Characterization of a KPC-84 harboring Klebsiella pneumoniae ST11 clinical isolate with ceftazidime-avibactam resistance.

A novel KPC variant, KPC-84, identified in a Klebsiella pneumoniae isolate from China, exhibits a threonine (T) to proline (P) amino acid substitution at Ambler position 243(T243P), altering from the KPC-2 sequence. Cloning and expression of blaKPC-84 in Escherichia coli, with subsequent MIC assessments, revealed increased resistance to ceftazidime-avibactam and significantly reduced carbapenemase activity compared to KPC-2. Kinetic measurements showed that KPC-84 exhibited sligthly higher hydrolysis of ceftazidime and reduced affinity for avibactam compared to KPC-2. This study emphasizes the emerging diversity of KPC variants with ceftazidime-avibactam resistance, underscoring the complexity of addressing carbapenem-resistant Klebsiella pneumoniae infections.

Physicians' knowledge of invasive fungal disease in China.

BACKGROUND: Invasive fungal disease (IFD) is associated with high morbidity and mortality. Data are lacking regarding physicians' perspectives on the diagnosis and management of IFD in China. OBJECTIVES: To evaluate physicians' perspectives on the diagnosis and management of IFD. METHODS: Based on current guidelines, a questionnaire was designed and administered to 294 physicians working in haematology departments, intensive care units, respiratory departments and infectious diseases departments in 18 hospitals in China. RESULTS: The total score and subsection scores for invasive candidiasis, invasive aspergillosis (IA), cryptococcosis and invasive mucormycosis (IM) were 72.0 ± 12.2 (maximum = 100), 11.1 ± 2.7 (maximum = 19), 43.0 ± 7.8 (maximum = 57), 8.1 ± 2.0 (maximum = 11) and 9.8 ± 2.3 (maximum = 13), respectively. Although the perspectives of the Chinese physicians were in good overall agreement with guideline recommendations, some knowledge gaps were identified. Specific areas in which the physicians' perspectives and guideline recommendations differed included use of the ß-D-glucan test to facilitate the diagnosis of IFD, relative utility of the serum galactomannan test and bronchoalveolar lavage fluid galactomannan test in patients with agranulocytosis, use of imaging in the diagnosis of mucormycosis, risk factors for mucormycosis, indications for initiating antifungal therapy in patients with haematological malignancies, when to start empirical therapy in mechanically ventilated patients, first-line drugs for mucormycosis and treatment courses for IA and IM. CONCLUSION: This study highlights the main areas that could be targeted by training programs to improve the knowledge of physicians treating patients with IFD in China.

Cryptococcal meningitis in apparently immunocompetent patients.

Cryptococcal meningitis (CM) is an invasive fungal disease that currently poses a threat to human health worldwide, with high morbidity and mortality, particularly in immunocompromised patients. Although CM mainly occurs in HIV-positive patients and other immunocompromised patients, it is also increasingly seen in seemingly immunocompetent hosts. The clinical characteristics of CM between immunocompromised and immunocompetent populations are different. However, few studies have focussed on CM in immunocompetent individuals. This review summarizes the clinical characteristics of apparently immunocompetent CM patients in terms of aetiology, immune pathogenesis, clinical presentation, laboratory data, imaging findings, treatment strategies and prognosis. It is of great significance to further understand the disease characteristics of CM, explore new treatment strategies and improve the prognosis of CM in immunocompetent individuals.

Preoperative and postoperative nomograms for predicting early recurrence of hepatocellular carcinoma without macrovascular invasion after curative resection.

