Treatment of multidrug-resistant Gram-negative bloodstream infections in critically ill patients: an update.

PURPOSE OF REVIEW: This review describes the latest information in the management of bloodstream infections caused by multidrug-resistant Gram-negative bacilli (MDRGNB) in critically ill patients. RECENT FINDINGS: The prevalence of bloodstream infections due to MDRGNB is high, and they pose a significant risk in critically ill patients. Recently, novel antimicrobial agents, including new ß-lactam/ß-lactamase inhibitor combinations and cefiderocol, have been introduced for treating these infections. Concurrently, updated guidelines have been issued to aid in treatment decisions. Prompt diagnosis and identification of resistance patterns are crucial for initiating effective antibiotic therapy. Current studies, especially with observational design, and with limited sample sizes and patients with bacteremia, suggest that the use of these new antibiotics is associated with improved outcomes in critically ill patients with MDRGNB bloodstream infections. SUMMARY: For critically ill patients with bloodstream infections caused by MDRGNB, the use of newly developed antibiotics is recommended based on limited observational evidence. Further randomized clinical trials are necessary to determine the most effective antimicrobial therapies among the available options.

Randomized trial of dentists' understanding: treatment benefit in absolute numbers vs relative risk reduction.

This study aimed to assess whether dentists correctly understand the benefit of a dental treatment when it is presented using absolute numbers or relative risk reduction (RRR). This parallel-group randomized controlled trial recruited dentists from 3 postgraduate courses in Rio de Janeiro, Brazil. Participants received, in sequentially numbered sealed opaque envelopes, the description of a hypothetical scenario of the benefit (avoidance of multiple tooth loss) of nonsurgical periodontal treatment without or with antibiotics. Treatment benefit was presented in 2 different formats: absolute numbers or RRR. Dentists were given 10 minutes to read the treatment scenario and answer 5 questions. The final sample for analysis included 101 dentists. When asked to estimate the number of patients out of 100 who would avoid multiple tooth loss without antibiotics, 17 dentists (33%) in the absolute numbers group and 12 (25%) in the RRR group provided the correct response (p = 0.39). Regarding treatment with antibiotics, 26 dentists (50%) in the absolute numbers group and 14 (29%) in the RRR group provided the correct response (p = 0.04). Only 16 dentists (31%) in the absolute numbers group and 12 (25%) in the RRR group gave correct answers for both questions (p = 0.51). Most dentists did not correctly understand the benefit of the treatment, irrespective of the format it was presented. Slightly more dentists correctly understood the benefit of the treatment when it was presented as absolute numbers than as RRR.

Change in Klebsiella pneumoniae susceptibility profile after the arrival of ceftazidime-avibactam in an Argentinean intensive care unit: a new ecological landscape.

OBJECTIVE: Ceftazidime-avibactam (CZA) is a good option for Gram-negative bacilli infections that produce carbapenemase Classes A (especially blaKPC) and D (blaOXA). However, it is unknown whether it would have an impact on metallo-ß-lactamases (blaMBL) selection. The aim of the study was to compare carbapenem and CZA Klebsiella pneumoniae (KPN) susceptibility profiles for a period of two years following the introduction of CZA. METHODS: The study was conducted in a 36-bed adult ICU of a tertiary hospital in Buenos Aires, Argentina. Antimicrobial consumption was expressed as days of treatment per 100 patients-day (DOT). RESULTS: A total of 123 KPN strains in the first year and 172 in the second year were analyzed. An alarming decrease in carbapenem susceptibility was detected in the second year (OR 0.5 [0.3-0.8] p<.001). In parallel, there was a decrease in CZA susceptibility (OR 0.5 [0.3-0.9] p<.05). These findings were linked to a rise in blaMBL-KPN (32.1% vs. 45.1%, OR 1.7 [1.1-2.9], p <.04) during the second year. This new KPN susceptibility profile promoted an increment in CZA (1.0 DOT vs. 6.6 DOT, OR 6.6 [4.9-9.1] p<.001) and aztreonam (0.3 DOT vs. 4.1 DOT, OR 16.3 [9.1-29.3] p<.001) consumption. Thus, there was a decrease in carbapenem prescription (17.8 DOT vs. 15.4 DOT, OR 0.8 [0.8-0.9] p<.001). CONCLUSIONS: There was an escalation of blaMBL-KPN rate two years after CZA introduction, leading to a decrease in CZA and carbapenem susceptibility and an increase in CZA and aztreonam prescriptions.

