Coccidioidomycosis and Host Microbiome Interactions: What We Know and What We Can Infer from Other Respiratory Infections.

Between 70 and 80% of Valley fever patients receive one or more rounds of antibiotic treatment prior to accurate diagnosis with coccidioidomycosis. Antibiotic treatment and infection (bacterial, viral, fungal, parasitic) often have negative implications on host microbial dysbiosis, immunological responses, and disease outcome. These perturbations have focused on the impact of gut dysbiosis on pulmonary disease instead of the implications of direct lung dysbiosis. However, recent work highlights a need to establish the direct effects of the lung microbiota on infection outcome. Cystic fibrosis, chronic obstructive pulmonary disease, COVID-19, and M. tuberculosis studies suggest that surveying the lung microbiota composition can serve as a predictive factor of disease severity and could inform treatment options. In addition to traditional treatment options, probiotics can reverse perturbation-induced repercussions on disease outcomes. The purpose of this review is to speculate on the effects perturbations of the host microbiome can have on coccidioidomycosis progression. To do this, parallels are drawn to aa compilation of other host microbiome infection studies.

Antibiotic use during coronavirus disease 2019 intensive care unit shape multidrug resistance bacteriuria: A Swedish longitudinal prospective study.

Objectives: High frequency of antimicrobial prescription and the nature of prolonged illness in COVID-19 increases risk for complicated bacteriuria and antibiotic resistance. We investigated risk factors for bacteriuria in the ICU and the correlation between antibiotic treatment and persistent bacteria. Methods: We conducted a prospective longitudinal study with urine from indwelling catheters of 101 ICU patients from Uppsala University Hospital, Sweden. Samples were screened and isolates confirmed with MALDI-TOF and whole genome sequencing. Isolates were analyzed for AMR using broth microdilution. Clinical data were assessed for correlation with bacteriuria. Results: Length of stay linearly correlated with bacteriuria (R2 = 0.99, p ≤ 0.0001). 90% of patients received antibiotics, primarily the beta-lactams (76%) cefotaxime, piperacillin-tazobactam, and meropenem. We found high prevalence of Enterococcus (42%) being associated with increased cefotaxime prescription. Antibiotic-susceptible E. coli were found to cause bacteriuria despite concurrent antibiotic treatment when found in co-culture with Enterococcus. Conclusion: Longer stays in ICUs increase the risk for bacteriuria in a predictable manner. Likely, high use of cefotaxime drives Enterococcus prevalence, which in turn permit co-colonizing Gram-negative bacteria. Our results suggest biofilms in urinary catheters as a reservoir of pathogenic bacteria with the potential to develop and disseminate AMR.

Infection prevention and control programme and COVID-19 measures: Effects on hospital-acquired infections in patients with cirrhosis.

Background & Aims: Bacterial infections affect survival of patients with cirrhosis. Hospital-acquired bacterial infections present a growing healthcare problem because of the increasing prevalence of multidrug-resistant organisms. This study aimed to investigate the impact of an infection prevention and control programme and coronavirus disease 2019 (COVID-19) measures on the incidence of hospital-acquired infections and a set of secondary outcomes, including the prevalence of multidrug-resistant organisms, empiric antibiotic treatment failure, and development of septic states in patients with cirrhosis. Methods: The infection prevention and control programme was a complex strategy based on antimicrobial stewardship and the reduction of patient's exposure to risk factors. The COVID-19 measures presented further behavioural and hygiene restrictions imposed by the Hospital and Health Italian Sanitary System recommendations. We performed a combined retrospective and prospective study in which we compared the impact of extra measures against the hospital standard. Results: We analysed data from 941 patients. The infection prevention and control programme was associated with a reduction in the incidence of hospital-acquired infections (17 vs. 8.9%, p <0.01). No further reduction was present after the COVID-19 measures had been imposed. The impact of the infection prevention and control programme remained significant even after controlling for the effects of confounding variables (odds ratio 0.44, 95% CI 0.26-0.73, p = 0.002). Furthermore, the adoption of the programme reduced the prevalence of multidrug-resistant organisms and decreased rates of empiric antibiotic treatment failure and the development of septic states. Conclusions: The infection prevention and control programme decreased the incidence of hospital-acquired infections by nearly 50%. Furthermore, the programme also reduced the prevalence of most of the secondary outcomes. Based on the results of this study, we encourage other liver centres to adopt infection prevention and control programmes. Impact and implications: Infections are a life-threatening problem for patients with liver cirrhosis. Moreover, hospital-acquired infections are even more alarming owing to the high prevalence of multidrug-resistant bacteria. This study analysed a large cohort of hospitalised patients with cirrhosis from three different periods. Unlike in the first period, an infection prevention programme was applied in the second period, reducing the number of hospital-acquired infections and containing multidrug-resistant bacteria. In the third period, we imposed even more stringent measures to minimise the impact of the COVID-19 outbreak. However, these measures did not result in a further reduction in hospital-acquired infections.

