Optimal Antibiotic Research Articles

Optimizing Treatment of Staphylococcus aureus Bloodstream Infections Following Rapid Molecular Diagnostic Testing and an Antimicrobial Stewardship Program Intervention.

Pending antibiotic susceptibility results, vancomycin is often used for bloodstream infections (BSIs) to ensure treatment of methicillin-resistant Staphylococcus aureus (MRSA). As rapid discrimination of methicillin-susceptible S. aureus (MSSA) from MRSA in BSIs could decrease vancomycin use and allow early optimization of beta-lactam therapy, this study evaluated the impact of the use of rapid molecular testing for MSSA and MRSA coupled with an antimicrobial stewardship program (ASP) intervention. Between January and July 2020, the Cepheid Xpert MRSA/SA blood culture assay was performed on blood cultures with Gram-positive cocci in clusters that were identified as S. aureus using matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The ASP team member then consulted with the treating physician. The time to optimal therapy (TTOT) and clinical outcomes, including length of hospital stay (LOS), were compared between the intervention (n = 29) and historical (n = 27) cohorts. TTOT was defined as the time from the first blood culture draw to the use of appropriately dosed antistaphylococcal beta-lactam monotherapy without vancomycin. Molecular testing significantly reduced the median time to MSSA and MRSA discrimination to 7.8 h, compared to 24.3 h with culture-based methods (P < 0.001). Compared to the control group, the median TTOT in the ASP intervention group was significantly shorter (P = 0.041) at 38.0 h (versus 50.1 h). Rapid discrimination between MRSA and MSSA using molecular testing, paired with an ASP intervention, significantly reduced the TTOT in patients with MSSA BSIs. IMPORTANCE Our research shows that time to optimal antibiotic treatment for serious bloodstream infections can be improved with rapid molecular sensitivity testing and feedback to prescribers. This can be implemented in laboratories without full microbiology services or training to improve patient outcomes by improving antimicrobial use.

Cancer is chronic but antimicrobial stewardship is iconic: A retrospective cohort of optimal antibiotic use in ambulatory oncology clinics.

To evaluate antibiotic prescribing in ambulatory oncology clinics and to identify opportunities to improve antibiotic use. Retrospective cohort of adult patients who received care at 4 ambulatory oncology clinics from May 2021 to December 2021. Patients were included if they actively followed with a hematologist-oncologist for a cancer diagnosis and received an antibiotic prescription for uncomplicated upper respiratory tract infection (URTI), lower respiratory tract infection (LRTI), urinary tract infection (UTI), or acute bacterial skin-skin structure infection (ABSSSI) at an oncology clinic. The primary outcome was receipt of optimal antibiotic therapy, defined as a composite of drug, dose, and duration according to local and national guidelines. Patient characteristics were described and compared; predictors of optimal antibiotic use were identified using multivariable logistic regression. In total, 200 patients were included in this study: 72 (36%) received optimal antibiotics and 128 (64%) received suboptimal antibiotics. The proportions of patients receiving optimal therapy by indication were ABSSSI (52%), UTI (35%), URTI (27%), and LRTI (15%). The most common suboptimal prescribing components were dose (54%), selection (53%) and duration (23%). After adjusting for female sex and LRTI, ABSSSI (adjusted odds ratio, 2.28; 95% confidence interval, 1.19-4.37) was associated with optimal antibiotic therapy. Antibiotic-associated adverse drug events occurred in 7 patients; 6 occurred patients who received prolonged durations and 1 occurred in a patient who received an optimal duration (P = .057). Suboptimal antibiotic prescribing in ambulatory oncology clinics is common and mostly driven by antibiotic selection and dosing. Duration of therapy may also be an area for improvement as national oncology guidelines have not adopted short-course therapy.

