Use Of Cephalosporins Research Articles

The impact of the COVID-19 pandemic on antibiotic consumption and prevalence of pathogens in primary and secondary healthcare settings in Northern Ireland.

To evaluate the impact of the COVID-19 pandemic on the patterns of antimicrobial use and the incidence of pathogens in primary and secondary healthcare settings in Northern Ireland. Data were collected on antibiotic use and Gram-positive and Gram-negative pathogens from primary and secondary healthcare settings in Northern Ireland for the period before (January 2015-March 2020) and during (April 2020-December 2021) the pandemic. Time series intervention analysis methods were utilized. In the hospital setting, the mean total hospital antibiotic consumption during the pandemic was 1864.5 defined daily doses (DDDs) per 1000 occupied-bed days (OBD), showing no significant change from pre-pandemic (P = .7365). During the pandemic, the use of second-generation cephalosporins, third-generation cephalosporins, co-amoxiclav and levofloxacin increased, there was a decrease in the percentage use of the hospital Access group (P = .0083) and an increase in the percentage use of Watch group (P = .0040), and the number of hospital Klebsiella oxytoca and methicillin-susceptible Staphylococcus aureus cases increased. In primary care, the mean total antibiotic consumption during the COVID-19 pandemic was 20.53 DDDs per 1000 inhabitants per day (DID), compared to 25.56 DID before the COVID-19 pandemic (P = .0071). During the pandemic, there was a decrease in the use of several antibiotic classes, an increase in the percentage use of the Reserve group (P = .0032) and an increase in the number of community-onset Pseudomonas aeruginosa cases. This study provides details of both changes in antibiotic consumption and the prevalence of infections in hospitals and primary care before and during the COVID-19 pandemic that emphasize the importance of antimicrobial stewardship in pandemic situations.

Surveillance of antimicrobial resistance in human health in Tanzania: 2016-2021.

Antimicrobial resistance (AMR) surveillance plays an important role in early detection of resistant strains of pathogens and informs treatments decisions at local, regional and national levels. In 2017, Tanzania developed a One Health AMR Surveillance Framework to guide establishment of AMR surveillance systems in the human and animal sectors. We reviewed AMR surveillance studies in Tanzania to document progress towards establishing an AMR surveillance system and determine effective strengthening strategies. We conducted a literature review on AMR studies conducted in Tanzania by searching Google Scholar, PubMed, and the websites of the Tanzania Ministry of Health and the World Health Organization for articles written in English and published from January 2012 to March 2021 using relevant search terms. Additionally, we reviewed applicable guidelines, plans, and reports from the Tanzanian Ministry of Health. We reviewed 10 articles on AMR in Tanzania, where studies were conducted at hospitals in seven of Tanzania's 26 regions between 2012 and 2019. Nine AMR sentinel sites had been established, and there was suitable and clear coordination under 'One Health'. However, sharing of surveillance data between sectors had yet to be strengthened. Most studies documented high resistance rates of Gram-negative bacteria to third-generation cephalosporins. There were few laboratory staff who were well trained on AMR. Important progress has been made in establishing a useful, reliable AMR surveillance system. Challenges include a need to develop, implement and build investment case studies for the sustainability of AMR surveillance in Tanzania and ensure proper use of third-generation cephalosporins. This article adds to the knowledge base of AMR trends in Tanzania and progress made in the implementation of AMR surveillance in human health sector as a contribution to the global AMR initiatives to reduce AMR burden worldwide. It has highlighted key gaps that need policy and implementation level attention.

Assessment of Effective Antimicrobial Regimens and Mortality-Related Risk Factors for Bloodstream Infections Caused by Carbapenem-Resistant Acinetobacter baumannii.