Profile of Co-Infection Prevalence and Antibiotics Use among COVID-19 Patients.

Bacterial co-infection in COVID-19 patients significantly contributes to the worsening of the prognosis based on morbidity and mortality. Information on the co-infection profile in such patients could help to optimize treatment. The purpose of this study was to describe bacterial co-infections associated with microbiological, clinical, and laboratory data to reduce or avoid a secondary infection. A retrospective cohort study was conducted at Sant'Anna and San Sebastiano Hospital from January 2020 to December 2021. Bacterial co-infection was detected in 14.3% of the COVID-19-positive patients. The laboratory findings on admission showed significant alterations in the median D-dimer, C-reactive protein, interleukin-6, and lactate dehydrogenase values compared to normal values. All inflammatory markers were significantly elevated. The most common pathogens isolated from blood cultures were E. faecalis and S. aureus. Instead, the high prevalence of respiratory tract infections in the COVID-19 patients was caused by P. aeruginosa (41%). In our study, 220 (82.4%) of the COVID-19 patients received antimicrobial treatment. Aminoglycosides and ß-lactams/ß-lactamase inhibitors showed the highest resistance rates. Our results showed that older age, underlying conditions, and abnormal laboratory parameters can be risk factors for co-infection in COVID-19 patients. The antibiotic susceptibility profile of bacterial pathogen infection provides evidence on the importance, for the clinicians, to rationalize and individualize antibiotic usage.

Changes in appendicitis treatment during the COVID-19 pandemic - A systematic review and meta-analysis.

BACKGROUND: During the COVID-19 pandemic in 2020 a decrease of emergency consultations and modification in treatment of numerous medical conditions were observed. Aim of this paper was to evaluate the effect of the COVID-19 pandemic on incidence, treatment strategies, severity, length of hospital stay and time of presentation in adults and children with acute appendicitis. METHODS: A systematic literature search of Pubmed, Embase and Cochrane databases was performed, and eligible studies used to perform a meta-analysis. RESULTS: 46 suitable studies were identified with an overall reduction of appendicitis cases by 20.9% in adults and an increase of 13.4% in children. The rate of open appendectomies increased without statistical significance in both groups (adults: 8.5% vs. 7.1%, P = 0.32; children: 7.1% vs. 5.3%, P = 0.13), whereas the rate of antibiotic treatment increased significantly (P = 0.007; P = 0.03). Higher rates of complicated appendicitis were observed in adults (adults: OR 2.00, P < 0.0001; children: OR 1.64, P = 0.12). Time to first consultation did not change significantly (adults: 52.3 vs. 38.5 h - P = 0.057; children: 51.5 vs. 32.0 h - P = 0.062) and length of stay was also not lengthened during the pandemic (adults: 2.9 vs. 2.7 days, P = 0.057; children: 4.2 vs. 3.7 days, P = 0.062). CONCLUSION: The COVID-19 pandemic of 2020 had major impact on incidence and treatment strategies of acute appendicitis. Results of this meta-analysis might be another hint to support the theory that appendicitis is not a progressive disease and surgeons can safely consider antibiotic therapy for acute uncomplicated appendicitis.

The impact of COVID-19 on primary health care and antibiotic prescribing in rural China: qualitative study.