Impact of direct disk-diffusion testing on time to optimal antibiotic therapy

Abstract We evaluated the impact of preliminary blood-culture antibiotic susceptibility testing on time to optimal antibiotic therapy in a cohort of 503 patients with monomicrobial bloodstream infections. The median time from blood-culture collection to optimal antibiotics was 17 hours earlier in the preliminary antibiotic susceptibility testing group.

Respiratory culture nudge improves antibiotic prescribing for Moraxella catarrhalis and Haemophilus influenzae lower respiratory tract infections

We compared optimal antibiotic prescribing before and after implementing an interpretive β-lactamase microbiology comment for Haemophilus influenzae and Moraxella catarrhalis in lower respiratory-tract infections. The postintervention group was associated with 5-fold increased odds of optimal de-escalation (adjusted odds ratio, 5.03; 95% confidence interval, 2.57-9.87).

Beta-lactam allergy in patients: an antibiotic stewardship challenge

BackgroundPatients are commonly reported as being allergic to beta-lactam (BL) antibiotics. However, many patients with this reported allergy are able to receive BL treatments because they do not have true...

968. The Impact of Film Array Detection of High-risk and Resistant Pathogens on the Time to Optimal Antibiotic Therapy at a Community Health System

Abstract Background The importance of effective antibiotic therapy for the treatment of bloodstream infections has been well described. Rapid diagnostic testing platforms like the BioFire® FilmArray® blood culture identification (BCID) have the potential to decrease time to effective antibiotics when acted on appropriately. The Cone Health stewardship team has collaborated with clinical pharmacists and infectious diseases physicians to define a process to optimize antibiotic therapy. This process involves microbiology calling a pharmacist with newly positive blood cultures, and the pharmacist notifies the attending physician with the results and evidence-based treatment recommendations. We transitioned from BCID to BCID2 in August, 2021. As CTX-M (marker for extended spectrum beta-lactamase production) was not a target on BCID, we were interested in how the addition of this marker could improve care in this subset of patients. Procedure for Positive Blood Culture Workup and Notification Treatment Recommendations for Selected Organisms Methods From August 2021 - March 2022, the times to administration of effective and optimal antibiotics were evaluated in patients with the following BCID2 organism and resistance gene targets identified: S. aureus, P. aeruginosa, CTX-M, KPC, OXA-48 like, IMP, VIM, NDM, and vancomycin resistant enterococci. An effective antibiotic was defined as an antibiotic with in vitro activity to the organism, and an optimal antibiotic was defined as the preferred agent based on institutional guidelines. For CTX-M isolates, we compared effective and optimal times to a historical control of ceftriaxone resistant enterobacterales and analyzed by student’s t-test. Results The combined mean time from BCID2 to administration of effective antibiotics = 1.2 hours (range 0-7.9 hours) and to optimal therapy =7.6 hours (range 0 – 113.8 hours). Prior to the BCID2 transition, patients found to be growing ceftriaxone resistant enterobacterales had an average time to optimal antibiotic administration of 17.7 hours, which improved to 2.8 hours after BCID2 implementation (p=0.0041). Time to Effective and Optimal Antibiotics after implementation of BCID2 (August 2021 – March 2022) Time to Effective and Optimal Antibiotics for Ceftriaxone Resistant Enterobacterales Prior to BCID2 Implementation (January 2021 - July 2021) Conclusion BioFire® FilmArray® coupled with antibiotic stewardship team support can help optimize time to effective and optimal antibiotic therapy in bloodstream infection. The addition of the CTX-M target to BCID2 was a helpful addition to the panel which allowed for decreased time to optimal antibiotic therapy. Disclosures All Authors: No reported disclosures.

