Long-term antibiotic exposure landscapes and resistant Escherichia coli colonization in a densely populated setting.

Antibiotic exposure is associated with resistant bacterial colonization, but this relationship can be obscured in community settings owing to horizontal bacterial transmission and broad distributions. Locality-level exposure estimates considering inhabitants' length of stay, exposure history, and exposure conditions of areas nearby could clarify these relationships. We used prescription data filled during 2010-2015 for 23 antibiotic types for members of georeferenced households in a population-based infectious disease surveillance platform. For each antibiotic and locality, we generated exposure estimates, expressed in defined daily doses (DDD) per 1000 inhabitant days of observation (IDO). We also estimated relevant environmental parameters, such as the distance of each locality to water, sanitation, and other amenities. We used data on ampicillin, ceftazidime, and trimethoprim-and-sulfamethoxazole resistant Escherichia coli colonization from stool cultures of asymptomatic individuals in randomly selected households. We tested exposure-colonization associations using permutation analysis of variance and logistic generalized linear mixed-effect models. Overall, exposure was highest for trimethoprim-sulfamethoxazole (1.8 DDD per 1000 IDO), followed by amoxicillin (0.7 DDD per 1000 IDO). Of 1,386 unique household samples from 195 locations tested between September 2015 and January 2016, 90%, 85% and 4% were colonized with E. coli resistant to trimethoprim and sulfamethoxazole, ampicillin, and ceftazidime, respectively. Ceftazidime-resistant E. coli colonization was common in areas with increased trimethoprim-sulfamethoxazole, cloxacillin, and erythromycin exposure. No association with any of the physical environmental variables was observed. We did not detect relationships between distribution patterns of ampicillin or trimethoprim-and-sulfamethoxazole resistant E. coli colonization and the risk factors assessed. Appropriate temporal and spatial scaling of raw antibiotic exposure data to account for evolution and ecological contexts of antibiotic resistance could clarify exposure-colonization relationships in community settings and inform community stewardship program.

Analysis of the Antimicrobial Activity of Epigallocatechin-3-Gallate (EGCG).

We studied antimicrobial activity of epigallocatechin-3-gallate (EGCG), a green tea polyphenolic catechin, and its combined use with ceftazidime (CAZ) against bacterial strains of Klebsiella pneumoniae. EGCG exhibited no activity against strains of K. pneumoniae with a different sensitivity to CAZ. However, for a "sensitive" strain, a decrease in minimum inhibitory concentration (MIC) of CAZ (from 0.064 to 0.023 mg/liter) was revealed when CAZ was co-administered with EGCG. For a "resistant" stain, MIC of CAZ remained high, but activation of EGCG at its high concentrations was observed. Indirect evidence of antimicrobial effect of EGCG co-administered with CAZ on Klebsiella was obtained.

Molecular characterization of carbapenem and ceftazidime-avibactam-resistant Enterobacterales and horizontal spread of bla NDM-5 gene at a Lebanese medical center.

Introduction: In the battle against multidrug-resistant bacterial infections, ceftazidime- avibactam (CZA) stands as a pivotal defense, particularly against carbapenemresistant (CR) Gram-negative pathogens. However, the rise in resistance against this drug poses a significant threat to its effectiveness, highlighting the critical need for in-depth studies about its resistance mechanisms. Methods: This research focuses on the genomic characterization of CR- and CZA-resistant Escherichia coli (n=26) and Klebsiella pneumoniae (n=34) strains, harboring the blaNDM and/or blaOXA-48-like genes, at a major Lebanese tertiary care medical center, using whole genome sequencing (WGS). Results: Our findings revealed a notable prevalence of blaNDM in all K. pneumoniae strains isolates, with 27 of these also harboring blaOXA-48. On the other hand, E. coli strains predominantly carried the blaNDM-5 gene. Whole genome sequencing (WGS) identified a predominance of ST383 among K. pneumoniae strains, which possessed a multi-replicon IncFIB-IncHI1B plasmid harboring the blaNDM-5. Additionally, various Inc group plasmids in K. pneumoniae across multiple sequence types were found to carry the blaNDM. Similarly, diverse STs of E. coli were observed to carry blaNDM-5 on different plasmids. Discussion: The study underscores NDM carbapenemases as a paramount resistance mechanism in Lebanon,jeopardizing critical last-resort treatments. It also illuminates the role of varied sequence types and mobile genetic elements in the spread of NDM resistance,stressing the urgent need for strategies to mitigate this threat, especially in nosocomial infections.

