2nd Generation Cephalosporins Research Articles

First report of Shigella sonnei carrying a blaCTX-M-15 sexually transmitted among men who have sex with men.

Epidemiology of shigellosis has drastically changed in recent years due to globalization and sexual risk behaviors. Here, through whole-genome sequencing, we characterized two ESBL-producing Shigella sonnei strains (ShSoBUH1 and ShSoBUH2) carrying a blaCTX-M-15 among men who have sex with men (MSM), who had not recently traveled and presented sexual risk behaviors. Both strains harbored IncB/O/K/Z and IncFII plasmids, which carry aadA1, aadA5, sul1, sul2, dfrA1, dfrA17, mph(A), erm(B), tet(B), qacE and blaCTX-M-15 genes conferring resistance to 2nd and 3rd generation cephalosporins, cotrimoxazole, erythromycin, azithromycin and quinolones. IncFII plasmids containing blaCTX-M-15 from ShSoBUH1 and ShSoBUH2 presented 99,8-99,9% similarity with plasmids from another five CTX-M-15 S. sonnei strains detected in Belgium and Switzerland. A single-nucleotide polymorphism (SNP) analysis determined that the study strains differed by 361 SNPs, belonging to different clusters. To the best of our knowledge, this is the first report describing two extensively drug-resistant (XDR) CTX-M-15 S. sonnei strains in MSM.

Antimicrobial utilization pattern in indoor patients of obstetrics and gynecology ward of a tertiary care hospital

Background: Rational prescribing of antimicrobials is fundamentally necessary to reduce incidence of antimicrobial resistance. To evaluate the rationality of antimicrobial prescribing practices in patients admitted to obstetrics and gynecology ward of a tertiary care hospital using ICMR guidelines and to check how many drugs were prescribed from NLEMI. Methods: It was a prospective observational study. Study included newly admitted patients in obstetrics and gynecology ward receiving antimicrobial therapy. Drugs prescribed to the patients during their hospital stay were noted from case sheets in case record form. WHO core and economic indicators were used to analyze prescribing patterns. Medguideindia.com was referred for prices of drugs. Results: Average number of drugs prescribed for a patient admitted in the obstetrics and gynecology ward were 3.22 and 4.31 respectively. Percentage of drugs prescribed by their generic name were 37.11% and 39.42% in obstetrics and gynecology ward respectively. 26.85% and 34.14% of patients received drugs through parenteral route in obstetrics and gynecology wards respectively. All antimicrobials were prescribed from NLEMI. Conclusions: WHO recommends prescribing all drugs by their generic names. Average duration of antimicrobial treatment was higher than recommended average duration suggested by ICMR. ICMR recommends use of 2nd generation cephalosporins but in the present study 3rd generation cephalosporins were used. For rational use of antimicrobials and to reduce their cost it is recommended to prescribe antimicrobials by their generic names and reduce treatment duration by referring to ICMR Guidelines and NLEMI.

Etiologies, risk factors, and antibiotic pattern of lower respiratory tract infection in patients coming to Deccan College of Medical Sciences, Hyderabad, South India

Background. Lower Respiratory Tract Infections (LRTI) impose a huge problem on society due to their tenacious and unescapable health problems, and they were the reasons for consultation and hospitalization. Patients with LRTI were present with a wide spectrum of diseases that range from life-threatening infections to minor self-limiting illnesses. Materials and methods. Sputum samples from 310 patients with complaints of lower respiratory tract infections were collected and analyzed. After microscopic analysis, 30 were excluded from the study. Of the 280 that were included in the study, 171 were males and 109 were females. The age group between 56 and 65 years comprised the highest number of patients in the study. Different antibiotics were used to check antibiotic sensitivity patterns against isolated Gram-positive and negative bacteria. Results. Of the 280 samples processed, 122 (43.5%) were culture-positive. Among the 122 bacterial isolates, the predominant organism was Klebsiella pneumoniae 55 (45%). The most common predisposing factor identified in 115 (37%) patients was smoking. Using the Double Disk Synergy Test, 11 (20%) out of a total of 55 K. pneumoniae isolates and 4 (30.7%) out of 13 Pseudomonas isolates showed Extended Spectrum Beta Lactamases (ESBL). The Klebsiella and Pseudomonas isolates showed resistance to 2nd and 3rd generation Cephalosporins. Conclusion. Because of different geographical regions and conditions, the etiology and the antibiotic sensitivity patterns of LRTI vary, so the etiology, predisposing factors, and the antibiotic sensitivity pattern of LRTI need to be updated regularly. The diagnostic facilities for early and rapid identification of LRTI also need to be improved.

