Fourth-generation Cephalosporins Research Articles

Diagnosis and Management of Febrile Neutropenia in Pediatric Oncology Patients-A Systematic Review.

Infectious diseases are associated with a high morbidity and mortality rate among pediatric cancer patients undergoing treatment or receiving a transplant. Neutropenia represents a potentially fatal complication of cancer treatment and is associated with a high risk of developing bacterial infections. Although febrile neutropenia (FN) can affect both adults and children, the latter has a higher chance of infections with an unknown origin. Prompt empiric broad-spectrum antibiotic administration is collectively considered the best therapeutic approach. This review aims to analyze the latest works from the literature regarding the therapeutic strategies, schemes, and approaches and the efficacy of these in pediatric febrile neutropenia. Following PRISMA guidelines, an advanced search on PubMed, Scopus, and Cochrane Library, using the keywords “febrile neutropenia”, “pediatric”, “cancer”, and “oncology”, was performed. A total of 197 articles were found to be eligible. After screening the abstracts and excluding unfit studies, 16 articles were analyzed. There were eight retrospective studies, five prospective studies, and two clinical trials. Altogether, these studies have described around 5000 episodes of FN. The median age of the participants was 7.6 years, and the underlying condition for most of them was acute leukemia. The infectious agent could only be determined in around one-fifth of cases, from which 90% were of bacterial origin. As such, empirical broad-spectrum antibiotics are used, with the most used treatment scheme comprising third- and fourth-generation cephalosporins and antipseudomonal penicillins. In order to improve the treatment strategies of FN episodes and to successfully de-escalate treatments toward narrower-spectrum antibiotics, hospitals and clinics should increase their efforts in identifying the underlying cause of FN episodes through blood culture urine culture and viral tests, wherever infrastructure enables it.

Use of cefepime/sulbactam in the treatment of infections caused by carbapenem-resistant bacteria

Cefepime/sulbactam is a combined antibiotic with a wide spectrum of antimicrobial activity, including cefepime, the fourth-generation cephalosporin, and sulbactam, the beta-lactamase inhibitor, in a 1:1 ratio. Cefepime/sulbactam has a bactericidal effect: it causes a disorder in cell wall synthesis due to blockade of transpeptidase and a disorder in the formation of cross-links in peptidoglycan [1]. Today, the problem of antibiotic resistance is growing rapidly. In the WHO list, a critically high level of priority for the development of new antibiotics is occupied by infections caused by ESBL-producing gram-negative bacteria that are resistant to cephalosporins, as well as carbapenem-resistant Enterobacterales, Acinetobacter baumannii and Pseudomonas aeruginosa [2]. Infections caused by multiresistant bacteria are characterized by a longer course, require prolonged hospitalization, are very difficult to treat with modern antibacterial drugs, and increase the risk of death [3]. In this regard, a deeper study of the action of individual antibacterial drugs and their combination with β-lactamase inhibitors in the treatment of diseases caused by multiresistant microorganisms is crucial.

Vitamin C Ameliorates the Cefepime-Induced Changes of Liver Enzymes, Histopathology and Proinflammatory Cytokines in Male Albino Rats

Cefepime belongs to the fourth generation cephalosporin family of antibiotics, it showed side effects such as nephrotoxicity and neurotoxicity. However little reports showed its hepatotoxic effects. The aim of the current study was to evaluate cefepime-induced hepatotoxicity and its associated histopathological changes in the liver. Also, it aimed to examine the effects of cefepime treatment on the proinflammatory cytokines as well as the protective and recovering roles of vitamin C against the cefepime-induced effects. . Blood samples were collected and the liver enzymes in serum ALT, AST and Total Bilirubin (T. Bil.) were estimated biochemically; liver tissues were collected and divided into two parts: the first part were fixed for histopathological examination by H&E staining whereas the other part was processed for RNA extraction and further for real time PCR examination of the mRNA expression of IL1β and TNFα. Cefepime could significantly increase the concentration of ALT, AST, T. Bil. as well as the mRNA expression of proinflammatory cytokines IL1β and TNFα; histopathological changes in the form of hepatic lobules distortion, marked degeneration, hepatocellular vacuolation and necrosis, nuclear pyknosis, scattered apoptosis, distortion of portal areas and marked fibrosis were observed after two weeks of cefepime administration; co- administration of vitamin C with cefepime or administration administering it for 7 days after cefepime could successfully improve the levels of ALT, AST, T. Bil., histopathological and mRNA expression of IL1β and TNFα. The current study suggested that cefepime has hepatotoxic effects shown as alternation of the liver enzymes, changing in the histopathological features as well as stimulating the inflammation in the liver tissue. Vitamin C can be used as a protective or recovering drug against cefepime-induced hepatotoxicity.

Retrospective data analysis for definition of multidrug resistance in gram-negative bacteria - a consensus proposal.

