Empirical Antibacterial Therapy Research Articles

Using targeted second-generation sequencing technique to guide clinical diagnosis and the effect of medication on the therapeutic effect and prognosis of respiratory tract infection in children: An observational study.

To explore the effect of targeted second-generation sequencing technique to guide clinical diagnosis and medication on the therapeutic effect and prognosis of respiratory tract infection (RTI) in children. During January 2021 to June 2022, 320 children with RTI cured were selected in our hospital as the object of this retrospective study. The control group accepted empirical broad-spectrum antibacterial therapy and the observation group accepted targeted second-generation sequencing technique to guide diagnosis and medication. The therapeutic effect, improvement time of clinical symptom index, laboratory-related index, level of inflammatory factors, incidence of complications, and parents' treatment satisfaction were compared. The observation group was considerably more efficacious (91.25%) versus the controlled group (72.50%). The duration of enhancement of fever, nasal congestion, tonsillar congestion, and cough symptoms was shorter in the observation group (P < .05). Serum levels of iron, IgA, IgG as well as IgM were substantially elevated in the observation group. The levels of IL-4 and IL-10 were markedly reduced in the observation group after treatment. The prevalence of complications was considerably below that of the comparison group (21.25%) in the observation group (8.75%). Parental satisfaction with therapy was markedly higher in the observation group (92.50%) than in the control group (66.25%). The application of targeted second-generation sequencing technology to guide clinical diagnosis and drug use can elevate the RTIs efficacy and prognosis in childhood. Targeted second-generation sequencing can achieve precise treatment, reduce drug resistance of drug-resistant strains, and improve the efficacy. It has high promotion and application value.

Community-acquired pneumonia in young children living in various climatogeographic zones of the Republic of Dagestan

Introduction. Community-acquired pneumonia (CAP) in early childhood continues to cause significant morbidity and remains one of the most common serious infections in childhood. Each region of the Russian Federation exhibits specific manifestations of CAP morbidity. Knowledge of CAP etiology is crucial for planning therapeutic and preventive measures. &#x0D; Aim. To determine the etiological and immunological features of CAP in early childhood, residing in various climatogeographical zones of the Republic of Dagestan.&#x0D; Materials and methods. The material includes the results of examination and treatment of CAP 204 young children. living in lowland, foothill and mountain climatogeographical zones of the Republic of Dagestan. The selection criterion was the clinical-radiological diagnosis of CAP, using the classification of clinical forms of bronchopulmonary diseases in children.&#x0D; Results. The study revealed a rise in the incidence of respiratory organ diseases, including CAP, among children in the Republic of Dagestan (RD) over the past 5 years. Among infants under one year, the CAP rate was twice as high. The prevalence can be attributed to the climatogeographical conditions of children’s living environments. Streptococcal infection was also observed to predominate in the ethnostructure of CAP in early childhood across all climatogeographical zones. Streptococcus pneumoniae (48.1%) was more frequently isolated in all climatogeographical zones, while Staphylococcus aureus (13.3%) dominated in the mid-mountain zone. In mild pneumonia, cellular immunity components, represented by reduced CD3, CD4, CD25, CD71, react primarily. Disease exacerbation leads to depletion of CD8, CD16, CD20. Severe pneumonia triggers the involvement of humoral immunity, leading to changes in clinical blood analysis — leukocytosis and an increase in mature and immature forms of neutrophils. The levels of IL-1, IL-6, IL-8 in blood serum increase depending on the area of inflammation and the CAP severity. In observed children with focal-draining and segmental CAP, their levels significantly increased. For empirical antibacterial therapy of CAP, recommendations include amoxicillin, protected ampicillins, third-generation cephalosporins, macrolides, and vancomycin in mono- or combination therapy.&#x0D; Conclusion. The conducted research highlights the need for managing ethnological monitoring with antibiotic sensitivity testing of infectious agents causing CAP in children.