This study aimed to determine the clinical features, risk factors, and effective antimicrobial therapy for Carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection (BSI). This was a retrospective analysis of data from patients with CRAB bacteremia in a Chinese tertiary hospital between January 2012 and October 2021. Risk factors, predictors of 30-day mortality, and effective antimicrobial therapy for CRAB BSI were identified using logistic and cox regression analyses. Data from 276 patients with Acinetobacter baumannii (AB) BSI were included, of whom 157 (56.9%) had CRAB BSI. The risk factors that were significantly associated with CRAB BSI included previous intensive care unit (ICU) stay (P < 0.001), immunocompromised status (P < 0.001), cephalosporin use (P = 0.014), and fluoroquinolone use (P = 0.007). The 30-day mortality of the CRAB BSI group was 49.7% (78/157). ICU stay after BSI (P = 0.047), sequential organ failure assessment (SOFA) score ≥10 (P < 0.001), and multiple organ failure (MOF) (P = 0.037) were independent predictors of 30-day mortality. Among antibiotic strategies for the treatment of patients with CRAB BSI, we found that definitive regimens containing cefoperazone/sulbactam were superior to those without cefoperazone/sulbactam in reducing the 30-day mortality rate (25.4% vs 53.4%, P = 0.005). After propensity score matching, we observed a significant increase in the 30-day mortality (77.8%vs 33.3%, P = 0.036) in patients receiving tigecycline monotherapy compared to those receiving cefoperazone/sulbactam monotherapy. The mortality rate of patients receiving tigecycline with cefoperazone/sulbactam was also higher than that of patients receiving cefoperazone-sulbactam monotherapy; however, the difference was not significant (28.6%vs 19.0%, P = 0.375). The severity of patient conditions was significantly associated with mortality in patients with CRAB BSI. Those Patients treated with cefoperazone/sulbactam had better clinical prognoses, and tigecycline should be used with caution.

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.

The Prevalence of Carbapenemase-Producing Microorganisms and Use of Novel Cephalosporins for the Treatment of Severe Infections Caused by Carbapenem-Resistant Gram-Negative Bacteria in a Pediatric Cardiac Intensive Care Unit.

The spread of carbapenem-resistant organisms (CROs) is an increasingly serious threat globally, especially in vulnerable populations, such as intensive care unit (ICU) patients. Currently, the antibiotic options for CROs are very limited, particularly in pediatric settings. We describe a cohort of pediatric patients affected by CRO infections, highlighting the important changes in carbapenemase production in recent years and comparing the treatment with novel cephalosporins (N-CEFs) to Colistin-based regimens (COLI). All patients admitted to the cardiac ICU of the Bambino Gesù Children's Hospital in Rome during the 2016-2022 period with an invasive infection caused by a CRO were enrolled. The data were collected from 42 patients. The most frequently detected pathogens were Pseudomonas aeruginosa (64%), Klebsiella pneumoniae (14%) and Enterobacter spp. (14%). Thirty-three percent of the isolated microorganisms were carbapenemase producers, with a majority of VIM (71%), followed by KPC (22%) and OXA-48 (7%). A total of 67% of patients in the N-CEF group and 29% of patients in the comparative group achieved clinical remission (p = 0.04). The increase over the years of MBL-producing pathogens in our hospital is challenging in terms of therapeutic options. According to the present study, N-CEFs are a safe and effective option in pediatric patients affected by CRO infections.

Antibiotic Practice in Patients With Acute Abdomen Admitted to a Danish Regional Hospital: A Clinical Qualitative Assurance Study.

Background Acute abdomen is often complicated by intra-abdominal infection requiring antibiotic therapy. Danish regional antibiotic guidelines emphasize the restricted use of broad-spectrum antibiotics such as cephalosporins. In this study, we aimed to evaluate antibiotic practices in relation to hospitalized patients with acute abdomen. Methodology This retrospective quality assurance study was conducted among patients admitted to the surgical emergency department at the North Denmark Regional Hospital during a four-month observation period. Data were extracted from electronic patient journals and entered in the Research Electronic Data Capture data management system for further analytical work. Results Of 331 patients, 174 (53%) were treated with antibiotics, of whom 98 (56%) had been treated with cephalosporin, 47 (27%) with benzylpenicillin and gentamicin, 22 (13%) with piperacillin/tazobactam, and seven (4%) with ciprofloxacin. Use of a cephalosporin-based antibiotic regimen was significantly more common in patients with acute appendicitis (75%) compared to other diagnostic groups, such as acute cholecystitis (57%), incarcerated hernia with strangulation (56%), acute pancreatitis (50%), and acute diverticulitis (30%). However, patients with uncomplicated diverticulitis (53%) were significantly more often treated with benzylpenicillin and gentamicin, whereas patients with complicated diverticulitis Hinchey stage 3-4 were significantly more often treated with piperacillin/tazobactam. In addition, as the severity of acute cholecystitis increased, it was more frequently treated with piperacillin/tazobactam. Conclusions The study revealed that cephalosporins are frequently used in patients hospitalized with acute abdomen. This finding conflicts with current regional antibiotic guidelines. Reinforcement of the guidelines is required as an essential measure against the development of antibiotic resistance associated with the use of cephalosporins.

