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 diarrhea 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 fecal microbiota transplantation (FMT) 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 summarizes 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.

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.

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.

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.

Treatment of Central Nervous System Infection Caused by Multidrug-Resistant Klebsiella pneumoniae with Colistin Sulfate Intravenously and Intrathecally: A Case Report.

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.

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.

Case Report: Visceral Leishmaniasis-associated Hemophagocytic Lymphohistiocytosis in Adults: A Case Series and Literature Review.

Hemophagocytic lymphohistiocytosis (HLH) is a rare and fatal complication of visceral leishmaniasis (VL). To provide a basis for early and correct diagnosis and to improve prognosis in the future, we describe a case series of VL-associated HLH in adults in our center in the past decade after review of all reported cases of adult VL-associated HLH in English through May 2022. In our case series, a total of 111 patients were diagnosed with VL. Among these patients, only six cases were diagnosed with VL-associated HLH. All patients tested positive for serology. Leishmania was detected for the first time by bone marrow aspiration (BMA) in three of the six patients and in the other three patients after three or four BMAs. It took more than 1 month from onset to diagnosis of VL for all the six cases, and the longest time was 6 months. Five of the six patients recovered after receiving sodium stibogluconate. VL-associated HLH is rare but potentially life-threatening in adults and predisposes to early delays in diagnosis. However, diagnostic techniques are not complicated or difficult, so it is more important to consider that it is not recognized by physicians. Although guidelines recommend liposomal amphotericin B as the most effective therapy, our experience suggests that sodium stibogluconate can be an alternative option when liposomal amphotericin B is unavailable or unaffordable.

Disseminated alveolar echinococcosis in a patient diagnosed by metagenomic next-generation sequencing: A case report.

Background: Alveolar echinococcosis (AE) is a parasitic zoonosis with high mortality and disability rates. Diverse clinical manifestations and mimicking of differential diagnoses such as tuberculosis and malignancy pose a diagnostic dilemma. With the rapid development of molecular diagnostic techniques in recent years, metagenomic next-generation sequencing (mNGS) has become an attractive approach for the etiological diagnosis of infectious diseases. Case presentation: we report a case of 51-year-old Chinese Tibetan male presented with 3-year low-back pain and 4-month discomfort in the right upper quadrant of the abdomen. He had been in good health. He was diagnosed with tuberculosis and was given anti-tuberculosis treatment a month prior to the visit, but the symptoms were not relieved. Abdominal computerized tomography (CT) revealed a hypodense lesion with uneven enhancement in the liver, and two ring-enhancing cystic lesions in the right abdominal wall. Lumbar spine enhanced MRI showed lesions of mixed density with uneven enhancement in the L1 vertebra and paraspinal tissue. The pathological results of the liver biopsy revealed parasitic infection and possibly echinococcosis. The metagenomic next-generation sequencing (mNGS) of the puncture fluid of abdominal cysts using Illumina X10 sequencer revealed 585 sequence reads matching Echinococcus multilocularis. Disseminated AE was diagnosed. Albendazole (400 mg, twice daily) was used, and the patient was in stable condition during follow-up. Conclusions: mNGS may be a useful tool for the diagnosis of AE. The case would help clinicians to improve their diagnostic skills.

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.

Emergent Virus Reactivation in SARS-CoV-2-Negative Community Acquired Pneumonia Patients During the COVID-19 Pandemic.

Emergent viruses (namely, HSV-1, CMV, and EBV) reactivation were common in critically ill patients and/or immunosuppressed patients. This study aimed to understand the clinical manifestations and reactivation of the emergent viruses in SARS-CoV-2-Negative community acquired pneumonia (CAP) patients during the COVID-19 pandemic. We retrospectively reviewed the medical records of CAP patients from January to March 2020, in our university hospital in China. The patients were divided into two groups based on the presence or absence of emergent viruses. In all patients, the positive rates of EBV, HSV, and CMV were 23.43% (15/64), 22.06% (15/68), and 12.50% (8/64), respectively. The most common presenting symptoms were fever (98, 57.99%) and dry cough (55, 32.54%). The levels of albumin, hemoglobin, lymphocyte count, and CD4 + T lymphocyte count in emergent viruses positive group were lower than those of viruses negative group (P < 0.05). The initial chest CT features of these patients were diverse. The most common manifestations were ground-glass opacity (91/169, 53.85%) and pulmonary nodule (88/169, 52.07%). More emergent viruses positive patients have bilateral upper lobes involvement than emergent viruses negative patients (P < 0.05). A total of 80.47% patients (136/169) received empirical antimicrobial treatment. The most commonly used antibiotic regimen was fluoroquinolone monotherapy (80/169, 47.34%). The emergent viruses positive patients have poorer clinical outcome (P < 0.05). In conclusion, emergent viruses reactivation was common in SARS-CoV-2-Negative CAP patients. Emergent viruses positive patients have poorer cellular immune function, more severer conditions and poorer prognosis. Fluoroquinolones may be a therapeutic option for CAP patients.

