4th Generation Cephalosporins Research Articles

Cefepime/Enmetazobactam: First Approval.

Cefepime/enmetazobactam (EXBLIFEP®), an intravenous (IV) antibacterial fixed-dose combination of a 4th generation cephalosporin and an extended-spectrum β-lactamase (ESBL) inhibitor, is being developed by Allecra Therapeutics and ADVANZ PHARMA for the treatment of infections caused by multi-drug-resistant (MDR) Gram-negative bacteria. In February 2024, cefepime/enmetazobactam was approved in the USA for use in adults with complicated urinary tract infections (cUTI) including pyelonephritis, caused by susceptible strains of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Proteus mirabilis, and Enterobacter cloacae complex. In March 2024, cefepime/enmetazobactam was approved in the EU for use in adults for the treatment of cUTI, including pyelonephritis, and hospital-acquired pneumonia, including ventilator associated pneumonia, and the treatment of patients with bacteraemia occurring in association with or suspected to be associated with any of these infections. This article summarizes the milestones in the development of cefepime/enmetazobactam leading to this first approval for the treatment of adults with infections caused by MDR Gram-negative bacteria.

A Five-Year Analysis of Antibiotic Resistance Trends among Bacteria Identified in Positive Urine Samples in a Tertiary Care Hospital from Bucharest, Romania.

The rise of multidrug-resistant bacteria (MDR) has resulted in limited treatment options and poorer outcomes for patients. The objective of this study was to analyze the overall antibiotic resistance trends and distribution for pathogens identified in urine samples at the National Institute of Infectious Diseases "Prof. Dr. Matei Balș" from Bucharest, Romania, over a 5-year period. Antibiotic susceptibility testing was performed using automatic systems and the disk diffusion method. ESBL- and carbapenemases-producing strains were identified using immunochromatography tests, and ROSCO Diagnostica kits were used for definitive confirmation. All results were interpreted according to EUCAST clinical breakpoints. Gram-negative rods (GNR) had overall resistance rates higher than 50% for penicillin and 40% for 3rd- and 4th-generation cephalosporins. Escherichia coli resistance to fosfomycin (3%) and nitrofurantoin (2%) remains low, and 33.30% of E. coli, 48% of Klebsiella spp., and 37% of Pseudomonas aeruginosa isolates were multidrug-resistant (MDR). All Acinetobacter baumannii isolates were MDR by the last year of the study. For Gram-positive cocci (GPC), 37% of all Enterococcus faecium strains and 2% of Enterococcus faecalis were vancomycin-resistant (VRE). E. coli's incidence in UTIs' etiology is on a downward trend. The incidence of Klebsiella spp. and GPCs is rising. Antibiotic stewardship strategies should be implemented after carefully considering regional variations in etiology and resistance trends.

The Occurrence, Antibiotic Susceptibility Pattern and Multiple Drug Resistance Index Studies of E. coli from Fresh Meats in Marathwada Region of Maharashtra

Background: Foodborne diseases are a huge social burden in both developed and underdeveloped countries. Escherichia coli is a natural inhabitant of the human and warm-blooded animal digestive tracts. It is considered as an indicator organism for direct or indirect faecal contamination of raw meats. The presence of antibiotic-resistant microorganisms in meat accounts for a public health risk. Methods: In current study, all 39 characterized E. coli isolates recovered on screening 405 fresh meat samples collected from different butcher shops in the Udgir city, Marathwada region of Maharashtra were also tested for Congo red dye binding assay and haemolysis assay. Antimicrobial resistance profiling of recovered isolates was carried out using the disc diffusion method. Result: Overall occurrence of E. coli in fresh meats was noted to the tune of 9.63% and the corresponding group wise occurrence in chicken and chevon samples were 12% and 7.32%, respectively. All E. coli tested positive in the Congo red dye binding assay and haemolysis assay, suggesting virulent nature of isolated organisms. On screening for antimicrobial resistance, these isolates were found resistant to mainly â-lactams (94.87%), lincosamides (84.62%), 4th Generation cephalosporins (82.05% each), DHFR Inhibitors (64.10%), glycopeptides (51.28%). The multidrug resistant isolates showed resistance to a minimum of 4 and maximum of 12 antibiotics with MAR index ranging from 0.27 to 0.8 and 9 resistance patterns.

Molecular mechanism of antimicrobial co-resistance Colistin (mcr-1) and ESBLs genes among Escherichia coli isolates from commercial chickens in Pakistan.

