Assessment of Risk Factors and Clinical Outcomes in Hospitalized COVID-19 Patients with Candida spp. Co-infections: Species Distribution and Antifungal Susceptibility Patterns of Isolates.

INTRODUCTION: Fungal co-infections are considered an important complication in hospitalized patients with SARS-CoV-2 that can be attributed to disease aggravation, increased mortality, and poor outcomes. This study was conducted to determine the species distribution and antifungal susceptibility patterns of Candida isolates from hospitalized COVID-19 patients in Shiraz, Iran, in addition to associated risk factors and outcomes of co-infections with Candida species. MATERIALS AND METHODS: In this single-center study, a total of 106 hospitalized COVID-19 patients were evaluated for clinical characteristics and outcomes. Species identification was performed by ITS1-5.8S-ITS2 gene sequencing. Antifungal susceptibility testing to fluconazole, itraconazole, voriconazole, posaconazole, caspofungin, amphotericin B, and nystatin was determined according to the M27-A3/S4 CLSI protocol. RESULTS: Candida species were recovered from 48% (51/106) of hospitalized COVID-19 patients. Statistical analysis showed that patients who had heart failure, bacterial co-infection, and were receiving empirical antifungal therapy had a higher risk of developing Candida co-infection. In total, 71 Candida isolates were recovered, of which C. albicans (69%) was the most prevalent isolate. The majority of the Candida isolates were susceptible to all classes of tested antifungal drugs. DISCUSSION: Our results elucidate a high rate of Candida co-infections among hospitalized COVID-19 patients. Comorbidities such as heart failure, HTN, COPD, bacterial infections as well as therapeutic interventions including catheterization, mechanical ventilation, and ICU admission increased the risk of Candida spp. isolation from the bloodstream, respiratory tract and urine samples, which led to a higher in-hospital mortality rate. Additionally, obtained data clarified that empirical antifungal therapy was not as successful as anticipated.

A Review of the Development of Multitarget Molecules against HIV-TB Coinfection Pathogens.

The human immunodeficiency virus (HIV) produces the pathologic basis of acquired immunodeficiency syndrome (AIDS). An increase in the viral load in the body leads to a decline in the number of T lymphocytes, compromising the patient's immune system. Some opportunistic diseases may result, such as tuberculosis (TB), which is the most common in seropositive patients. Long-term treatment is required for HIV-TB coinfection, and cocktails of drugs for both diseases are used concomitantly. The most challenging aspects of treatment are the occurrence of drug interactions, overlapping toxicity, no adherence to treatment and cases of resistance. Recent approaches have involved using molecules that can act synergistically on two or more distinct targets. The development of multitarget molecules could overcome the disadvantages of the therapies used to treat HIV-TB coinfection. This report is the first review on using molecules with activities against HIV and Mycobacterium tuberculosis (MTB) for molecular hybridization and multitarget strategies. Here, we discuss the importance and development of multiple targets as a means of improving adherence to therapy in cases of the coexistence of these pathologies. In this context, several studies on the development of structural entities to treat HIV-TB simultaneously are discussed.

A case report of fatal COVID-19 complicated by rapidly progressive sepsis caused by Klebsiella variicola.

BACKGROUND: There is a growing interest in Klebsiella variicola as a causative pathogen in humans, though its clinical features and the impact of co-infection or secondary infection with COVID-19 remain unknown. CASE PRESENTATION: A 71-year-old man presented with fever, altered mental status and generalized weakness and was admitted to ICU due to severe COVID-19 pneumonia. He was newly diagnosed with type II diabetes mellitus upon admission. On hospital day 3, his respiratory status deteriorated, requiring invasive mechanical ventilation. On hospital day 10, superimposed bacterial pneumonia was suspected and subsequently, broad-spectrum antibiotics were administered for the associated bloodstream infection. On hospital day 13, despite administration of active antibiotics and appropriate source control, he decompensated and died. The causative organism isolated from blood cultures was initially reported as K. pneumoniae, but it was identified as K. variicola by a genetic analysis. A representative isolate (FUJ01370) had a novel multilocus sequence typing allelic profile (gapA-infB-mdh-pgi-phoE-rpoB-tonB: 16-24-21-27-52-17-152), to which sequence type 5794 was assigned (GenBank assembly accession: GCA_019042755.1). CONCLUSIONS: We report a fatal case of respiratory and bloodstream infection due to K. variicola complicating severe COVID-19. Co-infection or secondary infection of K. variicola in COVID-19 is likely under-recognized and can be fulminant as in this case.