Executive Summary: Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations.

Executive Summary: Guidelines for the Management of Adult Acute and Acute-on-Chronic Liver Failure in the ICU: Neurology, Peri-Transplant Medicine, Infectious Disease, and Gastroenterology Considerations.

Penicillin Binding Protein Substitutions Cooccur with Fluoroquinolone Resistance in Epidemic Lineages of Multidrug-Resistant Clostridioides difficile.

Clostridioides difficile remains a key cause of healthcare-associated infection, with multidrug-resistant (MDR) lineages causing high-mortality (≥20%) outbreaks. Cephalosporin treatment is a long-established risk factor, and antimicrobial stewardship is a key control. A mechanism underlying raised cephalosporin MICs has not been identified in C. difficile, but among other species, this is often acquired via amino acid substitutions in cell wall transpeptidases (penicillin binding proteins [PBPs]). Here, we investigated five C. difficile transpeptidases (PBP1 to PBP5) for recent substitutions, associated cephalosporin MICs, and co-occurrence with fluoroquinolone resistance. Previously published genome assemblies (n = 7,096) were obtained, representing 16 geographically widespread lineages, including healthcare-associated ST1(027). Recent amino acid substitutions were found within PBP1 (n = 50) and PBP3 (n = 48), ranging from 1 to 10 substitutions per genome. β-Lactam MICs were measured for closely related pairs of wild-type and PBP-substituted isolates separated by 20 to 273 single nucleotide polymorphisms (SNPs). Recombination-corrected phylogenies were constructed to date substitution acquisition. Key substitutions such as PBP3 V497L and PBP1 T674I/N/V emerged independently across multiple lineages. They were associated with extremely high cephalosporin MICs; 1 to 4 doubling dilutions >wild-type, up to 1,506 μg/mL. Substitution patterns varied by lineage and clade, showed geographic structure, and occurred post-1990, coincident with the gyrA and/or gyrB substitutions conferring fluoroquinolone resistance. In conclusion, recent PBP1 and PBP3 substitutions are associated with raised cephalosporin MICs in C. difficile. Their co-occurrence with fluoroquinolone resistance hinders attempts to understand the relative importance of these drugs in the dissemination of epidemic lineages. Further controlled studies of cephalosporin and fluoroquinolone stewardship are needed to determine their relative effectiveness in outbreak control. IMPORTANCE Fluoroquinolone and cephalosporin use in healthcare settings has triggered outbreaks of high-mortality, multidrug-resistant C. difficile infection. Here, we identify a mechanism associated with raised cephalosporin MICs in C. difficile comprising amino acid substitutions in two cell wall transpeptidase enzymes (penicillin binding proteins). The higher the number of substitutions, the greater the impact on phenotype. Dated phylogenies revealed that substitutions associated with raised cephalosporin and fluoroquinolone MICs were co-acquired immediately before clinically important outbreak strains emerged. PBP substitutions were geographically structured within genetic lineages, suggesting adaptation to local antimicrobial prescribing. Antimicrobial stewardship of cephalosporins and fluoroquinolones is an effective means of C. difficile outbreak control. Genetic changes associated with raised MIC may impart a "fitness cost" after antibiotic withdrawal. Our study therefore identifies a mechanism that may explain the contribution of cephalosporin stewardship to resolving outbreak conditions. However, due to the co-occurrence of raised cephalosporin MICs and fluoroquinolone resistance, further work is needed to determine the relative importance of each.

Effect of Antimicrobial Exposure in Pregnancy on Adverse Pregnancy Outcomes and Admission Rate to the Neonatal Intensive Care Unit: A Multi-Center Cohort Study.