The main objective of this study was to propose a common definition of multidrug-resistant gram-negative organisms (GN-MDRO), which may be used for epidemiological surveillance and benchmarking. In this retrospective data analysis, we used interpreted qualitative susceptibility data (SIR) from blood culture isolates of different gram-negative microorganisms from the ANRESIS database from 2017-2021. We first analysed testing algorithms used by different Swiss laboratories and investigated cross-resistance patterns within antibiotic groups. Comparing these data with existing international definitions, we developed two different GN-MDRO definitions, an extended one for surveillance purposes (ANRESIS-extended) and a more stringent one for clinical purposes, aimed primarily at the identification of difficult-to-treat GN-MDRO (ANRESIS-restricted). Using these novel algorithms, the rates of invasive GN-MDRO identified in our national dataset were compared with international and national definitions: the European Centre for Disease Prevention and Control (ECDC) definition, the Commission for Hospital Hygiene and Infection (KRINKO) definition and the definition proposed by the University Hospital Zurich. SIR data of a total of 41,785 Enterobacterales, 2,919 , and 419 spp. isolates were used for the analyses. Five antibiotic categories were used for our MDRO definition: aminoglycosides, piperacillin-tazobactam, third- and fourth-generation cephalosporins, carbapenems and fluoroquinolones. Large differences were found between the testing algorithms of the different laboratories. Cross-resistance analysis within an antibiotic group revealed that the substance most likely to be effective against a particular gram-negative bacterium was not preferentially tested (e.g. amikacin for the aminoglycosides). For all bacterial species tested, the highest rates of multidrug-resistant isolates were found using the ECDC-MDR definition, followed by the ANRESIS-extended definition. The number of MDR-Enterobacterales identified using the ANRESIS-restricted definition (n = 627) was comparable to those identified using the KRINKO (n = 622) and UHZ definitions (n = 437). However, the isolates classified as MDR-Enterobacterales according to the KRINKO, UHZ and ANRESIS-restricted definitions (total n = 870) differed considerably. Only 242 of the isolates (27.8%) were uniformly classified as MDRO according to the KRINKO, UHZ and ANRESIS-restricted definitions. Comparable findings were made for Klebsiella spp. and Pseudomonas aeruginosa. The application of different MDRO definitions leads to significant differences in not only MDRO rates but also the isolates that are eventually classified as MDRO. Therefore, defining a nationwide MDRO algorithm is crucial if data are compared between hospitals. The definition of a minimal antibiotic susceptibility testing panel would improve comparability further.

Clinical Pharmacokinetics and Pharmacodynamics of Cefepime.

Cefepime is a broad-spectrum fourth-generation cephalosporin with activity against Gram-positive and Gram-negative pathogens. It is generally administered as an infusion over 30-60 min or as a prolonged infusion with infusion times from 3 h to continuous administration. Cefepime is widely distributed in biological fluids and tissues with an average volume of distribution of ~0.2 L/kg in healthy adults with normal renal function. Protein binding is relatively low (20%), and elimination is mainly renal. About 85% of the dose is excreted unchanged in the urine, with an elimination half-life of 2-2.3 h. The pharmacokinetics of cefepime is altered under certain pathophysiological conditions, resulting in high inter-individual variability in cefepime volume of distribution and clearance, which poses challenges for population dosing approaches. Consequently, therapeutic drug monitoring of cefepime may be beneficial in certain patients including those who are critically ill, have life-threatening infections, or are infected with more resistant pathogens. Cefepime is generally safe and efficacious, with a goal exposure target of 70% time of the free drug concentration over the minimum inhibitory concentration for clinical efficacy. In recent years, reports of neurotoxicity have increased, specifically in patients with impaired renal function. This review summarizes the pharmacokinetics, pharmacodynamics, and toxicodynamics of cefepime contemporarily in the setting of increasing cefepime exposures. We explore the potential benefits of extended or continuous infusions and therapeutic drug monitoring in special populations.

In vitro Susceptibility to β-Lactam Antibiotics and Viability of Neisseria gonorrhoeae Strains Producing Plasmid-Mediated Broad- and Extended-Spectrum β-Lactamases.