BACKGROUND: Postoperative early recurrence (ER) is a major obstacle to long-term survival after curative liver resection (LR) in patients with hepatocellular carcinoma (HCC). This study aimed to establish preoperative and postoperative nomograms to predict ER in HCC without macrovascular invasion. METHODS: Patients who underwent curative LR for HCC between January 2012 and December 2016 were divided into training and internal prospective validation cohorts. Nomograms were constructed based on independent risk factors derived from the multivariate logistic regression analyses in the training cohort. The predictive performances of the nomograms were validated using the internal prospective validation cohort. RESULTS: In total, 698 patients fulfilled the eligibility criteria. Among them, 265 of 482 patients (55.0%) in the training cohort and 120 of 216 (55.6%) patients in the validation cohort developed ER. The preoperative risk factors associated with ER were age, alpha-fetoprotein, tumor diameter, and tumor number, and the postoperative risk factors associated with ER were age, tumor diameter, tumor number, microvascular invasion, and differentiation. The pre- and postoperative nomograms based on these factors showed good accuracy, with concordance indices of 0.712 and 0.850 in the training cohort, respectively, and 0.754 and 0.857 in the validation cohort, respectively. The calibration curves showed optimal agreement between the predictions by the nomograms and actual observations. The area under the receiver operating characteristic curves of the pre- and postoperative nomograms were 0.721 and 0.848 in the training cohort, respectively, and 0.754 and 0.844 in the validation cohort, respectively. CONCLUSIONS: The nomograms constructed in this study showed good performance in predicting ER for HCC without macrovascular invasion before and after surgery. These nomograms would be helpful for doctors when determining treatments and selecting patients for regular surveillance or administration of adjuvant therapies.

Emergomyces orientalis Emergomycosis Diagnosed by Metagenomic Next-Generation Sequencing.

Emergomyces is a newly described dimorphic fungus genus; it may cause fatal infections in immunocompromised patients, but diagnosis is often delayed. We report a case of disseminated emergomycosis caused by the novel species Emergomyces orientalis in a kidney transplant recipient from Tibet. Infection was diagnosed early by metagenomic next-generation sequencing.

The utility of cerebrospinal fluid white cell count during the prognostic assessment for cryptococcal meningitis patients: a retrospective study.

BACKGROUND: The incidence of cryptococcal meningitis (CM) has gradually increased in recent years. Cerebrospinal fluid (CSF) cytology and cell count are very important for CM on etiology diagnosis and assessment of disease status and therapeutic response. However, the clinical significance of CSF white cell count (WCC) in CM patients is not fully understood. Using longitudinal data of CSF WCC and its relationship with clinical outcomes in CM patients, we aimed to elucidate the clinical significance of this test. METHODS: We retrospectively analyzed the medical records of 150 CM patients admitted to our hospital between January 2008 and December 2018. RESULTS: CM patients with lower baseline CSF WCC, CSF protein concentration or CD4/CD8 ratio, and those with altered mentation or HIV coinfection were more likely to have poor clinical outcome (P<0.05). CM patients with triple therapy during the induction period presented with a better clinical outcome (P<0.05). Baseline CSF WCC had a moderate positive correlation with peripheral CD4+ T lymphocyte count (r = 0.738, P < 0.001) and CD4+ T lymphocyte percentage (r = 0.616, P < 0.001). The best cut-off value to predict a poor clinical outcome was 40 cells/µL during baseline CSF WCC. The predictive model incorporating longitudinal data of CSF WCC had better sensitivity, specificity, and accuracy than a model incorporating only baseline CSF WCC data. CONCLUSIONS: Our results indicated that baseline CSF WCC and changes in CSF WCC over time could be used to assess the prognosis of CM patients.

Efficacy and Safety of Tedizolid Phosphate versus Linezolid in a Randomized Phase 3 Trial in Patients with Acute Bacterial Skin and Skin Structure Infection.