1657. Real-life implementation of a machine learning based algorithm for urinary tract infection antibiotic resistance management in the community setting

Abstract Background At outpatient visits, one of the most common reasons for antibiotics administration is Urinary Tract Infection (UTI), where selection of the appropriate empiric antibiotic requires consideration of multiple factors. The aim of this study was to assess the implementation and effectiveness of a machine learning based model for UTI antibiotic resistance, embedded in the physician's medical encounter workflow. Methods A longitudinal, nationwide prospective study, conducted by Maccabi Healthcare Services, a health organization in Israel serving 2.5 million members, with about 120,000 medical encounters with a UTI diagnosis per year. We adopted a machine-learning algorithm to predict antibiotic susceptibility using personal electronic health record data. Then, a designated order set was incorporated within our electronic health record interface, named 'UTI Smart-set' (UTIS). When a UTI diagnosis code is selected by the physician, a pop up screen emerges with the recommended antibiotics. The recommendation is based on the personal predicted susceptibility model developed, followed by the optimal narrow-spectrum antibiotic as recommended by the organizational clinical guidelines. . We analyzed the antibiotic prescriptions that were recommended by UTIS, the actual prescriptions given, and compared them to the culture results and the pathogen antibiotic resistance profile. Results From July 1st 2021 to April 1st 2022, among 73,148 medical encounters with a UTI diagnosis, 34,659 antibiotic prescriptions were provided. In 21,924 (63.2%) encounters the UTIS recommendation was accepted whereas in 12,736 (36.7%) it was declined. Use of the UTIS recommendation resulted in a 31.8% reduction of the measured resistance to antibiotics prescribed to patients, 10.9% (2,224) of cases who followed the UTIS recommendation for antibiotics versus 16.0% (1,879) case who did not. A 47% cumulative improvement in adherence to clinical guidelines was also observed using the tool. Conclusion This unique, point of care, antibiotic stewardship tool, based on a combination of clinical guidelines and personalized medicine, led to a major improvement in the selection of appropriate antibiotics. Disclosures Shirley Shapiro Ben David, MD, pfizer: Grant/Research Support.

189. Optimizing Empiric Antibiotic Therapy: a Probabilistic Approach

Abstract Background How to start optimal antibiotic therapy before the results of cultures and antimicrobial susceptibility tests are available? Here, we use the law of total probability to present a probabilistic approach based on antibiograms of bacterial isolates from healthcare and community-acquired infections to optimizing empiric antibiotic therapy. Methods Data on the microbiology of healthcare and community-acquired infections were analyzed from hospitals in Belo Horizonte, a three million inhabitants city from Brazil. Healthcare infections were defined by the National Healthcare Safety Network (NHSN)/CDC protocols. Only data obtained from infections with positive culture, both hospital and community, were considered. The success rate of an antibiotic (ATB) regimen, considering just one drug individually (monotherapy), was calculated by Law of Total Probability (Fig 1). In this sense, if a microorganism has not been tested for a specific antimicrobial, then, by definition, it was considered an antibiotic failure. For a regimen with more than one antibiotic, if the microorganism is sensitive to one of them, then it was considered a success of the scheme. For calculating the success probability of two or three antimicrobials A, B, and C, simultaneously (Fig 2), i.e., P(A and B) or P(A and B and C), the sensitivity to an antimicrobial was considered independent of sensitivity to any other. Then, P(A and B) = P(A) * P(B), and P(A and B and C) = P(A)*P(B) *P(C). Figure 1– Law of total probability: success rate of an antibiotic considering just one drug individually (monotherapy).Figure 2– Probability of the union of two events, success of ATB A or ATB B, and union of three events, success of ATB A or ATB B or ATB C. Results Microbiologic data from hospital acquired infections (HAI) and community-acquired infections (CAI) are analyzed once a year. Empiric antibiotic therapy to HAI were proposed for urinary tract infections (UTI), bloodstream infections (BSI), and pneumonia (Figures 2 and 3). Empiric antibiotic therapy to community-acquired infections were developed for UTI, pneumonia, gastrointestinal system infection, bone and joint infection, and skin and soft tissue infection. Figure 3– Success rate of each antibiotic alone, considering just one drug individually (monotherapy): analysis of hospital-acquired pneumonia.Figure 4– Success rate of one, two or three antibiotics: analysis of hospital-acquired pneumonia.Fig 5- Probability of the antimicrobial regimen being successful in treating an infection according to the length of stay at hospital. Conclusion We presented here a probabilistic approach to empiric antibiotic therapy. The next step is to validate all proposed regimens, that can be used to improve the success likelihood of empiric antibiotic decision making. Disclosures All Authors: No reported disclosures.