Neisseria gonorrhoeae plasmids can mediate high-level antimicrobial resistance. The emergence of clinical isolates producing plasmid β-lactamases that can hydrolyze cephalosporins, the mainstay treatment for gonorrhea, may be a serious threat. In this work, N. gonorrhoeae strains producing plasmid-mediated broad- and extended-spectrum β-lactamases (ESBLs) were obtained in vitro, and their viability and β-lactam antibiotic susceptibility were studied. Artificial pblaTEM-1 and pblaTEM-20 plasmids were constructed by site-directed mutagenesis from a pblaTEM-135 plasmid isolated from a clinical isolate. Minimum inhibitory concentration (MIC) values for a series of β-lactam antibiotics, including benzylpenicillin, ampicillin, cefuroxime, ceftriaxone, cefixime, cefotaxime, cefepime, meropenem, imipenem, and doripenem, were determined. The N. gonorrhoeae strain carrying the pblaTEM-20 plasmid exhibited a high level of resistance to penicillins and second–fourth-generation cephalosporins (MIC ≥2 mg/L) but not to carbapenems (MIC ≤0.008 mg/L). However, this strain stopped growing after 6 h of culture. The reduction in viability was not associated with loss of the plasmid but can be explained by the presence of the plasmid itself, which requires additional reproduction costs, and to the expression of ESBLs, which can affect the structure of the peptidoglycan layer in the cell membrane. Cell growth was mathematically modeled using the generalized Verhulst equation, and the reduced viability of the plasmid-carrying strains compared to the non-plasmid-carrying strains was confirmed. The cell death kinetics of N. gonorrhoeae strains without the pblaTEM-20 plasmid in the presence of ceftriaxone can be described by a modified Chick–Watson law. The corresponding kinetics of the N. gonorrhoeae strain carrying the pblaTEM-20 plasmid reflected several processes: the hydrolysis of ceftriaxone by the TEM-20 β-lactamase and the growth and gradual death of cells. The demonstrated reduction in the viability of N. gonorrhoeae strains carrying the pblaTEM-20 plasmid probably explains the absence of clinical isolates of ESBL-producing N. gonorrhoeae.

#31 Bloodstream Infections and Microbiology during Induction Chemotherapy over a Decade at a Community Pediatric Cancer Center

Abstract Background Bloodstream infections (BSIs) remain a significant cause of morbidity and mortality in children with leukemia. They are at an increased risk of infectious complications secondary to intense chemotherapeutic regimens during induction resulting in prolonged and profound neutropenia. To our knowledge, there is limited literature regarding pathogens and antibiotic resistance from smaller institutions similar to ours. The primary objective of this review was to describe the microbiology of BSIs, and second to evaluate our rates of BSIs during induction chemotherapy as compared to larger institutions. Method Retrospective chart review of 82 eligible patients between the age of 1 and 21 years with newly diagnosed leukemia between May 1, 2010 and May 31, 2020. Patients who did not complete the entirety of induction chemotherapy at our hospital were excluded. A microbiologically documented infection was defined as a causative pathogen isolated from the blood in the setting of fever and/or neutropenia. Neutropenia was defined as an absolute neutrophil count (ANC) of less than 0.5x109 cells/L. Results Of the 82 patients, 12 (14.6%) patients had a BSI during induction chemotherapy. The most common organisms identified were Gram-positive cocci (75%), Gram-negative bacilli (16.6%), and Gram-negative cocci (8.3%). Methicillin-susceptible Staphylococcus aureus (MSSA) was the most frequently isolated organism (42%) overall. No methicillin-resistant Staphylococcus aureus (MRSA) was identified. Of the Gram-negative bacteria isolated, Escherichia coli (8%) and Pseudomonas aeruginosa (8%) were identified. No extended spectrum beta-lactamase (ESBL) or multi-drug resistant organisms were identified. No fungi were isolated. Conclusion The incidence of BSIs in children during induction chemotherapy at our institution is similar to what is reported from larger, academic centers. Gram-positive cocci comprise 75% of BSIs with no MRSA isolates in 10 years. Our antibiogram shows no resistant Gram-negative bacteria. This is in contrast to what is reported to larger pediatric cancer centers. Therefore, current empiric monotherapy with a fourth generation cephalosporin at the onset of febrile neutropenia remains adequate for our pediatric oncology patients.

The Use of Antibiotics for Ventilator-Associated Pneumonia in the MIMIC-IV Database.

Purpose: By analyzing the clinical characteristics, etiological characteristics and commonly used antibiotics of patients with ventilator-associated pneumonia (VAP) in intensive care units (ICUs) in the intensive care database. This study aims to provide guidance information for the clinical rational use of drugs for patients with VAP. Method: Patients with VAP information were collected from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database, including their sociodemographic characteristics, vital signs, laboratory measurements, complications, microbiology, and antibiotic use. After data processing, the characteristics of the medications used by patients with VAP in ICUs were described using statistical graphs and tables, and experiences were summarized and the reasons were analyzed. Results: This study included 2,068 patients with VAP. Forty-eight patient characteristics, including demographic indicators, vital signs, biochemical indicators, scores, and comorbidities, were compared between the survival and death groups of VAP patients. Cephalosporins and vancomycin were the most commonly used. Among them, fourth-generation cephalosporin (ForGC) combined with vancomycin was used the most, by 540 patients. First-generati49n cephalosporin (FirGC) combined with vancomycin was associated with the highest survival rate (86.7%). More than 55% of patients were infected with Gram-negative bacteria. However, patients with VAP had fewer resistant strains (<25%). FirGC or ForGC combined with vancomycin had many inflammation-related features that differed significantly from those in patients who did not receive medication. Conclusion: Understanding antibiotic use, pathogenic bacteria compositions, and the drug resistance rates of patients with VAP can help prevent the occurrence of diseases, contain infections as soon as possible, and promote the recovery of patients.