Emergence of plasmid mediated colistin and extended spectrum β-lactamases (ESBL) resistant genes has been impacted the efficacy of colistin and β-lactams drugs like 3rd, 4th generation cephalosporin. Current study was aimed to investigate antimicrobial resistance genes (ARGs) among Escherichia coli isolates from meat producing commercial broilers in Pakistan. Two hundred (n=200) fecal samples were collected during January-2018 to August-2019. For isolation of E. coli, pink colonies on MacConkey agar were transferred to EMB agar. Metallic sheen color colonies were tested biochemically using API-20E kit. The molecular identification of E. coli (n=153) was targeted by amplification of uid gene through polymerase chain reaction (PCR) and different ARGs i.e. gentamicin, streptomycin, tetracycline, colistin, β-lactams drugs, quinolone and ampicillin followed by sequence analysis. Genotypically, followed by phenotypically of resistant ARGs of isolated PCR-confirmed E. coli (153) shoed resistant against gentamicin (aac(3)-IV), streptomycin (aadA1), tetracycline (tetA), colistine (mcr-1), ampicillin (bla-TEM) and bla-CTX-M were 86%, 88%, 86%, 88%, 83% & 77% respectively. 33/38 (86%) of the isolate was positive for quinolone resistance. Colistine (mcr-1), ESBLs (bla-TEM) and (bla-CTX-M) resistance genes were 88%, 83% and 77% respectively. About 33 isolated E. coli harbored the both mcr-1 and ESBLs genes. All of E. coli isolates were found sensitive to ceftriaxone (CTX-30) and imipenem (IMP-10). The Isolated E. coli showed single or multi clade decadency. The E. coli and ARGs sequences showed single or multi clade decadency. This is first comprehensive study from Pakistan that described the molecular evidences of ARGs and their co-existence in single isolates originated from commercial poultry. Commercial chicken (Broilers) can act as melting pot of antibiotic resistance genes for human being. It is alarming situation for surveillance of antibiotic resistance program because of more regulated prescription of antimicrobial agents in Pakistan.

Epidemiological indicators and predictors of lethality associated with fungal infections in a NICU: an historical series

ObjectivesFungal infections (FI) pose a public health concern and significantly increase mortality rates, especially within Neonatal Intensive Care Units (NICU). Thus, this study aimed to investigate epidemiological indicators, risk factors, and lethality predictors associated with FI in a NICU. MethodsThis study included 1,510 neonates admitted to the NICU of a reference hospital in Brazil between 2015 and 2022. Demographic data, such as sex, birth weight, gestational age, and use of invasive devices were analyzed. ResultsThirty neonates developed invasive FI, totaling 33 episodes and an incidence of 1.2 per 1,000 patient days. Candida albicans was the most frequent species (52.9 %), the bloodstream was the most affected site (78.9 %), and 72.7 % of infections occurred between 2015 and 2018. The lethality rate associated with FI was 33.3 %, and 90 % of deaths occurred within 30 days of diagnosis of infection. Weight < 750 g, prolonged hospital stay, use of parenteral nutrition, and broad-spectrum antimicrobials were independent risk factors for infection occurrence, especially glycopeptides and 4th generation cephalosporins, having a considerable role in the increase in fungal infections. Weight < 750 g was considered a significant predictor of lethality, and C. albicans had the highest lethality rate (40 %). ConclusionThese findings highlight the elevated lethality rate associated with these infections, reinforcing the importance of developing strategies to control FI within NICU.

Evolving trends among Pseudomonas aeruginosa: a 12-year retrospective study from the United Arab Emirates.

