Search

Sneathia sanguinegens is a fastidious, Gram-negative, rod-shape organism rarely isolated from human specimens. In the present report, we describe a case of periprosthetic knee joint infection due to the organism, which occurred in a female patient receiving immunosuppressants for underlying lupus nephritis. The causative organism was isolated from the synovial fluid in the affected knee joint through inoculating the material on chocolate agar and incubation for 15 days under 5% CO

Purpose We hypothesized that a protocol of standardized fixed dose using prolonged infusion during the early phase of sepsis may avoid insufficient β-lactam concentrations. Methods In this single center prospective study, patients with sepsis and vasopressors were enrolled if they were treated by either piperacillin-tazobactam, meropenem or cefepime. Βeta-lactams were administered at fixed dose by prolonged infusion. Targeted plasma concentrations for piperacillin, meropenem and cefepime were above 80 mg/L, 8 mg/L and 38 mg/L respectively. Three blood samples were collected per patient over the first 48 h of treatment. Primary endpoint was target concentration achievement during the 48 first hours, defined as all plasma concentrations above the targeted threshold. Results Among the 89 patients completing the three samples, target concentrations were achieved for 61 (69%). Target concentrations were achieved in 20 (53%), 32 (89%), and 9 (60%) of the patients treated with piperacillin, meropenem and cefepime, respectively. By multivariate analysis, lower APACHE 2 score, higher baseline MDRD creatinine clearance, and piperacillin use were independently associated with insufficient β-lactam concentrations. Conclusion Despite a fixed dose antibiotic administration protocol with prolonged infusion insufficient β-lactam concentration was frequent at the early phase of sepsis, especially in less severe patients, without renal failure, and treated with piperacillin. In septic patients with vasopressors, piperacillin dosing higher than 16 g may be needed to achieve the recommended target concentration. Trial registration: NCT02820987

Introduction Multidrug resistant microorganisms are a serious threat to human health. Under the circumstances, a front line of antimicrobials in clinical setting may be carbapenem β-lactams (CRBP). However, emergence of CRBP resistant (CRBP-r) Gram-negative bacteria are the most alarming. CRBP-r is mainly caused to the production of β-lactamase, down and up expression of the diffusion channel and the efflux pump genes, respectively. Among them, production of metallo-β-lactamase (MBL) is a major cause of high-level of CRBP-r. Method We analyzed the MBL subtypes by PCR and DNA sequencing in CRBP-r Psudomonas aeruginosa in the collection of the joint program by the Japanese Association for Infectious Diseases, Japan Society for Clinical Microbiology and Japanese Society of Chemotherapy (2006–2015 in Japan). Results Among 275 strains out of a total 1716 isolates, 23 (8.3%) were MBL-positive exhibiting resistant to meropenem (MEPM), imipenem, ceftazidime, cefepime, ciprofloxacin and levofloxacin without exception and the MIC of MEPM appeared over 128 μg/mL. Their MBL subtype analysis revealed that 16, 2, and 2 isolates were IMP-1, IMP-7 and VIM-2 positive, respectively, and one isolate each expressed either IMP-10, IMP-34 or IMP-41. Conclusions This study revealed that all the MBL-positive CRBP-r isolates were highly resistant to carbapenems dominating IMP-1 production.

Background The emergence of concurrent levofloxacin- and trimethoprim/sulfamethoxazole (TMP/SMX)-resistant Stenotrophomonas maltophilia (LTSRSM) in Taiwan is becoming a serious problem, but clinical data analysis on this has not been reported. Methods A matched case-control-control study was conducted to investigate risk factors for LTSRSM occurrence in hospitalized patients. For patients with LTSRSM infection/colonization (the case group), two matched control groups were used: control group A with levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) and control group B without S. maltophilia. Besides, tigecycline, ceftazidime, cefepime, ciprofloxacin, gentamicin, amikacin, and colistin susceptibilities in collected LTSRSM and levofloxacin- and TMP/SMX-susceptible S. maltophilia (LTSSSM) isolates were compared. Results From January 2014 to June 2016, 129 LTSRSM from cultured 1213 S. maltophilia isolates (10.6%) were identified. A total of 107 LTSRSM infected patients paired with 107 LTSSSM-, and 107 non-S. maltophilia-infected ones were included. When compared with control group A, previous fluoroquinolone and TMP/SMX use was found to be independently associated with LTSRSM occurrence. When compared with control group B, mechanical ventilation, cerebrovascular disease, and previous fluoroquinolone use were risk factors for LTSRSM occurrence. Eighty-five LTSRSM and 85 LTSSSM isolates were compared for antibiotic susceptibilities; the resistance rates and minimum inhibitory concentrations of tigecycline and ceftazidime were significantly higher for LTSRSM than for LTSSSM isolates. Conclusion The emergence of LTSRSM showing cross resistance to tigecycline and ceftazidime would further limit current therapeutic options. Cautious fluoroquinolone and TMP/SMX use may be helpful to limit such high-level resistant strains of S. maltophilia occurrence.

Purpose The risk of acute kidney injury (AKI) associated with concomitant vancomycin and piperacillin/tazobactam in the intensive care unit (ICU) remains controversial. The aim of this study was to compare the AKI incidence associated with concomitant vancomycin and piperacillin/tazobactam compared to either cefepime or meropenem with vancomycin in the ICU. Materials and methods A multicenter, retrospective, propensity score-matched cohort study was conducted in adult ICU patients administered vancomycin in combination with either piperacillin/tazobactam, cefepime, or meropenem were included. Patients developing AKI ≤48 h following combination therapy initiation were excluded. The primary endpoint was to compare the incidence of AKI associated with concomitant antimicrobial therapy. Multivariable Cox regression modeling in predicting AKI was also conducted. Results A total of 1044 patients were matched. The AKI incidence in vancomycin- piperacillin/tazobactam and vancomycin-cefepime/meropenem groups were 21.9% and 16.8%, respectively (p = 0.068). Multivariable prediction models showed concomitant vancomycin-piperacillin/tazobactam was an independent risk factor of AKI using serum creatinine only (HR 1.52, 1.10–2.10, p = 0.011) and serum creatinine with urine output-based KDIGO criteria (HR 1.77, 1.18–2.67, p = 0.006). No significant differences between groups were observed for AKI recovery patterns or mortality. Conclusion Concomitant vancomycin and piperacillin/tazobactam administration in adult ICU patients was independently associated with an increased risk of AKI.

Introduction Current standards recommend antibiotic prophylaxis administered after open fracture injury. The purpose of this study was to assess culture results in patients with open fracture-associated infections, hypothesizing that cultures obtained do not vary by Gustilo-Anderson (GA) classification. Methods We examined cultured bacterial species from patients with open long bone fractures that underwent irrigation and debridement at a Level 1 trauma center (2008-2016), evaluating our current and two hypothetical antibiotic protocols to assess whether they provided appropriate coverage. The antibiotic protocols included protocols 1 (cefazolin, with gentamicin added for type III fractures), 2 (vancomycin and cefepime) and 3 (ceftriaxone). Results GA classification was not associated with bacterial gram stain (P = 0.161), nor was it predictive of mono- versus polymicrobial infection (P = 0.094). Of 42 culture-positive infections, 31 were type III and 11 were type I or II fractures. 27% of the infections for type I or II fractures were caused by organisms targeted by protocol 1 (OR 0.18, 95% CI 0.04-0.82; P = 0.027). There was no difference in coverage by fracture type among protocol 2 (P = 0.771) or protocol 3 (P = 0.891). For type III fractures, protocol 2 provided 94% appropriate coverage compared to 68% and 61% coverage by protocols 1 and 3, respectively. Conclusion For open fractures complicated by infection, isolated bacterial organisms do not correlate with GA open fracture classification, suggesting that hypothetical protocol 2 should be used for all fracture types. Protocol 2’s broad coverage, across all GA fracture types, may prevent infection by organisms not covered by current antibiotic prophylaxis.

