The aim of present study was to investigate the clinical characteristics and prognosis of patients with multidrug-resistant gram-negative bacterial (MDR-GNB) infections treated with ceftazidime/avibactam during the period from September 2019 to June 2020 since ceftazidime/avibactam had been marketed in China. Twenty MDR-GNB infected patients were retrospectively collected by using electronic medical record systems in West China hospital. For all of the 20 patients, the mean age was 54.5 ± 17.37 years and 14 (70%) were male. Pneumonia (n = 12, 60%), complicated intra-abdominal infection (n = 10, 50%), and bloodstream infection (n = 7, 35%) were the most common infection sources. Klebsiella pneumoniae (18/33) was the predominant pathogen. Fourteen-day clinical cure rate was achieved in 45%. The 14-day and 30-day mortality rates were 25% and 55%, respectively. However, no significant difference was found in 30-day mortality between the treatment of ceftazidime/avibactam monotherapy and combination regimens (p > 0.05). Three patients suffered from adverse drug reactions such as diarrhea. No significant difference was found between the effectiveness of ceftazidime/avibactam clinical failure and cure groups as salvage treatment of MDR-GNB infection.

Objective: Polymyxins are currently the last line of defense in the treatment of carbapenem-resistant organisms (CRO). As a kind of polymyxin available for clinical use in China, we aim to explore the efficacy and safety of colistin sulfate (Polymyxin E sulfate, PES) in this study.Methods: This real-world retrospective study included 119 patients diagnosed with CRO infection and treated with PES for more than 72 h, from May 2020 to July 2022 at West China Hospital. The primary outcome was clinical efficacy at the end of treatment, and secondary outcomes included microbial response, in-hospital mortality and incidence of nephrotoxicity.Results: The effective clinical and microbiological responses were 53.8% and 49.1%, respectively. And the in-hospital mortality was 27.7%. Only 9.2% of patients occurred with PES-related nephrotoxicity. Multivariate analysis revealed that duration of PES was an independent predictor of effective therapy, while age-adjusted Charlson comorbidity index (aCCI) and post-treatment PCT(p-PCT) were independent risk factors for poor outcome.Conclusions: PES can be a salvage treatment for CRO-induced infections with favorable efficacy and low nephrotoxicity. The treatment duration of PES, aCCI and p-PCT were factors related to the clinical effectiveness of PES.

Gut microbiota plays a crucial role in providing colonization resistance against multi-drug resistant organisms including carbapenem-resistant Klebsiella pneumoniae (CRKP). However, the impact of different carbapenems on intestinal colonization resistance against CRKP remains poorly understood. In this study, we aimed to investigate the effects of three commonly used carbapenems (meropenem, imipenem, and ertapenem) administered at single-day doses, which are typically employed in emergency departments for managing infected patients, on CRKP gut colonization. We conducted experiments in mice by intravenously administering each carbapenem using human-simulated one-day regimens. The composition of the gut microbiota was analyzed using 16S rRNA amplicon sequencing before and after carbapenem administration. Our results revealed that all three carbapenems, when administered at a single-day dose significantly altered the abundance and diversity of the gut microbiota, leading to compromised colonization resistance against CRKP. Notably, the ertapenem and imipenem groups showed an increase in Allobaculum , Bifidobacterium , Enterobacteriaceae , while the meropenem and imipenem groups exhibited a decrease in Ruminococcaceae , S24-7, and Akkermania . Additionally, the Shannon index exhibited a negative correlation with both the number of days of CRKP colonization CFUs and the duration of bacteria shedding. Furthermore, the count of CRKP in mice after ertapenem administration on the first day and the duration of CRKP shedding were significantly lower compared to meropenem and imipenem. Predictive metabolic pathway analysis demonstrated that the three carbapenems similarly affected a range of metabolic pathways of gut microflora, including carbohydrate metabolism and vitamin B. Our findings emphasize that ertapenem, with its relatively narrow spectrum, minimizes perturbations of the gut microbiota and has a relatively less impact on gut colonization resistance against CRKP. IMPORTANCE: The intestinal colonization of carbapenem-resistant Klebsiella pneumoniae (CRKP) is an important source of clinical infection. Our research showed that even single-day dose use of carbapenems caused CRKP colonization and continuous bacterial shedding, which reminds clinical doctors to prescribe carbapenems cautiously. Whenever possible, ertapenem should be the preferred choice over other carbapenems especially when the identified or highly suspected pathogens can be effectively targeted by ertapenem.