Access to and utilisation of antimicrobials among forcibly displaced persons in Uganda, Yemen and Colombia: a pilot cross-sectional survey.

OBJECTIVES: Identifying key barriers to accessing quality-assured and affordable antimicrobials among forcibly displaced persons in Uganda, Yemen and Colombia and investigating their (1) utilisation patterns of antibiotics, (2) knowledge about antimicrobial resistance (AMR) and (3) perception of the quality of antimicrobials received. DESIGN: Pilot cross-sectional survey. SETTING: Data were collected from five health facilities in the Kiryandongo refugee settlement (Bweyale, Uganda), three camps for internally displaced persons (IDPs) in the Dar Sad district (Aden, Yemen) and a district with a high population of Venezuelan migrants (Kennedy district, Bogotá, Colombia). Data collection took place between February and May 2021. The three countries were selected due to their high number of displaced people in their respective continents. PARTICIPANTS: South Sudanese refugees in Uganda, IDPs in Yemen and Venezuelan migrants in Colombia. OUTCOME MEASURE: The most common barriers to access to quality-assured and affordable antimicrobials. RESULTS: A total of 136 participants were enrolled in this study. Obtaining antimicrobials through informal pathways, either without a doctor's prescription or through family and friends, was common in Yemen (27/50, 54.0%) and Colombia (34/50, 68.0%). In Yemen and Uganda, respondents used antibiotics to treat (58/86, 67.4%) and prevent (39/86, 45.3%) a cold. Knowledge of AMR was generally low (24/136, 17.6%). Barriers to access included financial constraints in Colombia and Uganda, prescription requirements in Yemen and Colombia, and non-availability of drugs in Uganda and Yemen. CONCLUSION: Our multicentred research identified common barriers to accessing quality antimicrobials among refugees/IDPs/migrants and common use of informal pathways. The results suggest that knowledge gaps about AMR may lead to potential misuse of antimicrobials. Due to the study's small sample size and use of non-probability sampling, the results should be interpreted with caution, and larger-scale assessments on this topic are needed. Future interventions designed for similar humanitarian settings should consider the interlinked barriers identified.

Medication Use Among Pregnant Women With SARS-CoV-2 Infection and Risk of Hospitalization-A Study in Two Brazilian Hospitals.

There is limited evidence about the use of medications among pregnant women with COVID-19, as well as risk factors for hospitalization due to COVID-19 in pregnancy. We aimed to describe the use of medications among SARS-CoV-2-positive pregnant women at the time around infection and identify predictors for hospitalization due to COVID-19 in two hospitals in Brazil. This is a hospital record-based study among pregnant women with positive SARS-CoV-2 tests between March 2020 and August 2022 from two Brazilian hospitals. Characteristics of sociodemographic, obstetrical, and COVID-19 symptoms were extracted retrospectively. The prevalence use of medications was based on self-reported use, and this was administered at the hospital. Logistic regression was used to estimate predictors of hospitalization due to COVID-19. There were 278 pregnant women included in the study, of which 41 (14.7%) required hospitalization due to COVID-19. The remaining 237 (85.3%) had mild symptoms or were asymptomatic. Most of the women had the infection in the third trimester (n = 149; 53.6%). The most prevalent medications used across all trimesters were analgesics (2.4% to 20.0%), antibacterials (15.0% to 23.1%), and corticosteroids (7.2% to 10.4%). Pre- or gestational hypertensive disorder (odds ratio (OR) 4.94, 95% confidence interval (CI) 1.65, 14.87) and having at least one dose of vaccine against SARS-CoV-2 (OR 0.13, 95% CI 0.04, 0.39) were associated with hospitalization due to COVID-19. Analgesics, antibacterials, and corticosteroids were the most frequently used medications among pregnant women with COVID-19. Women with hypertensive disorders have almost a five-fold increased risk of hospitalization due to COVID-19. Vaccination was the strongest protective factor for severe COVID-19. The COVID-19 vaccination among pregnant women should be promoted, and pregnant women diagnosed with COVID-19 who have hypertensive disorders should be closely monitored.