Pattern of Antibiotic Use in the Perinatal Period in a Public University Hospital in Romania.

Background and Objectives: Antibiotics are the most frequently prescribed drugs in hospitals and their prescription is increased during pregnancy and labor. There are limited data about this issue, and the safe use of antibiotics in pregnancy and antibiotic resistance remains a concern. The aim of the study is to evaluate the use of antibiotics among pregnant women attending hospital for five years. Materials and Methods: Antibiotic consumption and treatment information of patients were retrospectively collected from a hospital software program and expressed as defined daily dose (DDD) according to the World Health Organization (WHO) methodology for inpatients between 2017 and 2021. We evaluated antibiotic prescription by name, classes, and Food and Drug Administration (FDA) categories. Results: Antibiotic consumption shows a decreasing trend between 2017 and 2019, but an increasing one between 2020 and 2021. Ceftriaxone was the most prescribed antibiotic in each year, followed by cefixime, amoxicillin, metronidazole, cefuroxime, ampicillin, and ciprofloxacin. We noticed that first- and fourth-generation cephalosporins were not prescribed to these patients. A very small percentage of women in this study received antibiotics such as aminoglycosides; fluoroquinolones were generally contraindicated in the perinatal period. A large percentage of prescriptions were antibiotics classified as category B by the FDA. The most common infections that occurred in the perinatal period were those of the kidney and urinary tract in a higher number than in other studies. Conclusions: Our study shows that many classes of antibiotics used in perinatal women belong to category B antibiotics, the most prescribed being cephalosporins. Because of insufficient safety evidence and the potential for teratogenic effects on the fetus, restricted use among the category C and D antibiotic classes was seen and anticipated. Improving maternal health requires the involvement of healthcare experts in risk assessment and evaluation of existing data for appropriate antibiotic selection, dose, duration of medication, and monitoring.

Streptococcus agalactiae is resistant to β-lactam antibiotics in a diabetic patient with foot infection: a case report

Introduction: Diabetic foot infection is a complication that often occurs in people with diabetes mellitus. Staphylococcus aureus is the most common microorganism found in diabetic foot infections. In addition, coagulase-negative staphylococci, Enterococcus faecalis, Streptococcus agalactiae, and Pseudomonas aeruginosa can also be demonstrated. Diabetic foot infection treatment usually takes a long time which may increasing the risk of antibiotic resistance. This article will present a unique and interesting case about Streptococcus agalactiae resistant to β-lactam infection. Case description: A 56-year-old man presented with a long history of diabetes mellitus but had not taken anti-diabetic drugs and had no history of previous use of antibiotics. Since 2016 his right foot had a recurring wound that he routinely treated. Microbiology culture of the wound swab obtained three bacteria namely Streptococcus agalactiae, Proteus mirabilis and Klebsiella pneumoniae which is resistant to β-lactam antibiotics. Conclusion: The identification of Group B Streptococcus bacteria (Streptococcus agalactiae) which are resistant to β-lactam antibiotics (penicillin, third and fourth generation cephalosporins) which were found in this case, reminds all medical personnel to be more careful and prudent in the rational use of antibiotics.

Clonal and plasmid-mediated flow of ESBL/AmpC genes in Escherichia coli in a commercial laying hen farm

Resistance to third- and fourth-generation cephalosporins in Escherichia coli is mainly due to extended-spectrum beta-lactamases (ESBL) and AmpC cephalosporinases, which have been increasingly reported, mainly in isolates from humans and poultry.The aim of this study was to address the flow of antimicrobial resistance determinants in the full laying hen production cycle (four batches followed from day-old chicks to 83/84-week-old layers), using cephalosporin-resistant E. coli as a model and their characterization using whole genome sequencing (WGS).Fifteen out of 22 samples analysed yielded growth on MacConkey agar with cefotaxime (1 mg/L). Of these, 141 isolates were identified as E. coli and 47 were characterized by WGS.Genes detected were three ESBL (blaCTX-M-1 (n = 19); blaCTX-M-14 (n = 1); and blaSHV-12 (n = 9)) and one AmpC (blaCMY-2 (n = 13)). Some isolates only harboured blaTEM-1B (n = 2) or blaTEM-1D (n = 1).IncI1 plasmids were the main platform for ESBL/AmpC genes. In addition, five clones were identified harbouring blaCTX-M-1 (two), blaSHV-12 (one) and blaCMY-2 (two), drawing a clone-plasmid mixed flow model.Gene blaCTX-M-1 was found in the chromosomal DNA of clone 1 over 14 months, and in IncI1/ST3 plasmids over six months; over six months blaSHV-12 was found harboured by clone 3 (IncI1/ST26 plasmids), and 15 months later in a non-replicon detected plasmid. Finally, blaCMY-2 spread for at least 16 months, mainly by IncK2 (including clone 4) and IncI1/ST12 (clone 5) plasmids.Proper use of antimicrobials should be combined with other farm management strategies for the effective control of cephalosporin-resistant E. coli isolates in commercial layer farms.