This study describes KPC-204, a novel variant of Klebsiella pneumoniae carbapenemase, characterized by a Lys-Asp-Asp (KDD) amino acid insertion at Ambler position 269 deviates from KPC-2. This variant was identified in an ST11-type clinical isolate of carbapenem-resistant Klebsiella pneumoniae from China. Notably, KPC-204 exhibits resistance to both ceftazidime-avibactam and carbapenems. Genetic analysis revealed that bla_KPC-204 was located on a highly mobile IncFII/IncR plasmid within a complex genetic structure that facilitates its spread. Functional analysis, achieved through cloning into E. coli DH5α, validates KPC-204’s contribution to increased resistance to ceftazidime-avibactam. The kinetic parameters showed that KPC-204 exhibited similar affinity to KPC-2 toward ceftazidime and reduced sensitivity to avibactam. Docking simulations revealed a weaker interaction between KPC-204 and avibactam compared to KPC-2. Mating experiments demonstrated the resistance’s transmissibility. This investigation underscores the evolving diversity of KPC variants affecting ceftazidime-avibactam resistance, highlighting the necessity for continuous monitoring.

Background: Due to the blood–brain barrier and limited antibiotic choices, polymyxin is currently the first-line agent for the treatment of central nervous system infections (CNSIs) caused by multidrug-resistant Gram-negative bacteria (MDR-GNB). Colistin sulfate, as a polymyxin E different from CMS, is used in Chinese clinics, and there are limited reports on its use in the treatment of CNSIs. Case Presentation: This case describes a 76-year-old man who underwent complex neurosurgery for cervical spinal stenosis. Postoperatively, the patient developed a fever and a poorly healed surgical wound. Numerous blood routine tests, inflammatory markers, pathogenic tests of cervical secretions, cerebrospinal fluid (CSF), and sputum were sent for diagnosis. After empirical antimicrobial treatments failed, the CSF and wound pus cultured carbapenem-resistant Klebsiella pneumoniae. The regimen was adjusted to colistin sulfate intravenously and intrathecal injection combined with tigecycline. In addition, the management of infection foci, including continuous lumbar pool drain, cervical 3–5 internal fixation removal with cervical 1–6 spine dilation, CSF leak repair, and right thigh broad fasciotomy, were performed. After treatment, the patient was discharged with multiple sets of negative CSF cultures and the infection under control. Conclusions: For CNSIs caused by MDR-GNB, the selection of colistin sulfate for intravenous and topical combination treatment is a viable choice.

Background: Invasive mucormycosis (IM) poses a substantial morbidity and mortality burden among immunocompromised patients. Objectives: We aim to compare the real-world effectiveness and safety of isavuconazole with those of amphotericin B in patients with IM. Patients and methods: In this observational cohort study, we enrolled patients who were diagnosed with IM and treated with either isavuconazole or amphotericin B. Results: A total of 106 patients met the study criteria. Of these, 47 received isavuconazole, and 59 received amphotericin B as the primary treatment. The two cohorts had similar baseline characteristics, including a history of malignancy, use of immunosuppressants, infection sites, and pathogens. The amphotericin B group demonstrated a significantly greater incidence of renal disorders (p < 0.001) and hypokalemia (p < 0.001) than the isavuconazole group. The proportion of patients who received salvage therapy was greater in the amphotericin B group than in the isavuconazole group (42% vs. 6%, p < 0.001). Eighteen patients in the amphotericin B group discontinued treatment because of adverse events, whereas no patients in the isavuconazole group discontinued treatment because of adverse events. A significant difference in the primary therapeutic response between the isavuconazole and amphotericin B groups was noted (p = 0.013), with a higher treatment failure rate in the amphotericin B group (68% vs. 36%, p = 0.001). However, there were no significant differences in all-cause mortality or mucormycosis-attributable mortality rates between the two groups. Conclusions: Isavuconazole outperformed amphotericin B as a first-line treatment option for IM in terms of its clinical effectiveness and safety.