Mimicry of Rhabdomyosarcoma by Tonsillar Actinomycosis: Case Report.

Actinomycosis is a rare infectious disease characterized by slowly progressive, chronic suppurative lesions, often mistaken for malignancies due to its ability to mimic them. It is caused by Actinomyces bacteria, which are part of the normal flora of the human oropharynx, gastrointestinal, and urogenital tracts. This case report describes a 51-year-old male with a history of mandibular rhabdomyosarcoma presenting with severe shoulder and hip pain, dysphagia, and headaches, initially suspected to be a cancer recurrence. However, after further investigation, including a PET-CT and tonsillectomy, the diagnosis of actinomycosis was confirmed through histopathological examination. The case highlights the diagnostic challenges of actinomycosis, especially in patients with complex clinical histories, emphasizing the importance of considering it as a differential diagnosis in similar presentations. The patient was treated with long-term antibiotic therapy, predominantly beta-lactams, demonstrating the necessity of a comprehensive diagnostic approach and the implications of a delayed diagnosis. This case underscores the critical need for high clinical suspicion and awareness among healthcare professionals regarding the potential for actinomycosis to mimic more common diseases, ensuring timely and accurate treatment.

Bacteriophage therapy- a refurbished age-old potential strategy to treat antibiotic and multidrug resistant bacterial infections in future.

The worldwide prevalence of antimicrobial resistance coupled with the unavailability of newer antibiotics, has brought the sharp focus back among the scientific community, towards the discovery of novel alternative therapeutics to tackle the menace. Consequently, in the current post-antibiotic era, 'Bacteriophage Therapy' has emerged as one of the most promising option to address this problem. Bacteriophages, actually discovered long back, has shown greater potential to kill various bacterial pathogens, including the resistant clinical ones. Some of the other advantages for the use of bacteriophage therapy to treat infectious diseases include, wider availability of these microorganisms in nature, host-specific action, absence of any significant side-effects in humans and most often also exhibiting a broader anti-bacterial potential. In the recent times, the potential of phage therapy has been demonstrated in various treatments, clinical trials and infection models across the globe, where even antibiotics have completely failed. To address the global threat of AMR, WHO and UN have jointly illustrated "One Health" approach, recently extending the context to bacteriophage therapy. Many pharmaceutical companies have also recently started employing bacteriophages for developing different kinds of formulations for catering to medical and other industries. It has even shown great effect as combinatorial therapy along with antibiotics, to treat or manage various critical antibiotic resistant clinical infections. This continuously expanding potential of the bacteriophages holds great promise in the future, in the fight against the rising threat of AMR globally.

Seven-day antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients: toward a new paradigm.

PURPOSE: Data on short courses of antibiotic therapy for Enterobacterales bacteremia in high-risk neutropenic patients are limited. The aim of the study was to describe and compare the frequency of bacteremia relapse, 30-day overall and infection-related mortality, Clostridiodes difficile infection and length of hospital stay since bacteremia among those who received antibiotic therapy for 7 or 14 days. METHODS: This is a multicenter, prospective, observational cohort study in adult high-risk neutropenic patients with hematologic malignancies or hematopoietic stem cell transplant and monomicrobial Enterobacterales bacteremia. They received appropriate empirical antibiotic therapy, had a clinical response within 7 days, and infection source control. Clinical, epidemiological and outcomes variables were compared based on 7 or 14 days of AT. RESULTS: Two hundred patients were included (100, 7-day antibiotic therapy; 100, 14-day antibiotic therapy). Escherichia coli was the pathogen most frequently isolated (47.5%), followed by Klebsiella sp. (40.5%). Among those patients that received 7-day vs. 14-day antibiotic course, a clinical source of bacteremia was found in 54% vs. 57% (p = 0.66), multidrug-resistant Enterobacterales isolates in 28% vs. 30% (p = 0.75), and 40% vs. 47% (p = 0.31) received combined empirical antibiotic therapy. Overall mortality was 3% vs. 1% (p = 0.62), in no case related to infection; bacteremia relapse was 7% vs. 2% (p = 0.17), and length of hospital stay since bacteremia had a median of 9 days (IQR: 7-15) vs. 14 days (IQR: 13-22) (p = < 0.001). CONCLUSIONS: These data suggest that seven-day antibiotic therapy might be adequate for patients with high-risk neutropenia and Enterobacterales bacteremia, who receive appropriate empirical therapy, with clinical response and infection source control.