BACKGROUND: In China, the primary health care (PHC) system has been designated responsible for control and prevention of COVID-19, but not treatment. Suspected COVID-19 cases presenting to PHC facilities must be transferred to specialist fever clinics. This study aims to understand the impact of COVID-19 on PHC delivery and on antibiotic prescribing at a community level in rural areas of central China. METHODS: Qualitative semi-structured interviews were conducted with 18 PHC practitioners and seven patients recruited from two township health centres and nine village clinics in two rural residential areas of Anhui province. Interviews were transcribed verbatim and analysed thematically. RESULTS: PHC practitioners reported a major shift in their work away from seeing and treating patients (due to government-mandated referral to specialist Covid clinics) to focus on the key public health roles of tracing, screening and educating in rural areas. The additional work, risk, and financial pressure that PHC practitioners faced, placed considerable strain on them, particularly those working in village clinics. Face to face PHC provision was reduced and there was no substitution with consultations by phone or app, which practitioners attributed to the fact that most of their patients were elderly and not willing or able to switch. Practitioners saw COVID-19 as outside of their area of expertise and very different to the non-COVID-19 respiratory tract infections that they frequently treated pre-pandemic. They reported that antibiotic prescribing was reduced overall because far fewer patients were attending rural PHC facilities, but otherwise their antibiotic prescribing practices remained unchanged. CONCLUSIONS: The COVID-19 pandemic had considerable impact on PHC in rural China. Practitioners took on substantial additional workload as part of epidemic control and fewer patients were seen in PHC. The reduction in patients seen and treated in PHC led to a reduction in antibiotic prescribing, although clinical practice remains unchanged. Since COVID-19 epidemic control work has been designated as a long-term task in China, rural PHC clinics now face the challenge of how to balance their principal clinical and increased public health roles and, in the case of the village clinics, remain financially viable.

Lower antibiotic prescription rates in hospitalized COVID-19 patients than influenza patients, a prospective study.

BACKGROUND: COVID-19 patients are extensively treated with antibiotics despite few bacterial complications. We aimed to study antibiotic use in hospitalized COVID-19 patients compared to influenza patients in two consecutive years. Furthermore, we investigated changes in antibiotic use from the first to second pandemic wave. METHODS: This prospective study included both patients from two referral hospitals in Bergen, Norway, admitted with influenza (n = 215) during the 2018/2019 epidemic and with COVID-19 (n = 82) during spring/summer 2020, and national data on registered Norwegian COVID-19 hospital admissions from March 2020 to January 2021 (n = 2300). Patient characteristics were compared, and logistic regression analysis was used to identify risk factors for antibiotic use. RESULTS: National and local COVID-19 patients received significantly less antibiotics (53% and 49%) than influenza patients (69%, p < .001). Early antibiotics contributed to >90% of antibiotic prescriptions in the two local hospitals, and >70% of prescriptions nationally. When adjusted for age, comorbidities, symptom duration, chest X-ray infiltrates and oxygen treatment, local COVID-19 patients still had significantly lower odds of antibiotic prescription than influenza patients (aOR 0.21, 95%CI 0.09-0.50). At the national level, we observed a significant reduction in antibiotic prescription rates in the second pandemic wave compared to the first (aOR 0.35, 95% CI 0.29-0.43). CONCLUSION: Fewer COVID-19 patients received antibiotics compared to influenza patients admitted to the two local hospitals one year earlier. The antibiotic prescription rate was lower during the second pandemic wave, possibly due to increased clinical experience and published evidence refuting the efficacy of antibiotics in treating COVID-19 pneumonia.

Diagnosing hospital bacteraemia in the framework of predictive, preventive and personalised medicine using electronic health records and machine learning classifiers.