Antimicrobial agents are frequently prescribed during pregnancy. This study aims to explore the association between antimicrobial exposure and pregnancy outcomes. A multi-center retrospective cohort study of pregnant patients (n=370) was conducted in 22 tertiary hospitals in China. Adverse pregnancy outcomes and admission of neonate to neonatal intensive care unit (NICU) were considered as outcomes. The effect of antimicrobial exposure on pregnancy outcomes was assessed using a multivariate logistic regression model. Use of first-generation cephalosporins during pregnancy was associated with a significantly higher risk of adverse pregnancy outcomes (odds ratio [OR]: 3.64 [95% confidence interval, CI: 1.43-9.24], P = 0.007) and admission of neonate to the NICU (OR: 3.41, 95% CI: 1.37-8.53, P=0.009) compared with use of third-generation cephalosporins, after adjusting for gestational age of exposure to antimicrobial agents, cesarean section, and antimicrobial dose. Similarly, a higher risk of adverse pregnancy outcomes (OR: 14.76, 95% CI: 4.43-49.11) and neonatal NICU admission (OR: 11.74, 95% CI: 3.59-38.35) were observed among women with first-generation cephalosporins use compared with mothers with no antimicrobial use. Both first- and third-generation cephalosporins use was associated with an increased risk of adverse pregnancy and neonatal outcomes. In addition, first-generation cephalosporins were associated with an increased risk of those pregnant and neonatal outcomes, when compared with third-generation cephalosporins. We should require to determine the indications and contraindications for use of cephalosporins during pregnancy.

Risk Factors Associated with Multi-Drug Resistance in Neonatal Sepsis Caused by Escherichia coli.

An increasing number of cases of neonatal sepsis due to extended-spectrum beta-lactamase (ESBL)-producing multi-drug resistant (MDR) Escherichia coli (E. coli) have been reported worldwide. The aim of this study was to explore the risk factors associated with ESBL-producing MDR E. coli among neonates with culture-confirmed E. coli sepsis and thereby to help selection of appropriate empirical antibiotics. All newborn infants with a confirmed pathogen isolated from blood or cerebrospinal fluid (CSF) from 2016 to 2021 were identified and those with E. coli infection were included in this analysis. We compared a group of neonatal patients with ESBL-producing MDR E. coli sepsis (n=69) to a group with ESBL-negative E. coli (n=70) based on antimicrobial susceptibility reports. We used multivariable regression analysis to determine the risk factors associated with ESBL-producing MDR E. coli strains among the neonates with culture-confirmed E. coli sepsis. ESBL-producing MDR E. coli sepsis was more common in premature infants and newborns with hospital-acquired late-onset sepsis (HALOS). The mortality rate of neonatal sepsis caused by ESBL-producing E. coli was about twice as that of sepsis caused by ESBL-negative E. coli. Antepartum exposure to cephalosporins (OR=25.191, 95% CI: 3.184-199.326, P<0.01) and parenteral nutrition for more than 1 week (OR=4.495, 95% CI: 2.009-10.055, P<0.01) were independent risk factors for neonatal infection with ESBL-producing stains among infants with E. coli sepsis. E. coli remains the most common Gram-negative bacterial pathogen causing neonatal sepsis. A higher proportion of ESBL-producing MDR E. coli is seen in premature infants and those newborns with HALOS and is associated with higher mortality. Antepartum use of cephalosporins and prolonged use of parenteral nutrition may be important factors to consider in the selection of empirical antibiotics for use in neonatal sepsis caused by gram-negative rods prior to the availability of the results of antimicrobial susceptibility.

A Point Prevalence Survey of Antibiotic Prescribing in three Nigerian public children’s hospitals.