Are Mycoplasma pneumoniae coinfections frequent in COVID-19 patients? A systematic review.

Understanding the proportion of SARS-CoV-2 patients with Mycoplasmapneumoniae coinfection is crucial for treating patients suffering from coronavirus disease (COVID-19), help to ensure responsible use of antibiotics and minimize the negative consequences of overuse. In addition, this knowledge could have an impact on empirical antibiotic management guidelines for patients with COVID-19. This systematic review aimed to identify the prevalence of M. pneumoniae in patients with coronavirus disease 2019 (COVID-19). A bibliographic search of studies published in Spanish or English was conducted using the PubMed search engine. Fourteen articles from different continents (America, Asia and Europe) were included, involving a total of 5855 patients in these studies. The mean age of COVID-19 patients with M. pneumoniae was 48 years old (range 1-107), most of whom were male. The detection of laboratory-confirmed M. pneumoniae infection varied between 0 and 33.3%. Most of patients referred fever, cough, and dyspnea, and received empirical antibiotic treatment. Bacterial coinfection was not associated with increased ICU admission and mortality. The prevalence of coinfection showed extremely dissimilar figures according to the population studied and diagnostic criteria. However, it is important to develop Latin American studies, given the heterogeneity observed in the studies conducted in different countries. Standardized definitions should be developed in order to be able to assess the impact of coinfections in patients with a diagnosis of COVID-19.

Switching Vancomycin Monitoring From Trough Concentration to Area Under the Curve Estimation by Bayesian Forecasting: A Short Communication on a Cost-Benefit Study in Resource-Limited Settings.

BACKGROUND: This study was conducted to evaluate the cost-benefit indicators of a vancomycin monitoring protocol based on area under the curve estimation using commercial Bayesian software. METHODS: This quasi-experimental study included patients who were aged >18 years with a vancomycin prescription for >24 hours. Patients who were terminally ill or those with acute kidney injury (AKI) ≤24 hours were excluded. During the preintervention period, doses were adjusted based on the trough concentration target of 15-20 mg/L, whereas the postintervention period target was 400-500 mg × h/L for the area under the curve. The medical team was responsible for deciding to stop the antimicrobial prescription without influence from the therapeutic drug monitoring team. The main outcomes were the incidence of AKI and length of stay. Cost-benefit simulation was performed after statistical analysis. RESULTS: There were 96 patients in the preintervention group and 110 in the postintervention group. The AKI rate decreased from 20% (n = 19) to 6% (n = 6; P = 0.003), whereas the number of vancomycin serum samples decreased from 5 (interquartile range: 2-7) to 2 (interquartile range: 1-3) examinations per patient ( P < 0.001). The mean length of hospital stay for patients was 26.19 days after vancomycin prescription, compared with 17.13 days for those without AKI ( P = 0.003). At our institution, the decrease in AKI rate and reduced length of stay boosted yearly savings of up to US$ 369,000 for 300 patients receiving vancomycin therapy. CONCLUSIONS: Even in resource-limited settings, a commercial Bayesian forecasting-based protocol for vancomycin is important for determining cost-benefit outcomes.

Bone and Joint Infections in Children With Sickle Cell Disease in French Guiana: A 13-Year Retrospective Multicenter Review.