Evolution of blaKPC Under the Pressure of Carbapenems and Ceftazidime/Avibactam in a Patient With Persistent Bacteremia Caused by Klebsiella pneumoniae.

A 30-year-old Korean man with myelodysplastic syndrome admitted hospital due to undifferentiated fever and recurrent skin lesions. He received combination therapy with high doses of meropenem, tigecycline and amikacin, yielding carbapenem resistant Klebsiella pneumoniae (CRKP) harboring K. pneumoniae carbapenemase (KPC)-2 from blood cultures on hospital day (HD) 23. Ceftazidime/avibactam was started at HD 37 and CRKP was eradicated from blood cultures after 5 days. However, ceftazidime/avibactam-resistant CRKP carrying KPC-44 emerged after 26 days of ceftazidime/avibactam treatment and then ceftazidime/avibactam-resistant, carbapenem-susceptible K. pneumoniae carrying KPC-135 was isolated on HD 65. The 3-D homology of KPC protein showed that hot spot changes in the omega loop could be attributed to ceftazidime/avibactam resistance and loss of carbapenem resistance. Whole genome sequencing of serial isolates supported that phenotypic variation was due to clonal evolution than clonal replacement. The treatment regimen was changed from CAZ/AVI to meropenem-based therapy (meropenem 1 g iv q 8 hours and amikacin 600 mg iv per day) starting with HD 72. CAZ/AVI-susceptible CRKP was presented again from blood cultures on HD 84, and the patient expired on HD 85. This is the first Korean report on the acquisition of ceftazidime/avibactam resistance through the emergence of blaKPC variants.

Whole genome sequencing analysis of seven unknown resistance mechanisms of carbapenem-resistant Klebsiella pneumoniae strains resistance to ceftazidime-avibactam.

AIMS: To investigate alternative resistance mechanisms among seven ceftazidime-avibactam (CZA)-resistant carbapenem-resistant Klebsiella pneumoniae (CRKP) strains lacking common antimicrobial resistance genes (ARGs) using whole genome sequencing. METHODS AND RESULTS: ARG and virulence factors (VFs) were screened using the ARG database CARD and the VF database, respectively, and identified using genomic annotation data with BLAST+. Six strains were ST11 sequence types (STs), and one was ST2123. ST11 strains harbored more ARGs than the ST2123 strains. All seven strains carried multiple ARGs with efflux-mediated antibiotic resistance, including oqxA, oqxB, tet (A), qacEdltal, CRP, H-NS, Kpn-E, F, G, H, acrA, LptD, acrB, acrD, cpxA, mdtB, and mdtC. These efflux-mediated ARGs were identified in most strains and even all strains. Whole genome sequencing revealed that the ST11 strain carried multiple potential prophages, genomic islands, and integrative and conjugative elements, while the ST2123 strain carried an independent potential prophages and a genomic island. CONCLUSIONS: Whole genome sequencing analysis revealed that these seven CZA-resistant CRKP strains lacking common ARGs exhibited efflux-mediated antibiotic resistance-associated ARGs. The main mechanism by which CRKP resists CZA is antibiotic inactivation. Except for tet (A), no ARGs and validation experiments related to efflux were found. This study's results provide a new possibility for the resistance mechanism of CRKP to CZA, and we will verify this conclusion through experiments in the future.

Ceftazidime/avibactam resistance is associated with PER-3-producing ST309 lineage in Chilean clinical isolates of non-carbapenemase producing Pseudomonas aeruginosa.