2949. Emergency Department (ED) Discharge Antibiotic Prescription Review by Hospital Pharmacists at a Large Academic Medical Center

Abstract Background Direct patient discharge from the Emergency Department (ED) presents an ideal time to promote antimicrobial stewardship (AS). On March 1, 2021 we initiated a pilot program where ED pharmacists conduct a review of discharge antibiotic prescriptions (abx Rxs). The aim of this program is to ensure appropriate discharge abxs. Willow Pharmacy Epic Analysts, ED and AS pharmacists collaborated on this program which included Epic integration of Rx Discharge Track Board, ED Discharge InBasket, ED Discharge Rx iVent and AS-led education sessions. Methods Data for 2022 ED patients with discharge abx Rxs and iVents were extracted via Epic Reports. The first encounter per patient was included. We compared discharge abx Rxs and patient outcome data in Pharmacy vs No Pharmacy Review Groups (PRG, NPRG). Pharmacy iVents were used as a process measure. Results Among 5747 ED adult patients with discharge abx Rxs, 2638 (46%) were reviewed by pharmacy (PRG). PRG and NPRG had similar prevalence of chronic pulmonary disease (12% vs. 13%), diabetes mellitus (9% vs. 10%), malignancy (8% vs. 9%), peripheral vascular disease (6% vs. 8%), renal disease (4% vs. 5%), and HIV (1% vs. 2%) despite a difference in mean Charlson Comorbidity Index (0.64 vs 0.75, p< 0.01). The primary ED diagnosis was skin and soft tissue, urinary, intra-abdominal infections and pneumonia (25 vs 23%, 18 vs 17%, 8 vs 9%, 5 vs 6%, respectively all p=NS). In PRG, discharge abxs demonstrated an increase use of penicillin (26 vs 24%, p=0.017) and 2nd generation cephalosporin (17 vs 14%, p< 0.001). The PRG also decreased use of 3rd generation cephalosporin (11 vs 12%, p=NS), quinolones (6 vs 7%, p=NS) and clindamycin (1.7 vs 2.4%, p=NS). There was no difference in ED length of stay (LOS 4.8h in each group), C. difficile infection (CDI) within 8 weeks (0.1 vs 0.2%, p=NS), and 30 days repeat ED visit or inpatient admission with the same diagnosis as index ED encounter (2.8 vs 2.6%, p=NS). Pharmacists intervened in 10% (272/2638) of ED abx Rxs with 92% (249/272) acceptance rate. The top 3 pharmacy interventions were recommending alternative abx (42%), dose optimization (31%) and abx duration (6%). Conclusion Engaging pharmacists in ED discharge Rxs review resulted in use of narrower spectrum abx with lower CDI risk without any negative impact on ED LOS and clinical outcomes. Disclosures All Authors: No reported disclosures

Characterization of Carbapenemase- and ESBL-Producing Gram-Negative Bacilli Isolated from Patients with Urinary Tract and Bloodstream Infections.

A total of 199 Gram-negative bacterial isolates from urinary tract infections and 162 from bloodstream infections were collected from 12 healthcare systems throughout the United States between May 2021 and August 2022. The isolates, phenotypically non-susceptible to 2nd or 3rd generation cephalosporins or carbapenems, were characterized through antimicrobial susceptibility testing and whole genome sequence analysis to obtain a broad snapshot of beta-lactamase-mediated resistance among these two sample types. Overall, 23 different carbapenemase genes were detected among 13 species (20.5% of isolates). The blaKPC-3 and blaKPC-2 subtypes were the most common carbapenemase genes identified, followed by blaNDM and the co-carriage of two different blaOXA carbapenemases by Acinetobacter baumannii isolates. All carbapenemase-producing A. baumannii isolates were mCIM negative. Extended-spectrum beta-lactamase genes were identified in 66.2% of isolates; blaCTX-M-15 was the most common. AmpC genes, both plasmid and chromosomal, were detected in 33.2% of isolates. Importantly, 2.8%, 8.3%, and 22.2% of blaKPC-positive organisms were susceptible to ertapenem, imipenem, and meropenem, respectively. The correlation between broth microdilution and disk diffusion results was high for most drugs except cefepime, where the detection of resistance was statistically lower by disk diffusion. Thus, there were gaps in the accuracy of susceptibility testing for some mechanisms of resistance.

Antimicrobial Resistance and Major Virulence Gene Detection in Methicillin Resistant Staphylococcus aureus in Humans and Livestock Animals of Assam: A North Eastern State of India