Background Respiratory infections are one of the most common causes of morbidity and mortality. This study examined antimicrobial susceptibility of common respiratory isolates from veterans. Methods Sputum culture data from the Veteran Health Administration were obtained retrospectively between January 2009 and 2019. Cumulative antibiograms were constructed for bacterial isolate susceptibility. Results Sputum and bronchial cultures from approximately 10,345 veterans were included each year. Haemophilus influenzae has maintained high levels of susceptibility to third generation cephalosporins from 2009 (99.7%) to 2018 (97.2%). Third generation cephalosporin susceptibilities amongst Klebsiella pneumoniae have trended upward from 2009 to 2018 as well (79.1% vs 86.4%). In Pseudomonas aeruginosa isolates, there has been an increase in susceptibility rates to cefepime from 2009 to 2018 (79.6%, to 86.6%), gentamicin (81.5% to 89.1%), and piperacillin/tazobactam (86.5% to 90%). Fluoroquinolone susceptibilities amongst Escherichia coli have remained low but stable between 2009 and 2018. Third generation cephalosporin susceptibilities for S. pneumoniae improved slightly from 92.2% to 95% between 2009 and 2018 while susceptibility to azithromycin trended down slightly from 56.8% in 2009 to 51.7% in 2018 for S. pneumoniae. Discussion The antibiogram of sputum isolates from the VA Healthcare System were examined to determine changes in patterns of resistance over a decade of use. Conclusions This large-scale study investigated nationwide sputum culture susceptibility trends. Avoidance of macrolides for empiric treatment of community acquired pneumonia and avoidance of fluoroquinolones for empiric treatment of hospital acquired or ventilator associated pneumonia may be warranted based on susceptibility trends.

INTRODUCTION: Despite the high volume of infections, some clinical aspects of this disease are still unknown. There are currently no studies in Colombia that describe the disease's clinical and treatment aspects in detail. OBJECTIVE: Describe the characteristics and clinical management of a group of admitted patients with SARS-CoV-2 infection in a private clinic in Monteria, Cordoba-Colombia. PATIENTS AND METHODS: A descriptive observational study was carried out between May and August 2020 in 209 hospitalized patients with a confirmed diagnosis of COVID-19. Upon admittance, clinical, sociodemographic characteristics, comorbidities, and complications were analyzed. Additionally, the effect of the following medications was described: 1-antibiotics (cefepime, piperacillin, tazobactam, meropenem, vancomycin) + low molecular weight heparin (LMWH) + corticosteroids (dexamethasone-methylprednisolone) + colchicine. 2- Antibiotic + LMWH + corticosteroids. 3-LMWH + corticosteroids. 4-LMWH + corticosteroids + colchicine. 5-Other treatments (Tocilizumab). RESULTS: 107 (51%) of the 209 patients with a confirmed diagnosis of COVID-19 passed away. The main comorbidities related to mortality of these hospitalized patients with COVID-19 were obesity and kidney disease (P 

Objectives: This study aimed to investigate third-generation cephalosporin (3GC) resistance determinants [extended-spectrum β-lactamases (ESBLs), AmpC β-lactamases and OXA-type β-lactamases] in contemporary clinical Enterobacterales isolates and to determine the in vitro activity of β-lactams and β-lactam/β-lactamase inhibitor combinations, including the investigational combination of cefepime and the novel β-lactamase inhibitor enmetazobactam. Methods: Antibacterial susceptibility of 7168 clinical Enterobacterales isolates obtained between 2016–2018 from North America and Europe was determined according to CLSI guidelines. Phenotypic resistance to the 3GC ceftazidime (MIC ≥ 16 µg/mL) and/or ceftriaxone (MIC ≥ 4 µg/mL) but retaining susceptibility to meropenem (MIC ≤ 1 µg/mL) was determined. β-Lactamase genotyping was performed on clinical isolates with ceftazidime, ceftriaxone, cefepime or meropenem MIC ≥ 1 µg/mL. Results: Phenotypic resistance to 3GCs occurred in 17.5% of tested isolates, whereas 2.1% of isolates were resistant to the carbapenem meropenem. Within the 3GC-resistant subgroup, 60.1% (n = 752) of isolates encoded an ESBL, 25.6% (n = 321) encoded an AmpC-type β-lactamase and 0.9% (n = 11) encoded an OXA-type β-lactamase. Susceptibility of the subgroup to piperacillin/tazobactam (57.5%) and ceftolozane/tazobactam (71.3%) was

AmpC beta-lactamases confer resistance to a broad range of beta-lactams, including penicillins, oxyimino-beta-cephalosporins, cephamycins, and aztreonam. Susceptibility to cefepime, cefpirome, and the carbapenems is generally not affected. AmpC beta-lactamases can be found in a wide variety of Gram-negative organisms and are encoded, on transmissible plasmids and/or on the chromosome. In addition, the AmpC beta-lactamase can be expressed in several different ways which have some interesting implications for susceptibility testing and treatment. Most notably, AmpC beta-lactamases can be produced constitutively (i.e. always expressed), can be induced, or mutants can evolve to hyper-produce the enzyme. This article briefly reviews AmpC production in the Enterobacterales and attempts to answer questions that are commonly asked of the clinical microbiology laboratory.

Case Presentation A 47-year-old man with poorly controlled diabetes mellitus (glycosylated hemoglobin 12%) presented to the ED with a 1-week history of fevers, productive cough, and dyspnea. The patient was febrile and hypoxemic on presentation; laboratory testing was remarkable for hyperglycemia and ketoacidosis. The initial chest CT scan showed right lower lobe consolidation and ground-glass opacities ( Fig 1 A). He was admitted to the ICU and administered IV antibiotics (cefepime and vancomycin) for the treatment of community-acquired bacterial pneumonia.

Wounds are often recalcitrant to traditional wound dressings and a bioactive and biodegradable wound dressing using hydrogel membranes can be a promising approach for wound healing applications. The present research aimed to design hydrogel membranes based on hyaluronic acid, pullulan and polyvinyl alcohol and loaded with chitosan based cefepime nanoparticles for potential use in cutaneous wound healing. The developed membranes were evaluated using dynamic light scattering, proton nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy. The results indicated the novel crosslinking and thermal stability of the fabricated hydrogel membrane. The in vitro analysis demonstrates that the developed membrane has water vapors transmission rate (WVTR) between 2000 and 2500 g/m2/day and oxygen permeability between 7 and 14 mg/L, which lies in the range of an ideal dressing. The swelling capacity and surface porosity to liberate encapsulated drug (cefepime) in a sustained manner and 88% of drug release was observed. The cefepime loaded hydrogel membrane demonstrated a higher zone of inhibition against Staphylococcus aureus, Pseudomonas aeruginosa, and Escherichia coli and excisional rat model exhibit expeditious recovery rate. The developed hydrogel membrane loaded with cefepime nanoparticles is a promising approach for topical application and has greater potential for an accelerated wound healing process.

The spread of antibiotic resistance has been associated with consumption of food contaminated with pathogenic and non-pathogenic resistant bacteria. The objective of this study was to determine the prevalence of antibiotic resistant Escherichia coli isolates ( E. coli ) from local and imported retail raw chicken meat in Qatar. A total of 270 whole chicken carcasses locally-produced (chilled) and imported (chilled and frozen) were obtained from three different hypermarket stores in Qatar. A total of 216 E. coli isolates from the chicken samples were subjected to antibiotic susceptibility testing using disc diffusion method. Furthermore, extended-spectrum β-lactamase (ESBL) production was determined via double disc synergetic test. In addition, isolates harboring colistin resistant was determined using multiplex-PCR and DNA sequencing. Nearly 89% (192/216) of the isolates were resistant to at least one of the 18 antibiotics. In general, isolates from local and imported chicken carcasses showed relatively higher resistance to sulfamethoxazole (62%), tetracycline (59.7%), ampicillin and trimethoprim (52.3%), ciprofloxacin (47.7%), cephalothin, and colistin (31.9%). On the other hand, less resistance was recorded against amoxicillin/clavulanic acid (6%), ceftriaxone (5.1%), nitrofurantoin (4.2%) and piperacillin/tazobactam (4.2%), cefepime (2.3%), meropenem (1.4%), ertapenem (0.9%), and amikacin (0.9%). Nine isolates (4.2%) were ESBL producers. Furthermore, 63.4% (137/216) were multidrug resistant (MDR). The percentage of MDR, ESBL producers, and colistin-resistant isolates were significantly higher among local chilled isolates compared to imported chilled and frozen chicken samples. Our findings indicate the high antibiotic resistant E. coli prevalence in chicken meat sold at retail in Qatar.