Predictors and patterns of empirical antibiotic therapy and associated outcomes in COVID-19 patients: a retrospective study in a tertiary care facility in South India

ABSTRACT Background The coronavirus disease (COVID-19) led to a global health crisis. Inappropriate use of antibiotics in COVID-19 patients has been a concern, leading to antimicrobial resistance. This study evaluated the patterns and predictors of empirical antibiotic therapy in COVID-19 patients and associated outcomes. Methods A hospital-based retrospective study was conducted with 525 patients admitted to Kasturba Hospital, Manipal, India, with moderate and severe COVID-19 from 1 March to 1 August 2021. They were divided based on empirical therapy, and predictors of antibiotic usage were assessed by logistic regression. Results Four hundred and eighty (91.4%) COVID-19 patients received at least one course of antibiotics, with 440 (83.8%) initiating empirical therapy. Patients with severe COVID-19 manifestations were more likely to be prescribed empirical antibiotics. Multivariable analysis showed that patients initiated on empirical antibiotics had significantly elevated levels of procalcitonin [OR: 3.91 (95% CI: 1.66–9.16) (p = 0.001)], invasive ventilation [OR: 3.93 (95% CI: 1.70–9.09) (p = 0.001)], shortness of breath [OR: 2.25 (95% CI: 1.30–3.89) (p = 0.003)] and higher CRP levels [OR: 1.01 (95% CI: 1.00–1.01) (p = 0.005)]. Most antibiotics (65.9%) were prescribed from the ‘Watch’ group, the highest being ceftriaxone. Only 23.8% of the patients had microbiologically confirmed infections. Conclusion The study identified predictors for initiating empirical antibacterial therapy in our setting.

OPTIMIZATION OF EMPIRICAL ANTIBACTERIAL THERAPY OF VENTILATOR-ASSOCIATED PNEUMONIA, INDUCED BY GRAM-NEGATIVE MULTIRESISTANT STRAINS

Introduction: Ventilator-associated pneumonia is one of the most common healthcare associated infections, arising in the ICU. The greatest difficulty is presented by patients, whose infection is caused by gram-negative multidrug-resistant strains. That is why empirical antibacterial therapy of ventilator-associated pneumonia requires optimization and improvement.&#x0D; Aim of study: To compare the effectiveness of two schemes of empirical antibacterial therapy of ventilator-associated pneumonia, based on carbapenems, aminoglycosides and monobactams.&#x0D; Materials and methods: This is randomized controlled monocentral study, which included 64 patients older than 18 years, who have developed ventilator- associated pneumonia during long-term mechanical ventilation.&#x0D; Results: The use of combination of meropenem and aztreonam as an empirical antibiotic therapy of ventilator-associated pneumonia was accompanied by a significant increase of oxygenation indexes, effective purification of sputum from microorganisms, decrement of resistance and superinfection development in comparing with patients with traditional scheme empiric antibacterial therapy. The recommended scheme is also safe in nephrotoxicity context.&#x0D; Conclusion: The use as an empirical antibacterial therapy of ventilator-associated pneumonia the combination of meropenem and aztreonam was accompanied by significant decrement of length of mechanical ventilation and significant reduction of ICU-stay. The mortality levels were also less in investigation group compared with the group with traditional scheme of empirical antibacterial therapy.

Prevalence and Antibacterial Susceptibility of Isolates of Coliuria among Pregnant Women Attending Antenatal Clinic at State Specialist Hospital, Maiduguri