The effects of antibiotic cycling and mixing on acquisition of antibiotic resistant bacteria in the ICU: A post-hoc individual patient analysis of a prospective cluster-randomized crossover study.

BackgroundRepeated rotation of empiric antibiotic treatment strategies is hypothesized to reduce antibiotic resistance. Clinical rotation studies failed to change unit-wide prevalence of antibiotic resistant bacteria (ARB) carriage, including an international cluster-randomized crossover study. Unit-wide effects may differ from individual effects due to “ecological fallacy”. This post-hoc analysis of a cluster-randomized crossover study assesses differences between cycling and mixing rotation strategies in acquisition of carriage with Gram-negative ARB in individual patients.MethodsThis was a controlled cluster-randomized crossover study in 7 ICUs in 5 European countries. Clinical cultures taken as routine care were used for endpoint assessment. Patients with a first negative culture and at least one culture collected in total were included. Community acquisitions (2 days of admission or less) were excluded. Primary outcome was ICU-acquisition of Enterobacterales species with reduced susceptibility to: third- or fourth generation cephalosporins or piperacillin-tazobactam, and Acinetobacter species and Pseudomonas aeruginosa with reduced susceptibility for piperacillin-tazobactam or carbapenems. Cycling (altering first-line empiric therapy for Gram-negative bacteria, every other 6-weeks), to mixing (changing antibiotic type every empiric antibiotic course). Rotated antibiotics were third- or fourth generation cephalosporins, piperacillin-tazobactam and carbapenems.ResultsFor this analysis 1,613 admissions were eligible (855 and 758 during cycling and mixing, respectively), with 16,437 microbiological cultures obtained. Incidences of acquisition with ARB during ICU-stay were 7.3% (n = 62) and 5.1% (n = 39) during cycling and mixing, respectively (p-value 0.13), after a mean of 17.7 (median 15) and 20.8 (median 13) days. Adjusted odds ratio for acquisition of ARB carriage during mixing was 0.62 (95% CI 0.38 to 1.00). Acquired carriage with ARB were Enterobacterales species (n = 61), Pseudomonas aeruginosa (n = 38) and Acinetobacter species (n = 20), with no statistically significant differences between interventions.ConclusionsThere was no statistically significant difference in individual patients’ risk of acquiring carriage with Gram-negative ARB during cycling and mixing. These findings substantiate the absence of difference between cycling and mixing on the epidemiology of Gram-negative ARB in ICU.Trial registrationThis trial is registered with ClinicalTrials.gov, registered 10 January 2011, NCT01293071.

Retail chicken giblets contaminated with extended-spectrum cephalosporin- and carbapenem-resistant Salmonella enterica carrying blaCMY-2.

Background and Aim:Chickens are considered as the main source of Salmonella, with infection potentially spreading to the public through outlets. The study aimed to investigate poultry shops for Salmonella enterica resistant to extended-spectrum cephalosporins-resistant (ESCR) and carbapenems-resistant (CR).Materials and Methods:Samples were collected from chicken giblets, water tanks, and workers at retail shops. Salmonella was isolated and serotyped; the presence of invA, stn, ompA, and ompF was determined using polymerase chain reaction (PCR). The isolates were tested for ESCR and CR by a disk-diffusion test; a confirmatory extended-spectrum β-lactamase (ESBL) test was performed by combinational disk-diffusion test with clavulanic acid. The resistant isolates were screened for ESBL (blaTEM, blaSHV, blaCTX-M, and blaOXA-1), AmpC blaCMY-2, and carbapenemase (blaKPC, blaNDM, and blaOXA-48) genes using PCR.Results:S. enterica was isolated from chicken giblets (13/129) and the 13 isolates were ESCR. Based on the confirmatory ESBL test and CR, the 13 isolates were classified into the following resistance phenotypes: ESBL-producing and CR (n=4), ESBL-producing (n=1), non-ESBL-producing and CR (n=6), and non-ESBL-producing (n=2). All the five isolates with ESBL-producing phenotype carried predominantly blaTEM, blaSHV, and blaCMY-2. Regardless of being phenotypically CR, none of these isolates carried any of the tested carbapenemase genes. Surprisingly, the isolates with non-ESBL phenotype were found to carry blaTEM, blaSHV, and blaCMY-2. The blaKPC was present mainly in the isolates with non-ESBL and CR phenotypes. Interestingly, two isolates of the non-ESBL and CR phenotype showed resistance to cefepime, the fourth generation cephalosporins. Salmonella was also recovered from the water tanks (2/7) and the workers (2/16). The four isolates were ESCR and showed a non-ESBL-producing and CR phenotype; they harbored blaTEM, blaSHV, blaOXA-1, and blaKPC. The blaCMY-2 was found in one isolate from water and one from humans. All Salmonella isolates carried invA, stn, ompA, and ompF.Conclusion:Virulent ESCR S. enterica were identified in retail shops. The isolates carried blaCMY-2 and ESBL-genes, with a high proportion showing CR. Transmission of such strains to humans through food leads us to recommend regular inspection of retail outlets for antibiotic-resistant bacteria.