Viral hepatitis in persons living with HIV in the post-COVID era.

Coinfection with hepatitis viruses A to E is frequent in persons living with HIV (PLWH) and causes significant morbidity and mortality. Oro-fecal transmissible hepatitis A and E mostly produce acute self-limited episodes in poor income regions and in non-vaccinated travelers. In high-income countries, outbreaks of hepatitis A occur in men having sex with men (MSM) and chronic hepatitis E is occasionally reported among PLWH with severe immunodeficiency. Chronic hepatitis B, C, and D are frequent in PLWH in highly endemic regions and globally in persons who inject drugs (PWID) and MSM. Progression to liver cirrhosis and development of hepatocellular carcinoma (HCC) is major clinical complications in coinfected patients. Current estimates for PLWH are of 38 million worldwide. Roughly 12% have chronic viral hepatitis (5 million). Coinfection figures are of 5-10% for HBV (2-4 million), 4% for HCV (1.5 million), and 15% of HBsAg+ for HDV (0.5 million). Oral direct-acting antivirals (DAA) cure almost all treated patients with hepatitis C. However, given that there is no protective HCV immunity, PLWH with high-risk behaviors may experience HCV reinfection episodes. Tenofovir is the drug of choice in PLWH with chronic hepatitis B, given its dual effect on HIV and HBV. Lifelong oral tenofovir suppresses HBV replication and ameliorate liver damage. However, the risk of HCC persists even in the absence of cirrhosis. Finally, HDV causes the worst of viral hepatitis with faster progression to cirrhosis and HCC. An entry inhibitor, bulevirtide, has recently been approved and another drug, lonafarnib, is completing Phase 3 trials. Combination antiviral therapy for hepatitis D could improve dramatically the poor prognosis of HIV-HDV coinfected patients. The resumption of good medical practices in PLWH after the big disruption caused by COVID-19 will reduce the burden of viral hepatitis coinfections. Renewed efforts on HAV and HBV vaccination of susceptible individuals and earlier and wider prescription of antiviral therapy for HBV, HCV, and/or HDV coinfection should be prioritized in PLWH. The benefits of innovative strategies for viral hepatitis, including pre-exposure prophylaxis or use of long-acting antivirals, warrant further consideration in PLWH.

[Salmonella Bacteremia Accompanying COVID-19: The First Salmonella Co-Infection in the World Unrelated to Pakistan]. / COVID-19'a Eslik Eden Salmonella Bakteremisi: Pakistan ile Iliskisiz Dünyadaki Ilk Salmonella Ko-Enfeksiyonu.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection emerged in China at the end of 2019 and caused coronavirus disease 2019 (COVID-19). The lymphopenia seen in COVID-19 increases the incidence of susceptibility to other microorganisms and may cause co-infections. As the signs and symptoms of the diseases overlap with other infectious diseases and due to the intensity in health services, the diagnosis of co-infections becomes difficult and the treatment may be delayed. Therefore, infections accompanying COVID-19 cause an increase in morbidity and mortality.The isolation and quarantine measures taken during the COVID-19 process have reduced the number of infections transmitted from person to person. However, there was no significant decrease in diseases transmitted by food, such as salmonellosis. During the pandemic, salmonellosis continued to be a problem, especially in endemic areas such as Pakistan, and an increase in Salmonella infections associated with backyard poultry has been reported in countries such as the United States. A co-infection of COVID-19 and enteric fever associated with travel to Pakistan was reported for the first time in the literature in February 2021. In this case report, the first co-infection of COVID-19 and Salmonella in our country was presented. A 56-yearold male patient with no known systemic disease was admitted to the hospital with fever, shortness of breath, weakness and myalgia lasting for three days. SARS-CoV-2 polymerase chain reaction test was positive. The patient has been hospitalized and favipiravir, moxifloxacin, and methylprednisolone were started. Blood cultures were taken from the patient whose clinical picture worsened and fever continued despite of the medical treatment. Salmonella enterica spp. enterica was isolated and ceftriaxone treatment was started. The patient's anamnesis was deepened, but no diarrhea, abdominal pain, suspicious food consumption, travel history were determined. From the second day of the ceftriaxone treatment, the patient's fever decreased and no growth was detected in the control blood cultures. Ceftriaxone treatment was completed in 14 days and the patient was discharged on the 28th day. Approximately 87-95% of Salmonella strains isolated in our country are S.enterica spp. enterica, and S.enterica spp. enterica was also isolated in our case. Salmonella infections most commonly present as gastroenteritis, but the risk of bacteremia increases in case of immunosuppression. Although there was no additional disease in our case, it was considered that the infection in the form of bacteremia occurred due to an immunosuppression caused by COVID-19. In this context; drawing blood cultures of patients hospitalized with the diagnosis of COVID-19 is very important in terms of detecting co-infections and superinfections, and administering appropriate antibiotic therapy at appropriate treatment times. Presentation of first case of Salmonella bacteremia and simultaneous COVID-19 infection in our country was the strong side of our report. In addition, our case is also important as being the first SARS-CoV-2 and Salmonella co-infection unrelated to Pakistan in the literature. The limitation of our case was that S.enterica spp. enterica detected in the blood culture could not be subtyped and the stool culture could not be examined. However, this does not constitute a diagnostic requirement. In addition, the patient's pre-COVID-19 Salmonella carrier status was also unknown. As a result, patients become vulnerable to other infections due to the lymphopenia seen in COVID-19. Therefore, Salmonella bacteremia can be seen with SARS-CoV-2 infection without a comorbid condition. Drawing blood cultures in hospitalized patients with the diagnosis of COVID-19 is very important in terms of detecting concomitant infections in a short time. In patients whose clinical condition does not improve and fever continues despite of treatment, blood cultures should be taken, especially in the case of an advanced immunosuppresive treatment plan, and it should always be kept in mind that secondary infections and co-infections may occur.