INTRODUCTION: Sickle cell disease (SCD) is a genetic disorder with a high infectious morbidity and mortality and a heterogeneous distribution in France. One of the challenges is to differentiate a bone and joint infection (BJI) from a vaso-occlusive crisis. This challenge is particularly prevalent in French Guiana, an overseas territory with the highest incidence of SCD in France. The aim of this study was to describe the epidemiology of BJI in children with SCD in French Guiana. METHOD: This was a retrospective multicentric descriptive study of SCD patients living in French Guiana aged under 18 and diagnosed with a BJI between 2010 and 2022. These BJI were divided into 2 groups: those with microbiological documentation (d-BJI) and those without microbiological identification (ud-BJI). RESULTS: A total of 53 episodes of BJI in 42 patients (mean age 7.2 years) were reported. Clinical symptoms on arrival were comparable between the d-BJI and ud-BJI groups. Patients in the d-BJI group had longer average hospital stays (40.4 days vs. 16.8 days, P = 0.01) and Salmonella spp. were the most identified bacteria (n = 8/13). White blood cell count was greater in the d-BJI group (30.3 G/L vs. 18.G/L, P = 0.01) and a collection was more frequently identified on imaging (11/13 vs. 16/40, P = 0.01) in this group. Initial in-hospital antibiotic therapy was longer in the d-BJI group (17.2 days vs. 12.8, P = 0.02), as were infection-related complications (9/13 vs. 12/40 P = 0.01). CONCLUSION: BJI in children with SCD is not sufficiently microbiologically documented. Progress must be made to improve the documentation of BJI.

Evaluation of children's antibiotics use for outpatient pneumonia treatment in Vietnam.

OBJECTIVE: Antibiotic resistance is increasing globally, associated with many failures in pneumonia treatment. This study aimed to evaluate antibiotic use in children treated for outpatient CAP (Community-Acquired Pneumonia). METHODS: A cross-sectional descriptive retrospective study was conducted, focusing on data from outpatient prescriptions for pneumonia in patients aged 2‒192 months in 2019‒2021. RESULTS: All antibiotic prescriptions are considered empiric as no documented bacterial and viral tests exist for children with non-severe CAP. Single antibiotic therapy (66%) had a 2-fold higher rate than combination therapy (34%). Amoxicillin/clavulanic acid (50.77%) and azithromycin (30.74%) were the most commonly prescribed in both single and combination therapies, thus determining antibiotic cost (80.15%). Besides, azithromycin (97.92%), cefuroxime (86.26%), and cefpodoxime (60.48%) were prescribed with high adherence to dose guidelines, except for amoxicillin (34.57%). These medicines are prescribed highly compliant (>83%) with dosing interval guidelines. Furthermore, significantly more brand-name antibiotics (56.5%) are prescribed than generic antibiotics (43.5%). In particular, antibiotic class, antibiotic origin, and antibiotic therapies showed significant association with rational antibiotic prescriptions for dose and dose interval (p < 0.05). CONCLUSIONS: Amoxicillin/clavulanic acid is the most frequently prescribed medicine and the most inappropriate due to non-compliance with dose guidelines for CAP treatment. Generic antibiotic use for single therapy should be encouraged based on rapid and accurate diagnostic testing for viruses and bacteria to reduce antibiotic resistance in developing countries. Moreover, the study result has also shown that therapies and antibiotics (class and origin) exhibited significant association with rational prescriptions for CAP treatment for pediatrics.

Pneumococcal infective endocarditis in Brazil: a multicenter study on a severe condition.

BACKGROUND: Streptococcus pneumoniae bacteremia may result in Infective Endocarditis (IE). In the pre-antibiotic era, it caused 10 %‒15 % of IE, decreasing to < 3 % after penicillin availability. Although infrequent, it causes aggressive disease. METHODS: Retrospective analysis of endocarditis databases, prospectively implemented in 4 Brazilian institutions, 2005‒2023. RESULTS: From the prospective cohorts comprising 2321 adult patients with IE, we identified 11 (0.47%) with pneumococcal IE. Males represented 7/11 and mean age was 54 years (22‒77). All had native valve involvement; perivalvular abscess was present in 6/11. Only one patient had concurrent meningitis. Beta-lactams were the antibiotics used in 10/11. All had surgical indication, but only 6 had it, as the others were seriously ill. Overall, in hospital mortality was 6/11, but only 1/6 of those who underwent surgery died, compared to 5/5 of those who had an indication for surgery and did not have it. CONCLUSIONS: The high mortality rates and need for surgical intervention emphasize the need to promptly identify and manage pneumococcal endocarditis. Physicians ought to recommend vaccination to all patients at risk for severe pneumococcal disease.

More than a new name: Updates in the management of Clostridioides difficile infection.