678. Title: Treatment Outcomes with Carbapenems vs. Non-Carbapenem Beta-Lactams in Infections with Carbapenem-Discordant Enterobacter cloacae Complex

Abstract Background Carbapenem-discordant Enterobacter cloacae complex (CDECC) isolates are defined as ertapenem non-susceptible and meropenem susceptible drug phenotype. The optimal treatment of these infections is unknown. In 2021, the Infectious Diseases Society of America released guidance recommending extended infusion meropenem as the preferred treatment option. Newer agents, including ceftazidime-avibactam, may be effective but comparative data is lacking. Evaluation of treatment outcomes for use in infections with CDECC is necessary to establish optimal therapy. Methods This single center, retrospective, cohort study was conducted at The University of Kansas Hospital from January 2016 to June 2021. Individuals at least 18 years of age with non-urinary culture positive for CDECC that were treated with either meropenem (MEM) or a non-carbapenem beta-lactam (NCBL) were included. Individuals with polymicrobial infections, infections from a urinary source, or death within 72 hours of admission were excluded. The primary outcome was clinical failure, which was a composite endpoint. Secondary outcomes included individual components of the primary outcome. Results There were 29 unique episodes of monomicrobial, carbapenem-discordant Enterobacter cloacae complex infections during the study period. The primary outcome was met in 6 patients receiving a NCBL and 6 patients receiving MEM, respectively (67% vs. 30%, p=0.11). A total of 8 patients died within 30 days, 4 in the MEM group and 4 in the NCBL group (20% vs. 44%, p = 0.21). Univariate logistic regression analysis demonstrated a significant increase in need to modify antibiotic therapy in the NCBL group (OR 15.2, 95% CI, 1.37-168; p=0.02), with a trend towards increased risk for in-hospital 30-day mortality (OR, 3.2; 95% CI, 0.58-17.72; p = 0.18). Conclusion There was no difference in clinical failure rates between the MEM and NCBL treatment groups. However, treatment with NCBLs was associated with a trend towards increased in-hospital mortality and need for antibiotic modifications due to clinical decompensation. Larger studies are needed to assess treatment outcomes in carbapenem-discordant Enterobacter cloacae complex infections to define optimal antibiotic therapy. Disclosures All Authors: No reported disclosures.

Appropriate Antibiotic Selection during the in-hospital Waiting Period for Surgery for Appendicitis.

Acute appendicitis is a common disease that often requires emergency surgery. However, recently, not all cases are treated as an urgent operation, but surgery may be delayed to when medical resources are abundant to perform the operation safely. In such cases, preoperative antibiotics are administered during the waiting period. Though the choice is empiric, an appropriate choice is needed to avoid emergency surgery. Guidelines for the choice of antibiotics recognized as international standards cannot be applied in Asia due to the high rate of extended-spectrum β-lactamase (ESBL) producers or fluoroquinolone-resistant Escherichia coli. The purpose of this study was to determine the optimal antibiotic during the in-hospital waiting period for patients with appendicitis scheduled for surgery. Bacterial culture results and antibiotic susceptibility were retrospectively examined in 106 cases who underwent surgery for appendicitis. Bacterial cultures were positive in 53 cases (50%). Twenty-six strains of E. coli were identified. Of these, four (15%) were ESBL producers, and seven (27%) were fluoroquinolone resistant. Twenty-two strains of anaerobic bacteria were identified. Carbapenems and tazobactam/piperacillin were effective for all. The rates of susceptibility to clindamycin (CLDM) and cefmetazole (CMZ) were 59% and 82%, respectively. In Japan, from the point of view of reducing carbapenem use, CMZ must be considered a first-choice drug during the in-hospital waiting period for appendectomy.