Introduction: Ceftazidime/avibactam (CZA) is indicated against multidrug-resistant Pseudomonas aeruginosa, particularly those that are carbapenem resistant. CZA resistance in P. aeruginosa producing PER, a class A extended-spectrum ß-lactamase, has been well documented in vitro. However, data regarding clinical isolates are scarce. Our aim was to analyze the contribution of PER to CZA resistance in non-carbapenemase-producing P. aeruginosa clinical isolates that were ceftazidime and/or carbapenem non-susceptible. Methods: Antimicrobial susceptibility was determined through agar dilution and broth microdilution, while bla PER gene was screened through PCR. All PER-positive isolates and five PER-negative isolates were analyzed through Whole Genome Sequencing. The mutational resistome associated to CZA resistance was determined through sequence analysis of genes coding for PBPs 1b, 3 and 4, MexAB-OprM regulators MexZ, MexR, NalC and NalD, AmpC regulators AmpD and AmpR, and OprD porin. Loss of bla PER-3 gene was induced in a PER-positive isolate by successive passages at 43°C without antibiotics. Results: Twenty-six of 287 isolates studied (9.1%) were CZA-resistant. Thirteen of 26 CZA-resistant isolates (50%) carried bla PER. One isolate carried bla PER but was CZA-susceptible. PER-producing isolates had significantly higher MICs for CZA, amikacin, gentamicin, ceftazidime, meropenem and ciprofloxacin than non-PER-producing isolates. All PER-producing isolates were ST309 and their bla PER-3 gene was associated to ISCR1, an insertion sequence known to mobilize adjacent DNA. PER-negative isolates were classified as ST41, ST235 (two isolates), ST395 and ST253. PER-negative isolates carried genes for narrow-spectrum ß-lactamases and the mutational resistome showed that all isolates had one major alteration in at least one of the genes analyzed. Loss of bla PER-3 gene restored susceptibility to CZA, ceftolozane/tazobactam and other ß-lactamsin the in vitro evolved isolate. Discussion: PER-3-producing ST309 P. aeruginosa is a successful multidrug-resistant clone with blaPER-3 gene implicated in resistance to CZA and other ß-lactams.

Impact of extended-spectrum chromosomal AmpC (ESAC) of Escherichia coli on susceptibility to cefiderocol.

The impact of chromosomally encoded wild-type or extended-spectrum (ESAC) AmpC ß-lactamases of Escherichia coli on susceptibility to ceftazidime, cefepime, and cefiderocol was evaluated in different genetic backgrounds, including wild-type, PBP3-modified, and porin-deficient E. coli strains. Recombinant E. coli strains possessing the different backgrounds and producing variable ESACs were evaluated. Although ESAC enzymes conferred resistance to ceftazidime and decreased susceptibility to cefepime as expected, we showed here that cefiderocol was also a substrate of ESAC enzymes. IMPORTANCE: We showed here that chromosomally encoded intrinsic extended-spectrum cephalosporinases of Escherichia coli may impact susceptibility not only to ceftazidime and cefepime but also to cefiderocol.

Efficacy of ceftazidime/avibactam and plazomicin on carbapenem-resistant Klebsiella pneumoniae and Escherichia coli.

Carbapenem-resistant Enterobacterales (CRE) have become a major public health problem worldwide. The aim of this study was to investigate efficacy of ceftazidime/avibactam and plazomicin on carbapenem-resistant Klebsiella pneumoniae and Escherichia coli isolates. Susceptibility of imipenem, meropenem, ertapenem, ceftazidime/avibactam and plazomicin was investigated by broth-microdilution method. Major carbapenemases NDM, VIM, IMP, KPC, OXA-48 as well as other ß-lactamases namely, TEM, SHV, OXA-1-like, CTX-M, ACC, FOX, MOX, DHA, CIT, EBC, VEB, GES, PER were investigated by PCR. A total of 120 carbapenem-resistant isolates (60 E. coli and 60 K. pneumoniae) were included in this study and blaOXA-48-like was found in 78.33%, blaNDM in 26.66%, blaKPC in 7.5%, blaIMP in 5.83%, and blaVIM in 5%. Among 94 isolates with the blaOXA-48-like gene, 22.3% were resistant to ceftazidime/avibactam and 51.1% were resistant to plazomicin. Of 32 isolates with blaNDM, 31 (96.9%) were resistant to ceftazidime/avibactam and 30 (93.75%) were resistant to plazomicin, and both antibiotics had limited effects against blaNDM carriers (P < 0.001). Of the 12 isolates with blaNDM+OXA-48 combination, 11 (91.7%) were resistant to ceftazidime/avibactam and plazomicin. The effect of both antibiotics was significantly lower in strains with blaNDM+OXA-48 combination (P < 0.005).The most common carbapenemase genes in this study were blaOXA-48-like and blaNDM. Ceftazidime/avibactam demonstrated a good efficacy among OXA-48 producing K. pneumoniae and E. coli, however, plazomicin had a significantly lower antibacterial effect in our study. Both antimicrobial agents should be considered as an option by evaluating combined susceptibility results and gene patterns obtained by regional and global molecular data in the treatment of CRE infections.