Bacterial Co-Infection and Empirical Antibacterial Therapy in Patients With COVID-19.

BACKGROUND: The rate and composition of bacterial co-infection in patients with coronavirus disease 2019 (COVID-19) were evaluated when microbiological testing was conducted on the majority of patients. We also evaluated whether the use of empirical antibacterials was associated with mortality. METHODS: In this retrospective study, all of the adult patients with COVID-19 hospitalized in a single tertiary hospital in South Korea between February 2020 and December 2021 were included. Bacterial co-infection was assessed by sputum cultures, blood cultures, and molecular testing, including polymerase chain reaction sputum testing and urinary antigen tests. Mortality was compared between patients who received empirical antibacterials and those who did not. RESULTS: Of the 367 adult patients admitted during the study period, 300 (81.7%) had sputum culture results and were included in the analysis. Of these 300 patients, 127 (42.3%) had a history of antibiotic exposure. The co-infection rate within 48 hours was 8.3% (25/300): 6.4% (11/173) of patients without prior antibiotic exposure and 11% (14/127) of patients with prior antibacterial exposure. The co-infected bacteria were different according to antibacterial exposure before admission, and multi-drug resistant pathogens were detected exclusively in the antibacterial exposed group. Among the patients without positive results for the microbiological tests, empirical antibacterials were used in 33.3% of cases (100/300). Empirical antibacterial therapy was not significantly related to the 30-day mortality or in-hospital mortality rates in the study cohort before or after the propensity score-matching. CONCLUSION: In this study including only patients underwent microbiological testing, bacterial co-infection was not frequent, and the co-infected organisms varied depending on previous antibacterial exposures. Given the rarity of co-infection and the lack of potential benefits, empiric antibacterial use in COVID-19 should be an important target of antibiotic stewardship.

Antimicrobial resistance in patients with COVID-19: a systematic review and meta-analysis.