АНАЛИЗ РЕЗУЛЬТАТОВ АНКЕТИРОВАНИЯ СТУДЕНТОВ СТАРШИХ КУРСОВ МЕДИЦИНСКОГО УНИВЕРСИТЕТА ПО ВОПРОСАМ РАЦИОНАЛЬНОЙ АНТИБИОТИКОТЕРАПИИ ИНФЕКЦИЙ ВЕРХНИХ ДЫХАТЕЛЬНЫХ ПУТЕЙ И ЛОР-ОРГАНОВ У ДЕТЕЙ

Despite the availability of clinical guidelines, the issues of choosing the optimal first-line antibiotic therapy in the treatment of infections of the upper respiratory tract and ENT organs in children still remain relevant. Knowledge of the etiology of infections and the rational apply of systemic antibiotics are formed in senior medical students. Therefore, the purpose of this study is to analyze the knowledge of 6th year students of a medical university on the etiology and antibiotic therapy of upper respiratory tract infections and ENT organs in children, as well as comparing the results with knowledge on these issues of pediatricians. The article presents the results of a survey among the 350 volunteer students of the 6th year of the pediatric faculty on the etiology and antibacterial treatment of upper respiratory tract infections and ENT organs in children. These data have been compaired with the results of the large-scale multicenter study «PATRIOT» (2011-2013) among the pediatricians from 18 cities of Russia. It was revealed that most students overestimate the role of Staphylococcus aureus as the main pathogen in acute otitis media and acute tonsillopharyngitis (tonsillitis) in children. The main group of empirical antibiotic therapy were called aminopenicillins, often inhibitor-protected, whereas the role of natural penicillins in streptococcal tonsillopharyngitis and amoxicillin in acute otitis media and acute sinusitis was underestimated. Among district pediatricians, the frequency of correct answers to questions regarding the etiology and antibiotic therapy of these diseases was significantly higher than among students. It was found that only 9.4% of students and 6.1% of doctors would prescribe antibiotics for uncomplicated acute respiratory infection (ARI), but in real clinical practice they were prescribed in 59.6% of cases. These data indicate a different level of knowledge between students and doctors, as well as the difference in approaches to rational antibiotic therapy in theory and in real practice.

Early appropriate diagnostics and treatment of MDR Gram-negative infections.

The term difficult-to-treat resistance has been recently coined to identify Gram-negative bacteria exhibiting resistance to all fluoroquinolones and all β-lactam categories, including carbapenems. Such bacteria are posing serious challenges to clinicians trying to identify the best therapeutic option for any given patient. Delayed appropriate therapy has been associated with worse outcomes including increase in length of stay, increase in total in-hospital costs and ∼20% increase in the risk of in-hospital mortality. In addition, time to appropriate antibiotic therapy has been shown to be an independent predictor of 30 day mortality in patients with resistant organisms. Improving and anticipating aetiological diagnosis through optimizing not only the identification of phenotypic resistance to antibiotic classes/agents, but also the identification of specific resistance mechanisms, would have a major impact on reducing the frequency and duration of inappropriate early antibiotic therapy. In light of these considerations, the present paper reviews the increasing need for rapid diagnosis of bacterial infections and efficient laboratory workflows to confirm diagnoses and facilitate prompt de-escalation to targeted therapy, in line with antimicrobial stewardship principles. Rapid diagnostic tests currently available and future perspectives for their use are discussed. Early appropriate diagnostics and treatment of MDR Gram-negative infections require a multidisciplinary approach that includes multiple different diagnostic methods and further consensus of algorithms, protocols and guidelines to select the optimal antibiotic therapy.