Pseudomonas is a group of ubiquitous non-fermenting Gram-negative bacteria (NFGNB). Of the several species associated with humans, Pseudomonas aeruginosa (PA) can acclimate to diverse environments. The global frequency of PA infections is rising and is complicated by this organism's high intrinsic and acquired resistance to several clinically relevant antibiotics. Data on the epidemiology, levels, and trends of antimicrobial resistance of PA in clinical settings in the MENA/GCC region is scarce. A retrospective 12-year analysis of 56,618 non-duplicate diagnostic Pseudomonas spp. from the United Arab Emirates (UAE) was conducted. Data was generated at 317 surveillance sites by routine patient care during 2010-2021, collected by trained personnel and reported by participating surveillance sites to the UAE National antimicrobial resistance (AMR) Surveillance program. Data analysis was conducted with WHONET (https://whonet.org/). Among the total isolates (N = 56,618), the majority were PA (95.6%). Data on nationality revealed 44.1% were UAE nationals. Most isolates were from soft tissue (55.7%), followed by respiratory tract (26.7%). PA was more commonly found among inpatients than among outpatients, followed by ICUs. PA showed a horizontal trend for resistance to fluoroquinolones, 3rd- and 4th-generation cephalosporins, and decreasing trends of resistance for aminoglycosides and meropenem. The highest percentage of multidrug resistant (MDR) isolates was reported in 2011 at 35.6%. As an overall trend, the percentage of MDR, extensively drug-resistant (XDR), and possible pandrug-resistant (PDR) isolates generally declined over the study period. Carbapenem-resistant PA (CRPA) were associated with a higher mortality (RR: 2.7), increased admission to ICU (RR: 2.3), and increased length of stay (LOS) (12 excess inpatient days per case), as compared to carbapenem-susceptible PA (CSPA). The resistance trends in Pseudomonas species in the UAE indicated a decline in AMR and in percentages of Pseudomonas isolates with MDR and XDR profiles. The sustained Pseudomonas spp. circulation particularly in the hospital settings highlights the importance of surveillance techniques, infection control strategies, and stewardship to limit the continued dissemination. This data also shows that CRPA are associated with higher mortality, increased ICU admission rates, and a longer hospitalization, thus higher costs due to increased number of in-hospital and ICU days.

Antimicrobial Resistance and Plasmid Profiling of ESBL Producing Klebsiella spp. of Bovine Origin of Eastern Plain Zone of Uttar Pradesh

Emergence of antimicrobial resistance in animal husbandry is of utmost concern as it has resulted in therapeutic failure and nowadays it is one of the latest challenges faced by scientific community across the world. Extensive use of antibiotics without performing antibiotic susceptibility testing may lead to development of multidrug resistant (MDR) organisms. This study was undertaken to assess the AMR pattern and their correlation with plasmid profiling in ESBL producing Klebsiella spp. from bovine origin. Total 160 samples were collected from 2 district of Eastern Plain Zone of Uttar Pradesh (India) and 63 (39.37%) isolates were confirmed as Klebsiella spp. by conventional methods (cultural characteristics on selective media &amp; biochemical tests). Antimicrobial susceptibility testing of confirmed isolates revealed 82.0%-94.0% resistance to 3rd &amp; 4th generation cephalosporin, 100% to ampicillin and all isolates were found 100% sensitive to aminoglycosides, chloramphenicol and polypeptides class of antibiotics. Total 49 (77.8%) isolates were confirmed as ESBL producers using DDST and ESBL E-strip test, out of which 45 (71.43%) isolates revealed the presence of bla-CTX-M gp genes by PCR analysis. On plasmid profiling, total 82.82% isolates revealed the presence of plasmid with molecular weight between 2.5 kb to &gt;10 kb and number 1-2. These high molecular weight plasmids are mostly situated on conjugative plasmid, which are horizontally transferred from one species to another in highly populous country like India.

Characteristics, Outcomes, and Clinical Indicators of Bloodstream Infections in Neutropenic Patients with Hematological Malignancies: A 7-Year Retrospective Study.

The aim of this study was to investigate the current epidemiology, its changes during the study years, and inflammatory biomarkers of bacterial bloodstream infections (BSIs) in neutropenic patients with hematological malignancies. We assessed mortality risk factors and multidrug-resistant (MDR) gram-negative BSI predictors. We conducted a retrospective study from January 2015 to December 2021, which included adult neutropenic oncohematological patients with confirmed BSIs. We used univariable and multivariable analyses to analyze the risk factors. Each index's reliability for bacterial BSI diagnosis was assessed using the receiver-operating characteristic curve and area under the curve. A total of 514 isolates were obtained from the 452 patients. The average mortality was 17.71%. Gram-negative organisms were the predominant causes of BSI. Escherichia coli was the most common microorganism (49.90%). The overall variation trend of the isolation rate of MDR and carbapenem-resistant gram-negative bacteria increased. Multivariate analysis indicated that: 1) neutropenia that lasted for more than 7 days, patients ≥ 60 years of age, septic shock, hospitalization for >20 days, BSI with a carbapenem-resistant strain, and treatment with linezolid or vancomycin in infections lasting less than 30 days were independent mortality risk factors; 2) severe neutropenia exceeding 7 days, unreasonable empirical therapy, and receipt of aminoglycosides or 3rd or 4th generation cephalosporins in infections lasting less than 30 days were independent risk factors of MDR gram-negative bacteria. Procalcitonin, absolute neutrophil count, and white blood cell indicate higher diagnostic accuracy for BSIs. Moreover, bacteria time to detection was better at differentiating Gram-negative and Gram-positive bacterial infections. We analyzed the risk factors for BSI neutropenic patients with hematological malignancies, the distribution of bacteria, antibiotic resistance, and the changes in clinical parameters. This single-center retrospective study may provide clinicians with novel insights into the diagnosis and treatment of BSI to improve future clinical outcomes.