ABSTRACT: Infections from Clostridioides difficile (often called C. diff) have long presented challenges for both patients and clinicians. Traditionally, C. diff has been considered a nosocomial infection, but in recent years, a noticeable spike in community-acquired cases has occurred. C. diff infection (CDI) testing is often complicated, as various testing options with differing sensitivity and specificity for active infection are available. Also, recent guideline changes have altered the recommended treatment of infection. This article discusses recent changes to both the diagnosis and management of CDI and how they can be applied to everyday NP practice.

Influence of gender on clinical presentation, management practices and outcomes of ocular syphilis.

Ocular syphilis is a re-emerging inflammatory eye disease with a clear gender imbalance, disproportionately affecting men. We investigated the impact of gender on the presentation, management practices and clinical outcomes of this condition. Data generated from a study of patients consecutively diagnosed with ocular syphilis who attended a subspecialist uveitis service at one of four hospitals in Brazil over a 30-month period were disaggregated for analysis by gender. Two-hundred and fourteen eyes (161 men and 53 women) of 127 patients (96 men and 31 women) were included. Posterior uveitis was the most common presentation in both men and women (80.1% vs. 66.7%, p > 0.05), but men were significantly more likely to have vitritis as a feature of their disease (49.4% versus 28.8%, p = 0.019). Three eyes of women had nodular anterior scleritis (p = 0.015). Men were more likely to undergo a lumbar puncture to assess for neurosyphilis (71.9% vs. 51.6%, p = 0.048), but men and women undergoing a lumbar puncture were equally likely to have a cerebrospinal fluid abnormality (36.2% vs. 25.0%, p = 0.393). All patients were treated with aqueous penicillin G or ceftriaxone, and there was a trend towards more men receiving adjunctive systemic corticosteroid treatment as part of their management (65.2% vs. 46.7%, p = 0.071). There were no significant differences in the age of presentation, bilaterality of disease, anatomical classification of uveitis, initial or final visual acuity, and rates of ocular complications between men and women. Our findings indicate that ocular syphilis has comparable outcomes in men and women, but that there are differences in the type of ocular inflammation and management practices between the genders.

Effect of Cymbopogon olivieri-based herbal vaginal product on bacterial vaginosis.

OBJECTIVE: Bacterial vaginosis is the most common vaginal infection in reproductive-age women. If it is not treated, the quality of life will be reduced. In this study, the herbal medicine product Cymbopogon olivieri was used for its treatment. METHODS: This study was conducted with 90 women. The patients were randomly divided into two groups of 45: Cymbopogon olivieri and metronidazole. The treatment period was 7 days for each group. Improvement status was determined by eliminating at least three out of four of Amsel's criteria. A new variable with two order levels (negative and positive) was constructed. This new variable shows the status of the treatment process. Chi-square and Fisher's exact tests were used to examine the relationship between the new variable and treatment status. RESULTS: The results demonstrate that Cymbopogon olivieri and metronidazole significantly reduced the burning, itching, malodor, abnormal vaginal discharge, pH, clue cell, and positive whiff test (p<0.05). The findings also demonstrate that neither treatment was statistically different from the other for at least three of Amsel's criteria. CONCLUSION: This study shows that the effect of Cymbopogon olivieri on bacterial vaginosis is similar to that of metronidazole. Hence, Cymbopogon olivieri is a suitable option to treat bacterial vaginosis.

Burden and Management of Multi-Drug Resistant Organism Infections in Solid Organ Transplant Recipients Across the World: A Narrative Review.

Solid organ transplant (SOT) recipients are particularly susceptible to infections caused by multidrug-resistant organisms (MDRO) and are often the first to be affected by an emerging resistant pathogen. Unfortunately, their prevalence and impact on morbidity and mortality according to the type of graft is not systematically reported from high-as well as from low and middle-income countries (HIC and LMIC). Thus, epidemiology on MDRO in SOT recipients could be subjected to reporting bias. In addition, screening practices and diagnostic resources may vary between countries, as well as the availability of new drugs. In this review, we aimed to depict the burden of main Gram-negative MDRO in SOT patients across HIC and LMIC and to provide an overview of current diagnostic and therapeutic resources.