Urinary tract infection (UTI) is common among pregnant women and can be associated with negative outcome for both the mother and the foetus. In view of the increasing bacterial resistance, regular monitoring of resistance patterns is necessary to improve guideline for empirical antibacterial therapy. The aims of this study were to estimate prevalence of coliuria and determine the antibiogram of the isolates among pregnant women attending antenatal clinics at State Specialist Hospital, Maiduguri. This study involved pregnant women at any stage of gestation attending Antenatal Clinics at State Specialist Hospital, Maiduguri without signs of life-threatening conditions and focused on E. coli as a cause of UTI using urine samples. Plate streaking method was used in isolation of E. coli while disc diffusion method was used as technique for antibacterial susceptibility testing. The urine samples analysed showed a prevalence of coliuria of 39.1 % (59/151) among the subjects. The results of antibacterial sensitivity indicated that gentamicin (86.4%, 51/59) demonstrated significantly (p &lt; 0.05) highest activity against the isolates while streptomycin (10.2%, 6/59) and cephalexin (10.2%, 6/59) had the least activity. The antibacterial resistance of individual isolates revealed that most of the isolates were multi-drug resistant strains and majority (98.3%, 58/59) of the isolates was resistant to at least three (3) antibacterial drugs. Isolate 11 (Ec11) was resistant to all the ten (10) antibacterial drugs tested while isolate 35 (Ec35) had the least resistance of 10% as it was only sensitive to gentamicin. These findings suggest that there is a high prevalence of coliuria among pregnant women attending antenatal clinics at SSH, Maiduguri. Only gentamicin is suitable antibacterial agent in the treatment of the condition and this could contribute to effective treatment and effective discharge of antenatal care practice in Maiduguri.

Community-acquired pneumonia: antibiotic therapy approach after the COVID-19 pandemic. A review

Pneumonia is clearly differentiated from other focal inflammatory lung diseases of non-infectious origin. A patient with community-acquired pneumonia (CAP) should receive antibacterial drugs no later than 4 hours after the diagnosis. Initial antibacterial therapy in CAP should be based on factors affecting the potential causative agents and the risk of drug-resistant microorganisms. Rational use of amoxicillin in terms of dose and frequency in CAP patients without severe comorbidities and risk factors for PES pathogens, the use of -lactam in combination with a macrolide or moxifloxacin monotherapy in high-risk groups of patients is the most effective strategy of empirical antibacterial therapy.

Diagnostics and therapy of paediatric patients with febrile neutropenia

Febrile neutropenia is a common infectious complication in children and adolescents receiving chemotherapy for cancer, requiring immediate hospitalisation and empirical antibacterial therapy. The risk for a severe infection increases with lower neutrophil counts, but other factors such as underlying malignancy, remission state or the genetic background might also impact on the risk and severity of infection. Initial antibacterial treatment as well as modification and cessation of therapy depends on clinical performance, microbiological findings and haematological recovery. Although paediatric specific guidelines have been developed in the last decade, a number of questions are still unsolved. This article gives an overview on diagnostics and management of paediatric patients presenting with febrile neutropenia, on research gaps and will speculate on future perspective.

Prevalence and antimicrobial susceptibility pattern of bacterial uropathogens among adult patients in Madinah, Saudi Arabia

BackgroundUrinary tract infection (UTI) is considered one of the most prevalent infections that may lead to many renal complications. They account for almost 10% of all infections in Saudi Arabia, making them the second most common cause of emergency department admissions. Bacterial pathogens, primarily Escherichia coli, Klebsiella spp., Enterococcus spp., Proteus spp., and Staphylococcus spp. are the most causative agents of UTI. This study aims to evaluate the prevalence and antimicrobial susceptibility patterns of uropathogens in adult patients from Madinah, Saudi Arabia.MethodsA retrospective cross-sectional study was performed using data collected from patients who visited King Fahad General Hospital in Madinah, Saudi Arabia. Data included 16,803 urine bacterial cultures and their antimicrobial susceptibility profiles collected between January 2019 and October 2021.ResultsAmong the 16,803 tested samples, 3937 (23.4%) showed positive results for urine bacterial cultures. UTI prevalence was slightly higher in women (52.1%) than men (47.9%). Escherichia coli (29.8%) was the most prevalent, followed by Klebsiella spp. (23.2%) and Pseudomonas spp. (8.4%). As for Gram-positive bacteria, Enterococcus spp. (10.8%) were most common, followed by Streptococcus spp. (8%) and Staphylococcus spp. (3.3%). Gram-negative bacteria exhibited high resistance rates toward aztreonam (> 83.3%), ampicillin (78.8%), and cephalexin (68.5%). Enterococcus spp. displayed elevated resistance rates (> 62.3%) against ciprofloxacin, gentamicin, and tetracycline. Conversely, Streptococcus spp. showed substantial resistance rates (> 76.6%) toward colistin and trimethoprim/sulfamethoxazole.ConclusionTo optimize therapy and minimize the risk of multidrug-resistant uropathogenic infections, physicians should consider the local epidemiological trends and antimicrobial resistance patterns of prevalent uropathogens prior to initiating any empirical antibacterial therapy.