Efficacy and safety of polymyxin E sulfate in the treatment of critically ill patients with carbapenem-resistant organism infections.

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.

Pulmonary Mucormycosis as the Leading Clinical Type of Mucormycosis in Western China.

The aim was to better understand the clinical characteristics of patients with mucormycosis in western China. We retrospectively investigated the clinical, laboratory, radiological and treatment profiles of mucormycosis patients during a 10-year period (2010-2019). As a result, 59 proven mucormycosis were enrolled in this study. It was found that 52.5% of patients had worse clinical outcomes. Pulmonary mucormycosis (PM) was the most common clinical manifestation. The most frequent risk factor was diabetes mellitus (38, 64.4%) for mucormycosis patients. Cough (43, 93.5%), fever (24, 52.2%) and hemoptysis/bloody phlegm (21, 45.7%) were the most common manifestations of PM. There were no differences in clinical manifestations, risk factors and laboratory tests between different clinical outcome groups (P>0.05). Lymph node enlargement (30, 65.2%), patchy shadows (28, 60.9%), cavitation (25, 53.3%) and bilateral lobe involvement (39, 84.8%) were the most common on chest CT. Nodule was more common in good outcome group (P <0.05). A total of 48 cases (81.4%) were confirmed by histopathological examination, 22 cases (37.3%) were confirmed by direct microscopy. PM patients were treated with amphotericin B/amphotericin B liposome or posaconazale had better clinical outcomes (P <0.05). In conclusion, PM was the most common clinical type of mucormycosis in China. Diabetes mellitus was the most common risk factor. PM has diverse imaging manifestations and was prone to bilateral lobes involvement. Early diagnosis and effective anti-mucor treatment contribute to successful treatment.

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 Response Measures to the Coronavirus Disease 2019 Outbreak in China.

For China, the coronavirus disease 2019 (COVID-19) outbreak is a major public health emergency with the fastest spread, the most extensive infection, and the hardest to contain over the past 70 years. The different organizations and institutions in China have taken unprecedented public health responses to interrupt the virus transmission in the past several months. The outbreak in China was under control, but the number of confirmed cases abroad is still rising. Coronavirus disease 2019 has presented a global pandemic. We summarized the response measures adopted by different organizations at different levels (country, province, and hospital) in China, such as setting up an effective integrated system for disease prevention and control, effective deployment of medical staff, adjusting measures according to local conditions, establishing Fangcang hospitals, strengthening scientific research on COVID-19, epidemic prevention knowledge education, mass rapid testing for severe acute respiratory syndrome coronavirus 2, and correct personal protection including high compliance of wearing masks, hoping to provide some help for disease control in some regions.

A randomized, controlled, multicenter clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus moxifloxacin in adult patients with community-acquired pneumonia.