Assessment of bacteria exposure in vitro activity to 1st, 2nd, 3rd and 4th generation-cephalosporins and Comparison effects

The emergence and spread of resistance to cephalosporin generations are threateningto create species resistant to all currently available agents. Recently, we have seen thedevelopment and spread of bacteria carrying metallo-betalactamase genes that areresistant to cephalosporins (and all beta-lactams). This study was designed tocomparison the effects of first, second, third and fourth- generation-cephalosporin ondifferent bacterial species, which include: Escherichia coli, Enterobacter cloacae,proteus mirabilis, Klebsiella pneumonia, Pseudomonas aeruginosa, Streptococcuspneumonia and Staphylococcus aureus. 11 cephalpsporins antibiotics were used inthis study, which include: cefalexin, cefazolin, cephalothin, cefuroxime, cefoxitin,cefaclor, ceftibuten, cefotexime, ceftazidime, cefpirome and cefepime. kirby bauermethod was used to detect the activity of these antibiotics in vitro. Results showedthat cefpirome and cefepime antibiotics belonging to 4th generation cephalosporin,exhibit antibacterial spectrum effective, except Str. pneumonia and K. pneumonia.Some cases, 1st generation cephalosporin exhibit more antibacterial spectrum effectivethan other cephalosporin generation. In conclusion. This study indicated thatinsignificant influence among four cephalosporins generation on different bacterialspecies. Although, cephalosporins antibiotics have variant activity against differentbacterial species, but the resistant development among bacteria become the publicproblem during the past 2 decades.

Characterisation of antimicrobial usage in Danish pigs in 2020.

Denmark is one of the world's largest exporters of pigs and pig meat, so the sector plays an important role in the national antimicrobial use (AMU). The Danish government has run antimicrobial stewardship programs in collaboration with the pig industry for more than 25 years. These have resulted in substantial overall reductions in total AMU and limiting the use of fluoroquinolones, the 3rd and 4th generation cephalosporines and the polymyxin colistin. To understand where further reductions in AMU could take place, it is necessary to investigate which antimicrobials are being used, how, and for which reasons. We characterized the AMU in the Danish pig sector in 2020, providing new analytical insights based on data retrieved from the VetStat database. The AMU data were segmented into classes, routes of administration, treatment indications and age groups, and interpreted as an outcome of the interventions taken. We evaluated the current AMU regarding choice of antimicrobial class. Moreover, we discussed how to further improve the antimicrobial stewardship in Danish pig production to achieve additional reductions without jeopardizing animal welfare. Where relevant, two pig veterinary specialists were consulted. In 2020, 43.3 mg antimicrobials per population correction unit (PCU) were ascribed to the Danish pig sector. There was practically no use of fluoroquinolones, 3rd and 4th generation cephalosporins and polymyxins. Weaners related to 45% of the total AMU in pigs when measured in tonnes and 81% when measured in defined animal daily doses, of these 76% were ascribed to gastrointestinal indications and overall, 83% were administered perorally. To enable further reductions in AMU, it should be investigated how and when to replace group treatments (e.g., all animals in section or a pen) with individual treatments. Moreover, prevention of disease and promotion of animal health should be prioritized, e.g., through focus on feed, vaccination, biosecurity, and disease eradication.

First Detection of mcr-9 in a Multidrug-Resistant Escherichia coli of Animal Origin in Italy Is Not Related to Colistin Usage on a Pig Farm.

The emergence of colistin resistance raises growing concerns because of its use as a last-resort antimicrobial for the treatment of severe gram-negative bacterial infections in humans. Plasmid-borne mobile colistin resistance genes (mcr) are particularly worrisome due to their high propensity to spread. An mcr-9-positive Escherichia coli was isolated from a piglet in Italy, representing the first isolation of this gene from an E. coli of animal origin in the country. Whole genome sequencing (WGS) revealed that mcr-9 was borne by an IncHI2 plasmid carrying several other resistance genes. The strain was indeed phenotypically resistant to six different antimicrobial classes, including 3rd and 4th generation cephalosporins. Despite the presence of mcr-9, the isolate was susceptible to colistin, probably because of a genetic background unfavourable to mcr-9 expression. The lack of colistin resistance, coupled with the fact that the farm of origin had not used colistin in years, suggests that mcr-9 in such a multidrug-resistant strain can be maintained thanks to the co-selection of neighbouring resistance genes, following usage of different antimicrobials. Our findings highlight how a comprehensive approach, integrating phenotypical testing, targeted PCR, WGS-based techniques, and information on antimicrobial usage is crucial to shed light on antimicrobial resistance.