Certain anaerobic bacteria are important for maintenance of gut barrier integrity and immune tolerance and may influence the risk of graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT). We conducted a single-center retrospective cohort study of allogeneic HSCT recipients to evaluate associations between receipt of antibiotics with an anaerobic spectrum of activity and GVHD outcomes. We identified 1214 children and adults who developed febrile neutropenia between 7 days before and 28 days after HSCT and compared GVHD risk and mortality among patients who received anaerobic antibiotics (piperacillin-tazobactam or carbapenems; n=491) to patients who received only antibiotics with minimal activity against anaerobes (aztreonam, cefepime, or ceftazidime; n=723). We performed metagenomic sequencing of serial fecal samples from 36 pediatric patients to compare the effects of specific antibiotics on the gut metagenome. Receipt of anaerobic antibiotics was associated with higher hazards of acute gut/liver GVHD (hazard ratio: 1.26; 95% confidence interval: 1.03–1.54) and acute GVHD mortality (hazard ratio: 1.63; 95% confidence interval: 1.08–2.46), but not chronic GVHD diagnosis (hazard ratio: 1.04; 95% confidence interval: 0.84–1.28) or chronic GVHD mortality (hazard ratio: 0.88; 95% confidence interval: 0.53–1.45). Anaerobic antibiotics resulted in decreased gut bacterial diversity, reduced abundances of Bifidobacteriales and Clostridiales, and loss of bacterial genes encoding butyrate biosynthesis enzymes from the gut metagenome. Acute gut/liver GVHD was preceded by a sharp decline in bacterial butyrate biosynthesis genes with antibiotic treatment. Our findings demonstrate that exposure to anaerobic antibiotics is associated with increased risks of acute gut/liver GVHD and acute GVHD mortality after allogeneic HSCT. Use of piperacillin-tazobactam or carbapenems should be reserved for febrile neutropenia cases in which anaerobic or multidrug-resistant infections are suspected.

Achromobacter xylosoxidans (A. xylosoxidans) is an aerobic gram-negative bacillus and often isolated from aquatic environments. It is supposed to cause infections in patients with malignancy or immunodeficiency. It causes various healthcare-associated infections, but cellulitis is rare. Herein, we report the first case of sever cellulitis by A. xylosoxidans after allogeneic hematopoietic stem cell transplantation (HSCT). A 49-year-old man underwent allogeneic HSCT from 8/8 HLA-matched unrelated donor with myeloablative conditioning for relapsed acute myeloid leukemia. He developed skin chronic graft versus host disease 11 months after HSCT. During the prolonged treatment with prednisolone and cyclosporine, he developed cellulitis on his left leg and admitted to our hospital. Blood and exudate culture revealed A. xylosoxidans. Although empirical therapy with cefepime was ineffective, his symptoms were dramatically improved after administration of meropenem. To our knowledge, this is the first case of A. xylosoxidans cellulitis after allogeneic HSCT. A. xylosoxidans should be considered as a possible cause of cellulitis in post-allogeneic HSCT patients on prolonged immunosuppressive therapy.

Purpose Neutropenic fever in a pediatric oncology patient necessitates emergent initiation of efficacious broad spectrum antibiotics. We have utilized cefepime+/-vancomycin in this context for over two decades, and sough to evaluate the efficacy of this combination at our institution and, if necessary, to identify an optimal alternative regimen. Methods Blood culture isolates from pediatric oncology patients were reviewed over 12 years. Antibiotic susceptibilities for all unique isolates were analyzed via minimum inhibitory concentration breakpoints and interpretive categories as per the Clinical and Laboratory Standards Institute M100/M45 manuals. Percentage susceptibility was calculated, antibiograms generated, and intraspecies antibiotic susceptibility comparisons made. Billing data was analyzed to identify the number of oncology patients admitted for fever during this interval. Results 697 unique isolates were identified: 188 Gram-negative and 509 Gram-positive (155 Gram-positive and 343 total isolates, excluding coagulase negative Staphylococcal (CONS) species). Cefepime and meropenem each covered 95.7% of tested Gram-negatives. Stenotrophomonas (Xanthomonas) maltophilia was the most resistant Gram-negative organism; no antibiotic covered all Gram-negatives. No antibiotic offered significantly improved coverage compared to cefepime. 96.0% of total tested Gram-positives were vancomycin-susceptible (including all CONS); resistant organisms included Enterococcus faecium and Enterococcus faecalis. Linezolid did not offer significantly improved coverage, while daptomycin did. Including and excluding CONS, 46.3% and 72.5% of total Gram-positive isolates were cefepime-sensitive. Blood cultures were positive in 33.7% of admissions. Central venous catheters were routinely utilized in this patient population. Prophylactic antibacterial agents were not utilized. Conclusions Cefepime+/-vancomycin remains efficacious as first-line empiric therapy for febrile neutropenia, with notable minor exceptions. Unit-specific surveillance of antibiotic resistance is warranted to ensure ongoing appropriate empiric antibiotic usage.

Background Acute kidney injury is a major complication of vancomycin treatment, especially when it is co-administered with other nephrotoxins. Objectives This meta-analysis aims to comparatively assess the nephrotoxicity of antipseudomonal β-lactams when combined with vancomycin. Data sources Medline, Scopus, CENTRAL and Clinicaltrials.gov databases were systematically searched from inception through 20 August 2019. Study eligibility criteria Studies evaluating acute kidney injury risk following the concurrent use of antipseudomonal β-lactams and vancomycin were selected. Participants Adult and paediatric patients treated in hospital or intensive care unit. Interventions Administration of vancomycin combined with any antipseudomonal β-lactam. Methods Acute kidney injury incidence was defined as the primary outcome. Secondary outcomes included severity, onset, duration, need of renal replacement therapy, length of hospitalization and mortality. Quality of evidence was assessed using the ROBINS-I tool and the Confidence In Network Meta-Analysis approach. Results Forty-seven cohort studies were included, with a total of 56 984 patients. In the adult population, the combination of piperacillin-tazobactam and vancomycin resulted in significantly higher nephrotoxicity rates than vancomycin monotherapy (odds ratio (OR) 2.05, 95% confidence intervals (CI) 1.17-3.46) and its concurrent use with meropenem (OR 1.84, 95% CI 1.02-3.10) or cefepime (OR 1.80, 95% CI 1.13-2.77). In paediatric patients, acute kidney injury was significantly higher with vancomycin plus piperacillin-tazobactam than vancomycin alone (OR 4.18, 95% CI 1.01-17.29) or vancomycin plus cefepime OR 3.71, 95% CI 1.08-11.24). No significant differences were estimated for the secondary outcomes. Credibility of outcomes was judged as moderate, mainly due to imprecision and inter-study heterogeneity. Conclusions The combination of vancomycin and piperacillin-tazobactam is associated with higher acute kidney injury rates than its parallel use with meropenem or cefepime. Current evidence is exclusively observational and is limited by inter-study heterogeneity. Randomized controlled trials are needed to verify these results and define preventive strategies to minimize nephrotoxicity risk.