Methicillin resistant Staphylococcus aureus (MRSA) is highly divergent antibiotic resistant bacteria earmarked as “High” in global pathogens’ priority list varying the severity and resistance geographically. Here, MRSA were screened using mecA gene with Cefoxitin and other 27 antibiotics of 19 classes using disc diffusion method from a highly humid climate of India. Multiple Antibiotic Resistance (MAR) index was calculated. Minimum Inhibitory Concentration (MIC) was determined against 11 classes of antibiotics. Detection of major virulence genes tst-1 and lukPV were done. A total of 95.24% Hospital Associated (HA)-MRSA, 56.14% Community Associated (CA)-MRSA and 82.53 % Livestock Associated (LA)-MRSA were detected. Cefoxitin, Oxacillin, Ciprofloxacin, Fusidic acid and Ticarcillin-Clavulinic acid resistance was observed in more than 60% of HA-MRSA, CA-MRSA and LA-MRSA. Across the hosts, Mupirocin, Gentamicin, Linezolid, Co-trimoxazole, and Rifampicin were found effective. Vancomycin Intermediate Staphylococcus aureus (VISA) detected in CA-MRSA & LA-MRSA. Multidrug Resistant (MDR) was found very high but extensively drug-resistant (XDR) was detected moderately. No pan drug-resistant (PDR) was detected. Virulence gene tst-1 and lukPV were detected in 7.69% and 32.69% MRSA isolates. The gene tst-1 is reported for the first time in pre and post-caesarian samples from Gynaecology department in this region with high MDR. This study showed S. aureus and subsequent prevalence of MRSA is higher in this region then national data. 2nd generation Cephalosporins were found effective which is very encouraging due to their limited uses. Detection of tst-1 in caesarian samples is a serious threat as neonatal transmission of MRSA from mother is reported.

Nano-Conversion of Ineffective Cephalosporins into Potent One against Resistant Clinical Uro-Pathogens via Gold Nanoparticles.

Infections caused by resistant bacterial pathogens have increased the complications of clinicians worldwide. The quest for effective antibacterial agents against resistant pathogens has prompted researchers to develop new classes of antibiotics. Unfortunately, pathogens have acted more smartly by developing resistance to even the newest class of antibiotics with time. The culture sensitivity analysis of the clinical samples revealed that pathogens are gaining resistance toward the new generations of cephalosporins at a very fast rate globally. The current study developed gold nanoparticles (AuNPs) that could efficiently deliver the 2nd (cefotetan-CT) and 3rd (cefixime-CX) generation cephalosporins to resistant clinical pathogens. In fact, both CT and CX were used to reduce and stabilize AuNPs by applying a one-pot synthesis approach, and their characterization was performed via spectrophotometry, dynamic light scattering and electron microscopy. Moreover, the synthesized AuNPs were tested against uro-pathogenic resistant clinical strains of Escherichia coli and Klebsiella pneumoniae. CT-AuNPs characteristic SPR peak was observed at 542 nm, and CX-AuNPs showed the same at 522 nm. The stability measurement showed ζ potential as -24.9 mV and -25.2 mV for CT-AuNPs and CX-AuNPs, respectively. Scanning electron microscopy revealed the spherical shape of both the AuNPs, whereas, the size by transmission electron microscopy for CT-AuNPs and CX-AuNPs were estimated to be 45 ± 19 nm and 35 ± 17 nm, respectively. Importantly, once loaded onto AuNPs, both the cephalosporin antibiotics become extremely potent against the resistant strains of E. coli and K. pneumoniae with MIC50 in the range of 0.5 to 0.8 μg/mL. The findings propose that old-generation unresponsive antibiotics could be revived into potent nano-antibiotics via AuNPs. Thus, investing efforts, intellect, time and funds for a nano-antibiotic strategy might be a better approach to overcome resistance than investing the same in the development of newer antibiotic molecule(s).

1231. Microbial Profile of Biliary Stent, Bile and Surgical Site Cultures in Pancreaticoduodenectomy Patients – Implications for Surgical Prophylaxis

Abstract Background Surgical site infection (SSI) rates post pancreaticoduodenectomy (PD) range from 20 to 40%. Biliary obstruction (± stent in situ) leads to colonization of the biliary tract with gut flora, and bile contamination during surgery increases SSI risk. Current guidelines recommend surgical prophylaxis (ppx) with 1st or 2nd generation cephalosporins. However, emerging data favor targeted ppx based on biliary cultures to reduce SSI. We reviewed the microbial profile of pathogens isolated from perioperative biliary stent and bile cultures, and evaluated the impact of ppx on culture positive SSIs within 30 days of PD. Methods This was a retrospective study conducted in Singapore General Hospital. Patients who had PD from 1/1/2013 to 31/12/2019 were included. The first positive cultures from perioperative biliary stent, bile, and SSI cultures obtained within 30 days of surgery were reviewed. Antibiotic use 30 days prior and during surgery was collected. Results A total of 341 patients with a mean age of 63.9 ± 11.3 years were included; 202 (59.2%) were male and 137 (40.2%) received antibiotics in the past 30 days. For surgical ppx, patients received either cephalosporins ± metronidazole (216 [63.3%] ceftriaxone, 25 [7.3%] cefazolin), piperacillin-tazobactam (TZP) (35 [10.3%)], ciprofloxacin ± metronidazole (16 [4.7%)] or other antibiotics (14 [4.1%]), while 35 had missing data. Of the positive cultures from 84 biliary stent, 86 bile and 79 SSI, the most common organisms isolated were Enteroccocus spp., E. coli, Klebsiella spp., Enterobacter spp. and Candida spp. Ceftriaxone susceptibility rates in E. coli were 50.0%, 54.8% and 22.2% in biliary stent, bile and SSI cultures respectively; similarly low rates were also seen in Klebsiella spp. (Tables 1-3). Antibiotic use 30-days prior was associated with higher ceftriaxone resistance rates in E. coli and Klebsiella spp. from bile cultures (70.8% vs 36.4%, p=0.019). In patients with biliary stents cultured, use of TZP ppx showed a trend towards lower rates of culture positive SSIs compared to non-TZP ppx (9.1% vs 29.4%, p=0.054). Conclusion Our local gram-negative bacteria susceptibility rates to ceftriaxone are low in biliary stent, bile fluid cultures, and even lower for SSI post PD. Antibiotic ppx for PD in high-risk patients may need to be broadened. Disclosures All Authors: No reported disclosures.