Emerging Infections Due to Shewanella spp.: A Case Series of 128 Cases Over 10 Years.

BackgroundShewanella species are emerging pathogens that can cause severe hepatobiliary, skin and soft tissue, gastrointestinal, respiratory infections, and bacteremia. Here we reported the largest case series of infections caused by Shewanella species.AimTo identify the clinical features and risk factors predisposing to Shewanella infections. To evaluate resistance pattern of Shewanella species and appropriateness of antibiotic use in the study cohort.MethodsPatients admitted to a regional hospital in Hong Kong with Shewanella species infection from April 1, 2010 to December 31, 2020 were included. Demographics, antibiotics, microbiology, and outcomes were retrospectively analyzed.FindingsOver the 10 years, we identified 128 patients with Shewanella species infection. 61.7% were male with a median age of 78 (IQR 65–87). Important underlying diseases included hepatobiliary diseases (63.3%), malignancy (26.6%), chronic kidney disease or end-stage renal failure (25.8%), and diabetes mellitus (22.7%). Hepatobiliary infections (60.4%) were the most common clinical manifestation. Majority (92.2%) were infected with Shewanella algae, while 7.8% were infected with Shewanella putrefaciens. The identified organisms were usually susceptible to ceftazidime (98.7%), gentamicin (97.4%), cefoperazone-sulbactam (93.5%) and ciprofloxacin (90.3%). Imipenem-susceptible strains were only present in 76.6% of isolates.ConclusionThis largest case series suggested that Shewanella infections are commonly associated with underlying comorbidities, especially with hepatobiliary diseases and malignancy. Although Shewanella species remained largely susceptible to third and fourth generation cephalosporins and aminoglycosides, carbapenem resistance has been on a significant rise.

Prevalence and molecular characterization of foodborne and human-derived Salmonella strains for resistance to critically important antibiotics.

The primary goals of this cross-sectional study were to screen various food/water, and human samples for the presence of Salmonella species, and to assess the phenotypic and genetic relationship between resistances found in food and human Salmonella isolates to critically important antibiotics. Between November 2019 and May 2021, 501 samples were randomly collected for Salmonella isolation and identification using standard culturing methods, biochemical, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and PCR techniques. Antimicrobial susceptibility testing was performed on confirmed Salmonella species, and PCR was used to investigate the genetic components that confer these resistance traits. Salmonella enterica subspecies enterica was confirmed in 35 (6.99%) of the samples (raw food=23, ready-to-eat food/drink [REF/D]=5, human=7). Seventeen of them were antibiotic-resistant to at least one class, and eight were multidrug-resistant (MDR) isolates (raw food=7, human=1). All Salmonella isolates were susceptible to carbapenems, third- and fourth-generation cephalosporins and monobactam antibiotics. Resistance phenotypes to aminoglycosides (48.57%), β-lactams (20%) and tetracycline (17.14%), as well as associated genes such as aadA, blaTEM , blaZ and tetA, as well as dfrA and sul1, were prevalent in Salmonella isolates. Colistin resistance genotype (mcr1) was detected in three (8.57%) isolates recovered from egg, cattle mince and rabbit meat, and the total incidence was 14.29% when two isolates exhibited resistance phenotypes were considered. Furthermore, four (11.43%) MDR isolates shared the blaTEM and blaZ genes, and one (2.86%) isolate contained three extended spectrum β-lactams producing genes (ESBL), namely blaCTX , blaTEM and blaZ . The gyrA gene was expressed by one of three foodborne Salmonella isolates (8.57%) with ciprofloxacin resistance phenotypes. To the best of our knowledge, this is the first report from Egypt identifying colistin resistance in Salmonella enterica recovered from cattle minced meat and rabbit meat. Overall, thehighest incidence rate of Salmonella enterica was found in cattle-derived products, and it was slightly more prevalent in RTE/D foods than in raw foods. Resistance to critical and clinically important antibiotics, particularly in Salmonella from RTE/D food, suggests that these antibiotics are being abused in the investigated area's veterinary field, and raises the potential of these isolates being transmitted to high-risk humans, which would be a serious problem. Future research using whole-genome sequencing is needed to clarify Salmonella resistance mechanisms to critically important antimicrobial agents or those exhibiting multidrug resistance.