Tedizolid phosphate is approved for the treatment of acute bacterial skin and skin structure infection (ABSSSI) caused by Gram-positive bacteria in the United States, Europe, and other countries. In this multicenter, double-blind, phase 3 study, 598 adult ABSSSI patients in China, Taiwan, the Philippines, and the United States were randomized to receive 200 mg of tedizolid, intravenously (i.v.)/orally (p.o.), once daily for 6 days or 600 mg of linezolid, i.v./p.o. twice daily for 10 days. The primary endpoint was early clinical response rate at 48 to 72 h. Secondary endpoints included programmatic and investigator-assessed outcomes at end-of-therapy (EOT) and posttherapy evaluation (PTE) visits. Safety was also evaluated. In the intent-to-treat (ITT) population, 75.3% of tedizolid-treated patients and 79.9% of linezolid-treated patients were early responders (treatment difference, -4.6%; 95% confidence interval [CI], -11.2, 2.2). After exclusion of patients who never received the study drug (tedizolid, n = 8; linezolid, n = 1; modified ITT), comparable early response rates were observed (tedizolid, 77.4%; linezolid, 80.1%; treatment difference, -2.7%; 95% CI, -9.4, 3.9). Secondary endpoints showed high and similar clinical success rates in the ITT and clinically evaluable (CE) populations at EOT and PTE visits (e.g., CE-PTE for tedizolid, 90.4%; for linezolid, 93.5%). Both drugs were well tolerated, and no death occurred. Eight patients experienced phlebitis with tedizolid while none did with linezolid; hence, drug-related treatment-emergent adverse events were reported in a slightly higher proportion in the tedizolid (20.9%) arm than in the linezolid arm (15.8%). The study demonstrated that tedizolid in a primarily Asian population was an efficacious and well-tolerated treatment option for ABSSSI patients. (This study has been registered at ClinicalTrials.gov under registration no. NCT02066402.).

Acinetobacter sichuanensis sp. nov., recovered from hospital sewage in China.

A novel Acinetobacter strain, WCHAc060041T, was recovered from hospital sewage at West China Hospital in Chengdu, Sichuan Province, China. The strain was Gram-negative coccobacillus, non-spore-forming, non-motile and strictly aerobic. The genomic DNA G+C content was 37.02 mol%. The 16S rRNA and rpoB gene sequences of the strain were ≤98.2 and≤89.5 % identical to the type strains of all known Acinetobacter species, respectively. The strain formed a distinct branch based on the genus-wide comparison of whole-cell mass fingerprints generated by matrix-assisted laser desorption/ionization-time-of flight mass spectrometry. Strain WCHAc060041T was subjected to whole genome sequencing. The average nucleotide identity based on blast (ANIb) and in silico DNA-DNA hybridization (isDDH) values between strain WCHAc060041T and type strains of other Acinetobacter species were ≤82.7 and ≤26.9 %, respectively. Strain WCHAc060041T could be distinguished from all known Acinetobacter species by its ability to assimilate gentisate and levulinate, but not to citrate (Simmons'). Genotypic and phenotypic characteristics from this study indicate that strain WCHAc060041T represents a novel species of the genus Acinetobacter, for which the name Acinetobacter sichuanensis sp. nov. is proposed. The type strain is WCHAc060041T (=CCTCC AB 2018118T=GDMCC 1.1383T=KCTC 62575T).

RAPIDLY PROGRESSIVE PULMONARY CRYPTOCOCCOSIS WITH CAVITATION IN AN IMMUNOCOMPETENT WOMAN: A CASE REPORT AND LITERATURE REVIEW.

Pulmonary cryptococcosis with pulmonary cavitation is rare, especially in immunocompetent cryptococcosis patients. We describe here a case of rapidly progressive pulmonary with cavitation in an immunocompetent woman. A 29-year-old woman had a routine chest X-ray as part of a routine examination. The chest X-ray showed pulmonary nodules. She was diagnosed as having bacterial pneumonia even though she had no symptoms and was treated with ampicillin orally. A chest X-ray was repeated 12 days later as follow-up which showed an increase in the nodules. She continued to be asymptomatic and had a normal lung examination. Her complete blood count revealed a normal white blood cell count and her anti-human immunodeficiency virus test was normal, as were her immunoglobulin levels and CD4 counts. She had a computed tomography (CT) scan of the lungs that showed two pulmonary nodules, one with cavitation. She then underwent a CT guided needle biopsy of the cavitary lesion which revealed pulmonary cryptococcosis. A serum latex cryptococcal antigen test revealed a titer of 1:32. She was treated with fluconazole 400 mg IV daily for 7 days, followed by oral fluconazole 200 mg daily for a year. The cavitary lesion gradually disappeared and the nodules decreased in size. A follow-up CT 1 year later was normal. Although rare, cryptococcosis of the lungs with pulmonary cavitation can occur in otherwise healthy patients, requiring long term treatment to improve.