BACKGROUND: Frequent use of antibiotics in patients with COVID-19 threatens to exacerbate antimicrobial resistance. We aimed to establish the prevalence and predictors of bacterial infections and antimicrobial resistance in patients with COVID-19. METHODS: We did a systematic review and meta-analysis of studies of bacterial co-infections (identified within ≤48 h of presentation) and secondary infections (>48 h after presentation) in outpatients or hospitalised patients with COVID-19. We searched the WHO COVID-19 Research Database to identify cohort studies, case series, case-control trials, and randomised controlled trials with populations of at least 50 patients published in any language between Jan 1, 2019, and Dec 1, 2021. Reviews, editorials, letters, pre-prints, and conference proceedings were excluded, as were studies in which bacterial infection was not microbiologically confirmed (or confirmed via nasopharyngeal swab only). We screened titles and abstracts of papers identified by our search, and then assessed the full text of potentially relevant articles. We reported the pooled prevalence of bacterial infections and antimicrobial resistance by doing a random-effects meta-analysis and meta-regression. Our primary outcomes were the prevalence of bacterial co-infection and secondary infection, and the prevalence of antibiotic-resistant pathogens among patients with laboratory-confirmed COVID-19 and bacterial infections. The study protocol was registered with PROSPERO (CRD42021297344). FINDINGS: We included 148 studies of 362 976 patients, which were done between December, 2019, and May, 2021. The prevalence of bacterial co-infection was 5·3% (95% CI 3·8-7·4), whereas the prevalence of secondary bacterial infection was 18·4% (14·0-23·7). 42 (28%) studies included comprehensive data for the prevalence of antimicrobial resistance among bacterial infections. Among people with bacterial infections, the proportion of infections that were resistant to antimicrobials was 60·8% (95% CI 38·6-79·3), and the proportion of isolates that were resistant was 37·5% (26·9-49·5). Heterogeneity in the reported prevalence of antimicrobial resistance in organisms was substantial (I2=95%). INTERPRETATION: Although infrequently assessed, antimicrobial resistance is highly prevalent in patients with COVID-19 and bacterial infections. Future research and surveillance assessing the effect of COVID-19 on antimicrobial resistance at the patient and population level are urgently needed. FUNDING: WHO.

Risk factors and effect on mortality of superinfections in a newly established COVID-19 respiratory sub-intensive care unit at University Hospital in Rome.

BACKGROUND: Little is known on the burden of co-infections and superinfections in a specific setting such as the respiratory COVID-19 sub-intensive care unit. This study aims to (i) assess the prevalence of concurrent and superinfections in a respiratory sub-intensive care unit, (ii) evaluate the risk factors for superinfections development and (iii) assess the impact of superinfections on in-hospital mortality. METHODS: Single-center retrospective analysis of prospectively collected data including COVID-19 patients hospitalized in a newly established respiratory sub-intensive care unit managed by pneumologists which has been set up from September 2020 at a large (1200 beds) University Hospital in Rome. Inclusion criteria were: (i) COVID-19 respiratory failure and/or ARDS; (ii) hospitalization in respiratory sub-intensive care unit and (iii) age > 18 years. Survival was analyzed by Kaplan-Meier curves and the statistical significance of the differences between the two groups was assessed using the log-rank test. Multivariable logistic regression and Cox regression model were performed to tease out the independent predictors for superinfections' development and for mortality, respectively. RESULTS: A total of 201 patients were included. The majority (106, 52%) presented severe COVID-19. Co-infections were 4 (1.9%), whereas 46 patients (22%) developed superinfections, mostly primary bloodstream infections and pneumonia. In 40.6% of cases, multi-drug resistant pathogens were detected, with carbapenem-resistant Acinetobacter baumannii (CR-Ab) isolated in 47%. Overall mortality rate was 30%. Prior (30-d) infection and exposure to antibiotic therapy were independent risk factors for superinfection development whereas the development of superinfections was an independent risk factors for in-hospital mortality. CR-Ab resulted independently associated with 14-d mortality. CONCLUSION: In a COVID-19 respiratory sub-intensive care unit, superinfections were common and represented an independent predictor of mortality. CR-Ab infections occurred in almost half of patients and were associated with high mortality. Infection control rules and antimicrobial stewardship are crucial in this specific setting to limit the spread of multi-drug resistant organisms.

Bacterial co-infection and antibiotic stewardship in patients with COVID-19: a systematic review and meta-analysis.

INTRODUCTION: Understanding the proportion of patients with COVID-19 who have respiratory bacterial co-infections and the responsible pathogens is important for managing COVID-19 effectively while ensuring responsible antibiotic use. OBJECTIVE: To estimate the frequency of bacterial co-infection in COVID-19 hospitalized patients and of antibiotic prescribing during the early pandemic period and to appraise the use of antibiotic stewardship criteria. METHODS: Systematic review and meta-analysis was performed using major databases up to May 5, 2021. We included studies that reported proportion/prevalence of bacterial co-infection in hospitalized COVID-19 patients and use of antibiotics. Where available, data on duration and type of antibiotics, adverse events, and any information about antibiotic stewardship policies were also collected. RESULTS: We retrieved 6,798 studies and included 85 studies with data from more than 30,000 patients. The overall prevalence of bacterial co-infection was 11% (95% CI 8% to 16%; 70 studies). When only confirmed bacterial co-infections were included the prevalence was 4% (95% CI 3% to 6%; 20 studies). Overall antibiotic use was 60% (95% CI 52% to 68%; 52 studies). Empirical antibiotic use rate was 62% (95% CI 55% to 69%; 11 studies). Few studies described criteria for stopping antibiotics. CONCLUSION: There is currently insufficient evidence to support widespread empirical use of antibiotics in most hospitalised patients with COVID-19, as the overall proportion of bacterial co-infection is low. Furthermore, as the use of antibiotics during the study period appears to have been largely empirical, clinical guidelines to promote and support more targeted administration of antibiotics in patients admitted to hospital with COVID-19 are required.