Efficacy of Amikacin and Ceftriaxone in the empiric antibacterial therapy of friable appendicular infiltrate and periappendicular abscess at different age groups

Introduction. In the structure of acute pathology in the abdominal cavity of children associated with appendicular peritonitis, local limited forms occur in 10–16.8% of cases, mainly in older patients.Purpose. To make a comparative assessment of Amikacin and Ceftriaxone efficacy in the empiric antibacterial therapy of appendicular infiltrate and periappendicular abscess in children of different age groups under the dynamics of inflammatory process and results of bacteriological tests.Material and methods. The article provides a retrospective analysis of 43 medical records of children of various ages with appendicular infiltrate and periappendicular abscess. All patients had a quantitative assessment of inflammatory markers and bacteriological findings in their gastric content. Amikacin and Ceftriaxone were prescribed as a starting antibacterial therapy.Results. The present trail revealed a rather high incidence of appendicular infiltrate and periappendicular abscess in children. The maximum increase in leukocytes number, C-reactive protein were registered before surgery and one day after it, mostly in little children. The acid α1-glycoprotein level was increasing during the first day after surgery in little patients, while in adolescents and teenagers it didn’t change significantly.Bacteriological examination of the gastric content revealed that the most common pathogens were Escherichia coli (34.9%) and Pseudomonas aeruginosa (14%). Many pathogenic bacteria were highly sensitive to Amikacin and little sensitive to Ceftriaxone. In two children, lack of sensitivity of microorganisms to antibacterial drugs caused the development of abdominal abscesses in the postoperative period.Conclusion. The empiric antibiotic therapy is of great importance in the management of appendicular infiltrate and periappendicular abscess. While prescribing the starting antibiotic therapy, a physician has to use his/her experience and to know or to anticipate possible microflora nature and its sensitivity to antimicrobial preparations.

Bacterial (Septic) Arthritis

In modern conditions, the problem of bacterial arthritis (BA) is very relevant. The leading etiological agent of BA is Staphylococcus aureus. The frequency of deaths in BA has not changed significantly over the past 25 years and is 5-15%. The article highlights current data on the etiology, pathogenesis, clinical picture, diagnosis of BA. Indications for open surgical drainage of an infected joint are presented. The main schemes of empirical and etiotropic antibacterial therapy of BA are presented.

Prevalence and Antibiotic-Resistance Indices of Bacterial Pathogens of Otitis Media among Patients Attending a Tertiary Hospital in Calabar, Nigeria

Background: Otitis media is linked to middle ear inflammation and sequelae, frequently occurring in infants and early childhood dealing with the accumulation of fluid behind the eardrum. It is often associated with the absence of timely and appropriate antibacterial interventions.&#x0D; Aim: To investigate the identity and antibiogram of bacterial agents of otitis media among patients attending a tertiary health facility in Calabar, Nigeria.&#x0D; Methods: Ear specimens collected from a total of 70 subjects were processed by conventional bacteriological methods for isolation and identification of pathogens. Antibiotic susceptibility testing was carried out on all the isolates using the Kirby-Bauer disk diffusion method. Multiple antibiotic resistance (MAR) indices of the isolates were evaluated.&#x0D; Results: The prevalence of bacterial otitis media was 72.9% in the study population. A total of 51 bacterial isolates including Pseudomonas aeruginaosa (26), Staphylococcus aureus (17), Proteus mirabilis (6), and Klebsiella pneumoniae (2) were found. Isolates of P. aeruginosa and S. aureus showed high susceptibility to amoxicillin-clavulanate (92.3%) and ciprofloxacin (88.3%), respectively. The prevalence of multidrug resistant (MDR) isolates was 25.4%. MDR percentages such as 100%, 33.3%, 30.7% and 29.4% were reported for isolates of K. pneumoniae, P. mirabilis, P. aeruginosa and S. aureus respectively. MAR indexing revealed high values ranging from 0.4 to 0.87 for all the isolates.&#x0D; Conclusion: High susceptibility of the predominant isolates to amoxicillin-clavulanate and ciprofloxacin may underscore the drugs’ potential as antibiotics of choice for prompt treatment of otitis media in the population. However, the overall high drug-resistance indices of the isolates would suggest dire implications for empiric antibacterial therapy in the population. Choice of antibiotics for treatment of bacterial infections in this population should be driven by results of microbiological drug-susceptibility tests.