An overview of surgical site infection and prophylactic antibiotics in vascular surgery

Background: Vascular surgery is a complex procedure with many complications such as surgical site infections, graft infections, pneumonia, myocardial infarction, hemorrhage, and thromboembolism or thrombosis, in which, the most common complications are surgical site infection, and graft infection. Currently, antibiotic prophylaxis is considered the most effective practice to suppress surgical site infection in surgical procedures including vascular surgery. The aim of this paper is to review the surgical site infection and prophylactic antibiotics in vascular surgery.[1]
 Method: A search was made by using Medline, PubMed, Scopus and Web of Science databases, and databases of journals in Vietnam.
 Result: 1227 records were identified, of which 112 were included in this review. This included 90 researches, and 22 guidelines.
 Conclusion: In vascular surgery, antibiotic prophylaxis is recommended in most guidelines for abdominal aortic surgery, lower limb vascular surgery, vascular surgery with prosthetic grafts or stents. The common antibiotic regimens are 1st generation cephalosporins – C1G (cefazolin), 2nd generation cephalosporins – C2G (cefuroxim) administrated 60 minutes before incision, and discontinued within 24 hours of surgery.

Assessment of nationally recommended antibiotics for treatment of UTI in U.S.-Mexico border emergency departments

BackgroundUrinary tract infections (UTIs) seen in the emergency department are commonly treated as an outpatient with oral antibiotics. Given that antibiotics are available for over-the-counter purchase in Mexico, there is speculation that potential misuse and overuse of antibiotics in United States-Mexico border areas could lead to antibiotic resistance patterns that would render some empiric treatments for UTIs less effective. The purpose of this study was to examine the effectiveness of Infectious Disease Society of America (IDSA) guideline-recommended antibiotics for treatment of outpatient UTI diagnosed in the emergency department. Data were collected from a county hospital on the U.S.-Mexico border with a metropolitan area of over 2 million people. Secondary analysis included frequency of urine culture isolated, resistance rates of urine pathogens, and prescriber habits. MethodsThis study was a retrospective chart review of adult patients diagnosed and treated for UTI from August 1, 2019, to February 29, 2020. Culture results of included patients were analyzed against in vitro-tested antibiotics. Bacterial isolate frequency, resistance rates, and prescribing habits were collected. ResultsA total of 985 patient charts were reviewed, of which 520 patients met inclusion criteria for analysis of prescribing habits. Of these, 329 positive bacterial culture growths were included in the analysis of antibiotic resistance rates. Oral antibiotics with comparatively lower resistance rates were amoxicillin/clavulanate, cefdinir, cefuroxime, and nitrofurantoin. Oral antibiotics with notably high resistance rates included trimethoprim-sulfamethoxazole (TMP-SMX), tetracycline, ciprofloxacin, levofloxacin, and cephalexin. Nitrofurantoin was prescribed most frequently for outpatient treatment of UTI/cystitis (41.6%) while cephalexin was the most commonly prescribed antibiotic for outpatient treatment of pyelonephritis (50%). ConclusionOur findings suggest that, while part of standard IDSA guidelines, fluoroquinolones and TMP-SMX are not ideal empiric antibiotics for treatment of outpatient UTI in the U.S.-Mexico border region studied due to high resistance rates. Although not listed as first line agents per current IDSA recommendations, 2nd and 3rd generation cephalosporins, and amoxicillin/clavulanate would be acceptable options given resistance patterns demonstrated in accordance with IDSA allowance for tailoring selection to local resistance. Nitrofurantoin appears to be consistent with recommendations and demonstrates a favorable resistance profile for treatment of outpatient UTI within this region.

Prevalence and Molecular Characterization of Metallo β-Lactamase Producing Gram-Negative Pathogens Causing Eye Infections.