Cefepime is known to exert bactericidal activity against Pseudomonas aeruginosa. Cefepime-induced neurotoxicity, most likely caused by increased exposure, has recently become a major concern in clinical practice; therefore, appropriate dose reduction of cefepime should be applied with respect to patients with low cefepime clearance (mostly eliminated by the kidneys). Here, we report a case in which Bayesian prediction-based therapeutic drug monitoring (Bayes-TDM) was effectively used to reduce the dose of cefepime in a patient with pneumonia to prevent neurotoxic complications. A woman (age: 59 years, body weight: 32.5 kg, serum creatinine concentration: 1.02 mg/dL) developed pneumonia caused by P. aeruginosa while receiving treatment for scleroderma and systemic lupus erythematosus. She started treatment with a dosing regimen of 1.0 g of cefepime every 8 h (day X). On day X+5, aphasia developed, and the serum cefepime concentration was 71.3 mg/L at trough. This concentration was twice or thrice higher than the reported safe concentration of cefepime (22 or 35 mg/L at trough). Therefore, we reduced the dose of cefepime to 0.5 g every 12 h using Bayes-TDM from day X+7. As a result, the severity of aphasia decreased by day X+10, and this dose was successfully continued up to day X+13 without further adjustment. In conclusion, individualizing doses by Bayes-TDM may be useful in preventing adverse effects associated with cefepime treatment.

Introduction The objective of this study was to analyse the susceptibility to antibiotic of Citrobacter freundii, Klebsiella aerogenes, Enterobacter cloacae, Serratia marcescens, Providencia stuartii and Morganella morganii (CESPM group), detected in urine cultures. Methods Between 2006 and 2016, we analysed CESPM group Enterobacteria isolated from urine cultures from both primary health-care centres and Hospital Virgen de las Nieves (Granada). We studied the susceptibility to aminoglycosides, fosfomycin, nitrofurantoin, quinolones, piperacillin/tazobactam, cefepime, imipenem and trimethoprim/sulfamethoxazole following CLSI interpretation criteria. Results A total of 736 isolates were studied: 30.57% E. cloacae, 23.50% M. morganii, 20.38% K. aerogenes, 10.32% C. freundii, 8.83% S. marcescens and 6.38% P. stuartii. A significant decrease in the antibiotic susceptibility was observed. Gentamicin, ciprofloxacin, imipenem and cefepime showed susceptibility over 80%. Conclusions E. cloacae, M. morganii and K. aerogenes were the most common isolates. Cefepime and imipenem are still a good empiric therapeutic alternative given its activity in vitro.

A wide range of intrinsic Acinetobacter-derived cephalosporinases (ADC) along with other carbapenemases has now been detected in Acinetobacter baumannii leaving clinicians with few treatment options. The present study reports the spread of ADC-30 co-producing KPC-2 along with other β-lactamases among carbapenem resistant A. baumannii strains obtained from ICU patients in two Indian hospitals. Primer extension analysis revealed higher transcript level of the ADC gene when induced with cefoxitin at 8 μg/ml (170 fold), ceftriaxone at 8 μg/ml (136 fold), ceftazidime at 4 μg/ml (65 fold), cefepime at 8 μg/ml (77 fold) and aztreonam at 8 μg/ml (21 fold) when compared with the basal level without antibiotic pressure. Slight increase in expression of blaADC-30 when induced with imipenem and meropenem at 0.25 μg/ml (3 and 6 fold) was observed and may help in conferring resistance to carbapenem. MLST analysis revealed the circulation of A. baumannii sequence types ST188, ST386, ST583 and ST390 in these hospitals.

Objectives This study aimed to compare the activity of ceftazidime–avibactam (C/A), ceftolozane–tazobactam (C/T) and three anti-pseudomonal β-lactams (piperacillin–tazobactam, ceftazidime and cefepime) against a collection of meropenem-non-susceptible Pseudomonas aeruginosa (P. aeruginosa) clinical isolates recovered from two centres in Turkey. Methods A total of 102 unique patient isolates of meropenem-non-susceptible P. aeruginosa were included in the study. MICs of antimicrobials were determined by the gradient diffusion method. Results Overall susceptibility rates for C/A and C/T were 83.3% and 82.4%, respectively. Both C/A and C/T had better activity than any one of the three anti-pseudomonal β-lactams. According to the MIC50 values, C/T was the most potent agent against isolates. Although the susceptibility rates of isolates to C/T and C/A were similar, C/T (MIC50, 1 μg/mL) was four-fold more potent than C/A (MIC50, 4 μg/mL). The MIC50 values of C/A and C/T for the isolates that were non-susceptible to three β-lactams were significantly higher than those for isolates that were non-susceptible to zero, one or two β-lactams. Also, the C/A MIC50 value for the isolates that were non-susceptible to two β-lactams was higher than that for isolates which were non-susceptible to one β-lactam. Conclusions C/A and C/T showed good activity against meropenem-non-susceptible P. aeruginosa isolates. However, resistance to these agents was not uncommon among these isolates. The overall β-lactam susceptibility profile of isolates seems to have an effect on the probability of susceptibility to C/A and C/T. Antimicrobial susceptibility testing should be performed for C/A and C/T if these agents are considered for treatment of infections caused by meropenem-non-susceptible P. aeruginosa.

Background Treatment of aspiration pneumonia is an important problem due to aging of populations worldwide. However, the effectiveness of cefepime in aspiration pneumonia has not yet been evaluated. Aim To compare the clinical efficacy and safety of cefepime and meropenem in patients with moderate-to-severe aspiration pneumonia. Methods In this open-label, randomized study, either cefepime 1 g or meropenem 0.5 g was administered intravenously every 8 h to patients with moderate-to-severe community-acquired or nursing-home acquired pneumonia at risk for aspiration for an average of 10.5 days. The primary outcome was the clinical response rate at the end of treatment (EOT) in the validated per-protocol (VPP)-population. Secondary outcomes were clinical response during treatment (days 4 and 7) and at the end of study (EOS) in the VPP-population, and survival at day 30 in the modified intention-to-treat (MITT)-population. Results There was no difference between the groups in the primary or secondary outcomes or safety. Significant improvement was observed in each group on day 4. Conclusion Cefepime is as effective and safe as meropenem in the treatment of moderate-to-severe aspiration pneumonia. Clinical trials identifier UMIN000001349.

El objetivo de nuestro estudio fue describir las características clínicoepidemiológicas de los pacientes pediátricos con diarrea por Aeromonas spp. y estudiar la sensibilidad antibiótica de dicho agente, a partir del análisis de casos ocurridos en un período de 7 a˜nos. Aeromonas caviae fue identificada en 93 muestras de heces recuperadas de ni˜nos, el 52,2% de ellos fueron varones y el 85,6% menores de 36 meses. La estación del a˜no con menor cantidad de aislamientos fue el invierno (14,4%). Hubo coinfección con otros microorganismos diarreogénicos en el 31,1% de esas muestras. El mayor número de muestras procedió del servicio de urgencias de nuestro hospital (45,6%). El 43,3% de los pacientes presentaron fiebre; el 87,8%, diarrea (43% con productos patológicos) y el 67,8%, vómitos. El 73,3% de los pacientes no precisó ingreso hospitalario. Se encontró una sensibilidad superior al 87% frente a trimetoprima-sulfametoxazol, ciprofloxacina, cefotaxima y cefepime. Todos los pacientes superaron el proceso infeccioso aun cuando el 63,3% no recibió ningún tratamiento antibiótico. Concluimos que el tratamiento antibiótico estaría indicado en casos seleccionados, cuando existe gravedad clínica. The aim of our study was to describe the epidemiological features of pediatricpatients with diarrhea caused by Aeromonas spp. and to study the antibiotic susceptibilityof this agent during a seven-year period. Aeromonas caviae was identified in 93 stool samplesfrom 52.2% males and 85.6% patients younger than 36 months. The season with the lowest num-ber of isolates was winter (14.4%). Co-infection with other diarrheagenic microorganisms wasobserved in 31.1% of the cases. The largest number of isolates was obtained from EmergencyDepartment samples (45.6%); 43.3% of the patients presented with fever, 87.8% with diarrhea(43% of these cases were associated with pathological products) and 67.8% with vomiting, while73.3% of the patients did not require hospital admission. Susceptibility higher than 87% wasobserved to trimethoprim-sulfamethoxazole, ciprofloxacin, cefotaxime and cefepime. All thepatients overcame the infectious process and 63.3% of them did not receive any antibiotic treat-ment during the process. A. caviae was the isolated species associated with intestinal infection.Antibiotic treatment would be specifically indicated in cases selected for their clinical severity.