Diagnostic markers of yersiniosis in patients with inflammatory bowel diseases

Relevance. This study is related to the study of the etiology, pathogenesis and clinic of inflammatory bowel diseases (IBD). In a number of patients with IBD who are refractory to anti-inflammatory/immunosuppressive therapy, there are signs of current or transferred yersiniosis infection, not diagnosed by routine methods.Aim. According to the scientific literature and the results of our own research, to identify the presence and assess the nature of the influence of yersinia on the occurrence and development of IBD.Materials Methods. In our study, we conducted a bacteriological examination of feces by polymerase chain reaction (PCR) in patients with a diagnosis of IBD (UC and CD) in the acute phase (MMDAI ≥ 4 points for UC and Best index ≥ 150 points for CD), as well as immunological diagnostics using enzyme immunoassay (IFA) in the version of line-blotting (IB). Using the results obtained, clinical and instrumental semiotics were evaluated in subgroups of individuals suffering from IBD with confirmed yersiniosis ("IBD+ IER+") and without it ("IBC+ IER–"). We also assessed the role of intestinal infection by determining the effectiveness of initial antibacterial therapy in the treatment of exacerbation of IBD.Results. A significant part (in the case of our sample – 45%) of patients with IBD, when examined by high-tech methods, demonstrate the presence of markers of a transferred or current yersiniosis infection. Its role in the initiation and development of autoimmune intestinal inflammatory process requires further clarification.Conclusions. In 45% of patients with IBD, high-precision examination reveals markers of transferred or current yersiniosis infection. Routine clinical methods for the diagnosis of yersiniosis have low sensitivity and do not allow us to convincingly assess the role of this bacterial agent as a trigger factor for the onset or recurrence of IBD. There is a tendency for greater manifestation in the debut of IBD in patients with markers of systemic yersiniosis. The fact of improvement against the background of empirical antibacterial therapy in 24% of patients with IBD, achievement of early clinical remission in 57% of patients receiving antibiotic therapy, indicates a significant role of bacterial enterocolopathogens in the genesis of chronic intestinal inflammation in a number of patients.

Will &lt;i&gt;E. coli&lt;/i&gt; retain its leading position as a causative agent of urinary tract infection in children?

Introduction. According to information from various literature sources, Escherichia coli is the most common (80–90%) causative agent of urinary tract infection (UTI) in children, it also significantly exceeds the frequency of occurrence of other bacteria, although there is a tendency to gradually decrease its specific gravity, especially against the background of other pathogens of the intestinal group.Aim. To determine the specific gravity of E. coli as the causative agent of UTI, depending on age against the background of other pathogens.Materials and methods. The study involved 133 children aged 1–17 years with UTI, girls – 107, boys – 26. The bacteriological method determined the pathogen, its sensitivity to standard antibiotics and the ability to produce extended-spectrum beta-lactamases (ESBL). Statistical processing was carried out in the Excel program. In the statistical study of the conjugacy of the signs age and infection, the Kruskal – Wallis criterion was used. Patients are grouped into the following age categories: 1–3, 4–7, 8–11, 12–14 and 15–17 years.Results. The authors of the article provided information that E. coli, although it is the leader, but its share is not as large as is commonly believed and is only 26–29%, while 18% of the total are producers of ESBL. The article shows the distribution of UTI pathogens by age groups of children and calculates the empirical probability of detecting various pathogens at different ages. It is shown that the age group of 8–11 years is most susceptible to mixed infection. According to the structure of mixed infections, these are combinations of pathogens of the intestinal group: E. coli with E. faecalis or E. faecium or with Klebsiella pneumoniae.Conclusions. The authors raised the question of the need in the near future to correct the schemes of empirical antibacterial therapy in connection with the excess of the justified 10–20% resistance of E. coli to cephalosporins of the 3rd generation due to an increase in the frequency of ESBL production.