Resistance Pattern in Mostly Gram-negative Bacteria Causing Urinary Tract Infections.

The antimicrobial prescription in urinary tract infections (UTI) is driven by local data on its pathogenic spectrum and the resistance pattern exhibited by the disease-causing pathogens. We aimed to determine the bacteriological diversity of UTI causing pathogens and antimicrobial resistance in mostly gram-negative bacteria. This retrospective hospital-based cross-sectional study analyzed the culture and sensitivity reports of urine samples from a referral centre in the Aljouf region of Saudi Arabia. All the antibiograms from January 1, 2020, to December 31st 2020, were included. The bacterial identification and antimicrobial testing were carried out by the BD Phoenix system (BD Diagnostics, Sparks, MD, USA). Antimicrobial testing was performed as per the Clinical and Laboratory Standard Institute recommendations. Frequencies of multidrug- and extensive drug resistance were calculated. Of the 1334 non-duplicate urine samples received, 422 (31.6%) bacterial growths were observed. Of these, 383 (90.8%) and 39 (9.2%) were gram-negative and gram-positive bacterial isolations, respectively. E. coli 161 (38.1%), K. pneumoniae 97 (23.0%), and E. faecalis 18 (4.3%) were frequent aetiologies of UTI. 309 (80.7%) of gram-negative bacteria were multidrug-resistant including 88 (23.0%) extensively drug-resistant. Overall, a resistance rate of > 55 % to 1st through 4th generation cephalosporins was observed except for cefoxitin (43.7%). A resistance rate of 37.6% was observed towards carbapenems, with the lowest rate (34.0%) to meropenem. Multi-drug resistant gram-negative bacteria dominate the pathogenic spectrum of UTI in the region. A high resistance rate to cephalosporins and carbapenems exists in gram-negative organisms, causing UTI.

Antimicrobial resistance of Salmonella strains isolated from food products of animal origin in Ukraine between 2018-2021

Salmonellosis is a zoonotic infection of humans and animals. In recent years, an increase in the number of resistant strains of Salmonella from animals and animal products have been recorded. We conducted microbiological testing and antibiotic resistance profile of 34 Salmonella strains isolated from foods of animal origin between 2018 to 2021 in Ukraine. Twenty isolates were successfully assigned to six different serovars [S. Enteritidis (n=13, S. Infantis (n=2), S. Schwarzengrund (n=1), S. Livingstone (n=2), S. Vuadens (n=1) and S. Hadar (n=1)], and 14 isolates remained untyped. Most of the isolated strains were recovered from poultry products. The strains were tested for six antibacterial groups: quinolones, aminoglycosides, β-lactams, cephalosporins, phenols, and dihydrofolate reductase inhibitors by disc diffusion method. The highest level of resistance was recorded to 4th generation cephalosporins, e.g., cefepime (88.2%). The lowest level of resistance was to cefotaxime and ceftriaxone (5.9%). No resistance was found to imipenem and aminoglycoside antibiotics, particularly gentamicin and amikacin. The study results are of concern because antibiotic-resistant bacteria and their genes can cause human infections by penetration and transmission at any stage of the food production cycle. Further research is required to monitor the contamination of food products of animal origin with salmonellosis pathogens, including antibiotic-resistant strains.