In the era of antibiotic resistance, antimicrobial polymers represent state of the art innovation evolved to fight biofilm-associated infections. In the present study, novel self-disinfecting polyu...

Objectives Recently, multidrug-resistant (MDR) Gram-negative bacteria (GNB) have become a serious concern causing infections in hospitalised burn patients. This meta-analysis was conducted to detect the prevalence of infections caused by MDR-GNB in hospitalised burn patients in Iran. Methods An electronic search was performed using PubMed, Scopus, Web of Science, EMBASE and Iranian databases. Statistical analysis was performed using STATA13. According to the results of the heterogeneity test, a fixed- or random-effects model was used. Publication bias was detected based on Egger’s test. Of 1292 articles identified in the initial search, 107 studies were included in this review. Results According to the results, the lowest resistance rate was observed in Acinetobacter baumannii and Pseudomonas aeruginosa to colistin, estimated at 21% [95% confidence interval (CI) 2–49%; I2 = 97.30%] and 27% (95% CI 0–82%; I2 = 99.27%), respectively. Moreover, the highest rate was to cefepime, estimated 98% (95% CI 93–100%; I2 = 88.28%) and 87% (95% CI 81–92%; I2 = 96.27%). Conclusion The prevalence of MDR-GNB in Iranian burn patients is very high. Thus, a comprehensive infectious control programme, a reduction in the use of antibiotic prophylaxis, and thorough information regarding antimicrobial resistance patterns is required.

Background Enterobacter spp. are a common cause of nosocomial pneumonia and treatment can be complicated by AmpC resistance. Carbapenems are the treatment of choice; however, alternatives are needed. Cefepime has been shown to be non-inferior to carbapenems. There are limited data to support the use of piperacillin/tazobactam. The objective of this study was to determine if piperacillin/tazobactam is non-inferior to cefepime or ertapenem for Enterobacter pneumonia treatment. Objectives To compare the rate of clinical cure in patients with Enterobacter pneumonia receiving definitive treatment with piperacillin/tazobactam, cefepime, or ertapenem. Secondary outcomes included hospital mortality, infection-related length of stay, duration of mechanical ventilation, recurrent pneumonia, and resistance. Methods Retrospective, single-center study. Results Of 114 patients included, 59 received definitive treatment with piperacillin/tazobactam and 55 received cefepime or ertapenem. There was no difference in the proportion of patients who achieved clinical cure in the piperacillin/tazobactam group compared to the cefepime or ertapenem group (76.3% vs. 87.3%, P = 0.13). Treatment group was not associated with clinical cure when controlling for confounders in multivariable logistic regression (adjusted odds ratio [OR] 0.59, 95% confidence interval [CI] 0.15-2.37). The rate of recurrent pneumonia was 11.4% in the piperacillin/tazobactam group and 6.7% in the cefepime or ertapenem group (P = 0.48). Other secondary outcomes did not differ between the groups. Conclusions In this retrospective study of patients with Enterobacter pneumonia, clinical cure with piperacillin/tazobactam was comparable to that with cefepime or ertapenem; however, a prospective trial with a larger population is needed to determine if definitive treatment with piperacillin/tazobactam is non-inferior to definitive treatment with cefepime or ertapenem.

Background OXA-48 is an Ambler class D β-lactamase that hydrolyses penicillin and imipenem but has poor hydrolytic activity against cephalosporins. However, very few clinical experiences of treating extended-spectrum β-lactamase (ESBL)-negative OXA-48 producers with cephalosporins have been published. Objectives The aim of this study was to report clinical experience of infections due to ESBL-negative OXA-48-producing Klebsiella pneumoniae (K. pneumoniae) treated with cephalosporins. Patients and methods A retrospective study was conducted at Vall d’Hebron University Hospital, in Barcelona (Spain). It reviewed all microbiological isolates of OXA-48-producers that did not co-produce ESBL from May 2014 to May 2017, and included only clinical strains of patients treated with a cephalosporin for ≥72 h. Results From the 75 isolations of OXA-48 producers, there were 17 isolations of ESBL-negative OXA-48-producing K. pneumoniae. Three patients were treated with cephalosporins with successful outcomes: a pneumonia in a neutropenic patient treated with cefepime and amikacin; an acute focal nephritis of a renal graft treated with ceftriaxone; and an intrabdominal post-surgical infection treated with cefepime in combination with tigecycline at the beginning, and ciprofloxacin afterwards. Conclusions Cephalosporins could be an alternative treatment in selected patients with ESBL-negative OXA-48-producing K. pneumoniae infections, especially to avoid carbapenem use. However, it remains unknown if they should be given in combination.

Rationale & Objective Compared to combination therapy, intraperitoneal (IP) cefepime monotherapy for continuous ambulatory peritoneal dialysis (CAPD)-associated peritonitis may provide potential benefits in lowering staff burden, shortening time-consuming antibiotic preparation, and reducing bag contamination risk. This study sought to evaluate whether cefepime monotherapy is noninferior to combination regimens. Study Design Multicenter, open-label, noninferiority, randomized, controlled trial. Setting & Participants Adult incident peritoneal dialysis (PD) patients with CAPD-associated peritonitis in 8 PD centers in Thailand. Interventions Random assignment to either IP monotherapy of cefepime, 1g/d, or IP combination of cefazolin and ceftazidime, 1g/d, both given as continuous dosing. Outcomes Primary end point: resolution of peritonitis at day 10 (primary treatment response). Secondary outcomes: initial response (day 5), complete cure (relapse/recurrence-free response 28 days after treatment completion), relapsing/recurrent peritonitis, and death from any cause. Noninferiority would be confirmed for the primary outcome if the lower margin of the 1-sided 95% CI was not less than−10% for difference in the primary response rate. A 2-sided 90% CI was used to demonstrate the upper or lower border of the 1-sided 95% CI. Results There were 144 eligible patients with CAPD-associated peritonitis, of whom 70 and 74 patients were in the monotherapy and combination-therapy groups, respectively. Baseline demographic and clinical characteristics were not different between the groups. The primary response was 82.6% in the monotherapy group and 81.1% in the combination-therapy group (treatment difference, 1.5%; 90% CI, −9.1% to 12.1%; P=0.04). There was no significant difference in the monotherapy group compared with the combination-therapy group in terms of initial response rate (65.7% vs 60.8%; treatment difference, 4.9%; 95% CI, −10.8% to 20.6%; P=0.5) and complete cure rate (80.0% vs 80.6%; treatment difference, −0.6%; 95% CI, −13.9% to 12.8%; P=0.7). Relapsing and recurrent peritonitis occurred in 4.6% and 4.6% of the monotherapy group and 4.2% and 5.6% of the combination-therapy group (P=0.9and P=0.8, respectively). There was nominally higher all-cause mortality in the monotherapy group (7.1% vs 2.7%; treatment difference, 4.4%; 95% CI, −2.6% to 11.5%), but this difference was not statistically significant (P = 0.2). Limitation Not double blind. Conclusions IP cefepime monotherapy was noninferior to conventional combination therapy for resolution of CAPD-associated peritonitis at day 10 and may be a reasonable alternative first-line treatment. Funding This study is supported by The Kidney Foundation of Thailand (R5879), Thailand; Rachadaphiseksompotch Fund (RA56/006) and Rachadaphicseksompotch Endorsement Fund (CU-GRS_61_06_30_01), Chulalongkorn University, Thailand; National Research Council of Thailand (156/2560), Thailand; and Thailand Research Foundation (IRG5780017), Thailand. Trial Registration Registered at ClinicalTrials.gov with study number NCT02872038.