Confronting multidrug-resistant Klebsiella meningitis after mid-clival Cerebrospinal Fluid leak repair: a therapeutic odyssey.

A man in his 40s with type 2 diabetes mellitus had persistent right-sided watery nasal discharge for 6 months following cerebrospinal fluid (CSF) leak repair at another hospital, prompting his visit to us due to recurring symptoms. Imaging revealed a CSF leak from the mid-clivus for which revision endoscopic CSF leak repair was done. Regrettably, he developed postoperative meningitis caused by multidrug-resistant (MDR) Klebsiella pneumoniaeManaging this complex case was a challenging task due to the pathogen's resistance to conventional drugs and the scarcity of scientific evidence. We initiated a culture-guided combination regimen with ceftazidime, avibactam, aztreonam and tigecycline. This decision stemmed from meticulous literature review and observed antibiotic synergy while testing for this organism.After 4 weeks of vigilant treatment, the patient's symptoms improved significantly, and CSF cultures were sterile. We present our approach to effectively confront and manage a challenging instance of postoperative MDR bacterial meningitis.

A rare case of successful treatment of peritoneal dialysis patient with Serratia marcescens peritonitis without catheter removal: case report and literature review.

Serratia marcescens, as a Gram-negative opportunistic pathogen, is a rare cause of peritonitis and has worse clinical outcomes than Gram-positive peritonitis. In this case report, we describe a case of Serratia marcescens associated peritonitis that was successfully cured without catheter removal. A 40-year-old male patient with peritoneal dialysis who worked in the catering industry was admitted to the hospital for 16 hours after the discovery of cloudy peritoneal dialysate and abdominal pain. Ceftazidime and cefazolin sodium were immediately given intravenously as an empirical antibiotic regimen. After detecting Serratia marcescens in the peritoneal diasate culture, the treatment was switched to ceftazidime and levofloxacin. The routine examination of peritoneal dialysate showed a significant decrease in white blood cells, the peritoneal dialysate became clear, and the peritoneal dialysis catheter was retained. The patient was treated for 2 weeks and treated with oral antibiotics for 1 week. It is necessary to further strengthen the hygiene of work environment to prevent Serratia marcescens infection in peritoneal dialysis patients. We recommend that patients with Serratia marcescens associated peritonitis should be treated with a combination of antibiotics as early as possible empirically, and at the same time, the peritoneal dialysis fluid culture should be improved, and the antibiotic regimen should be timely adjusted according to the drug sensitivity results. For patients with clinical symptoms for more than 3 days, considering the strong virulence of Serratia marcescens, whether to use meropenem directly or not can provide a reference for clinical decision-making. Further clinical studies are needed to achieve more precise anti-infective treatment.

Molecular mechanisms responsible KPC-135-mediated resistance to ceftazidime-avibactam in ST11-K47 hypervirulent Klebsiella pneumoniae.

Ceftazidime-avibactam resistance attributable to the blaKPC-2 gene mutation is increasingly documented in clinical settings. In this study, we characterized the mechanisms leading to the development of ceftazidime-avibactam resistance in ST11-K47 hypervirulent Klebsiella pneumoniae that harboured the blaKPC-135 gene. This strain possessed fimbriae and biofilm, demonstrating pathogenicity. Compared with the wild-type KPC-2 carbapenemase, the novel KPC-135 enzyme exhibited a deletion of Glu168 and Leu169 and a 15-amino acid tandem repeat between Val262 and Ala276. The blaKPC-135 gene was located within the Tn6296 transposon truncated by IS26 and carried on an IncFII/IncR-type plasmid. Compared to the blaKPC-2-positive cloned strain, only the MIC of ceftazidime increased against blaKPC-135-positive K. pneumoniae and wasn't inhibited by avibactam (MIC 32 µg/mL), while clavulanic acid and vaborbactam demonstrated some inhibition. Kinetic parameters revealed that KPC-135 exhibited a lower Km and kcat/Km with ceftazidime and carbapenems, and a higher (∼26-fold) 50% inhibitory concentration with avibactam compared to KPC-2. The KPC-135 enzyme exerted a detrimental effect on fitness relative to the wild-type strain. Furthermore, this strain possessed hypervirulent determinants, which included the IncHI1B/FIB plasmid with rmpA2 and expression of type 1 and 3 fimbriae. In conclusion, we reported a novel KPC variant, KPC-135, in a clinical ST11-K47 hypervirulent K. pneumoniae strain, which conferred ceftazidime-avibactam resistance, possibly through increased ceftazidime affinity and decreased avibactam susceptibility. This strain simultaneously harboured resistance and virulence genes, posing an elevated challenge in clinical treatment.