174 The EXTEND Trial: EXTENDed Antibiotics to Improve Outcomes in Patients with Complicated Intra-Abdominal Infection

Abstract Introduction Complicated intra-abdominal infections (cIAI) pose a major challenge in surgical patients. Despite the heterogenous aetiology they have a common disease process, which is bacterial infection of the peritoneal space. Hence, all cIAIs are managed with source control, plus antibiotic therapy. However, there is uncertainty regarding the optimal antibiotic treatment strategy in order to prevent relapse or extra-abdominal spread of infection1. At present, there is no UK guidance on the management of cIAIs2. For other serious infections outside the abdomen microbiologists often advise at least 28-days of antibiotic therapy. Currently the effectiveness of extended duration antibiotics in patients with cIAI is unknown. This trial aims to compare the clinical and cost effectiveness of 28-day duration antibiotics with standard care with respect to rate of treatment failure in patients with cIAIs. Secondary outcomes include complications and quality of life. Trial Design A multicentre, open label, two-arm, parallel group, pragmatic, randomised controlled trial with internal pilot. 1166 consenting adult patients with cIAI will be recruited over 3 years and randomised on a 1:1 basis between 28-days antibiotic course and standard care antibiotics, based on local protocol and clinical assessment. Patients will be recruited from ICUs and hospital in-patient wards across 30 sites. Trial management and funding EXTEND is sponsored by University of Leeds, hosted by York Trials Unit and funded by NIHR. The Trial Management Group will oversee design and running of the trial. Each site will have a Principal Investigator (PI) with local responsibility. The NIHR Associate PI scheme will enable trainees to participate in the trial.

TH7.2 The EXTEND trial: EXTENDed antibiotics to improve outcomes in patients with complicated Intra-Abdominal Infection (cIAI)

Abstract Introduction Complicated intra-abdominal infections (cIAI) pose a major challenge in surgical patients. Despite the heterogenous aetiology they have a common disease process, which is bacterial infection of the peritoneal space. Hence, all cIAIs are managed with source control, plus antibiotic therapy. However, there is uncertainty regarding the optimal antibiotic treatment strategy in order to prevent relapse or extra-abdominal spread of infection. Presently, there is no UK guidance on the management of cIAIs. For other serious infections outside the abdomen microbiologists often advise at least 28-days of antibiotics. Currently the effectiveness of extended duration antibiotics in patients with cIAI is unknown. This trial aims to compare the clinical and cost effectiveness of 28-day duration antibiotics with standard care with respect to rate of treatment failure in patients with cIAIs. Secondary outcomes include complications and quality of life. Method A multicentre, open label, two-arm, parallel group, pragmatic, randomised controlled trial with internal pilot. A total of 1166 consenting adult patients with cIAI will be recruited over 3 years and randomised on a 1:1 basis between 28-days antibiotics and standard care antibiotics. Patients will be recruited from ICUs and hospital in-patient wards across 30 sites. Trial management and funding EXTEND is sponsored by University of Leeds and hosted by York Trials Unit. It is funded by the NIHR. The Trial Management Group will oversee design and running of the trial. Each site will have a Principal Investigator (PI) with local responsibility. The NIHR Associate PI scheme will be adopted to enable trainees to participate in the trial.

Etiology, clinical features, management, and outcomes of skin and soft tissue infections in hospitalized children: A 10-year review.