СОВРЕМЕННЫЕ ПРЕДСТАВЛЕНИЯ О ПОСЛЕРОДОВОМ ЭНДОМЕТРИТЕ (ОБЗОР ЛИТЕРАТУРЫ)

The review is based on the databases https://cyberleninka.ru/, PubMed, MedArt, and CNMB. Postpartum endometritis is the leading infectious and inflammatory disease of the postpartum period and one of the stable leading causes of maternal mortality. In Russia, the incidence of postpartum endometritis in the population is 3-8%, in pathological deliveries it is 10-20%, and in women with a high infection risk it is 13.3-54.3%. Infection occurs predominantly by the ascending route, as a rule, with active participation in associations of opportunistic pathogenic flora. The leading position among the risk factors of postpartum endometritis is taken by surgical delivery and, primarily, by cesarean section. Immune disorders play one of the key roles in the pathogenesis of this disease according to modern researchers. In case of insufficient effectiveness of empirical antibacterial therapy, the choice of antibacterial drugs must be made on the basis of blood cultures. The second local component of treatment of patients with postpartum endometritis is the evacuation of uterine cavity contents. Careful emptying is one of the most important criteria for choosing the method of evacuation. An immunomodulatory component should be included in the treatment to increase its effectiveness. Thus, postpartum endometritis is a serious obstetric problem, in the treatment of which gentle evacuation of the uterine cavity contents in combination with local use of immunomodulatory drugs is promising.

Guideline for the Management of Fever and Neutropenia in Pediatric Patients With Cancer and Hematopoietic Cell Transplantation Recipients: 2023 Update.

To update a clinical practice guideline (CPG) for the empiric management of fever and neutropenia (FN) in pediatric patients with cancer and hematopoietic cell transplantation recipients. The International Pediatric Fever and Neutropenia Guideline Panel reconvened to conduct the second update of this CPG. We updated the previous systematic review to identify new randomized controlled trials (RCTs) evaluating any strategy for the management of FN in pediatric patients. Using the Grading of Recommendations Assessment, Development and Evaluation framework, evidence quality was classified as high, moderate, low, or very low. The panel updated recommendations related to initial management, ongoing management, and empiric antifungal therapy. Changes from the 2017 CPG were articulated, and good practice statements were considered. We identified 10 new RCTs in addition to the 69 RCTs identified in previous FN CPGs to inform the 2023 FN CPG. Changes from the 2017 CPG included two conditional recommendations regarding (1) discontinuation of empiric antibacterial therapy in clinically well and afebrile patients with low-risk FN if blood cultures remain negative at 48 hours despite no evidence of marrow recovery and (2) pre-emptive antifungal therapy for invasive fungal disease in high-risk patients not receiving antimold prophylaxis. The panel created a good practice statement to initiate FN CPG-consistent empiric antibacterial therapy as soon as possible in clinically unstable febrile patients. The updated FN CPG incorporates important modifications on the basis of recently published trials. Future work should focus on addressing knowledge gaps, improving CPG implementation, and measuring the impact of CPG-consistent care.