Ceftazidime Poloxamer Gel: Expanding the Therapeutic Armamentarium for Ciprofloxacin-Resistant Pseudomonas Mastoid Cavity Otorrhea.

OBJECTIVE: To present and evaluate the treatment of ciprofloxacin-resistant Pseudomonas mastoid cavity otorrhea with a ceftazidime thermosensitive poloxamer gel. STUDY DESIGN: A retrospective clinical capsule report. PATIENTS: Three patients diagnosed with ciprofloxacin-resistant Pseudomonas otorrhea in the setting of a previous canal-wall-down mastoidectomy between March 2019 and June 2023 visiting our tertiary care institution were retrospectively reviewed. INTERVENTION: Application of a 2% ceftazidime thermosensitive poloxamer gel to mastoid cavity. MAIN OUTCOME MEASURES: No evidence of disease during microscopic inspection of the ear within a month of initial treatment or bacterial eradication on subsequent culture. RESULTS: Two patients had complete resolution of symptoms and achieved a safe and dry ear after topical application of the hydrogel. The second patient had pseudomonal eradication on culture, but persistent otorrhea due to other multidrug-resistant bacteria and an anatomically unfavorable mastoid cavity, which ultimately resolved after revision surgery. CONCLUSIONS: This small case series suggests that topical treatment of mastoid cavity otorrhea with a 2% ceftazidime poloxomer gel is a potential therapeutic avenue in patients with ciprofloxacin-resistant Pseudomonas .

First report of KPC variants conferring ceftazidime-avibactam resistance in Colombia: introducing KPC-197.

Resistance to ceftazidime-avibactam (CZA) due to Klebsiella pneumoniae carbapenemase (KPC) variants is increasing worldwide. We characterized two CZA-resistant clinical Klebsiella pneumoniae strains by antimicrobial susceptibility test, conjugation assays, and WGS. Isolates belonged to ST258 and ST45, and produced a KPC-31 and a novel variant KPC-197, respectively. The novel KPC variant presents a deletion of two amino acids on the Ω-loop (del_168-169_EL) and an insertion of two amino acids in position 274 (Ins_274_DS). Continued surveillance of KPC variants conferring CZA resistance in Colombia is warranted. IMPORTANCE: Latin America and the Caribbean is an endemic region for carbapenemases. Increasingly high rates of Klebsiella pneumoniae carbapenemase (KPC) have established ceftazidime-avibactam (CZA) as an essential antimicrobial for the treatment of infections due to MDR Gram-negative pathogens. Although other countries in the region have reported the emergence of CZA-resistant KPC variants, this is the first description of such enzymes in Colombia. This finding warrants active surveillance, as dissemination of these variants could have devastating public health consequences.

Ceftazidime-Avibactam resistance in clinical isolates of carbapenem-resistant Klebsiella pneumoniae: A phenotypic and genotypic analysis.

OBJECTIVE: To find the prevalence of Ceftazidime-Avibactam (CAZ-AVI) resistant Klebsiella pneumoniae in clinical isolates and to determine the genes responsible for Ceftazidime-Avibactam resistance using PCR. METHODS: A total of 89 carbapenem resistant Klebsiella pneumoniae from various clinical samples were included in the study. CAZ-AVI resistance was tested using E-test. CAZ-AVI resistant strains were subjected to conventional PCR for detection of carbapenamase genes blaNDM- 1, blaOXA-48, blaVIM, blaIMP, blaKPC. RESULTS: Of the 89 isolates screened for CAZ-AVI resistance, 45(50.5%) isolates were found to be resistant. 42 isolates were subjected to PCR for detection of ß lactamase genes.34 isolates were positive for blaNDM-1 and all 42 isolates were positive for blaOXA-48. Co-expression of NDM-1 and OXA-48 was seen in 34 isolates. Sensitivity of mCIM test to identify a carbapenamse compared to PCR was 61.9%. Sensitivity of eCIM test to identify NDM-1 was 80%. CONCLUSION: CAZ-AVI was effective in vitro in 49.4% of the isolates. Indicating that CAZ-AVI is a promising addition to antibiotics against CRE as well as a carbapenem sparing drug in ESBL producing organisms. ß-Lactamase-related mutations are the main mechanism leading to CAZ-AVI resistance.