Background: Antibiotic resistance continues to impact public health globally hence the need to monitor antibiotic use in hospitals and&nbsp; in children in order to identify gaps in prescribing practices for possible intervention. This study investigated the prevalence and&nbsp; characteristics of antibiotic prescribing in three government hospitals in Lagos Nigeria in November/December 2015 using the Global point prevalence survey of antimicrobial consumption and resistance (G-PPS) as a tool. Data were analysed using the Statistical&nbsp; Package for Social Sciences (SPSS) software version 22. Results: Of the 207 inpatients, 180 (87%) were prescribed at least one antibiotic&nbsp; during the survey period. Furthermore, 81% and 89.3% of neonates and paediatric patients respectively were on antibiotics. The most&nbsp; commonly prescribed antibiotic class for neonates were the aminoglycosides (38.1%) and the third- generation cephalosporins (31%).&nbsp; In paediatric patients, the third-generation cephalosporins were the most prescribed (26.2%). Most common diagnosis in neonates&nbsp; was sepsis (38.3%) while lower respiratory tract infections (25.7%) were most occurring in paediatric patients. Community acquired&nbsp; infections were the most common indications for prescribing accounting for 48.8% and 56.6% of neonatal and paediatric prescriptions&nbsp; respectively. Overall, parenteral antibiotic accounted for 96.4% and 80.5% of antibiotics prescribed for neonates and paediatric&nbsp; patients. Targeted antibiotic prescribing was observed in 8.3% and 5.8% of neonatal and paediatric prescriptions. Furthermore, biomarker was used to guide prescribing in only 1.2 % of neonatal prescriptions. Antibiotic stop /review dates were documented in&nbsp; 11.9% and 12.5% of neonatal and paediatric prescriptions. Conclusion: A high prevalence of antibiotic prescribing was observed in the&nbsp; surveyed children's hospitals. The high use of third generation cephalosporins, the predominant use of parenteral antibiotic&nbsp; formulations and the low documentation of stop review dates were among the identified areas for improving prescribing practices at&nbsp; these hospitals. The identified gaps can form the basis for implementing Antibiotic Stewardship Interventions in the hospitals of study.&nbsp; &nbsp;&nbsp

Consensus for the treatment of upper urinary tract infections during pregnancy

To generate evidence-based recommendations through formal consensus regarding the treatment of upper urinary tract infections during gestation. Experts in microbiology, public health, internal medicine, infectious diseases, obstetrics, maternal fetal medicine and obstetric and gynecological infections participated in the consensus development group. The group also included professionals with training in clinical epidemiology, systematic data search, and representatives from the Health Secretariat and the Bogota Obstetrics and Gynecology Association. The participants disclosed their conflicts of interest. Starting with a clinical question, outcomes were graded and a systematic search was conducted in the Medline via PubMed, Embase, Lilacs, and Bireme databases. The search was expanded to include institutional repositories and antimicrobial resistance surveillance systems, with no language or date restrictions. The search was updated on October 1, 2022. The GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology was used to assess the quality of the evidence and determine the strength of the recommendations. Finally, the RAND/UCLA (Research and Development/University of California Los Angeles) methodology was applied for the formal consensus. This document was reviewed by academic peers before publication. The following are the consensus recommendations. Recommendation 1. The initial management of pregnant women with upper urinary tract infections (UTIs) should be approached in a hospital setting. Recommendation 2. The use of second generation cephalosporins is the suggested first option for empirical antimicrobial management in pregnant women with upper UTI in order to improve the rates of clinical and microbiological cure. Recommendation 3. Because of the risk-benefit balance, the use of aminoglycosides is suggested as a second option for empirical antimicrobial treatment in pregnant women presenting with upper UTIs in the second and third trimester. Recommendation 4. The use of third-generation cephalosporins is suggested as the third option for empirical antimicrobial treatment in pregnant women with upper UTIs given that the risk of inducing microbial resistance is high with this group of antibiotics. Recommendation 5. The use of carbapenems is suggested as a first option in pregnant women with upper UTIs and a history of infections caused by microorganisms with resistance to third or fourth-generation cephalosporins. Recommendation 6. The use of aminoglycosides or fourth-generation cephalosporins is suggested as a second option in pregnant women with upper UTIs and a history of infection caused by microorganisms with resistance to third-generation cephalosporins, taking risk-benefit into account. Recommendation 7. The use of piperacillin/tazobactam is suggested as a third option in pregnant women with upper UTIs and a history of infection caused by microorganisms with resistance to third or fourthgeneration cephalosporins. Recommendation 8. Getting a urine culture is recommended in pregnant women with upper UTIs before initiating empirical antimicrobial treatment. Recommendation 9. In pregnant women with upper UTIs, it is suggested to modify therapy in accordance with the results of the sensitivity test when the culture report shows resistance to the antimicrobial agent initiated empirically. Recommendation 10. In pregnant women hospitalized due to upper UTIs, it is suggested to switch to oral antimicrobial therapy after at least 48 hours of modulation of the systemic inflammatory response and the clinical signs of infection, and when tolerance to oral intake is adequate. Recommendation 11. In pregnant women with upper UTIs with no complications secondary to the primary infection, it is recommended to administer antibiotic therapy for a period of 7 to 10 days. It is expected that with this Colombian upper UTI consensus variability in clinical practice will be reduced. It is recommended that groups doing research in maternal fetal medicine assess the implementation and effectiveness of these recommendations.