Background: The bacteraemia prediction is relevant because sepsis is one of the most important causes of morbidity and mortality. Bacteraemia prognosis primarily depends on a rapid diagnosis. The bacteraemia prediction would shorten up to 6 days the diagnosis, and, in conjunction with individual patient variables, should be considered to start the early administration of personalised antibiotic treatment and medical services, the election of specific diagnostic techniques and the determination of additional treatments, such as surgery, that would prevent subsequent complications. Machine learning techniques could help physicians make these informed decisions by predicting bacteraemia using the data already available in electronic hospital records. Objective: This study presents the application of machine learning techniques to these records to predict the blood culture's outcome, which would reduce the lag in starting a personalised antibiotic treatment and the medical costs associated with erroneous treatments due to conservative assumptions about blood culture outcomes. Methods: Six supervised classifiers were created using three machine learning techniques, Support Vector Machine, Random Forest and K-Nearest Neighbours, on the electronic health records of hospital patients. The best approach to handle missing data was chosen and, for each machine learning technique, two classification models were created: the first uses the features known at the time of blood extraction, whereas the second uses four extra features revealed during the blood culture. Results: The six classifiers were trained and tested using a dataset of 4357 patients with 117 features per patient. The models obtain predictions that, for the best case, are up to a state-of-the-art accuracy of 85.9%, a sensitivity of 87.4% and an AUC of 0.93. Conclusions: Our results provide cutting-edge metrics of interest in predictive medical models with values that exceed the medical practice threshold and previous results in the literature using classical modelling techniques in specific types of bacteraemia. Additionally, the consistency of results is reasserted because the three classifiers' importance ranking shows similar features that coincide with those that physicians use in their manual heuristics. Therefore, the efficacy of these machine learning techniques confirms their viability to assist in the aims of predictive and personalised medicine once the disease presents bacteraemia-compatible symptoms and to assist in improving the healthcare economy.

Antibiotics in treatment of COVID-19 complications: a review of frequency, indications, and efficacy.

OBJECTIVES: To report available information in the literature regarding frequency, indications, types of antibiotic usage, duration, and their efficacy in Covid-19 infected patients. METHODS: The search was conducted on April 30 and May 7, 2020, using Ovid database and Google search. Patients' characteristics, clinical outcomes, as well as selected characteristics regarding antibiotic use (indication, class used, rates and types of bacterial secondary and co-infection, and duration of treatment) were analyzed. RESULTS: Nineteen clinical studies reporting data from 2834 patients were included. Mean rate of antibiotic use was 74.0 % of cases. Half the studies reported occurrence of a bacterial co-infection or complication (10 studies). Amongst the latter, at least 17.6 % of patients who received antibiotics had secondary infections. Pooled data of 4 studies show that half of patients receiving antibiotics were not severe nor critical. Detailed data on antibiotic use lack in most articles. CONCLUSIONS: The present review found a major use of antibiotics amongst Covid-19 hospitalized patients, mainly in an empirical setting. There is no proven efficacy of this practice. Further research to determine relevant indications for antibiotic use in Covid-19 patients is critical in view of the significant mortality associated with secondary infections in these patients, and the rising antimicrobial resistance.

The clinical impact of PCR-based point-of-care diagnostic in respiratory tract infections in children.

BACKGROUND: Children are commonly affected by respiratory tract infections. Based on clinical symptoms, laboratory evaluation, and imaging, the causative pathogen often cannot be delineated. Point-of-care-testing systems that provide an opportunity for fast detection of common viruses and some bacteria can therefore influence treatment's options. We aimed to examine whether the Biofire® FilmArray® has an effect on antibiotic treatment, duration of antibiotic therapy, and length of hospital stay within a pediatric cohort. METHODS: We included children who were admitted to inpatient treatment with an acute respiratory tract infection from 02/2017 to 04/2018 using the FA respiratory panel for pathogen detection. The study group data were compared to the retrospective data of children admitted from 02/2016 to 02/2017, using a proprietary multiplex RT-PCR. RESULTS: A total of 322 children of the study group and 464 children of the control group were analyzed for clinical symptoms, laboratory findings, antibiotic treatment, and length of hospital stay. There was no significant reduction (P < .05) of antibiotic treatment and length of hospital stay. CRP, prehospital antibiotic treatment, antibiotic treatment, past medical history, age, and further pathogen detection showed a significant impact on antibiotic therapy, duration of antibiotic treatment, and length of hospital stay. CONCLUSION: The use of the FA did not result in a significant reduction of antibiotic treatment or in length of hospital stay. Other parameters had a more significant impact. Therefore, we suggest that standard operation procedures with therapy guidelines are necessary to provide an effective application of POCT systems.