Purpose:Metallo β-lactamases (MβL) production is a worldwide problem, particularly in gram-negative bacteria. As scanty data is available on the prevalence of MBL, the present study is being undertaken to determine the prevalence, antibacterial sensitivity patterns, and molecular characterization of MβL associated resistant genes in gram-negative bacteria isolated from ocular infections.Material and MethodsAt a tertiary eye care center in south India, 359 gram-negative pathogens, 200 isolates from eye infections, and 159 isolates from normal flora of the eye were studied. A gold standard microbiology method was used to identify the isolates. An antibiotic double disc synergy test and a combination disc test were used to detect MβL production. Multiplex PCR was used to investigate the molecular characteristics of the MβL encoding genes blaVIM, blaIMP, and blaNDM.ResultsOf the 359 gram-negative bacterial pathogens, Pseudomonas aeruginosa 108 (30.1%) and Enterobacter agglomerans 46 (12.8%) were commonly isolated. High prevalence of P. aeruginosa 81% (17 strains) was detected as an MβL producer and it shows 100% resistance to 2nd and 3rd generation cephalosporins and meropenem. Multiplex PCR detected only the blaVIM gene in 56 (28%) of various eye infections and 27 (17%) of normal flora of the gram-negative bacteria (GNB). The blaVIM gene is detected predominantly in 51.8% of keratitis and 21.4% of postoperative endophthalmitis. High prevalence of the gene was detected in P. aeruginosa 42.9% (24 of 56) and Alcaligens denitrificans 10.7% (6 of 56) from eye infections. Whereas, in the control group, P. aeruginosa and E. coli each had 14.8% (4 of 27) that were shown positive.ConclusionThe emerging MβLs mediated resistance among P. aeruginosa is a challenging task for ophthalmologists, especially in patients with endophthalmitis and bacterial keratitis. This local knowledge will aid in advising appropriate antibiotic use and avoiding unnecessary antibiotic prescriptions, which are highly warranted.

Role of cefuroxime as antibiotic prophylaxis for general surgery: An expert opinion

Surgical site infections (SSIs) are serious postoperative complications reported globally, which lead to perioperative antibiotics use during routine practice in surgical procedures. Selection of appropriate antibiotic/s for prophylaxis is a vital step in the management and care of invasive surgical procedures. This expert opinion review was developed based on expert discussion and literature search on scientific databases with special emphasis on cefuroxime in surgical prophylaxis for general surgeries. Cephalosporins are globally considered to be the drugs of choice for surgical prophylaxis in general surgeries owing to good safety, bactericidal activity, penetration to critical tissues, and proven efficacy in clinical trials. Cefuroxime, a 2nd generation cephalosporin, is an effective, safe and low-cost antibiotic for surgical prophylaxis in general surgeries, in particular for patients who need sequential antibiotic therapy. Cefuroxime can be administered alone or in combination with other classes of antibiotics based on clinical characteristics of individual patients and surgeon’s discretion to reduce the risk of postoperative SSIs, abscess, septicemia, and microbial growth.Cefuroxime can be administered alone or in combination with other classes of antibiotics based on clinical characteristics of individual patients and surgeon’s discretion to reduce the risk of postoperative SSIs, abscess, septicemia, and microbial growth.

1004. Cladophora in Lake Michigan May Serve as Important Reservoirs for Antibiotic-Resistant Bacteria

BackgroundCladophora is a green algae, native to the Great Lakes, and found in large quantities along Lake Michigan shorelines. Previous studies have shown that Cladophora provide protection and nutrients for the Enterobacteriaceae (Ent) family, allowing persistence and regrowth. Chicago waterways harbor concerning antibiotic-resistant (AR) Ent, however the community reservoirs are unknown. Our primary objective was to assess whether Cladophora harbor AR Ent and to secondarily assess AR Ent in local beach waters where Cladophora are present. Figure 1. Map of Lake Michigan showing sites (S1-S3) where Cladophora samples were collected. NB, North Beach, Racine, Wisconsin; Michigan City, Indiana; PL, Portage Lakefront, Indiana Dunes National Park, Indiana. Figure 2. Map of Lake Michigan showing sites (S4-S7) where beach surface water samples were obtained. Montrose, Foster, 63rd St, & Calumet beaches in Chicago, Illinois.MethodsCladophora were processed from three Indiana Lake Michigan sites (S1 and S2; Fig 1) in 2002 and 2012 (S3; Fig 1) at the USGS Lake Michigan Ecological Research Station (Chesterton, IN). In 2015, surface water samples were obtained by the USGS at four Chicago beaches (S4-S7; Fig 2), which also amass Cladophora. Bacteria were isolated shortly after collection. In 2019-2020, Ent were cultivated and susceptibilities were performed at Rush.ResultsIn 2002-2003 (S1 and S2), 160 E. coli were cultured from Cladophora. There was AR to multiple classes, highest overall in tetracyclines (7.5%, range 6.2%-18.7%), cefoxitin (8%), and cefazolin (5.6%). Resistance to cefuroxime was 0.6%. Four Salmonella isolates from 2012 (S3) were pan-susceptible, while two Citrobacter isolates were resistant to penicillins, 1st and 2nd generation cephalosporins, and cephamycins. Beach surface water samples from 2015 revealed more pronounced AR in E. coli (n=185) involving multiple classes, including highest in ampicillin (12.4%), tetracyclines (8.1%); piperacillin (7%); cefazolin (3.8%), cephamycins (3.2%) and amoxicillin-clavulanate (2.7%). Resistance to 3rd-generation cephalosporins, fluoroquinolones, trimethoprim/sulfamethoxazole ranged from 0.5-2%. AR Ent varied by beach site with highest percentages at S4, the only site with an associated dog beach. ConclusionThese findings suggest that Cladophora in recreational waterways may serve as reservoirs for AR Ent. Differences in AR Ent at beach sites may reflect varying degrees of fecal contamination. Identifying community reservoirs is key to better understanding the acquisition of antibiotic resistant Ent among healthy populations and has long-term ecological and public health implications.Disclosures All Authors: No reported disclosures