Survey on the use of antibiotics among Swiss equine veterinarians

The aim of this study was to evaluate the current use of antibiotics by Swiss equine veterinarians and to compare the results with a similar study from 2013 before the introduction of the web tool Antibiotic Scout. The survey was sent to equine veterinarians according to the member database of the Swiss Veterinary Association (GST, SVS). The demographic data of the respondents and their antibiotics usage were collected. In addition, six different case scenarios were presented with questions to their potential antibiotic usage, active substance/preparation and the dosing scheme. The dosage provided was compared with the dosage information approved by Swissmedic in the information for healthcare professionals and the recommendations of the antibiotic scout. A backward logistic regression analysis was performed to assess the association between different aspects of antibiotic use and demographic data. The response rate was 94/739 (13 %), 22 of the 94 (23 %) had also participated in the 2013 study. 47/94 (50 %) of the respondents obtained their information from the antibiotic scout. The respondents indicated that they used an antibiotic in 16 %-88 % depending on the case scenario. Neither 3rd nor 4th generation cephalosporins or fluoroquinolones were used in the case scenarios. Dihydrostreptomycin was indicated as a possible antibiotic in a case scenario by 14/94 (15 %) of the respondents. Respondents who had already taken part in the 2013 survey used dihydrostreptomycin significantly more frequently (7/22, 32 % vs. 7/72, 10 %; p = 0,047). 29/81 (36 %) had underdosed compared to the prescribing information and 38/81 (47 %) compared to the antibiotic scout; neither was associated with demographic data. The use of non-equine-licensed antimicrobial products was directly related to the number of veterinarians in the practice (p = 0,007) and to the percentage of horses (p = 0,02). No association between demographics and peri-operative antibiotic use >24h (17/44, 39 %) was detected. The antibiotic prescribing habits of Swiss equine veterinarians have improved over the last 10 years. The antibiotic use decreased compared to the study of Schwechler et al. in 2013 by 0-16 % depending on the case scenario. The use of 3rd and 4th generation cephalosporins was reduced by 4 % and fluoroquinolones by 7 %. Underdosing according to scientific recommendations was reduced by 32 %. Furthermore, there is a need for additional information regarding the indication for antimicrobial use and the adequate use of perioperative antibiotics.

Antibiotic prescription patterns and non-clinical factors influencing antibiotic use by Ecuadorian veterinarians working on cattle and poultry farms: A cross-sectional study

Understanding antibiotic prescription patterns and non-clinical factors influencing antibiotic use is essential for implementing strategies to promote appropriate antibiotic use. There is, however, limited research exploring these issues with Ecuadorian veterinarians. Therefore, a questionnaire was developed and applied cross-sectionally to veterinarians (n = 173) from two professional organizations to explore the antibiotic prescription patterns and non-clinical factors (e.g., attitudes and perceptions) influencing antibiotic use, and to identify strategies to reduce antibiotic use. The response rate was 78.4%. Responses were compared between veterinarians working mainly on cattle and poultry farms using Mann-Whitney U tests. The most important attitudes, beliefs and perceptions towards antimicrobial resistance (AMR) and antibiotic use were identified with the Relative Importance Index (RII). Veterinarians showed high awareness of AMR and its implications for public health, as well as the necessity of reducing antibiotic use. However, some veterinarians appear to underestimate the potential contribution of veterinary antibiotic use on AMR in humans. Veterinarians self-reported high prescription (> 20%) of antibiotics for cattle and poultry that are critically important for human medicine, such as 3rd and 4th generation cephalosporins, polymyxins and quinolones. Further, antibiotic therapy was not tailored to disease type. Cattle and poultry veterinarians perceived similar barriers to increasing antibiotic stewardship including: poor biosecurity measures, animal confinement, low feed quality, farmers’ behaviors (such as stopping antibiotic treatment, storing antibiotics on farms, buying antibiotics in veterinary supply stores), and sales agents’ roles as non-professional prescribers of antibiotics. Overall, veterinarians were broadly supportive (>90%) of most strategies to promote appropriate antibiotic use. They saw more merit in improving biosecurity of farms and implementing educational programs for farmers and veterinarians. This study provides insight into the complexity of antibiotic use on Ecuadorian farms and the need for holistic strategies in a One Health context, to achieve antibiotic stewardship.