[Clinical Analysis of 94 Patients with Neurocysticercosis in Sichuan Province].

Objective: To analyze the clinical features of neurocysticercosis（NCC） to provide evidence for clinical diagnosis and treatment of the disease. Methods: Medical records of NCC patients in the West China Hospital of Sichuan University received between January 2003 and January 2013 were reviewed retrospectively. The epidemiological data, clinical manifestations, therapeutic procedures and outcomes of the patients were analyzed. Results: A total of 94 NCC patients met the recruiting criteria, of whom 67.0%（63/94） were male, 59.6%（56/94） ranged 30-55 years old, 73.4%（69/94） had a living history in endemic regions such as Aba, Ganzi and Liangshan prefectures, 80.9%（76/94） lived in rural areas. NCC was clinically characterized by epilepsy, headache and intracranial hypertension. The positive rate for anti-T. solium antibodies by ELISA was 96.8%（91/94）, and the total positive scan rate of neuroimaging including CT and MRI was 95.7%（90/94）. In addition, 73 patients were suspected to have NCC at the first diagnosis, with a misdiagnosis rate of 22.3%（21/94）. Seventy-nine of the patients received albendazole treatmentï¼»20 mg/（kg·d）, twice per day for 10 days as one treatment course, 1-3 courses as neededï¼½. Eleven patients received praziquantel（total dose of 120-180 mg/kg, 3 times per day for 3 days as one treatment course, 1-3 courses）, and 4 received a combination of albendazole and praziquantel. Symptoms improved in 77 cases（81.9%）, but 12 of them（12/77, 15.6%） relapsed. The improvement rate of the albendazole group（6/11, 84.8%） was significantly higher than that of the praziquantel group（54.6%）（P<0.05）. Conclusion: NCC more commonly occurs in young males and lacks specific clinical manifestations. Neuroimaging combined with serum specific antibody tests is crucial for diagnosis. Albendazole has better therapeutic effects than praziquantel.

Analysis of cerebrospinal fluid protein concentrations of patients with cryptococcal meningitis treated with antifungal agents.

BACKGROUND: Many neurological diseases are accompanied by an increase in the cerebrospinal fluid (CSF) protein concentration, which indicates dysfunction of the blood-CSF/blood-brain barrier. However, the significance CSF protein concentration of patients with cryptococcal meningitis (CM) is not fully understood. The aim of the present was to determine whether CSF protein concentrations correlated with the responses of patients to treatment with antifungal drugs. METHODS: We conducted a retrospective study of the analytical data of 623 lumbar punctures of 46 patients with CM who were treated at West China Hospital. We divided the patients into groups with good or poor responses to antifungal treatment. We used a generalized linear mixed model (GLMM) to evaluate the significance of the differences between the two groups. RESULTS: The baseline CSF protein concentrations of the good antifungal response group (GR-group) (median = 0.97 g/L) were higher compared with those of the poor antifungal response group (PR-group) (median = 0.72 g/L). Analysis using the GLMM indicated that the CSF protein concentration of the GR-group decreased at a rate of 1.8 mg/L per day after antifungal treatment started and was 2.1 mg/L higher compared with that of the PR-group. CONCLUSIONS: Compared with poor responders, we found that the baseline CSF protein concentrations of good responders were higher and decreased at faster rate after the initiation of antifungal treatment.

Identification of a Novel KPC Variant, KPC-204, Conferring Resistance to Both Carbapenems and Ceftazidime-Avibactam in an ST11 Klebsiella pneumoniae Strain.

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 blaKPC-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.