Invasive Mucormycosis and Aspergillosis Coinfection Associated with Post-COVID-19 Pneumonia in a Tertiary Care Hospital.

Acute invasive fungal rhinosinusitis is a rare infection primarily affecting patients with co-morbidities like immunosuppression and poorly controlled diabetes. Mucormycosis is increasingly being reported in patients with SARS-CoV-2 (COVID-19). However, reports of coinfection of aspergillosis and mucormycosis involving nose, paranasal sinuses, orbit, and brain are rare in literature. We aimed to evaluate the patient demographics, clinical presentation, and management of cases presenting with mixed infection. We carried out retrospective analysis of 12 patients with confirmed diagnosis of mixed invasive fungal infections post-COVID-19 disease out of 70 cases of COVID-19-associated mucormycosis (CAM) presenting to a tertiary-level hospital in North India from May to June 2021. All patients had diabetes mellitus; the mean age was 48 years. The common presenting features were headache, nasal congestion, palatal ulcer, and vision loss accompanied by facial pain and swelling. Two patients developed cerebral abscess during the course of treatment; three patients had concurrent COVID-19 pneumonia. All patients received systemic liposomal amphotericin B and serial surgical debridements. The overall mortality rate was 16.7%. Our study demonstrates that mucormycosis and aspergillosis are angioinvasive mycoses that are clinically and radiologically identical. KOH direct mount of clinical sample showing septate hyphae should be extensively searched for aseptate hyphae after digestion and clearing of the tissue. A high index of suspicion of mixed infection post-COVID-19 and early initiation of liposomal amphotericin B followed by prompt surgical intervention can reduce the overall morbidity and mortality among patients with this condition.

Corticosteroid treatment in severe patients with SARS-CoV-2 and chronic HBV co-infection: a retrospective multicenter study.

BACKGROUND: The impact of corticosteroids on patients with severe coronavirus disease 2019 (COVID-19)/chronic hepatitis B virus (HBV) co-infection is currently unknown. We aimed to investigate the association of corticosteroids on these patients. METHODS: This retrospective multicenter study screened 5447 confirmed COVID-19 patients hospitalized between Jan 1, 2020 to Apr 18, 2020 in seven centers in China, where the prevalence of chronic HBV infection is moderate to high. Severe patients who had chronic HBV and acute SARS-cov-2 infection were potentially eligible. The diagnosis of chronic HBV infection was based on positive testing for hepatitis B surface antigen (HBsAg) or HBV DNA during hospitalization and a medical history of chronic HBV infection. Severe patients (meeting one of following criteria: respiratory rate > 30 breaths/min; severe respiratory distress; or SpO2 ≤ 93% on room air; or oxygen index < 300 mmHg) with COVID-19/HBV co-infection were identified. The bias of confounding variables on corticosteroids effects was minimized using multivariable logistic regression model and inverse probability of treatment weighting (IPTW) based on propensity score. RESULTS: The prevalence of HBV co-infection in COVID-19 patients was 4.1%. There were 105 patients with severe COVID-19/HBV co-infections (median age 62 years, 57.1% male). Fifty-five patients received corticosteroid treatment and 50 patients did not. In the multivariable analysis, corticosteroid therapy (OR, 6.32, 95% CI 1.17-34.24, P = 0.033) was identified as an independent risk factor for 28-day mortality. With IPTW analysis, corticosteroid treatment was associated with delayed SARS-CoV-2 viral RNA clearance (OR, 2.95, 95% CI 1.63-5.32, P < 0.001), increased risk of 28-day and in-hospital mortality (OR, 4.90, 95% CI 1.68-14.28, P = 0.004; OR, 5.64, 95% CI 1.95-16.30, P = 0.001, respectively), and acute liver injury (OR, 4.50, 95% CI 2.57-7.85, P < 0.001). Methylprednisolone dose per day and cumulative dose in non-survivors were significantly higher than in survivors. CONCLUSIONS: In patients with severe COVID-19/HBV co-infection, corticosteroid treatment may be associated with increased risk of 28-day and in-hospital mortality.