Skin and Soft Tissue Infections due to Aeromonas spp.: An Emerging Pathogen

Introduction: Aeromonas spp., the emerging human pathogens, can cause various diseases like gastrointestinal infections, Skin and Soft-Tissue Infections (SSTIs), respiratory tract infections, urinary tract infection, hepatobiliary tract infection, blood stream infections etc. Aeromonas consists of important pathogenic species like Aeromonas hydrophila being the most common one followed by A.sobria, A.veroni, A.caviae and A.salmonicida. SSTIs due to Aeromonads are most often associated with preexisting ulcer, traumatic wound and exposure to water. Aim: The present study was carried out to analyse socioepidemiological factors, clinical features, risk factors and antibiotic resistance potential of Aeromonas spp., SSTIs. Materials and Methods: In this prospective study, all Gramnegative fermenting motile isolates which are positive for oxidase, H2 S production, indole reaction, lysine decarboxylase were further identified by Vitek 2 compact system (Biomerieux, France). The study period was 2 years. Results: A total of 39 patients with Aeromonas spp., SSTIs were identified during the period from 2020 to 2022. Majority of patients hailed from urban areas, were in middle age group and were farmers. A.hydrophila (n=24, 62%) was the predominant isolate. Majority of the infections were superinfection of wound (n=16, 41%) and chronic non healing ulcer (n=13, 33.3%). A total of 33.3% of infections were polymicrobial, common concomitant pathogens being, Pseudomonas aeruginosa and Methicillin Resistant Staphylococcus aureus (MRSA). Trauma and water exposure were main risk factors with co-morbidities like diabetes, hypertension and liver cirrhosis. A 20.5% of patients were immunocompromised. There was one case of Necrotising Fasciitis (NF) which resulted in patient’s death. Cotrimoxazole, 3rd and 4th generation cephalosporins. Aztreonam and Tigecycline were the most effective antibiotics while eight of the isolates were Multidrug Resistant (MDR). Thirty-three patients recovered completely and three patients died of complications. Conclusion: Aeromonas hydrophila must be regarded as an emerging pathogen of SSTIs mainly in patients with preexisting ulcers and can be MDR. Such infections have a good prognosis if prompt medical, surgical and supportive treatment is given.

Detection of AmpC β-lactamases in gram-negative bacteria

AmpC β-lactamase genes are clinically important because they often confer resistance to most β-lactams other than 4th-generation cephalosporins and carbapenems. However, traditional and existing detection methods are expensive, labor-intensive and range-limited. We established an efficient multiplex PCR method to simultaneously identify six families of ampC β-lactamase genes, ACC, EBC, CIT, DHA, MOX and FOX, and evaluated the sensitivity and specificity of this assay. The multiplex method could accurately identify ACC, EBC, CIT, DHA, MOX and FOX variants among a total of 175 ampC β-lactamase genes. The minimum concentration of genomic DNA that could be detected was 1.0×103 copies/μL. We subsequently used this method to analyze 2 Salmonella spp. with carrying CMY-2 and DHA-1, and 167 Enterobacteriaceae isolates in blinded PCR testing. Positive isolates produced bright bands that corresponded with their genotype. Results were in concordance with those of the traditional method but showed increased sensitivity and accuracy. This indicates that the newly developed multiplex PCR system could be used as a diagnostic tool to accurately distinguish the six families of ampC β-lactamase genes with high efficiency, wide range, easy operation and good discrimination.

In Vitro Susceptibility of Colistin Against Multidrug Resistant Klebsiella Pneumoniae Clinical Isolates

Objectives: To determine in-vitro efficacy of colistin against resistant Klebsiella Pneumoniae clinical isolates. &#x0D; Study Design: Cross-sectional study.&#x0D; Place and Duration of Study: Microbiology Department of Pathology Lab, Armed Forces Institute of Cardiology &amp; National Institute of Heart Diseases, Rawalpindi, Pakistan, from Jan 2021 to Dec 2021.&#x0D; Methodology: This cross-sectional study was carried out at the microbiology department of pathology lab, Armed Forces institute of Cardiology &amp; National Institute of Heart Diseases, Rawalpindi through Jan 2021 to Dec 2021. Sampling was done by nonprobability consecutive technique. Antimicrobial susceptibility testing was done for all clinical isolates of KP.&#x0D; Results: A total of 3066 culture and sensitivity requests were received, out of these 663(21.6%) specimens revealed growth of different microorganisms. Amongst 663 culture positive isolates, 150(22.6 %) were identified as KP. Antibiotic susceptibility of KP showed &gt;90% isolates resistant to 3rd &amp; 4th generation cephalosporins, cotrimoxazole, ampicillin+salbactum and coamoxiclav. Aminoglycosides, quinolones, meropenem, aztreonam and tazobactum+pipracillin were found resistant in &gt;80% isolates and doxycycline and imipenem in &gt;70% isolates. Resistance to minocycline was 58%, chloramphenicol 40.7% and Tigecycline 38.7%. The least resistance was noted in Colistin 16%.&#x0D; Conclusion: A very high antimicrobial resistance was observed in KP isolates against penicillins, cephalosporins, ampicillin beta lactamase inhibitor combinations, quinolones, aminoglycosides, carbapenems and cotrimoxazole. Comparatively tigecyclines and chloramphenicol were found to be less resistant than other antimicrobials to manage MDR and XDR cases. Colistin has excellent efficacy against MDR and XDR KP isolates.