Intravenous fosfomycin is undergoing clinical development in the United States for treatment of complicated urinary tract infections (cUTIs) and may be prescribed as a component of dual antibiotic regimens against carbapenemase-producing Enterobacteriaceae (CPE). Fosfomycin, aztreonam, cefepime, ceftazidime, ceftazidime/avibactam, ceftolozane/tazobactam, meropenem, piperacillin/tazobactam, and tobramycin minimum inhibitory concentrations (MICs) were determined by gradient diffusion strip (GDS) against CPE isolates (N = 49). The GDS cross method was used to assess antibiotic interactions between fosfomycin and the aforementioned parenteral antibiotics. The resultant fractional inhibitory concentration index was used to classify interactions. Fosfomycin-containing combinations were evaluated only if nonsusceptible to the second agent. The fosfomycin MIC50 was ≥1024 mg/L by GDS. Synergy or additivity was detected in 80 (22%) fosfomycin-containing combinations. Antagonism was not observed. Ceftolozane/tazobactam most frequently displayed synergy [8 (16.3%) isolates]. When CPE are isolated, clinical laboratories should consider performing GDS synergy tests to identify favorable antibiotic interactions.

Background Gram-negative organisms (GNOs) have increasing resistance rates to levofloxacin at Virginia Commonwealth University Health System (VCUHS), where levofloxacin is the most common agent added to provide double coverage of gram-negative infections. The goal of this study was to determine the adequacy of empiric gram-negative coverage for septic patients at our institution. Methods A retrospective review of patients admitted to VCUHS, from January 1, 2014, to December 31, 2014, with a diagnosis of sepsis, severe sepsis, or septic shock and documented infection, was performed to determine the adequacy of various empiric antibiotic combinations. Results Of 219 patients who met the inclusion criteria, 56% of patients received monotherapy and 21% of patients received combination therapy (2 antibiotics) covering GNOs. GNOs (84%) were susceptible to piperacillin-tazobactam. When used in combination with cefepime and meropenem, levofloxacin did not increase coverage. However, levofloxacin provided an 8% increase in coverage and gentamicin provided an additional 13% increase in coverage, respectively, when used in combination with piperacillin-tazobactam. Conclusions Among septic patients at VCUHS, gentamicin provided increased gram-negative coverage when compared with levofloxacin. Although susceptibility to piperacillin-tazobactam alone was relatively low, the combination of piperacillin-tazobactam and gentamicin provided nearly equivalent coverage to meropenem and gentamicin.

Previous literature has attributed the use of certain antibiotics to Clostridioides difficile infection (CDI); however, the time from administration to CDI onset is not adequately evaluated. We aimed to determine the type of antibiotics and duration of therapy associated with the highest CDI incidence at a tertiary academic medical center. This was a retrospective, case-control study of adult inpatients who received at least one course of antibiotic treatment. Patients were divided into either cases or controls. For cases, their first episode of CDI was a determining factor. Primary outcome were the types of antibiotics associated with risk of CDI development and the median time of antibiotic usage defining this risk. Of 601 patients who developed CDI, 313 were included as cases while 150 of 291 who received antibiotics but did not develop CDI were included as controls. Cefepime and cefazolin were significantly associated with increased risk for CDI with odds ratios of 3.01 (95% CI, 1.96-4.65; P 0.001) and 1.71 (95% CI, 1.02-2.95; P 0.05), respectively. Cefepime was associated with CDI after a median time of 8 days while CDI may have occurred after 6 days of therapy with cefazolin. Use of antineoplastic agents was significantly associated with CDI (odds ratio, 2.32; 95% CI, 1.35-4.13; P 0.01). Antibiotic use increased the risk of CDI, particularly with cefepime and cefazolin with a median time to incidence of 8 and 6 days, respectively. CDI risk was also increased with the use of antineoplastic agents.

Cefepime is commonly used in pediatric intensive care units, where unpredictable variations in the patients' pharmacokinetic (PK) variables may require drug dose adjustments. The objectives of the present study were to build a population PK model for cefepime in critically ill children and to optimize individual initial dosing regimens.Children (aged from 1 month to 18 years; body weight3 kg) receiving cefepime were included. Cefepime total plasma concentrations were measured using high performance liquid chromatography. Data were modelled using nonlinear, mixed-effect modeling software, and Monte Carlo simulations were performed with a PK target of 100% fTFifty-nine patients (median (range) age: 13.5 months (1.1 months to 17.6 years)) and 129 cefepime concentration measurements were included. The cefepime concentration data were best fitted by a one-compartment model. The selected covariates were body weight with allometric scaling and estimated glomerular filtration rate on clearance. Mean population values for clearance and volume were 1.21 L/h and 4.8 L, respectively. According to the simulations, a regimen of 100 mg/kg/d q12 h over 30 min or 100 mg/kg/d as a continuous infusion was more likely to achieve the PK target in patients with renal failure and in patients with normal or augmented renal clearance, respectively.Appropriate cefepime dosing regimens should take renal function into account. Continuous infusions are required in critically ill children with normal or augmented renal clearance, while intermittent infusions are adequate for children with acute renal failure. Close therapeutic drug monitoring is mandatory, given cefepime's narrow therapeutic window.

Ochrobactrum anthropi is an opportunistic, low-virulence pathogen occasionally associated with human infections and found largely in immunocompromised patients and those with intravascular devices. We report the case of a healthy 70-year-old man who presented with an infection of the hand, who had no history of trauma but had been gardening for 4 months. Despite surgical debridement and empirical antibiotics, the infection could not be controlled. Cultures revealed O anthropi. Antibiotic treatment was adapted to intravenous cefepime for 15 days and the infection was finally controlled after a second surgery. Oral cotrimoxazole was continued for another 2 weeks. Ochrobactrum anthropi infection of the hand must be considered not only in immunosuppressed patients but also in healthy patients without intravascular devices. Local debridement and empiric antibiotic may be insufficient. Antibiotic therapy should follow susceptibility testing, but usually includes a broad-spectrum intravenous beta-lactam such as imipenem–cilastatin or cefepime, or oral cotrimoxazole or ciprofloxacin.

This study determined the pharmacokinetics of cefepime in patients requiring extracorporeal membrane oxygenation (ECMO) support to guide dosage selection. Cefepime population pharmacokinetics where characterized in Pmetrics for R for six critically ill patients receiving ECMO. Simulation was employed to determine the fTMIC and total trough concentration of varying regimens in each patient to evaluate ability to achieve optimal pharmacodynamic exposure and thresholds for cefepime-associated neurotoxicity. Of the six participants, two required continuous veno-venous hemodiafiltration (CVVHDF) while four had a CrCL between 92-199 ml/min. All patients received 2 g q8h as a 3h infusion. A two-compartment model fitted the data best with median (range) parameter estimates as follows: clearance, 5.99 (4.10-10.29) L/h; volume of central compartment, 10.08 (2.45-15.14) L; and intercompartment transfer constants (k

Multidrug-resistant Acinetobacter baumannii is a noteworthy nosocomial-pathogen and these pathogen-borne infections are difficult to treat. It is significant to make strain typing with WGS and to add new genome data to the literature. Therefore, in our study, we aimed to strain typing of the A. baumannii (A24) isolated from Turkey and reveal informations about ADC-73 β-lactamase.VITEK 2 system was used for the determination of antibiotic susceptibility. WGS was done on the Illumina NovaSeq 6000 platform. WGS results were analyzed with VFDB, ResFinder, PubMLST, IS Finder. Web-based bioinformatics software, homology modelling, molecular docking and dynamics simulations were used to determine all structural information about ADC-73 β-lactamase.A24 was found to be multidrug-resistant. Various virulence factors were found in A24. The sequence type of the isolate was determined as ST218. Genes encoding β-lactamase and aminoglycoside modifying enzymes, and IS elements were present in the genome of A24. Besides, secondary and 3D structures of ADC-73 were analyzed. Following, cefepime and imipenem were docked to ADC-56, ADC-68, and ADC-73 and interactions and stability of substrates were simulated. The binding-energies of imipenem to ADC-68 and ADC-73 were calculated -9.44 and -5.98 kcal/mol, respectively. Likewise, binding-energies of cefepime to ADC-56 and ADC-73 were calculated as -19.84 and -36.54 kcal/mol.A. baumannii ST218 isolate containing ADC-73 was reported for the first time in Turkey by WGS, and the effect of G225S mutation in this β-lactamase on conformational change and possible interactions with cefepime and impinem were investigated in silico.