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

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. 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. 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. 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 therapy of chronic obstructive pulmonary disease exacerbations in a multidisciplinary hospital

Objective. To study the real practice of management of patients with COPD exacerbations on the example of a single hospital. Materials and Methods. During the retrospective descriptive study the data of medical records of 219 patients with COPD were processed, the profile of the studied patients with distribution by phenotypes and determination of the Charlson comorbidity index was compiled and analyzed. StatPlus 7.0 program was used for statistical analysis. Results. According to GOLD guidelines, the majority of patients were in category D (93.2%). Bacteriologic examination of respiratory specimens was done in 127 (57.9%) patients. The microbiological results indicated a high probability of contamination of the majority of samples with oral microflora. Empiric antibacterial therapy was given to 215 (98.2%) patients. In 191 (88.8%) patients, antibiotics were used in monotherapy, and in 24 patients (11.2%) – in combinations. The most frequently used antimicrobials were fluoroquinolones – levofloxacin (34.3%) and ciprofloxacin (43.6%). Cephalosporins of III and IV generations were used much less frequently (2.5 to 7%). There was a weak direct statistically significant association between CRP level and the use of combination antibiotic therapy (V = 0.14, p = 0.047). The purulent sputum had a more pronounced influence on the choice of antibiotic combinations (V = 0.257, p &lt; 0.001). Modification of empirical initial therapy was required in 37 (17.2%) patients. Conclusions. Microbiological results in our study indicate that the majority of respiratory samples were contaminated with oral microflora during the collection of clinical material. The antibiotic therapy prescribed in most cases corresponded to current clinical recommendations, the combined antibiotic therapy was most characteristic of purulent sputum character.

Retrospective Analysis of the Initial Empirical Antibiotic Therapy Effectiveness for Community-Acquired Pneumonia in Young Individuals in Moscow Multidisciplinary Hospital

Despite the fact that the incidence of community-acquired pneumonia (CAP) among young people is significantly lower than among older patients, the frequency of hospitalizations for severe CAP among people under 45 years of age remains high. The effectiveness and duration of treatment directly depend on the rationally selected initial empirical antibacterial therapy (ABT).The aim of the study is to analyze the factors influencing the effectiveness of initial empiric antibacterial therapy for CAP in young people in multidisciplinary medical institutions.Materials and methods. The study was designed as a retrospective observational study; it analyzes 105 medical records of young patients with CAP admitted to one of the multidisciplinary hospitals in Moscow from 2017 to 2019.Results. The empiric ceftriaxone + azithromycin ABT regimen (70% of all prescriptions) was ineffective in 13.7% of cases; monotherapy with ceftriaxone (13% of all prescriptions) was ineffective in 57% cases. Severe CAP, acute respiratory failure, systemic inflammatory response syndrome, and exudative pleurisy were diagnosed with significantly higher frequency in the group of patients with ineffective initial empirical ABT. There was no predominance of any comorbid pathology and Charlson Comorbidity Index in groups where the initial ABT was changed and in groups without a change in initial ABT. The microbiological spectrum of CAP pathogens did not significantly differ in young patients between groups with a changed initial empirical ABT and a group without changing initial ABT.Conclusion. The reasons for the ineffectiveness of the initial empirical ABT could be such factors as: underestimation of the risk of the presence of multidrug-resistant pathogens; underestimation of the risk of viral genesis of CAP; underestimation of the severity of CAP, as well as the severity of CAP complications.

272. Do Empiric Antibiotics Improve Outcomes in Clinically Stable Patients Admitted with COVID-19 Pneumonia? Retrospective Cohort Study of 221 U.S. Hospitals, March 1st, 2020-December 31st, 2020