Comparison between antimicrobial stewardship program and intervention by infection control team for managing antibiotic use in neurogenic bladder-related urinary tract infection patients: A retrospective chart audit

BackgroundAntimicrobial prescriptions are relatively common in urologic outpatients. Therefore, it is necessary to investigate the impact of antimicrobial stewardship program (ASP) interventions. MethodsIn urology outpatients, antimicrobial use density (AUD), antimicrobial agent costs, isolation of urinary tract infection (UTI)-causing organisms and their antimicrobial susceptibilities were compared between intervention by infection control team (ICT) era (pre-2014) and ASP era (post-2014) in 2739 patients with lower urinary tract symptoms, including neurogenic bladder patients with UTI or suspected UTI, from 2011 to 2020. ResultsIn the ASP, overall AUD (P<.001), cefotiam (CTM) (P=.0013), 2nd-generation cephalosporins (P=.026), cefdinir (CFDN) (P<.001), levofloxacin (LVFX) (P<.001), sitafloxacin (STFX) (P=.0016), and tosufloxacin (TFLX) (P=.0044) showed a significant decrease, but cefaclor (P=.019) showed a significant increase. Regarding antimicrobial agent costs, overall (P=.016), CTM (P=.021), 2nd-generation cephalosporins (P=.033), CFDN (P=.016), LVFX (P=.016), STFX (P=.033), and TFLX (P=.033) showed a significant decrease in the ASP. UTI-causing antimicrobial susceptibilities, CTM (P=.035), LVFX (P=.026) and sulfamethoxazole/trimethoprim (P=.048) in E. coli, and minocycline (P=.026) in K. pneumoniae showed a significant improve in the ASP. ConclusionASP contributed to decrease AUD and antimicrobial agent costs, and to improve antimicrobial susceptibilities of E. coli and K. pneumoniae to several antibiotics, compared to ICT. Further prospective studies are necessary for definitive conclusions.

Диагностика и лечение внебольничной пневмонии у детей

На практике, особенно в амбулаторных условиях, серьезными проблемами педиатрии являются ранняя диагностика и рациональная терапия пневмонии у детей. Наиболее распространенными возбудителями при внебольничной пневмонии являются Streptococcus pneumoniae, Haemophilus influenzae и другие микроорганизмы, в том числе вирусы и грибы. Следует уточнить, что этиология заболеваний нижнего респираторного тракта резко отличается в разных возрастных группах. Самой частой причиной внебольничной пневмонии (до 50 %) является S.pneumoniae, реже встречаются такие палочки, как E.сoli, Klebsiella spp., C.trachomatis, Mycoplasma, Ureаplasma. У детей старше 5 лет в этиологической структуре внебольничной пневмонии наряду с S.рneumoniae возрастает значимость Mycoplasma рneumoniae. Резистентность возбудителей инфекции к антибактериальным препаратам — нарастающая глобальная проблема. Алгоритм диагностики внебольничной пневмонии включает фебрильную температуру продолжительностью &gt; 3 дней, цианоз, одышку при отсутствии признаков бронхиальной обструкции, кашель. Тахипноэ является одним из лучших предикторов пневмонии у детей всех возрастов. При физикальном обследовании — наличие укорочения перкуторного звука в зоне поражения, бронхиальное или ослабленное дыхание, звучные мелкопузырчатые или крепитирующие хрипы. Для диагностики нетяжелых внебольничных пневмоний вполне достаточно ограничиться клиническими симптомами, рентгенографией легких, общим анализом крови. Начальная антибиотикотерапия внебольничной пневмонии проводится эмпирическим путем. При лечении нетяжелых внебольничных пневмоний у детей от 2 мес. до 5 лет препаратом выбора является амоксициллин перорально. Макролиды — препараты выбора у детей от 5 до 16 лет. При тяжелой пневмонии препаратами выбора являются амоксициллин/клавуланат, цефалоспорины II, III, IV поколения. В целом продолжительность антибиотикотерапии при внебольничной пневмонии, вызванной типичными бактериями, составляет 7–10 дней, атипичными бактериями — 10–14 дней. В реальной клинической практике при проведении антибактериальной терапии нередко наблюдаются ошибки, связанные с выбором препарата, пути введения, дозировки, режима применения, длительности курса.