Species distribution and antimicrobial susceptibility of Burkholderia cepacia complex isolates in clinical infections: Experience from a tertiary care hospital, Southern India.

PURPOSE: Burkholderia cepacia complex (Bcc) is a diverse group of environmental bacteria associated with opportunistic infections. The identification of Bcc using conventional methods poses challenges. Bcc infections are difficult to treat due to intrinsic antibiotic resistance. The study aimed to investigate the species distribution and antimicrobial susceptibility of clinical Bcc isolates. METHODS: A total of 153 Bcc isolates obtained from clinical samples were analysed. Species identification was carried out using automated methods, including MALDI-TOF MS and VITEK2. Antimicrobial susceptibility testing was performed using the disc diffusion method. RESULTS: Burkholderia cenocepacia (70.5%) emerged as the most prevalent species, followed by Burkholderia contaminans (9.8%) and Burkholderia cepacia (7.2%). Ventilator-associated pneumonia (38.6%) was the most common infection, followed by sepsis (28.1%). Co-existence of Bcc with other pathogens in many cases suggested potential co-infection scenarios. Antimicrobial susceptibility revealed that ceftazidime, co-trimoxazole and meropenem were the most effective drugs, while levofloxacin proved to be the least effective. Moderate susceptibility was noted to minocycline, with 4.6% of isolates exhibiting multi-drug resistance. CONCLUSION: This study provides valuable insights into the prevalence, clinical associations, and antibiotic susceptibility of Bcc in India. It highlights the importance of Bcc as a nosocomial pathogen, especially in vulnerable patient populations. The findings contribute to understanding Bcc infections, their distribution, and emphasize the necessity for accurate identification methods in clinical settings.

Fuzheng Touxie Jiedu Huayu Decoction inhibits the MexAB-OprM efflux pump and quorum sensing-mediated biofilm formation in difficult-to-treat multidrug resistance Pseudomonas aeruginosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzheng Touxie Jiedu Huayu Decoction (FTJHD) is a commonly used clinical formula that has been found effective in resisting multidrug resistance-Pseudomonas aeruginosa in previous in vivo and in vitro studies. AIM OF THE STUDY: To investigate the antimicrobial effects of FTJHD and its drug-containing serum alone or in combination with ceftazidime on difficult-to-treat multidrug resistance-P. aeruginosa (DTMDR-P. aeruginosa). MATERIALS AND METHODS: The antibacterial effects of FTJHD and its drug-containing alone or in combination with ceftazidime against DTMDR-P. aeruginosa were examined by the tube dilution method and bacterial growth curves. The changes in the bacterial ultrastructure were examined by transmission electron microscopy. The biofilm formation ability of bacteria was examined by crystal violet staining and scanning electron microscopy. The expression of the MexAB-OprM efflux pump and quorum sensing system genes were validated through quantitative polymerase chain reaction. Molecular docking was used to evaluate the interaction between active components and the MexAB-OprM efflux pump. RESULTS: FTJHD-containing serums at 1-, 2-, 4-, and 8-fold concentrations reduced the minimal inhibitory concentration (MIC) of ceftazidime against DTMDR-P. aeruginosa from 128 µg/mL to 64 µg/mL. Sub-inhibitory concentrations of ceftazidime in combination with FTJHD and FTJHD-containing serum prolonged the lag period of bacterial growth and reduced bacterial numbers. Additionally, 1/2 MIC of ceftazidime combined with FTJHD-containing serum significantly inhibited the activity of the MexAB-OprM efflux pump and quorum sensing system, thus reducing biofilm formation while causing more severe damage to the bacteria. Molecular docking revealed a strong affinity of quercetin, baicalein, luteolin, kaempferol, and ß-sitosterol for the efflux pump regulatory proteins OprM and MexR. CONCLUSION: FTJHD can exert synergistic anti-DTMDR-P. aeruginosa effects with ceftazidime by inhibiting biofilm formation mediated by the MexAB-OprM efflux pump and quorum sensing.