Fighting against Clostridioides difficile infection: Current medications.

Clostridioides difficile (formerly Clostridium difficile) has been regarded as an 'urgent threat' and a significant global health problem, as life-threatening diarrhoea and refractory recurrence are common in patients with C. difficile infection (CDI). Unfortunately, the available anti-CDI drugs are limited. Recent guidelines recommend fidaxomicin and vancomycin as first-line drugs to treat CDI, bezlotoxumab to prevent recurrence, and faecal microbiota transplantation for rescue treatment. Currently, researchers are investigating therapeutic antibacterial drugs (e.g. teicoplanin, ridinilazole, ibezapolstat, surotomycin, cadazolid, and LFF571), preventive medications against recurrence (e.g. Rebyota, Vowst, VP20621, VE303, RBX7455, and MET-2), primary prevention strategies (e.g. vaccine, ribaxamase, and DAV132) and other anti-CDI medications in the preclinical stage (e.g. Raja 42, Myxopyronin B, and bacteriophage). This narrative review summarises current medications, including newly marketed drugs and products in development against CDI, to help clinicians treat CDI appropriately and to call for more research on innovation.

A multicentre, randomised, double-blind, double-dummy, parallel-controlled, phase 3 clinical trial assessing the efficacy and safety of intravenous nemonoxacin malate vs. levofloxacin for community-acquired pneumonia in adult patients.

BACKGROUND: Nemonoxacin malate is a novel non-fluorinated quinolone for oral and intravenous (IV) administration. This phase 3, multicentre, randomised, double-blind, double-dummy, parallel-controlled clinical trial (NCT02205112) evaluated the efficacy and safety of IV nemonoxacin vs. levofloxacin for the treatment of community-acquired pneumonia (CAP) in adult patients. METHODS: Eligible patients were randomised to receive 500 mg nemonoxacin or levofloxacin via IV infusion, once daily for 7-14 days. The primary endpoint was the clinical cure rate at the test-of-cure (TOC) visit in the modified intent-to-treat (mITT) population. Secondary efficacy and safety were also compared between nemonoxacin and levofloxacin. RESULTS: Overall, 525 patients were randomised and treated with nemonoxacin (n = 349) or levofloxacin (n = 176). The clinical cure rate was 91.8% (279/304) for nemonoxacin and 85.7% (138/161) for levofloxacin in the mITT population (P > 0.05). The clinical efficacy of nemonoxacin was non-inferior to levofloxacin for treatment of CAP. Microbiological success rate with nemonoxacin was 88.8% (95/107) and with levofloxacin was 87.8% (43/49) (P > 0.05) at the TOC visit in the bacteriological mITT population. The incidence of drug-related adverse events (AEs) was 37.1% in the nemonoxacin group and 22.2% in the levofloxacin group. These AEs were mostly local reactions at the infusion site, nausea, elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST), and QT interval prolongation. The nemonoxacin-related AEs were mostly mild and resolved after discontinuation of nemonoxacin. CONCLUSIONS: Nemonoxacin 500 mg IV once daily for 7-14 days is effective and safe and non-inferior to levofloxacin for treating CAP in adult patients.

Biapenem versus meropenem in the treatment of bacterial infections: a multicenter, randomized, controlled clinical trial.