Plant Spices as a Source of Antimicrobial Synergic Molecules to Treat Bacterial and Viral Co-Infections.

The COVID-19 pandemic exposed the lack of antiviral agents available for human use, while the complexity of the physiological changes caused by coronavirus (SARS-CoV-2) imposed the prescription of multidrug pharmacotherapy to treat infected patients. In a significant number of cases, it was necessary to add antibiotics to the prescription to decrease the risk of co-infections, preventing the worsening of the patient's condition. However, the precautionary use of antibiotics corroborated to increase bacterial resistance. Since the development of vaccines for COVID-19, the pandemic scenario has changed, but the development of new antiviral drugs is still a major challenge. Research for new drugs with synergistic activity against virus and resistant bacteria can produce drug leads to be used in the treatment of mild cases of COVID-19 and to fight other viruses and new viral diseases. Following the repurposing approach, plant spices have been searched for antiviral lead compounds, since the toxic effects of plants that are traditionally consumed are already known, speeding up the drug discovery process. The need for effective drugs in the context of viral diseases is discussed in this review, with special focus on plant-based spices with antiviral and antibiotic activity. The activity of plants against resistant bacteria, the diversity of the components present in plant extracts and the synergistic interaction of these metabolites and industrialized antibiotics are discussed, with the aim of contributing to the development of antiviral and antibiotic drugs. A literature search was performed in electronic databases such as Science Direct; SciELO (Scientific Electronic Library Online); LILACS (Latin American and Caribbean Literature on Health Sciences); Elsevier, SpringerLink; and Google Scholar, using the descriptors: antiviral plants, antibacterial plants, coronavirus treatment, morbidities and COVID-19, bacterial resistance, resistant antibiotics, hospital-acquired infections, spices of plant origin, coronaviruses and foods, spices with antiviral effect, drug prescriptions and COVID-19, and plant synergism. Articles published in English in the period from 2020 to 2022 and relevant to the topic were used as the main inclusion criteria.

Antimicrobial prescribing practices at a tertiary-care center in patients diagnosed with COVID-19 across the continuum of care.

In a single-center review of antibiotic prescribing in COVID-19 patients, 10% of patients received antimicrobials, and inpatients encounters had the highest rate and spectrum of prescribing. Prescribing rate, spectrum, and duration appeared to increase with disease severity in inpatients. Antimicrobial prescribing in patients managed in ambulatory encounters was less common.

Bacterial infection in coronavirus disease 2019 patients: co-infection, super-infection and how it impacts on antimicrobial use.

PURPOSE OF REVIEW: Since the beginning of the severe acute respiratory syndrome coronavirus 2 pandemic, there has been a large increase in the consumption of antimicrobials, both as a form of treatment for viral pneumonia, which has been shown to be ineffective, and in the treatment of secondary infections that arise over the course of the severe presentation of coronavirus disease 2019 (COVID-19). This increase in consumption, often empirical, ends up causing an increase in the incidence of colonization and secondary infections by multi and pan-resistant germs. RECENT FINDINGS: The presence of a hyperinflammatory condition induced by the primary infection, associated with the structural damage caused by viral pneumonia and by the greater colonization by bacteria, generally multiresistant, are important risk factors for the acquisition of secondary infections in COVID-19. Consequently, there is an increased prevalence of secondary infections, associated with a higher consumption of antimicrobials and a significant increase in the incidence of infections by multi and pan-resistant bacteria. SUMMARY: Antimicrobial stewardship and improvement in diagnostic techniques, improving the accuracy of bacterial infection diagnosis, may impact the antibiotic consumption and the incidence of infections by resistant pathogens.

Co-infection and ICU-acquired infection in COIVD-19 ICU patients: a secondary analysis of the UNITE-COVID data set.