Cefaclor-induced hypersensitivity: Differences in the incidence of anaphylaxis relative to other 2nd and 3rd generation cephalosporins.

Cefaclor, a second-generation oral cephalosporin, is the most frequently prescribed cephalosporin in Korea. Studies, however, have yet to analyze the incidence of cefaclor-associated adverse drug reactions (ADRs), including hypersensitivity (HS), according to total national usage rates. This study aimed to investigate the incidence rates and clinical features of cefaclor ADRs reported to the Korean Adverse Event Reporting System (KAERS) and Health Insurance Review and Assessment Service (HIRA) database for the most recent 5 years. Reviewing the HIRA database, which contains information on all insurance claims, including prescribed medications and patient demographics, we identified the total number of individuals who had been prescribed cefaclor and other cephalosporins including 2nd generation without cefaclor and 3rd generation antibiotics from January 2014 to December 2018. Additionally, we retrospectively analyzed all ADRs reported to the KAERS for these drugs over the same study period. Incidence rates for ADRs, HS, and anaphylaxis to cefaclor were 1.92/10,000 persons, 1.17/10,000 persons, and 0.38/10,000 persons, respectively, lower than those to other 2nd and 3rd cephalosporins. Among all ADRs, HS (60.9% vs. 43.6% vs. 44.8%, P <0.001) and anaphylaxis (19.8% vs. 4.6% vs. 4.7%, P <0.001) were more common for cefaclor than for other 2nd and 3rd cephalosporins. Females, individuals under 65 years of age, concomitant use of drugs, and serious ADRs were more strongly associated with HS to cefaclor than with HS to other 2nd and 3rd cephalosporins. In a nationwide database for the Korean population, the incidence of cefaclor-induced ADRs, particularly HS and anaphylaxis, was high. Female sex, age younger than 65 years, and concomitant use of drugs may be associated with HS to cefaclor.

Acute Hand Infections - Survey of the Pathogen Spectrum and appropriate Antibiotics

Acute infections of the hand can be a pathology with severe consequences. Alongside the surgical therapy, it is necessary to establish a systemic antiinfective therapy as well. The most frequent bacteria in acute hand infections are Staphylococcus aureus and, less frequently, different Streptococci. If the infection is the result of a bite wound, the most frequently found bacterium is Pasteurella multocida. Fortunately, the susceptibility to frequently used antibiotics in the (middle-)European area is quite good - according to the literature, resistances are rare. First line antibiotics are 1st and 2nd generation cephalosporins as well as aminopenicillins in combination with beta-lactamase inhibitors. Especially in multi-morbid patients or infections with unusual aetiology, a broader bacterial spectrum is to be expected. It is very effective to collect a tissue sample or swab for microbiological analysis before the establishment of the antiinfective therapy to gain valuable information about the prospective therapy. Ultimately, hand infections are a pathology to be treated with increased attention to avoid severe complications. A close cooperation with the involved specialties and physiotherapists should be sought to guarantee the best possible outcome.

Antibiotic resistance among major pathogens compared to hospital treatment guidelines and antibiotic use in Nordic hospitals 2010–2018

Background The Nordic countries have comparable nationwide antibiotic resistance surveillance systems and individual antibiotic stewardship programmes. The aim of this study was to assess antibiotic resistance among major pathogens in relation to practice guidelines for hospital antibiotic treatment and antibiotic use in Nordic countries 2010–2018. Methods Antibiotic resistance among invasive isolates from 2010–2018 and aggregated antibiotic use were obtained from the European Centre for Disease Prevention and Control. Hospital practice guidelines were obtained from national or regional guidelines. Results Antibiotic resistance levels among Escherichia coli and Klebsiella pneumoniae were similar in all Nordic countries in 2018 and low compared to the European mean. Guidelines for acute pyelonephritis varied; 2nd generation cephalosporin (Finland), 3rd generation cephalosporins (Sweden, Norway), ampicillin with an aminoglycoside or aminoglycoside monotherapy (Denmark, Iceland and Norway). Corresponding guidelines for sepsis of unknown origin were 2nd (Finland) or 3rd (Sweden, Norway, Iceland) generation cephalosporins, carbapenems, (Sweden) combinations of penicillin with an aminoglycoside (Norway, Denmark), or piperacillin-tazobactam (all Nordic countries). Methicillin-resistant Staphylococcus aureus rates were 0–2% and empirical treatment with anti-MRSA antibiotics was not recommended in any country. Rates of penicillin non-susceptibility among Streptococcus pneumoniae were low (<10%) except in Finland and Iceland (<15%), but benzylpenicillin was recommended for community-acquired pneumonia in all countries. Conclusion Despite similar resistance rates among Enterobacteriaceae there were differences in practice guidelines for pyelonephritis and sepsis. National surveillance of antibiotic resistance can be used for comparison and optimization of guidelines and stewardship interventions to preserve the low levels of antibiotic resistance in Nordic countries.