Antibiotic Utilization Patterns for Different Wound Types among Surgical Patients: Findings and Implications.

Antimicrobial prophylaxis is effective in reducing the rate of surgical site infections (SSIs) post-operatively. However, there are concerns with the extent of prophylaxis post-operatively, especially in low- and middle-income countries (LMICs). This increases antimicrobial resistance (AMR), which is a key issue in Pakistan. Consequently, we conducted an observational cross-sectional study on 583 patients undergoing surgery at a leading teaching hospital in Pakistan with respect to the choice, time and duration of antimicrobials to prevent SSIs. The identified variables included post-operative prophylactic antimicrobials given to all patients for all surgical procedures. In addition, cephalosporins were frequently used for all surgical procedures, and among these, the use of third-generation cephalosporins was common. The duration of post-operative prophylaxis was 3-4 days, appreciably longer than the suggestions of the guidelines, with most patients prescribed antimicrobials until discharge. The inappropriate choice of antimicrobials combined with prolonged post-operative antibiotic administration need to be addressed. This includes appropriate interventions, such as antimicrobial stewardship programs, which have been successful in other LMICs to improve antibiotic utilization associated with SSIs and to reduce AMR.

Phylogenomic investigation of an outbreak of fluoroquinolone-resistant Salmonella enterica subsp. enterica serovar Paratyphi A in Phnom Penh, Cambodia.

In early 2020, the Medical Biology Laboratory of the Pasteur Institute of Cambodia isolated an unusually high number of fluoroquinolone-resistant Salmonella enterica subspecies enterica serovar Paratyphi A strains during its routine bacteriological surveillance activities in Phnom Penh, Cambodia. A public-health investigation was supported by genome sequencing of these Paratyphi A strains to gain insights into the genetic diversity and population structure of a potential outbreak of fluoroquinolone-resistant paratyphoid fever. Comparative genomic and phylodynamic analyses revealed the 2020 strains were descended from a previously described 2013-2015 outbreak of Paratyphi A infections. Our analysis showed sub-lineage 2.3.1 had remained largely susceptible to fluoroquinolone drugs until 2015, but acquired chromosomal resistance to these drugs during six separate events between late 2012 and 2015. The emergence of fluoroquinolone resistance was rapidly followed by the replacement of the original susceptible Paratyphi A population, which led to a dramatic increase of fluoroquinolone-resistant blood-culture-confirmed cases in subsequent years (2016-2020). The rapid acquisition of resistance-conferring mutations in the Paratyphi A population over a 3 year period is suggestive of a strong selective pressure on that population, likely linked with fluoroquinolone use. In turn, emergence of fluoroquinolone resistance has led to increased use of extended-spectrum cephalosporins like ceftriaxone that are becoming the drug of choice for empirical treatment of paratyphoid fever in Cambodia.

Antibiotic associated diarrhea in outpatient pediatric antibiotic therapy

BackgroundAntibiotic-associated diarrhea is one of the most frequent side effects of antimicrobial therapy. We assessed the epidemiological data of antibiotic-associated diarrhea in pediatric patients in our region.MethodsThe prospective multi-center study included pediatric patients who were initiated an oral antibiotic course in outpatient clinics and followed in a well-established surveillance system. This follow-up system constituded inclusion of patient by the primary physician, supply of family follow-up charts to the family, passing the demographics and clinical information of patient to the Primary Investigator Centre, and a close telephone follow-up of patients for a period of eight weeks by the Primary Investigator Centre.ResultsA result of 758 cases were recruited in the analysis which had a frequency of 10.4% antibiotic-associated diarrhea. Among the cases treated with amoxicillin-clavulanate 10.4%, and cephalosporins 14.4% presented with antibiotic-associated diarrhea. In the analysis of antibiotic-associated diarrhea occurrence according to different geographical regions of Turkey, antibiotic-associated diarrhea episodes differed significantly (p = 0.014), particularly higher in The Eastern Anatolia and Southeastern Anatolia. Though most commonly encountered with cephalosporin use, antibiotic-associated diarrhea is not a frequent side effect.ConclusionThis study on pediatric antibiotic-associated diarrhea displayed epidemiological data and the differences geographically in our region.