Clinical characteristics and antibiotic treatment of peritoneal dialysis-associated peritonitis caused by Pseudomonas species: a review of 15 years' experience from southern China.

Pseudomonas can lead to peritoneal dialysis-associated peritonitis, which is characterized by a poor prognosis, such as a substantial failure rate and a high death rate. This study aimed to provide an overview of Pseudomonas peritonitis's clinical features, the regimens of antibiotic, antibiotic resistance, and outcomes in peritoneal dialysis (PD) patients. This study observed patients with Pseudomonas peritonitis in two large PD centers in South China from January 2008 to December 2022. The demographics, symptomatology, antibiotics regimens, resistance to common antibiotics, and clinical outcomes of all included patients were reviewed. A total of 3,459 PD patients were included, among them 57 cases of peritonitis caused by Pseudomonas, including 48 cases (84.2%) of Pseudomonas aeruginosa. The incidence rate of Pseudomonas peritonitis was 0.0041 episode per patient-year. Of them, 28.1% (16 cases) of the patients were accompanied by exit site infection (ESI), and all had abdominal pain and turbid ascites at the time of onset. The most commonly used antibiotic combination was ceftazidime combined with amikacin. Approximately 89% of Pseudomonas species were sensitive to ceftazidime, and 88% were sensitive to amikacin. The overall primary response rate was 28.1% (16 patients), and the complete cure rate was 40.4% (23 patients). There was no significant difference in the complete cure rate of peritonitis using three and other antibiotic treatment regimens (44.8% vs 46.4%; P = 0.9). The successful treatment group had higher baseline albumin level (35.9 ± 6.2; P = 0.008) and residual urine volume (650.7 ± 375.5; P = 0.04). Although the incidence of peritonitis caused by Pseudomonas was low, the symptoms were serious, and prognosis was very poor. Pseudomonas was still highly susceptible to first-line antibiotics currently in use against Gram-negative bacteria. Patients with successful treatment had higher albumin levels and higher urine output. IMPORTANCE: Although the incidence of peritoneal dialysis-associated peritonitis caused by Pseudomonas is very low, it seriously affects the technique survival of peritoneal dialysis patients. However, there are few studies and reports on Pseudomonas peritonitis in the Chinese mainland area. Therefore, the purpose of this study is to describe the clinical characteristics, the regimens of antibiotic, drug resistance, and outcome of peritoneal dialysis patients in southern China in the past 15 years and summarize the clinical experience in the treatment of Pseudomonas peritonitis.

Effect of ceftazidime-avibactam combined with different antimicrobials against carbapenem-resistant Klebsiella pneumoniae.

This study aimed to assess the in vitro efficacy of ceftazidime-avibactam (CZA) in combination with various antimicrobial agents against carbapenem-resistant Klebsiella pneumoniae (CRKP). We selected 59 clinical CRKP isolates containing distinct drug resistance mechanisms. The minimum inhibitory concentrations (MICs) of meropenem (MEM), colistin (COL), eravacycline (ERA), amikacin (AK), fosfomycin (FOS), and aztreonam (ATM), both individually and in combination with CZA, were tested using the checkerboard method. The interactions of antimicrobial agent combinations were assessed by fractional inhibitory concentration index (FICI) and susceptible breakpoint index (SBPI). The time-kill curve assay was employed to dynamically evaluate the effects of these drugs alone and in combination format. In the checkerboard assay, the combination of CZA+MEM showed the highest level of synergistic effect against both KPC-producing and carbapenemase-non-producing isolates, with synergy rates of 91.3% and 100%, respectively. Following closely was the combination of FOS+CZA . For metallo-beta-lactamases (MBLs) producing strains, ATM+CZA displayed complete synergy, while the combination of MEM+CZA showed a synergy rate of only 57.14% for NDM-producing strains and 91.67% for IMP-producing strains. In the time-kill assay, MEM+CZA also demonstrated significant synergistic effects against the two KPC-2-producing isolates (Y070 and L70), the two carbapenemase-non-producing isolates (Y083 and L093), and the NDM-1-producing strain L13, with reductions in log10 CFU/mL exceeding 10 compared to the control. Against the IMP-producing strain Y047, ATM+CZA exhibited the highest synergistic effect, resulting in a log10 CFU/mL reduction of 10.43 compared to the control. The combination of CZA and MEM exhibited good synergistic effects against KPC-producing and non-enzyme-producing strains, followed by the FOS+CZA combination. Among MBL-producing strains, ATM+CZA demonstrated the most pronounced synergistic effect. However, the combinations of CZA with ERA, AK, and COL show irrelevant effects against the tested clinical isolates. IMPORTANCE: Our study confirmed the efficacy of the combination CZA+MEM against KPC-producing and non-carbapenemase-producing strains. For metalloenzyme-producing strains, CZA+ATM demonstrated the most significant synergy. Additionally, CZA exhibited a notable synergy effect when combined with FOS. These combination therapies present promising new options for the treatment of CRKP infection.