BACKGROUND & OBJECTIVES: Biapenem is a newly developed carbapenem to treat moderate and severe bacterial infections. This multicenter, randomized, parallel-controlled clinical trial was conducted to compare the clinical efficacy, bacterial eradication rates and safety of biapenem and meropenem in the treatment of bacterial lower respiratory tract infections and urinary tract infections (UTIs) at nine centres in China. METHODS: Patients diagnosed with bacterial lower respiratory tract infections or UTIs were randomly assigned to receive either biapenem (300 mg every 12 h) or meropenem (500 mg every 8 h) by intravenous infusion for 7 to 14 days according to their disease severity. The overall clinical efficacy, bacterial eradication rates and drug-related adverse reactions of biapenem and meropenem were analyzed. RESULTS: A total of 272 enrolled cases were included in the intent-to-treat (ITT) analysis and safety analysis. There were no differences in demographics and baseline medical characteristics between biapenem group and meropenem group. The overall clinical efficacies of biapenem and meropenem were not significantly different, 94.70 per cent (125/132) vs. 93.94 per cent (124/132). The overall bacterial eradication rates of biapenem and meropenem showed no significant difference, 96.39 per cent (80/83) vs. 93.75 per cent (75/80). Drug-related adverse reactions were comparable in biapenem and meropenem groups with the incidence of 11.76 per cent (16/136) and 15.44 per cent (21/136), respectively. The most common symptoms of biapenem-related adverse reactions were rash (2.2%) and gastrointestinal distress (1.5%). INTERPRETATION & CONCLUSIONS: Biapenem was non-inferior to meropenem and was well-tolerated in the treatment of moderate and severe lower respiratory tract infections and UTIs.

[Clinical analysis of 137 patients with visceral leishmaniasis].

OBJECTIVE: To analyze the clinical and epidemiological characteristics of visceral leishmaniasis cases in Sichuan. METHODS: The medical records of 137 patients with visceral leishmaniasis were reviewed between January 2000 and April 2012 in West China Hospital. The epidemiological data, clinical manifestations, laboratory features, diagnosis, therapeutic procedures and outcome of the patients were retrospectively analyzed. RESULTS: Eighty-eight (64.2%) out of 137 cases were the residents in the endemic area of Sichuan Province and adjacent areas, and 49 (35.8%) were non-endemic area residents with a history of visiting endemic area. Patients living in rural areas accounted for 84.7% (116/137), in town for 15.3% (21/137). Visceral leishmaniasis should be strongly suspected in a patient with prolonged fever, marked hepatosplenomegaly, lymphadenectasis, cytopenia and hypergammaglobulinemia. All patients showed positive in rk39 dipstick test, and were treated with antimony sodium gluconate. Among these patients, 86.1% (118/137) were cured by drug, 2.9% (4/137) received splenectomy, and 6.6% (9/137) relapsed. The misdiagnosis rate was 23.4% (32/137). CONCLUSION: Bone marrow smear staining and biopsy, combined with rk39 antibody detection and epidemiological history are crucial for early diagnosis and treatment of visceral leishmaniasis. Antimonials is still an effective therapeutic choice.

The impact of three carbapenems at a single-day dose on intestinal colonization resistance against carbapenem-resistant Klebsiella pneumoniae.

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.

Real-world effectiveness of ceftazidime/avibactam versus polymyxin B in treating patients with carbapenem-resistant Gram-negative bacterial infections.

OBJECTIVES: To compare the effectiveness of ceftazidime/avibactam (CAZ/AVI) and polymyxin B against carbapenem-resistant Gram-negative bacteria (CRGNB) infections in western China. METHODS: The medical records of patients with CRGNB infections in this hospital from 2018-2022 were retrospectively reviewed. The data included demographic characteristics, laboratory results, antibiotic strategies and clinical outcomes. RESULTS: A total of 378 patients with CRGNB infections were enrolled, including 112 patients in the CAZ/AVI group and 266 patients in the polymyxin B group. The most common pathogen was carbapenem-resistant Klebsiella pneumoniae (44.44%). The rates of treatment failure at 28 days (65.04% vs. 45.54%; P = 0.000) and 28-day in-hospital mortality (20.30% vs. 9.82%; P = 0.014) in the polymyxin B group were higher than those in the CAZ/AVI group. Multivariable analysis revealed that multiple organ dysfunction syndrome (OR 2.730; P = 0.017), acute renal failure (OR 2.595; P = 0.020), higher Charlson comorbidity index (CCI) (OR 1.184; P = 0.011) and Acute Physiology And Chronic Health Evaluation (APACHE) Ⅱ scores (OR 1.149; P = 0.000) were independent risk factors for treatment failure, whereas CAZ/AVI therapy (OR 0.333; P = 0.002) had a protective effect. Multivariate Cox regression analysis revealed that CCI ≥ 5 and APACHE II score ≥ 15 were associated with a higher 28-day in-hospital mortality rate (P < 0.001). CONCLUSION: CAZ/AVI therapy was associated with treatment success among patients with CRGNB infection. However, CAZ/AVI therapy did not improve 28-day in-hospital survival compared with polymyxin B. The CCI ≥ 5 and APACHE II score ≥ 15 affected 28-day in-hospital mortality of CRGNB-infected patients.