Abstract Background Patients admitted with COVID19 pneumonia often receive initial empiric antibacterial therapy (IEAT) despite a known low probability of bacterial co-infection. However, evidence supporting this practice is lacking. We studied the impact of IEAT on the risk of in-hospital mortality, clinical deterioration and antibiotic-associated risks in stable inpatients with COVID-19. Methods Adult inpatients coded for COVID-19 pneumonia stable (no mechanical ventilation or vasopressors) on admission (+1 day) without a clear indication for antibiotics, were identified at hospitals in the Premier Healthcare Database. Patients who received IEAT, defined as the receipt of ≥ 1 antibacterial agent on admission (+1 day), were compared to a control group, using binomial regression with overlap weight matching and downstream adjustment for baseline characteristics (age, gender, race, admission month, surge index, Elixhauser score, any AOFS organ failure POA, ICU admission on day 0 to +2, receipt of remdesivir, corticosteroids, and tocilizumab). The primary outcome was in-hospital mortality or discharge to hospice; secondary outcomes included need for mechanical ventilation on day2+, and rates of non-POA-acute kidney injury (AKI). Results At 221 hospitals between March–December 2020, 39,517 (74%) of 53,431 stable COVID-19 admits received IEAT. Patient and encounter characteristics are shown in Table 1. The crude mortality rates were 12.2% in IEAT recipients and 10.9% in controls. In adjusted analysis of patients who survived beyond admission day, mortality was 11.57% (95% CI 11.24-11.90%) in IEAT recipients and 11.23% (95% CI 10.72-11.74) in controls, for a difference of 0.34% (95% CI -0.23-0.91%, p = 0.24). Subsequent mechanical ventilation occurred similarly between groups (5.72% vs. 5.77%, p=0.83). The adjusted rate of AKI was 2.47% (95% CI 2.31-2.64%) in IEAT recipients, and 3.04% (95% CI 2.74-3.35%) in controls, for a difference of -0.57% (95% CI -0.92-0.22%, p = 0.0014). Table 1.Demographics, clinical and hospital characteristics for patients treated with initial empiric antibiotic therapy (intervention) versus those not treated (control).Figure 1.Standardized mean differences in included covariates before and after several matching strategies comparing covariate values for patients treated and not treated empirically with antibiotics Conclusion In patients with COVID19 initially admitted to the ward, IEAT was not associated with a reduction in mortality or deterioration requiring mechanical ventilation, but with a clinically insignificant reduction in AKI. Empiric antibiotics can likely be safely withheld in this population. Disclosures All Authors: No reported disclosures.

GC-MS profiling of volatile metabolites produced by Klebsiella pneumoniae.

Currently used methods for diagnosing ventilator-associated pneumonia (VAP) are complex, time-consuming and require invasive procedures while empirical antibacterial therapy applies broad spectrum antibiotics that may promote antimicrobial resistance. Hence, novel and fast methods based on alternative markers are needed for VAP detection and differentiation of causative pathogens. Pathogenic bacteria produce a broad range of volatile organic compounds (VOCs), some of which may potentially serve as biomarkers for microorganism identification. Additionally, monitoring of dynamically changing VOCs concentration profiles may indicate emerging pneumonia and allow timely implementation of appropriate antimicrobial treatment. This study substantially extends the knowledge on bacterial metabolites providing the unambiguous identification of volatile metabolites produced by carbapenem-resistant and susceptible strains of Klebsiella pneumoniae (confirmed with pure standards in addition to mass spectra match) but also revealing their temporary concentration profiles (along the course of pathogen proliferation) and dependence on the addition of antibiotic (imipenem) to bacteria. Furthermore, the clinical strains of K. pneumoniae isolated from bronchoalveolar lavage specimens collected from mechanically ventilated patients were investigated to reveal, whether bacterial metabolites observed in model experiments with reference strains could be relevant for wild pathogens as well. In all experiments, the headspace samples from bacteria cultures were collected on multibed sorption tubes and analyzed by GC-MS. Sampling was done under strictly controlled conditions at seven time points (up to 24h after bacteria inoculation) to follow the dynamic changes in VOC concentrations, revealing three profiles: release proportional to bacteria load, temporary maximum and uptake. Altogether 32 VOCs were released by susceptible and 25 VOCs by resistant strain, amongst which 2-pentanone, 2-heptanone, and 2-nonanone were significantly higher for carbapenem-resistant KPN. Considerably more metabolites (n = 64) were produced by clinical isolates and in higher diversity compared to reference KPN strains.