Emphysematous pyelonephritis

ABSTRACTUrinary tract infections are commonly encountered and managed worldwide, and emphysematous pyelonephritis (EPN) is among the most serious types of urinary tract infections. EPN is an acute necrotizing infection of the kidney, often associated with high rates of renal loss and mortality. The symptoms of EPN infection can be nonspecific, but the clinical triad of fever, flank pain, and nausea represent the most common presentations. The diagnosis and classification are performed with the assistance of computed tomography (CT). The imaging-based classification system created by Huang and Tseng is widely used in clinical assessments. They defined EPN into four different class (1–4), with the higher number the more severe disease. Optimal EPN treatment is controversial, with emergent nephrectomy suggested during early studies, whereas more recent evidence favors more conservative approaches. Escherichia coli, Klebsiella pneumoniae and Proteus mirabilis are most common pathogens. The initial use of broad-spectrum antibiotics such as Third-or fourth-generation cephalosporins and carbapenems are recommended. Diabetes, obstructive uropathy and hypertension are the most common risk factors and often need treatment together. Emergent drainage is indicated with a larger-sized drainage tube to achieve better drainage function. CT guidance has a better success rate than insertion under the guidance of ultrasonography. Nephrectomy should be reserved as the last resort for those who fail to respond to conservative therapy. This review aims to provide comprehensive, evidence-based recommendations for the diagnosis and management of this life-threatening urological infection.

A Cross-Sectional Study of Veterinarians in Germany on the Impact of the TÄHAV Amendment 2018 on Antimicrobial Use and Development of Antimicrobial Resistance in Dogs and Cats.

To minimize the use of third- and fourth-generation cephalosporins and fluoroquinolones, the 2018 amendment to the regulations of veterinary pharmacies (TÄHAV) introduced legal restrictions in Germany. In an online survey among German veterinarians, we investigated the influence of these requirements on the use of antibiotics in the treatment of dogs and cats and the development of resistance rates. It was found that, on average, between 21% and 30% of daily treated dogs and cats received antimicrobial therapy. The TÄHAV amendment led to a less frequent use of highest priority critically important antimicrobials (HPCIA) in 79% (240/303) of respondents and less antimicrobial use in general in 36% (108/303). As a result of these legal changes, 63% (190/303) of participants requested antimicrobial susceptibility testing (AST) more frequently. Participants consulted ASTs particularly frequently for treatment of otitis externa with 63% (190/303), cystitis with 55% (168/303), wounds with 44% (132/303), and pyoderma with 29% (88/303). Veterinarians also noted an increased loss of antimicrobial efficacy, especially when treating these diseases. The results of our survey confirm that the TÄHAV amendment is having a positive impact on prudent antibiotic use, with participants performing more ASTs, using HPCIA less frequently, and choosing alternative antimicrobials for therapy.

Carbapenem Resistant Pseudomonas aeruginosa Infections in Elderly Patients: Antimicrobial Resistance Profiles, Risk Factors and Impact on Clinical Outcomes.

ObjectiveThe prevalence and clinical impact on mortality of carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection are unclear in elderly patients. Here, we aimed to clarify the prevalence, the clinical manifestations, antimicrobial resistance, risk factors and outcomes of elderly inpatients with CRPA infection.MethodsA retrospective study of 600 elderly inpatients infected with P. aeruginosa was conducted at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine from January 1st 2018 to December 31st 2020. All 155 patients with CRPA infection were designated as a case group. Patients with carbapenem-susceptible Pseudomonas aeruginosa (CSPA) were randomly selected from remaining 445 cases in a 1:1 ratio to case group as a control group.ResultsOf 600 P. aeruginosa isolates, the overall rates of CRPA, MDR PA (multidrug-resistance Pseudomonas aeruginosa) were 25.8% (155), 22.3% (134), respectively. The rankings of the top five resistant rates of CRPA to tested antimicrobial drugs were imipenem (87.7%), meropenem (70.3%), ciprofloxacin (51.0%), levofloxacin (48.4%), cefoperazone (43.2%). Independent risk factors for patients with CRPA infection were cerebrovascular disease (OR = 3.517, P < 0.001), foley catheter (OR = 2.073, P = 0.018), length of hospital stay ≥ 14 days (OR = 1.980, P = 0.013), albumin < 35 g/L (OR = 2.049, P = 0.020), previous antibiotic exposure to carbapenems (OR = 7.022, P = 0.004), previous antibiotic exposure to third- or fourth-generation cephalosporins (OR = 12.649, P = 0.002). Of 155 patients with CRPA infection, the mortality rate was 16.8% (26/155). Independent risk factors for mortality were receiving mechanical ventilation (OR = 3.671, P = 0.007) and neutrophil percentage ≥ 80% (OR = 2.908, P = 0.024).ConclusionThe study revealed high rates of CRPA, MDR PA among the hospitalized elderly patient with P. aeruginosa infection. The analysis of antimicrobial susceptibility emphasizes the necessity for antimicrobial stewardship and infection control in hospitals. These findings of risk factors are practical significant to identify patients at high risk for CRPA infection and mortality that may benefit from alternate empiric treatment.