Guidelines for the diagnosis, treatment, prevention and control of infections caused by carbapenem-resistant gram-negative bacilli.

The dissemination of carbapenem-resistant Gram-negative bacilli (CRGNB) is a global public health issue. CRGNB isolates are usually extensively drug-resistant or pandrug-resistant, resulting in limited antimicrobial treatment options and high mortality. A multidisciplinary guideline development group covering clinical infectious diseases, clinical microbiology, clinical pharmacology, infection control, and guideline methodology experts jointly developed the present clinical practice guidelines based on best available scientific evidence to address the clinical issues regarding laboratory testing, antimicrobial therapy, and prevention of CRGNB infections. This guideline focuses on carbapenem-resistant Enterobacteriales (CRE), carbapenem-resistant Acinetobacter baumannii (CRAB), and carbapenem-resistant Pseudomonas aeruginosa (CRPA). Sixteen clinical questions were proposed from the perspective of current clinical practice and translated into research questions using PICO (population, intervention, comparator, and outcomes) format to collect and synthesize relevant evidence to inform corresponding recommendations. The grading of recommendations, assessment, development and evaluation (GRADE) approach was used to evaluate the quality of evidence, benefit and risk profile of corresponding interventions and formulate recommendations or suggestions. Evidence extracted from systematic reviews and randomized controlled trials (RCTs) was considered preferentially for treatment-related clinical questions. Observational studies, non-controlled studies, and expert opinions were considered as supplementary evidence in the absence of RCTs. The strength of recommendations was classified as strong or conditional (weak). The evidence informing recommendations derives from studies worldwide, while the implementation suggestions combined the Chinese experience. The target audience of this guideline is clinician and related professionals involved in management of infectious diseases.

Prulifloxacin versus levofloxacin in the treatment of respiratory and urinary tract infections: a multicentre, double-blind, randomized controlled clinical trial.

BACKGROUND: Prulifloxacin is a promising fluoroquinolone antibiotic. A multicentre, double-blind, randomized clinical study was designed to evaluate its efficacy and safety compared to that of levofloxacin for the treatment of respiratory and urinary infections of Chinese patients. METHODS: A total of 267 patients were enrolled and each was randomly assigned to either the treatment or the control group. Prulifloxacin 264.2 mg (equivalent to ulifloxacin 200 mg) b.i.d. or levofloxacin hydrochloride 200 mg b.i.d. was administered orally for 5-14 days according to a patient's condition. The clinical response, bacterial eradication and incidence of adverse events were evaluated. RESULTS: Two hundred and forty-three patients completed the study. For the modified intention-to-treat population, the cure and effective rates were 45.53 and 82.93% in the prulifloxacin group and 49.18 and 83.61% in the levofloxacin group. For the per-protocol analysis population, the cure and effective rates were 45.90 and 83.61% in the prulifloxacin group and 49.59 and 83.47% in the levofloxacin group. The bacterial eradication rates were 96.59 and 95.35%, and the drug-related adverse event rates were 7.87 and 5.51% in the prulifloxacin and levofloxacin group, respectively. The cure rate and efficacy rate of respiratory and urinary tract infections of the levofloxacin group were better than those of the prulifloxacin group. However, the difference between the 2 groups was not statistically significant (p > 0.05). CONCLUSION: Prulifloxacin is as effective and well tolerated as levofloxacin in the treatment of respiratory and urinary tract infections.