BACKGROUND: The COVID-19 pandemic presented major challenges for critical care facilities worldwide. Infections which develop alongside or subsequent to viral pneumonitis are a challenge under sporadic and pandemic conditions; however, data have suggested that patterns of these differ between COVID-19 and other viral pneumonitides. This secondary analysis aimed to explore patterns of co-infection and intensive care unit-acquired infections (ICU-AI) and the relationship to use of corticosteroids in a large, international cohort of critically ill COVID-19 patients. METHODS: This is a multicenter, international, observational study, including adult patients with PCR-confirmed COVID-19 diagnosis admitted to ICUs at the peak of wave one of COVID-19 (February 15th to May 15th, 2020). Data collected included investigator-assessed co-infection at ICU admission, infection acquired in ICU, infection with multi-drug resistant organisms (MDRO) and antibiotic use. Frequencies were compared by Pearson's Chi-squared and continuous variables by Mann-Whitney U test. Propensity score matching for variables associated with ICU-acquired infection was undertaken using R library MatchIT using the "full" matching method. RESULTS: Data were available from 4994 patients. Bacterial co-infection at admission was detected in 716 patients (14%), whilst 85% of patients received antibiotics at that stage. ICU-AI developed in 2715 (54%). The most common ICU-AI was bacterial pneumonia (44% of infections), whilst 9% of patients developed fungal pneumonia; 25% of infections involved MDRO. Patients developing infections in ICU had greater antimicrobial exposure than those without such infections. Incident density (ICU-AI per 1000 ICU days) was in considerable excess of reports from pre-pandemic surveillance. Corticosteroid use was heterogenous between ICUs. In univariate analysis, 58% of patients receiving corticosteroids and 43% of those not receiving steroids developed ICU-AI. Adjusting for potential confounders in the propensity-matched cohort, 71% of patients receiving corticosteroids developed ICU-AI vs 52% of those not receiving corticosteroids. Duration of corticosteroid therapy was also associated with development of ICU-AI and infection with an MDRO. CONCLUSIONS: In patients with severe COVID-19 in the first wave, co-infection at admission to ICU was relatively rare but antibiotic use was in substantial excess to that indication. ICU-AI were common and were significantly associated with use of corticosteroids. Trial registration ClinicalTrials.gov: NCT04836065 (retrospectively registered April 8th 2021).

Secondary bacterial infections of the respiratory tract in COVID-19 patients.

INTRODUCTION: Secondary Bacterial Infections (SBIs) of the respiratory system are one of the biggest medical concerns in patients undergoing hospitalization with a diagnosis of COVID-19. This study aims to provide relevant data for the initiation of appropriate empirical treatment after examining the etiology and antimicrobial resistance of SBIs in COVID-19 patients under care in the Intensive Care Units (ICUs) in the largest pandemic hospital of our country. METHODOLOGY: Between March 16, 2020 and December 31, 2021, 56,993 COVID patients were hospitalized, of which 7684 were admitted to ICUs. A total of 1513 patients diagnosed with SBIs have been included in this study. During the course of the study, demographic data, clinical course, etiology and antimicrobial resistance data of all patients were collected. RESULTS: The most common causative agents of SBIs were inferred as Acinetobacter baumanii (35.1%), Staphylococcus aureus (15.2%), Klebsiella pneumoniae (12.3%) and Pseudomonas aeruginosa (10.4%). The isolation rates of carbapenem-resistant and colistin-resistant A. baumannii, K. pneumoniae and P. aeruginosa were 83.7%; 42.7%, 79.2%, and 5.6%, 42.7%, 1.7%, respectively. Acinetobacter pittii clustering was seen in one of the ICUs in the hospital. Multidrug resistant 92 (5.4%) Corynebacterium striatum isolates were also found as a causative agent with increasing frequency during the study period. CONCLUSIONS: SBI of the respiratory system is one of the major complications in patients hospitalized with COVID-19. The antimicrobial resistance rates of the isolated bacteria are generally high, which indicates that more accurate use of antibacterial agents is necessary for SBIs in patients hospitalized with COVID-19 diagnosis.

Clostridioides difficile co-infection in patients with COVID-19.

Aim: To assess the impact of Clostridioides difficile infection on the course of COVID-19. Methods: The authors included 809 patients with COVID-19 in this retrospective study: 55 had C. difficile infection, 23 had C. difficile-negative antibiotic-associated diarrhea and 731 had no diarrhea. C. difficile in feces was determined by immunochromatographic test for its toxins. Results:C. difficile infection was associated with increased risk of death (hazard ratio = 2.6; p = 0.021), especially after 20 days of disease (hazard ratio = 6.5; p < 0.001). C. difficile infection-associated diarrhea was longer and more severe than C. difficile-negative antibiotic-associated diarrhea. Unlike patients with C. difficile-negative antibiotic-associated diarrhea, patients with C. difficile infection were admitted to the intensive care unit and needed mechanical ventilation more often than those without diarrhea. Conclusion:C. difficile infection worsens the course and prognosis of COVID-19.