A study of Extended Spectrum ß-Lactamases in Gram-negative Bacterial Isolates in a Tertiary Care Hospital in Mumbai

Background: Injudicious use of antimicrobials for any infection causes microbes to undergo changes through selective pressure and ultimately leads to the development of antimicrobial resistance. The production of ß-Lactamase is one of the most important mechanisms adopted by bacteria to evade action by penicillins and cephalosporins. Materials and Methods: This prospective in vitro study was conducted in a tertiary care hospital in Mumbai over a 6-month period with the aim of identifying extended spectrum b-lactamases (ESBLs) in Gram-negative bacteria in clinical isolates, by double disk diffusion test and E test. Results: Five thousand five hundred and forty-eight g-negative bacilli were isolated of which 2354 (42.42%) were ESBL producers. Maximum numbers of ESBL production were seen in isolates from the blood sample (53.91%) followed by pus (47%) and urine samples (42.27%). Conclusion: ESBL-producing organisms are increasing in the community; therefore, restricted and judicious use of the third generation cephalosporins is to be followed to prevent and control such types of resistance.

Role of previous systemic antibiotic therapy on the probability of recurrence after an initial episode of Clostridioides difficile infection treated with vancomycin.

To investigate the role of previous antibiotic therapy in the risk of recurrence after a Clostridioides difficile infection (CDI) treated with vancomycin. Multicentre observational study. Patients with a CDI episode achieving clinical cure with oral vancomycin and followed up 8 weeks were included. Previous antibiotic exposure up to 90 days was collected. Multivariate analysis of predictors of recurrence adjusted by the propensity score (PS) of being previously treated with each non-CDI antibiotic was performed. Two hundred and forty-one patients were included; 216 (90%) had received systemic antibiotics. Fifty-three patients (22%) had a CDI recurrence. Rates of recurrence were lower in those treated with piperacillin/tazobactam in the last month when compared with those not receiving piperacillin/tazobactam [3 (7%) versus 50 (25%); P = 0.01], whereas higher rates were seen in those treated with cephalosporins in the last month [26/87 (30%) versus 27/154 (17%); P = 0.03]. In multivariate analysis controlled by the inverse probability of treatment weighting by PS, receiving ≥5 days of piperacillin/tazobactam in the last month as the last antibiotic regimen prior to CDI was independently associated with a lower risk of recurrence [adjusted OR (AOR) 0.13; 95% CI: 0.06-0.29; P < 0.0001] whereas exposure for ≥5 days to cephalosporins (versus piperacillin/tazobactam) was associated with an increased risk (AOR 10.9; 95% CI: 4.4-27.1; P < 0.0001). Recent use of piperacillin/tazobactam might be associated with a lower risk of CDI recurrence, while recent use of cephalosporins might promote an increased risk. These findings should be considered when treating hospitalized patients.

Attitudes and Practices of the Use of Third-Generation Cephalosporins among Medical Doctors Practicing in Cameroon.

Third-generation cephalosporins (3GC) are among the most prescribed antibiotics worldwide. Antibiotic resistance, usually due to misuse and overuse, is a feared complication of public health concern. However, there are limited data in Cameroon concerning the knowledge and use of 3GC in our health services. The aim of this study was to assess the knowledge and use of 3GC among medical doctors in Cameroon and to generate baseline information for a wider scale research and policy implementation. This study was a cross-sectional study conducted among medical doctors practicing in Cameroon in general. Convenience sampling was used and the data were collected from both the online questionnaire and the review of files of patients admitted and discharged within the month of April 2021 and analysed with the use of IBM SPSS v25. Results and Discussion. A total of 52 respondents from the online questionnaire and 31 reviewed files were retained. Of the respondents, 27% were female and 73% were male. The mean age and years of experience were 29.6 ± 2.9 and 3.6 ± 2.1 years, respectively. Only 32.7% had correct knowledge of the number of generations of cephalosporins, and 48.1% had knowledge of the antimicrobial target. All medical doctors (MD) identified ceftriaxone as a 3GC, and it was the most commonly prescribed 3GC (71%). Most of the MD considered 3GC to be an efficient antibiotic. Just over half (54.7%) knew the correct posology of ceftriaxone. Only 17% and 9.4% knew the right posology for cefotaxime and ceftazidime, respectively, for the management of early-onset neonatal infection (EONNI). The misuse of 3GC was mostly attributed to nurses, MD, and poor institutional policies. There is average knowledge on 3GC among MD, with ceftriaxone being the most widely known and prescribed. Misuse is common among nurses and doctors. Poor institutional policies and limited laboratory capacities are to be blamed.

