methods is needed for its accurate identification. Although in the absence of histopathologic evidence the aetiologic role of A. chartarum could not be established unequivocally, nonetheless, in view of the rarity of its isolation from clinical specimens and demonstration of hyphal elements in bronchoalveolar lavage sample, this report assumes considerable significance. It serves to create awareness about environmental fungi that previously have missed attention but may play a role in respiratory infections.

Candiduria: Evidence-based approach to management, are we there yet?

Candiduria is considered one of the most controversial issues in patient management. Neither the diagnosis nor the optimal treatment options are standardized. This is further complicated by lack of defined laboratory criteria for diagnosis as most of the studies were set for bacterial rather than fungal urinary tract infection (UTI). Furthermore, since Candida species is a known commensal of the genitourinary tract its presence in the urine sample adds ambiguity to making a definitive diagnosis of candidal UTI. Guidelines for diagnosis and management of candiduria have changed considerably over the past decades. In 1960s, the condition was believed to be benign with no intervention required. However, over the years new dimensions were added to address the issues associated with candiduria until the latest Infectious Diseases Association of America (IDSA) guidelines were published in 2009, which indicated that there was an increase in the incidence of candiduria caused by more resistant non-Candida albicans species. Further complicating the issue is the observation that candiduria may be the only indicator of a more serious invasive candidiasis, especially in immunocompromised patients. Long-term urinary catheterization is considered to be the most significant risk factor for candiduria followed by antibiotic use and diabetes. Strategies for management are based on the evaluation of candiduria in the context of the clinical setting to determine its relevance and make an appropriate decision about the need for antifungal therapy. Fluconazole is the main drug used for its efficacy and least complications. Other options include bladder irrigation with amphotericin B, flucytosine or parenteral amphotericin B. Since azoles other than fluconazole and all echinocandins are poorly excreted in urine they have been found to be less effective in candiduric patients.

Species spectrum and antifungal susceptibility profile of vaginal isolates of Candida in Kuwait.

OBJECTIVE: The study was undertaken to determine the prevalence of vulvovaginal candidiasis (VVC) among patients with vaginitis, frequency of different Candida species, and their susceptibility profile. PATIENTS AND METHODS: Over six months period, high vaginal swabs were cultured on Sabouraud's dextrose agar and isolates were identified by culture on CHROMagar Candida and Vitek2 yeast identification system or/and API 20C (BioMerieux, France). Antifungal susceptibility of the Candida isolates was determined by E-test against amphotericin B, flucytosine, fluconazole, voriconazole, posaconazole and caspofungin. RESULTS: One thousand seven hundred and fifty-two women with vaginitis were screened for the prevalence of Candida spp. Vaginal swab cultures of 231 (13.2%) women yielded Candida spp. The isolation rates of different species were as follows: Candida albicans (73.9%), Candida glabrata (19.8%), Candida kefir (1.94%), Candida tropicalis (0.96%), Candida parapsilosis (0.96%), Candida krusei (0.96%), Candida guilliermondii (0.96%), and Saccharomyces cerevisiae (0.52%). All strains of C. albicans and non-C. albicans were susceptible to most of the antifungal agents tested. CONCLUSION: The high frequency with which C. albicans was recovered and its azole susceptibility support the continued use of azole agents for empirical therapy of uncomplicated VVC. However, a larger controlled study is required to determine the role of non-C. albicans in recurrent VVC.

Role of early intravenous to oral antibiotic switch therapy in the management of prosthetic hip infection treated with one- or two-stage replacement.

OBJECTIVES: To determine outcomes for an antibiotic regimen using early switch to oral antibiotics for treatment of infected total hip replacement (THR) treated by either a one-stage or two-stage procedure. METHODS: Cases of infected THR were identified from the microbiology records on all orthopaedic infections in a 24 month period. Diagnosis was made by microbiological culture of theatre specimens and findings at the time of surgery. A standard approach of 10-14 days intravenous (iv) antibiotic followed by a switch to oral antibiotics either for 6-8 weeks until second-stage re-implantation or for up to 3 months following a one-stage procedure was used. The exact date of oral switch and antibiotic duration was determined by clinical resolution and C-reactive protein (CRP). Outcome was recorded as no microbiological or clinical evidence of relapse of infection or relapse after completing the antibiotic course. Follow-up duration for all cases at the time of study was 24-36 months after completion of antibiotic treatment. RESULTS: In 24 months, 19 patients underwent two-stage THR for infection, of which 17 were treated with oral antibiotics after a median of 14 days initial iv antibiotics. None relapsed. Four patients underwent one-stage THR and had 12-20 days iv then 6-26 weeks oral antibiotics with no relapse. CONCLUSIONS: Early oral antibiotic switch therapy was effective in patients treated at the Avon Orthopaedic Centre with infected THR and plays an important role in enabling patients to return to independence after revision surgery and avoid complications of prolonged iv access.