Antimicrobial Resistance Patterns, Extended-Spectrum Beta-Lactamase Production, and Associated Risk Factors of Klebsiella Species among UTI-Suspected Patients at Bahir Dar City, Northwest Ethiopia.

Introduction Klebsiella species cause pneumonia, UTI, and septicemia in human beings. Beta-lactam drugs are used extensively to treat patients infected with Klebsiella, but most of the Klebsiella species are resistant to third- and fourth-generation cephalosporins and monobactams to which data are scarce in the study area. Objective To determine the prevalence, antimicrobial resistance, ESBL production, and associated risk factors of Klebsiella species among UTI-suspected patients in Bahir Dar City, Northwest Ethiopia. Methods A multi-institution-based prospective cross-sectional study was conducted from January to May 2019. Midstream urines were collected from 385 patients and inoculated onto CLED and MacConkey agars. Identification of growth was done by a battery of biochemical tests. Antimicrobial resistance and ESBL production patterns were determined by using the disc-diffusion method on Mueller–Hinton agar. Quality of data was maintained by following SOPs and using Klebsiella pneumoniae (ACTT700603). Logistic regression statistical analysis was done using the SPSS, version 25, statistical package. A pvalue ≤ 0.05 was considered statistically significant. Results The median age of the study participants was 32 years. Majority of them were female, urban residents, and unable to read and/or write. The total Klebsiella species detected were 38 (9.9%). Of which, 25 (65.8%) were Klebsiella pneumoniae, followed by 6 (15.8%) Klebsiella ozaenae. 20 (80%), 19 (76%), and 19 (76%) Klebsiella pneumoniae showed resistance to amoxicillin/clavulanic acid, ampicillin, and cotrimoxazole, respectively. All K. oxytoca were resistant to ampicillin, and all K. rhinoscleromatis were resistant to cefoxitin and cefotaxime. Klebsiella species that showed resistance to ≥3 antimicrobials were 26 (68%). ESBL-producing Klebsiella species were 10 (26.3%). Patients who had history of antibiotic use, hospitalization, and tight dressing habit had more risk of getting UTI (p < 0.05) than their counterparts. Conclusions Overall UTI prevalence in our study was lower than that of previous Ethiopian studies. High MDR and ESBL-producing Klebsiella species were detected. Patients' history of antibiotic use, hospitalization, and tight dressing habit were risk factors for UTI. It calls up for improving prevention/control systems of Klebsiella species.

Ex Vivo Pharmacokinetics and Pharmacodynamics Modeling and Optimal Regimens Evaluation of Cefquinome Against Bovine Mastitis Caused by Staphylococcus aureus.

Cefquinome, the fourth-generation cephalosporin applied solely for veterinary medicine, is commonly used for bovine mastitis caused by Staphylococcus aureus. The present study aims to establish an optimal dose and provide a PK/PD Cutoff value (COPD) for cefquinome against S. aureus based on ex vivo pharmacokinetics and pharmacodynamics (PK/PD) integration. This study investigated the pharmacokinetics (PK) of cefquinome when administered as three consecutive intramammary (IMM) doses of cefquinome in three healthy dairy cows at 75 mg/gland. Drug concentration was determined by HPLC-MS/MS assay. The ex vivo pharmacodynamics (PD) of cefquinome were evaluated by using a milk sample from a PK experiment. The relationship between the AUC/ MIC of cefquinome and bacterial loading reduction was simulated using a Sigmoid Emax model. The cefquinome concentration in milk attained a maximum level of 1.55 ± 0.21 mg/mL at 1.8 h after the third administration. The mean value of the area under the concentration-time curve (AUC0−24) was 26.12 ± 2.42 mg·h/mL after the third administration. The elimination half-life was 10.6 h. For PD profile, the MICs of cefquinome in milk were 2–4 times higher than those in the broth. In vitro time-killing curve shows that initial bacterial concentration has a huge impact on antibacterial effect on three strains. The antibacterial effect was weakened with the initial bacterial concentration increasing from 106 to 108 CFU/mL. The AUC0−24h/MIC index correlated well with ex vivo efficacy both for the initial inoculum of 106 CFU/mL and 108 CFU/mL (R2 > 0.84). According to the inhibitory sigmoid Emax model analysis, the PK/PD surrogate (AUC0−24/MIC) values were 8,638, 1,397, and 3,851 for bactericidal effect (E = −3) with an initial inoculum of 106 CFU/mL, while the corresponding values were 12,266, 2,295, and 5,337, respectively, with the initial inoculum of 108 CFU/mL. The ex vivo PK/PD based population dose prediction indicated a target attainment rate (TAR) of 90% of 55 mg/gland/12 h. The COPD for cefquinome against S. aureus was 2 μg/mL under the recommended dose of 55 mg/gland/12 h. However, it should be validated in clinical practice in future investigations. These results contribute to the rational use of cefquinome for mastitis treatment in clinical veterinary medicine.