Second-Generation Cephalosporins-Associated Drug-Induced Liver Disease: A Study in VigiBase with a Focus on the Elderly.

Background: The objective of this study was to characterize individual case safety reports (ICSRs) and adverse drug reactions (ADRs) related to second-generation cephalosporins and resulting in hepatobiliary disorders, in VigiBase, WHO global database. Methods: All second-generation cephalosporins hepatobiliary ADRs reported up to July 2019 were included. Characteristic of cephalosporins and ADRs, aside from disproportionality data were evaluated. Results: A total of 1343 ICSRs containing 1585 ADRs were analyzed. Cefuroxime was suspected to have caused hepatobiliary disorders in most cases—in 38% of adults and in 35% of elderly. Abnormal hepatic function was the most frequent ADR, followed by jaundice and hepatitis. For 49% of the ADRs reported in the elderly and 51% in the adult population, the outcome was favorable, with fatal outcome for 2% of the adults and 10% of the elderly. Higher proportional reporting ration (PRR) values were reported in the elderly for cefotetan-associated jaundice, cefuroxime-associated acute hepatitis and hepatitis cholestatic as well as for cefotiam and cefmetazole-associated liver disorder. Conclusion: Hepatobiliary ADRs were reported for 2nd generation cephalosporins, with over 50% of cases in adults, without gender differences. Cholestatic hepatitis was predominately reported in the elderly and this category was more prone to specific hepatic reactions.

S3340 Recurrent High Grade Enterobacter aerogenes Bacteremia in a Patient With Hepatocellular Carcinoma

INTRODUCTION: Enterobacter species are important nosocomial pathogens. Enterobacter aerogenes is generally found in the human GI tract and does not cause disease in healthy people. We present a case of recurrent enterobacter bacteremia in a patient with hepatocellular carcinoma (HCC). CASE DESCRIPTION/METHODS: A 66 year old male with a history of hemochromatosis, HCC post chemoembolization, hepatitis C, portal vein thrombosis treated with Xarelto who presented with lower abdominal pain, vomiting, and poor oral intake for several weeks. His exam was significant for generalized abdominal tenderness. Vitals, cell counts were unremarkable and LFTs were mildly abnormal with ALP of 436 U/L. CRP was 203 mg/L. COVID-19 PCR negative. Blood cultures were 4/4 positive for Enterobacter aerogenes sensitive to ceftriaxone, cefepime, ertapenem and resistant to ampicillin/sulbactam and 1st and 2nd generation cephalosporins. He had been treated with ertapenem for 2 weeks for enterobacter bacteremia with unclear etiology, and the differential at this presentation included vascular infection such as thrombus or infective endocarditis. CT abdomen/pelvis showed tumor thrombosis versus bland thrombus extending from the ablation field in into the inferior vena cava (IVC). Abdominal MRI confirmed 2.6 cm focus of signal intensity in right hepatic lobe contiguous with non occlusive IVC thrombus. TTE was negative for vegetations. Patient was discharged with 6 weeks of Ertapenem for suspicion of thrombophlebitis given the high grade recurrent bacteremia. DISCUSSION: To date there has been no major case reports or case series demonstrating a case of recurrent high grade enterobacter bacteremia with hepatocellular carcinoma. Spontaneous bacterial peritonitis caused by Enterobacter infections is more commonly associated with underlying HCC and upper gastrointestinal bleeding as compared to infection caused by E coli. For over the last two decades, there has been increasing suspicion about the induction of beta-lactam resistance in enterobacter infections mediated by chromosomally encoded amp-c beta lactamase following antibiotic exposure hence we opted to treat the patient with ertapenem for the 6 week duration. Our case demonstrates a patient with hepatocellular carcinoma with likely/presumed thrombophlebitis requiring prolonged antibiotic course.Figure 1.: CT abdomen pelvis showed tumor thrombus versus bland thrombus extending from the ablation field in hepatic segment 6 into the inferior vena cava.Figure 2.: MRI abdomen showing a ∼2.6 cm focus of abnormal pre and postcontrast signal intensity in the right hepatic lobe that is contiguous with the nonocclusive IVC thrombus.