Patients with COVID-19 usually receive antibiotic treatment, which predisposes them to antibiotic-associated diarrhea. In some cases, antibiotic-associated diarrhea can be caused by Clostridioides difficile bacteria. To learn more about the impact of C. difficile infection on COVID-19, the authors analyzed data from the medical records of 809 patients with COVID-19. The authors found that C. difficile co-infection worsens the course and prognosis of COVID-19. The authors suggest that patients with COVID-19 who develop diarrhea after taking antibiotics be tested for C. difficile and treated for this co-infection if the test is positive.

Antifungal therapy in the management of fungal secondary infections in COVID-19 patients: A systematic review and meta-analysis.

OBJECTIVES: The prevalence of fungal secondary infections among COVID-19 patients and efficacy of antifungal therapy used in such patients is still unknown. Hence, we conducted this study to find the prevalence of fungal secondary infections among COVID-19 patients and patient outcomes in terms of recovery or all-cause mortality following antifungal therapy (AFT) in such patients. METHODS: We performed a comprehensive literature search in PubMed®, Scopus®, Web of Sciences™, The Cochrane Library, ClinicalTrial.gov, MedRxiv.org, bioRxiv.org, and Google scholar to identify the literature that used antifungal therapy for the management fungal secondary infections in COVID-19 patients. We included case reports, case series, prospective & retrospective studies, and clinical trials. Mantel Haenszel random-effect model was used for estimating pooled risk ratio for required outcomes. RESULTS: A total of 33 case reports, 3 case series, and 21 cohort studies were selected for final data extraction and analysis. The prevalence of fungal secondary infections among COVID-19 patients was 28.2%. Azoles were the most commonly (65.1%) prescribed AFT. Study shows that high survival frequency among patients using AFT, received combination AFT and AFT used for >28 days. The meta-analysis showed, no significant difference in all-cause mortality between patients who received AFT and without AFT (p = 0.17), between types of AFT (p = 0.85) and the duration of AFT (p = 0.67). CONCLUSION: The prevalence of fungal secondary infections among COVID-19 patients was 28.2%. The survival frequency was high among patients who used AFT for fungal secondary infections, received combination AFT and AFT used for >28 days. However, meta-analysis results found that all-cause mortality in COVID-19 patients with fungal secondary infections is not significantly associated with type and duration of AFT, mostly due to presence of confounding factors such as small number of events, delay in diagnosis of fungal secondary infections, presence of other co-infections and multiple comorbidities.

A Comparative Study on Bacterial Co-Infections and Prevalence of Multidrug Resistant Organisms among Patients in COVID and Non-COVID Intensive Care Units.

Introduction: Secondary bacterial infections have been reported in majority of patients hospitalized with coronavirus disease 2019 (COVID-19). A study of the antimicrobial susceptibility profiles of these bacterial strains revealed that they were multidrug resistant, demonstrating their resistance to at least three classes of antimicrobial agents including beta-lactams, fluoroquinolones and aminoglycosides. Bacterial co-infection remains as an important cause for high mortality in patients hospitalized with COVID-19. Methods: In our study, we conducted a retrospective comparative analysis of bacterial co-infections and the antimicrobial resistance profile of bacterial isolates obtained from inpatients admitted in COVID-19 and non-COVID-19 intensive care units. The goal was to obtain the etiology and antimicrobial resistance of these infections for more accurate use of antimicrobials in clinical settings. This study involved a total of 648 samples collected from 356 COVID-19 positive patients and 292 COVID-19 negative patients admitted in the intensive care unit over a period of six months from May to October 2020. Results: Among the co-infections found, maximum antimicrobial resistance was found in Acinetobacter species followed by Klebsiella species in both the ICU's. Incidence of bacterial co-infection was found to be higher in COVID-19 intensive care patients and most of these isolates were multidrug resistant strains. Conclusion: Therefore, it is important that co-infections should not be underestimated and instead be made part of an integrated plan to limit the global burden of morbidity and mortality during the SARS-CoV-2 pandemic and beyond.