Exposure to nephrotoxic medications is a common risk factor for acute kidney injury (AKI) in pediatric stem cell transplantation (SCT). We hypothesized that reducing nephrotoxic antimicrobial exposure for SCT patients would be associated with lower nephrotoxin-associated AKI (NTMx-AKI) rates and no increase in infection treatment failures. We conducted a prospective cohort analysis of all inpatient SCT patients at Cincinnati Children's Hospital Medical Center between January 2014 and December 2017. In January 2016, first line fever coverage was changed from piperacillin-tazobactam to cefepime, acknowledging that the change resulted in a loss of enterococcal coverage, and the duration of antimicrobial exposures was limited, specifically including vancomycin. We collected data using prospective NTMx-AKI and antimicrobial utilization monitoring platforms within the electronic health record. AKI days and severity were extracted for patients exposed to 3+ nephrotoxins, 3+ days of IV aminoglycosides, or 3+ days of IV vancomycin. AKI was identified using KDIGO serum creatinine criteria. We assessed rates of nephrotoxin exposure and NTMx-AKI in all SCT inpatients for 2 years pre- and post-intervention. Data were grouped and analyzed by calendar month, normalized to a denominator of 1000 patient-days. Statistical process control methods were used to monitor adherence to the intervention and identify changes in mean rate of nephrotoxin exposure and NTMx-AKI. Infection rates, alternate antimicrobial usage rates, and the fraction of repeat positive cultures were used to identify treatment failures. PTZ usage decreased from 196 to 33 days/1000 patient days, cefepime usage increased from 62 to 290 days/1000 patient days, and vancomycin usage decreased from 62 to 41 days/1000 patient days. High nephrotoxin exposure decreased by 33% (143 to 96 days/1000 patient days), and NTMx-AKI decreased by 74% (24 to 6 days/1000 patient days). Rates of all KDIGO stages of NTMx-AKI decreased ≥50% after the intervention. Stage 3, the most severe, decreased by >80%. The fraction of repeat positive cultures remained stable between the two eras at .1 (standard deviation 0.21) and .07 (standard deviation 0.17), respectively. There were no increases in infection rates, alternate antimicrobial usage rates, or treatment failures. Reduction of nephrotoxic antimicrobial exposure can decrease the amount and severity of NTMx-AKI in SCT patients without an increase in treatment failures.

Objectives Pseudomonas aeruginosa is an important aetiological agent causing pneumonia, urinary tract infections and bacteraemia. High antibiotic use in nosocomial settings and for immunocompromised conditions results in increasing multidrug resistance. This study analysed the antimicrobial resistance profile of P. aeruginosa isolates in an HIV setting. Methods A total of 7386 clinical specimens were collected from HIV patients attending YRG CARE from 2010–2017. P. aeruginosa isolated from clinical specimens were identified conventionally, and antimicrobial susceptibility testing was performed by the Kirby–Bauer disk diffusion method. Results A total of 260 P. aeruginosa strains were isolated, with 165 P. aeruginosa (63.5%) being isolated from hospitalised patients. A higher incidence of P. aeruginosa infection (25.8%) was observed in 2017, and most of the P. aeruginosa were isolated from sputum specimens (57.3%). A high level of resistance was noted to ceftazidime (49.6%), followed by ticarcillin (41.5%). Imipenem and meropenem resistance was observed in 15.0% and 16.9% of P. aeruginosa isolates, respectively. A high rate of imipenem resistance was noted in 2016 (46.2%) and a high rate of meropenem resistance was noted in 2017 (20.5%). An increasing resistance rate of P. aeruginosa was observed against aztreonam, cefepime, levofloxacin, meropenem, piperacillin, piperacillin/tazobactam, ticarcillin and tobramycin from 2010 to 2017. Conclusion A constant increase in drug-resistant P. aeruginosa isolates from HIV patients was observed from 2010 to 2017. Findings from this study urge the need for periodical monitoring and surveillance of the P. aeruginosa resistance profile, especially in hospitalised and immunocompromised patients in resource-limited settings.

Members of the viridans group streptococci (VGS) are the cause of local and invasive infections. Due to the severity of these infections and taking into account that reports regarding epidemiological aspects are scarce, the aims of this work were the identification and the study of the antibiotic susceptibility profiles of the isolates recovered from patients that were hospitalized in order to find out about the resistance level and the epidemiology of infections in which VGS are involved. A hundred and thirty two isolates identified as VGS were isolated at Hospital de Clínicas «José de San Martín» during the period 2011-2015. The identification was performed by biochemical test and mass spectrometry by Matrix Assisted Laser Desorption Ionization -Time of Flight Mass Spectrometry. Streptococcus anginosus group was prevalent (42%) followed by Streptococcus mitis group (33%). In the latter, isolates of Streptococcus pneumoniae were excluded. All the VGS isolates were susceptible to ertapenem, meropenem, linezolid and vancomycin; 25.8% were resistant (I+R) to penicillin, being prevalent in the S. mitis group. Regarding ceftriaxone and cefepime 96.9% of the isolates were susceptible. Only two isolates were resistant to levofloxacin, 27.2% to tetracycline and it was not found high level resistance to gentamycin (MIC range 0.5-32 μg/ml). Resistance to erythromycin was 17.4% with no significant difference between M and MLS phenotypes. The most active antibiotics were in addition to ceftriaxone and cefepime, vancomycin, ertapenem, meropenem and linezolid. These results highlight the importance of the continuous surveillance of the infections caused by VGS in order to predict a correct antibiotic therapy. Fil: Heine, Adriana C.. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: García, Susana. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Barberis, Claudia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Vay, Carlos Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina Fil: Mollerach, Marta Eugenia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina Fil: Bonofiglio, Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Microbiología, Inmunología y Biotecnología; Argentina Fil: Famiglietti, Ángela. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; Argentina

This study aimed to evaluate the in vitro synergy of polymyxin B (PMB) combined with 11 other antibiotics against PMB-resistant gram-negative bacilli (GNBs).Thirty-six clinical isolates of PMB-resistant GNBs were used. The MICs of all the antimicrobials tested were determined by the broth microdilution method and the checkerboard assay method. Carbapenemase genes were detected by PCR. In vitro synergy results were interpreted using the fractional inhibitory concentration index (FICI). Four combinations that showed positive interactions were subsequently evaluated in a time-kill study.Among the 36 strains, 15 harboured the carbapenemase gene, and blaKPC was the predominant carbapenemase. The resistance rates of the 36 strains to tigecycline, meropenem, ceftazidime, and cefepime were 100% (36/36), 97% (35/36), 94% (34/36), and 97% (35/36), respectively. For Enterobacteriaceae and Pseudomonas aeruginosa, the resistance rates to aztreonam and ceftazidime-avibactam (avibactam at a fixed concentration of 4 mg/L) were 95% (19/20) and 25% (5/20), respectively. The PMB-based combinations exhibited synergism to a certain degree. The most synergistic combinations were PMB plus meropenem-avibactam (avibactam at a fixed concentration of 4 mg/L) and PMB plus tigecycline, with the synergy rates of 83.3% and 80.6%, respectively. Compared to tazobactam- and sulbactam-based β-lactam-β-lactamase inhibitor combinations (BL-BLIs), PMB with avibactam-based BL-BLIs exhibited a better synergistic effect. For Acinetobacter baumannii, PMB plus sulbactam exhibited a strong synergism with a 2∼7-fold MIC reduction of PMB. In time-kill studies, the highest degree of synergism was observed for PMB with cefepime-avibactam on all the tested isolates. For isolates with low-level resistance to PMB, PMB combined with other partner antimicrobials also showed a certain degree of synergism.PMB in combination with tigecycline and avibactam-based BL-BLIs could be a potential clinical option for clinical treatment of infections caused by PMB -resistant GNBs.