This study aimed to describe the etiology, clinical features, hospital course, and outcomes of hospitalized children with skin and soft tissue infections (SSTIs) and to test if clinical and laboratory variables at admission could differentiate between community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) and community-acquired methicillin-sensitive S. aureus (CA-MSSA). We reviewed the clinical, laboratory, treatment, and outcome data for children hospitalized with SSTIs, aged 0-18 years at MacKay Children's Hospital between 2010 and 2019. Multivariable logistic regression was used to identify independent predictors of CA-MRSA and CA-MSSA SSTIs. A total of 1631 patients were enrolled. Erysipelas/cellulitis (73.8%) was the most common pediatric SSTI type, followed by acute lymphadenitis (13.6%) and abscess/furuncle/carbuncle (8.6%). Among the 639 culture-positive isolates (purulent SSTIs), 142 (22.2%) were CA-MSSA and 363 (56.8%) were CA-MRSA. The age group 0-1 month (OR, 6.52; 95% CI 1.09-38.92; P=0.04) and local lymph node reaction (OR, 2.47; 95% CI 1.004-6.08; P=0.049) were independent factors for differentiating children with CA-MSSA from those with CA-MRSA SSTIs. MRSA isolates in our cohort were highly susceptible to glycopeptides (100%), linezolid (100%), daptomycin (100%), and sulfamethoxazole/trimethoprim (98.6%) but were significantly less susceptible to clindamycin compared with MSSA (34.2% vs. 78.2%, P<0.001). S. aureus is the leading pathogen of culture-proven SSTIs in hospitalized children with MRSA accounting for more than half. Determining the optimal empirical antibiotics in CA-SSTIs may rely on the patient's age, disease severity, and local epidemiologic data.

Process optimization and kinetics study for photocatalytic ciprofloxacin degradation using TiO2 nanoparticle: A comparative study of Artificial Neural Network and Surface Response Methodology

The photocatalytic degradation of ciprofloxacin was investigated by developing a predictive mathematical model using response surface methodology and an artificial neural network. The four independent variables involve solution pH, reaction time, catalyst dose, and initial antibiotic concentration considered as factors in central composite design to observe the response in the form of antibiotic degradation. Accordingly, at an optimum antibiotic concentration of 5.02 mg/L, catalyst dose of 44.51 mg/L, solution pH of 5.04, and reaction time of 75.80 min, the photocatalysis method achieved a ciprofloxacin degradation of 88.30%. The experimental outputs were very much consistent along with the predicted output of experiments through response surface methodology (R2 = 0.9969) and artificial neural network (R2 = 0.975). The adsorption isotherm and kinetic study reveal that Langmuir isotherm and pseudo-second-order kinetic models respectively were best fitted for degradation of ciprofloxacin through photocatalysis. The finding provides a novel method for evaluating the photocatalysis process for the optimization of ciprofloxacin antibiotic removal from pharmaceutical waste using experiments and computer simulation tools.

Microbial Infection and Antibiotic Susceptibility of Diabetic Foot Ulcer in China: Literature Review.

ObjectiveTo investigate the microbial spectrum isolated from foot ulcers among diabetic patients in China, which was conducted to help clinicians choose optimal antibiotics empirically.MethodThe PubMed, MEDLINE, Web of Science, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), WanFang, and VIP databases were searched for studies published between 2015 to 2019, that report primary data on diabetic foot infection (DFI) and antibiotic susceptibility in China.ResultA total of 63 articles about DFI and antibiotic susceptibility tests among diabetic patients in China were included. There were 11,483 patients with an average age of 60.2 ± 10.1 years and a mean course of 10.6 ± 5.0 years between 2010 and 2019, covering most geographical regions of China. The prevalence of Gram-positive (GP) bacteria (43.4%) was lower than that of Gram-negative (GN) (52.4%). The most prevalent pathogens isolated were Staphylococcus aureus (17.7%), Escherichia coli (10.9%), Pseudomonas aeruginosa (10.5%), Klebsiella pneumoniae (6.2%), Staphylococcus epidermidis (5.3%), Enterococcus faecalis (4.9%), and fungus (3.7%). The prevalence of polymicrobial infection was 22.8%. GP bacteria were sensitive to linezolid, vancomycin, and teicoplanin. More than 50% of GN bacteria were resistant to third-generation cephalosporins, while the resistance rates of piperacillin/tazobactam, amikacin, meropenem, and imipenem were relatively low. Among the 6017 strains of the isolated organisms, 20% had multi-drug resistance (MDR). Staphylococcus aureus (30.4%) was the most predominant MDR bacteria, followed by extended-spectrum β-lactamase (ESBL) (19.1%).ConclusionThe microbial infection of foot ulcers among diabetic patients in China is diverse. The microbial spectrum is different in different geographic regions and Staphylococcus aureus is the predominant bacteria. Polymicrobial and MDR bacterial infections on the foot ulcers are common. This study could be valuable in guiding the empirical use of antibiotics for diabetic foot infections.