Development of a Method for the Fast Detection of Extended-Spectrum β-Lactamase- and Plasmid-Mediated AmpC β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae from Dogs and Cats in the USA.

Antibiotic resistance, such as resistance to beta-lactams and the development of resistance mechanisms, is associated with multifactorial phenomena and not only with the use of third-generation cephalosporins. Many methods have been recommended for the detection of ESBL and pAmpC β-lactamase production but they are very subjective and the appropriate facilities are not available in most laboratories, especially not in clinics. Therefore, for fast clinical antimicrobial selection, we need to rapidly detect ESBL- and pAmpC β-lactamase-producing bacteria using a simple method with samples containing large amounts of bacteria. For the detection of ESBL- and pAmpC phenotypes and genes, the disk diffusion test, DDST and multiplex PCR were conducted. Of the 109 samples, 99 (90.8%) samples were grown in MacConkey broth containing cephalothin, and 71 samples were grown on MacConkey agar containing ceftiofur. Of the 71 samples grown on MacConkey agar containing ceftiofur, 58 Escherichia coli and 19 Klebsiella pneumoniae isolates, in particular, harbored β-lactamase genes. Of the 38 samples that did not grow in MacConkey broth containing cephalothin or on MacConkey agar containing ceftiofur, 32 isolates were identified as E. coli, and 10 isolates were identified as K. pneumoniae; β-lactamase genes were not detected in these E. coli and K. pneumoniae isolates. Of the 78 ESBL- and pAmpC β-lactamase-producing E. coli and K. pneumoniae, 55 (70.5%) isolates carried one or more ESBL genes and 56 (71.8%) isolates carried one or more pAmpC β-lactamase genes. Our method is a fast, and low-cost tool for the screening of frequently encountered ESBL- and pAmpC β-lactamase-producing bacteria and it would assist in diagnosis and improve therapeutic treatment in animal hospitals.

The First Experience of Combined Use of Cefepime/Sulbactam and Aztreonam in ICU Patients with Nosocomial Infections Caused by Carbapenem-Resistant Gram-Negative Microorganisms Producing Class B and D Carbapenemases

Background. The difficulties of antibacterial therapy of infections caused by carbapenemase-producing gram-negative bacteria are associated with limited options for adequate therapy since, in addition to resistance to carbapenems and other beta-lactams, these microorganisms are often characterized by associated resistance to other classes of antibiotics, including polymyxins. In vitro data support the idea of combined use of inhibitor-protected cephalosporins with aztreonam for the treatment of such infections. The aim of the study was to investigate the effectiveness of cefepime/sulbactam (FEP/SB) in combination with aztreonam (ATM) in infections caused by class B and D carbapenemase producers.Methods. A prospective observational study evaluated the effectiveness of the combination of FEP/SB + ATM in ICU patients with nosocomial infections complicated by sepsis or septic shock caused by carbapenem-resistant pathogens with documented production of class B or D carbapenemase. The ineffectiveness of previous treatment and the absence of other options for adequate therapy were used as inclusion criteria. Microbiological, clinical efficacy, and 30-day mortality were indicators of therapy evaluation.Results. The study included 25 patients with nosocomial infection (76% of them was VAP), with sepsis (60%) or septic shock (40%) and an average SOFA score of 6 points caused by Klebsiella pneumoniae (23 patients) or Pseudomonas aeruginosa (2) producing carbapenemases OXA-48 (56%), NDM (20%), NDM + OXA-48 (16%), and class B carbapenemase in two strains of P. aeruginosa. The average daily dose of FEP/SB and ATM was 6.6 g, the duration of therapy was 9.9 days. As a result of the treatment, eradication was achieved in 68% of patients, clinical efficacy was 72%, and the 30-day mortality rate was 28%.Conclusion. Our results show good clinical and bacteriological efficacy of the combination of FEP/SB and ATM in infections caused by extremely resistant K. pneumoniae, non-susceptible to carbapenems and producing class B or D carbapenemase.