Summary Pseudomonas aeruginosa is a common pathogen causing nosocomial infection. In particular, bloodstream infection (BSI) is associated with a high rate of morbidity and mortality. Ceftolozane/tazobactam is a new β-lactam/β-lactamase antimicrobial with activity against P. aeruginosa as well as multidrug resistant (MDR) Gram negative Enterobacteriaceae. Ceftolozane/tazobactam has frequently been used in salvage therapy for MDR P. aeruginosa infections. The aim of this study was to determine the activity of ceftolozane/tazobactam against P. aeruginosa isolates from BSIs collected from three clinical microbiology laboratories in Queensland, Australia, with a high proportion of isolates demonstrating β-lactam resistance. Antimicrobial susceptibility testing was performed by broth microdilution using custom made sensititre plates sourced from ThermoFisher Scientific. In addition to ceftolozane/tazobactam, we also tested piperacillin/tazobactam, ceftazidime, cefepime, meropenem, doripenem, imipenem, aztreonam, ciprofloxacin, levofloxacin, gentamicin, amikacin, tobramycin and colistin. Overall, ceftolozane/tazobactam was the most active agent tested [(MIC50/90 = 1/2 μg/mL, 96% susceptible (S)]. Against 44 isolates with resistance to at least one other β-lactam agent, 40 were susceptible to ceftolozane/tazobactam. Three ceftolozane/tazobactam resistant isolates were susceptible to colistin, with one of those isolates also susceptible to levofloxacin but not to any other antimicrobials tested. One ceftolozane/tazobactam resistant isolate was susceptible only to meropenem and doripenem but was non-susceptible to imipenem. An association was found between fluoroquinolone resistance and aminoglycoside resistance but not with β-lactam resistance. In summary, ceftolozane/tazobactam was active against most strains tested, including those resistant to other β-lactams. Laboratories should consider testing P. aeruginosa against ceftolozane/tazobactam in suspected MDR or extensively drug resistant (XDR) infections.

Micellization and related thermodynamic parameters of conventional cationic surfactants (cetyltrimethylammonium bromide and dodecyltrimethylammonium bromide) at different concentrations of cefepime (0.00, 0.001, 0.005, and 0.010 mol·kg−1) in aqueous medium have been thoroughly assessed by means of conductivity at different temperatures (293.15–313.15 K) and fluorescence spectroscopy at temperature 298.15 K. The thermodynamic data on micellization and degree of ionization have been obtained by conductometry. The effect of drug cefepime on the CMC (critical micelle concentration) and energetics of micellization of the surfactant has also been examined. From CMC values as a function of temperature, it is observed that micellization tendency of the surfactant increases in the presence of cefepime. The applicability of fluorescence spectroscopy to study cefepime/surfactant systems has also been investigated using pyrene as a probe. The interaction of cationic surfactant with the drug changes the micropolarity of ternary system as well as the micellar assembly of surfactant. The results have been rationalized in terms of physico-chemical concepts and relations. It would therefore, be interesting to evaluate the region of micelle formation in order to assess and develop surfactant immobilized cefepime for better biological activity.

Management of micro-organisms harbouring AmpC β-lactamases remains challenging. Carbapenems are often considered first-line agents. Due to growing concern regarding carbapenem-resistant Enterobacteriaceae, integrating non-carbapenem treatment strategies is being explored for these pathogens. The primary objective of this study was to evaluate clinical outcomes in patients with bacteraemia secondary to AmpC-producing organisms treated with cefepime or piperacillin/tazobactam (TZP). A retrospective study of adult patients receiving cefepime or TZP for the treatment of AmpC -producing organisms with positive cefoxitin screen (i.e. Citrobacter, Enterobacter or Serratia spp. along with cefoxitin resistance) isolated from blood cultures was conducted. The primary endpoint was clinical cure at end of therapy (EOT). Secondary endpoints included microbiological eradication, frequency of susceptibility changes following treatment, and 7- and 30-day all-cause mortality. Clinical cure at EOT was 87.1%, with 93.2% of patients achieving microbiological eradication. The 7- and 30-day mortality rates were 3.8% and 10.6%, respectively. Organism susceptibility was exceptionally high, with minimum inhibitory concentrations (MICs) of ≤2 μg/mL in 90% of patients treated with cefepime (n = 108). Selection for resistance to third-generation cephalosporins or primary antimicrobial therapy was infrequent at 6.1% (8/132). In conclusion, use of cefepime or TZP for management of AmpC bloodstream infections was associated with clinical and microbiological cure with infrequent selection for resistance.

Polymerized impurities in β-lactam antibiotics can induce allergic reaction, which seriously threaten the health of patients. In order to study the polymerized impurities in cefotaxime sodium and cefepime, a HPSEC method with TSK-gel G2000SWxl column and a RP-HPLC method with C18 column were established to replace the classical gel filtration chromatography with Sephadex G-10 gel as stationary phase. Two-dimensional (2D) liquid chromatography was employed to further investigate the HPSEC and RP-HPLC method and ion trap/time-of-flight mass spectrometry was applied to characterize the structures of polymerized impurities eluted from the two methods. The structures of the polymerized impurities in cefotaxime sodium and cefepime were deduced based on the MSn data, six of which were previously unknown. The corresponding relationship of impurities between the two methods was established, and the specificity of the two methods was compared. The results showed that the polymerized impurities in cefotaxime sodium and cefepime were co-eluted with other small molecular weight impurities with high polarity in HPSEC, leading to a poor specificity. The newly established RP-HPLC methods could effectively separate and detect polymerized impurities and were suitable for the quality control in daily analysis.

Cefepime is a first-line antibiotic for the treatment of febrile neutropenia (FN) in haematological cancer patients. Therapeutic drug monitoring (TDM) of cefepime is frequently advocated. However, it remains unclear what range of concentrations should be targeted for maximal efficacy and minimal toxicity. Therefore, we examined the relationship between cefepime exposure and clinical efficacy or neurotoxicity in FN patients. This prospective, observational, single-centre study included all adult hospitalised patients presenting with FN at the haematology ward and treated with cefepime from August 2019 until October 2020. Primary outcomes were incidence of breakthrough infection and neurotoxicity and their relationship with free cefepime serum trough concentrations. A total of 76 patients were included, contributing 96 cefepime treatment courses. The median (interquartile range) estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology Collaboration equation (eGFRCKD-EPI) and free cefepime trough concentration were 101 (85-112) mL/min/1.73m2 and 8.6 (4.9-16.2) mg/L, respectively. Interpatient and intrapatient variability in cefepime trough concentrations was largely explained by renal function. No cefepime-related breakthrough infections occurred during cefepime treatment. Neurotoxicity, probably induced by cefepime administration, occurred during 6/96 (6.3%) treatment courses. Patients with neurotoxicity showed a significant trend for higher trough concentrations (median 15.4 mg/L vs. 8.6 mg/L; P 1 mg/L.

Several composite cathodes were prepared using graphite, carbon nanotube (CNT) and PTFE, and their elemental composition, surface morphology, physical and electrochemical properties were studied by various characterization techniques. It was found that the hydrophobic property of the prepared cathodes could be greatly enhanced by changing their surface morphologies using polyurethane sponge in cathode-shaping, which successfully allowed the preparation of super-hydrophobic carbon cathode, resulting in the enhanced reduction of O2 to H2O2. Based on the above finding, a sandwich-like super-hydrophobic carbon cathode was fabricated and used in the electro-Fenton process for the degradation of cefepime. The recommended cathode exhibited an ideal performance for H2O2 electro-generation and a favorable stability. The cathode submerged in air-aeration solution (pH 3.0) has produced 376 mg L−1 H2O2 with an observed current efficiency (CE) of 40 % via the electrolysis of 60 min at the optimum potential. The developed electro-Fenton process presented the degradation efficiency of nearly 100 % within 10 min for 60 mg L−1 cefepime, in which the degradation of cefepime mainly depended on the generation of hydroxyl radicals (∙OH). The organic intermediates formed during cefepime degradation were identified and the degradation pathway was proposed. More over, the electro-Fenton degradation of cefepime evidently reduced the solution toxicity and improved the biodegradability, suggesting the electro-Fenton oxidation may be adopted as a pretreatment alternative prior to the biological treatment of cefepime-containing wastewater.