Clinical outcomes and risk factors for mortality in recipients with carbapenem-resistant gram-negative bacilli infections after kidney transplantation treated with ceftazidime-avibactam: a retrospective study.

Background: Ceftazidime-avibactam is a treatment option for carbapenem-resistant gram-negative bacilli (CR-GNB) infections. However, the risk factors associated with ceftazidime-avibactam (CAZ-AVI) treatment failure in kidney transplant (KT) recipients and the need for CAZ-AVI-based combination therapy remain unclear. Methods: From June 2019 to December 2023, a retrospective observational study of KT recipients with CR-GNB infection treated with CAZ-AVI was conducted, with the primary outcome being 30-day mortality and secondary outcomes being clinical cure, microbiological cure, and safety. Risk factors for 30-day mortality and clinical failure were also investigated. Results: A total of 81 KT recipients treated with CAZ-AVI were included in this study. Forty recipients (49.4%) received CAZ-AVI monotherapy, with a 30-day mortality of 22.2%. The clinical cure and microbiological cure rates of CAZ/AVI therapy were 72.8% and 66.7%, respectively. CAZ-AVI alone or in combination with other medications had no effect on clinical cure or 30-day mortality. Multivariate logistic regression analysis revealed that a higher Acute Physiology and Chronic Health Evaluation (APACHE) II score (odds ratio [OR]: 4.517; 95% confidence interval [CI]: 1.397-14.607; P = 0.012) was an independent risk factor for 30-day mortality. Clinical cure was positively associated with the administration of CAZ-AVI within 48 hours of infection onset (OR: 11.009; 95% CI: 1.344-90.197; P=0.025) and negatively associated with higher APACHE II scores (OR: 0.700; 95% CI: 0.555-0.882; P=0.002). Four (4.9%) recipients experienced recurrence within 90 days after the initial infection, 3 (3.7%) recipients experienced CAZ-AVI-related adverse events, and no CAZ-AVI resistance was identified. Conclusion: CAZ-AVI is an effective medication for treating CR-GNB infections following kidney transplantation, even as monotherapy. Optimization of CAZ/AVI therapy (used within 48 hours of infection onset) is positively associated with potential clinical benefit. Further larger-scale studies are needed to validate these findings.

Successful phage-antibiotic therapy of P. aeruginosa implant-associated infection in a Siamese cat.

Antibiotic-resistant pathogens are a growing global issue, leading to untreatable infectious diseases in both humans and animals. Personalized bacteriophage (phage) therapy, the use of specific anti-bacterial viruses, is currently a leading approach to combat antibiotic-resistant infections. The implementation of phage therapy has primarily been focused on humans, almost neglecting the impact of such infections on the health and welfare of companion animals. Pets also have the potential to spread resistant infections to their owners or the veterinary staff through zoonotic transmission. Here, we showcase personalized phage-antibiotic treatment of a cat with a multidrug-resistant Pseudomonas aeruginosa implant-associated infection post-arthrodesis surgery. The treatment encompassed a tailored combination of an anti-P. aeruginosa phage and ceftazidime, precisely matched to the pathogen. The phage was topically applied to the surgical wound while the antibiotic was administered intramuscularly. After two treatment courses spanning 7 and 3 weeks, the surgical wound, which had previously remained open for five months, fully closed. To the best of our knowledge, this is the first case of personalized phage therapy application in felines, which provides further evidence of the effectiveness of this approach. The successful outcome paves the way for personalized phage-antibiotic treatments against persistent infections therapy in veterinary practice.