DESCRIPTION AND ANTIBIOTIC RESISTANCE OF BACTERIA ISOLATED FROM SPUTUM SPECIMENS AT CAN THO UNIVERSITY OF MEDICINE AND PHARMACY HOSPITAL FROM JULY 2021 TO DECEMBER 2021

Background: Bacteria causing respiratory infections tend to rapidly increase antibiotic resistance, prolong treatment time, increase treatment costs and increase mortality. Objectives: 1). To determine the proportion of bacterial strains isolated from sputum specimens; 2). To describe the antibiotic resistance of bacterial strains isolated from sputum specimens. Materials and methods: A cross-sectional descriptive study was carried out on 96 patients with positive sputum cultures using convenient sampling method. Results: Streptococcus pneumoniae (44.8%) was found to be the predominant pathogen isolated followed by Klebsiella pneumoniae (20.8%), Acinetobacter baumannii (13.5%) and Staphylococcus aureus (8.3%). The highest resistance was observed with piperacillin, ampicillin, erythromycin, cefaclor, azithromycin. Streptococcus pneumonia isolated were mostly resistant to azithromycin, cefaclor, and erythromycin (85.7%), while 0% resistance was observed for vancomycin, ampicillin and gentamycin. Klebsiella pneumoniae were highly resistant to ampicillin (95%), trimeth/sulfa (85%), and piperacillin (85%). Acinetobacter baumannii had a resistant rate of over 50% to most antibiotics, especially gentamycin and meropenem (84.6%). Staphylococcus aureus were completely resistant to ampicillin, clindamycin, penicillin, while vancomycin resistance was observed among 12.5% of the isolated bacteria. Conclusions: The most common pathogen was Streptococcus pneumoniae, Klebsiella pneumoniae, Acinetobacter baumannii and Staphylococcus aureus. The highest resistance was observed with piperacillin, ampicillin, erythromycin, cefaclor, and azithromycin. Streptococcus pneumoniae was highly resistant to macrolides. Klebsiella pneumoniae was highly resistant to most antibiotics of the 2nd, 3rd generation cephalosporins and beta lactams (penicillin and monobactam). Acinetobacter baumannii showed a noticeable resistance to fluoroquinolones, aminoglycosides, and 4th generation cephalosporins. Staphylococcus aureus was highly resistant to penicillin, lincosamides, fluoroquinolone, while 12.5% vancomycin resistance was observed.

Frequency of Bacteremia and Urinary Tract Infection in Pediatric Renal Transplant Recipients.

Our primary goal was to determine the frequency of bacteremia and urinary tract infections (UTI) in pediatric renal transplant recipients presenting with suspected infection within 2 years of transplant and to identify clinical and laboratory factors associated with bacteremia. We conducted a retrospective cross-sectional study for all pediatric ( < 18 years old) renal transplant recipients seen at 3 large children's hospitals from 2011 to 2018 for suspected infection within 2 years of transplant date, defined as pyrexia ( > 38°C) or a blood culture being ordered. Patients with primary immunodeficiencies, nontransplant immunosuppression, intestinal failure, and patients who had moved out of the local area were excluded. The primary outcome was bacteremia or UTI; secondary outcomes included pneumonia, bacterial or fungal meningitis, respiratory viral infections, and antibiotic resistance. The unit of analysis was the visit. One hundred fifteen children had 267 visits for infection evaluation within 2 years of transplant. Bacteremia (with or without UTI) was diagnosed in 9/213 (4.2%) and UTIs in 63/189 (33.3%). Tachycardia and hypotension were present in 66.7% and 0% of visits with documented bacteremia, respectively. White blood cell (12,700 cells/mm 3 vs. 10,900 cells/mm 3 ; P = 0.43) and absolute neutrophil count (10,700 vs. 8200 cells/mm 3 ; P = 0.24) were no different in bacteremic and nonbacteremic patients. The absolute band count was higher in children with bacteremia (1900 vs. 600 cells/mm 3 ; P = 0.02). Among Gram-negative pathogens, antibiotic resistance was seen to 3rd (14.5%) and 4th (3.6%) generation cephalosporins, 12.7% to semisynthetic penicillins, and 3.6% to carbapenems. Bacteremia or UTIs were diagnosed in one-quarter of all pediatric renal transplant recipients presenting with suspected infection within 2 years of transplant. Evaluations were highly variable, with one-third of visits not having urine cultures obtained. No single demographic, clinical or laboratory variable accurately identified patients with bacteremia, although combinations of findings may identify a high-risk population.