Prevalence and Antimicrobial Resistance of Causative Agents to Ocular Infections.

Bacterial ocular infections are a worldwide health problem and, if untreated, can damage the structure of the eye and contribute to permanent disability. Knowledge of the prevalence and antimicrobial susceptibility patterns of the main causative agents involved in ocular infections is necessary for defining an optimal antibiotic therapy. The aim of this study was to analyse bacterial species involved in ocular infections and the antimicrobial susceptibility patterns. Conjunctival swab samples were collected from patients with bacterial conjunctivitis at the University Hospital San Giovanni di Dio e Ruggi d’Aragona between January 2015 and December 2019. The identification and antibiotic sensitivity tests were performed using the VITEK 2 system. A total of 281 causative agents of ocular infections were isolated, 81.8% of which were Gram-positive bacteria. Coagulase-negative staphylococci (CoNS) were the most commonly isolated species among Gram-positive bacteria, followed by Staphylococcus aureus. In contrast, Pseudomonas spp. and Escherichia coli were the main species isolated among Gram-negative bacteria (18.2%). Overall, linezolid, teicoplanin, tigecycline and vancomycin were the most effective antimicrobials. Analysis of resistance rates over time highlighted increasing resistance for azithromycin, clarithromycin and erythromycin among CoNS, and clindamycin and erythromycin among Staphylococcus aureus. This study has identified the profiles of the major pathogens involved in ocular infection and their susceptibility patterns, which will help improve the treatments and the choice of antibiotics in ocular infections.

The Use of Comparative Genomic Analysis for the Development of Subspecies-Specific PCR Assays for Mycobacterium abscessus.

Mycobacterium abscessus complex (MABC) is an important pathogen of immunocompromised patients. Accurate and rapid determination of MABC at the subspecies level is vital for optimal antibiotic therapy. Here we have used comparative genomics to design MABC subspecies-specific PCR assays. Analysis of single nucleotide polymorphisms and core genome multilocus sequence typing showed clustering of genomes into three distinct clusters representing the MABC subspecies M. abscessus, M. bolletii and M. massiliense. Pangenome analysis of 318 MABC genomes from the three subspecies allowed for the identification of 15 MABC subspecies-specific genes. In silico testing of primer sets against 1,663 publicly available MABC genomes and 66 other closely related Mycobacterium genomes showed that all assays had >97% sensitivity and >98% specificity. Subsequent experimental validation of two subspecies-specific genes each showed the PCR assays worked well in individual and multiplex format with no false-positivity with 5 other mycobacteria of clinical importance. In conclusion, we have developed a rapid, accurate, multiplex PCR-assay for discriminating MABC subspecies that could improve their detection, diagnosis and inform correct treatment choice.

Antibiotic Prophylaxis in Congenital Cardiac Surgery: The Jury Is Still Out

Postoperative infection in cardiac surgical patients is a major cause of morbidity and mortality, and appropriate antibiotic prophylaxis is the key strategy to prevent surgical site infections. Current recommendations on the optimal antibiotic dosing regimens in children undergoing cardiac surgery with cardiopulmonary bypass (CPB) are still mainly based on extrapolation from adults.1 In this issue of The Annals of Thoracic Surgery, Suna and colleagues2 present a single-center prospective observational study of 64 children, aged 1 day to 16 years, who underwent cardiac surgery with CPB and received a standard hospital protocol of cefazolin perioperatively.