OBJECTIVES: To evaluate the efficacy and safety of oral sitafloxacin versus oral moxifloxacin in the treatment of Chinese adults with community-acquired pneumonia (CAP). PATIENTS AND METHODS: This is a multicenter, randomized, open-label, positive-controlled clinical trial (chinadrugtrials.org.cn identifier: CTR20130046). CAP patients received sitafloxacin tablets 100 mg once daily (qd) or 100 mg twice daily (bid) to compare with moxifloxacin tablets 400 mg qd, for 7-10 days. The primary outcome was non-inferiority of sitafloxacin to moxifloxacin in clinical cure rate at test of cure (TOC) visit in per-protocol set (PPS). RESULTS: A total of 343 patients were randomized (sitafloxacin 100 mg qd, n = 117; sitafloxacin 100 mg bid, n = 116; moxifloxacin, n = 110), 291 patients were included in the PPS (sitafloxacin 100 mg qd, n = 96; sitafloxacin 100 mg bid, n = 94; moxifloxacin, n = 101). The clinical cure rate was 94.8% in the sitafloxacin 100 mg qd group, 96.8% in the sitafloxacin 100 mg bid group and 95.0% in the moxifloxacin group. At the TOC visit, the microbiological success rate was 97.0% (32/33) in the sitafloxacin 100 mg qd group, 97.1% (34/35) in the sitafloxacin 100 mg bid group and 94.9% (37/39) in the moxifloxacin group in the microbiological evaluable set (MES). The incidence of study-drug-related adverse events (AEs) was 23.3% (27/116) in the sitafloxacin 100 mg qd group, 29.8% (34/114) in the sitafloxacin 100 mg bid group and 28.2% (31/110) in the moxifloxacin group (p > .05). The common AEs related to study drug were dizziness, nausea, diarrhea, increased platelet count and alanine transaminase (ALT) elevation. All the AEs resolved completely after discontinuation of study drug. CONCLUSION: Sitafloxacin 100 mg qd or 100 mg bid for 7-10 days is not inferior to moxifloxacin 400 mg qd for 7-10 days in clinical efficacy for adult CAP patients. Sitafloxacin provides a safety profile comparable to moxifloxacin.

Antibiotic strategies and clinical outcomes for patients with carbapenem-resistant Gram-negative bacterial bloodstream infection.

Carbapenem-resistant Gram-negative bacterial bloodstream infection (CRGNB-BSI) has become a rapidly growing global threat with limited antibiotic options and significant mortality. The aim of this study was to explore the antibiotic strategies and clinical outcomes of patients with CRGNB-BSI in Western China. We retrospectively investigated the demographic, microbiological and clinical characteristics of 355 patients with CRGNB-BSI from 2012-2017. Treatment failure and 28-day in-hospital mortality rates were 49.3% (175/355) and 23.7% (84/355), respectively. The most frequently isolated micro-organism was Acinetobacter baumannii (58.6%; 208/355). Patients with treatment failure had higher procalcitonin and interleukin-6 levels (P < 0.05). High-dosage tigecycline therapy (200 mg loading dose followed by 100 mg every 12 h) was not superior to standard tigecycline dosing (P > 0.05). Multivariable analysis revealed that multiple organ dysfunction syndrome (MODS) (OR = 2.226, 95% CI 1.376-3.602; P = 0.001) and intensive care unit (ICU) admission (OR = 3.116, 95% CI 1.905-5.097; P = 0.000) were independent risk factors for treatment failure, whereas monotherapy (OR = 0.386, 95% CI 0.203-0.735; P = 0.004) had a protective effect. Survival analysis revealed that inappropriate therapy, MODS and ICU admission were associated with a higher 28-day in-hospital mortality rate (P < 0.001). Combination antimicrobial therapy was not superior to monotherapy (P = 0.387). This study demonstrates that appropriate therapy is significantly associated with lower treatment failure and 28-day in-hospital mortality rates. Tigecycline might not be a suitable option for CRGBN-BSI. Patients with MODS and admitted to the ICU had poor clinical outcomes.

A randomized, active-controlled, multicentre clinical trial to evaluate the efficacy and safety of oral sitafloxacin versus levofloxacin in Chinese adults with acute uncomplicated or complicated urinary tract infection.

PURPOSE: To evaluate the efficacy and safety of oral sitafloxacin versus levofloxacin in Chinese adults with acute uncomplicated urinary tract infection (UTI) or complicated UTI. METHODS: In this randomized, active-controlled clinical trial, the patients with acute uncomplicated UTI were randomized to receive sitafloxacin 100-mg once-daily (qd) or levofloxacin 500-mg qd orally for 3-5 days. The patients with complicated UTI were randomized to receive sitafloxacin 100-mg twice daily or levofloxacin 500-mg qd orally for 10-14 days. The primary endpoint was the clinical efficacy at test-of-cure (TOC) visit. RESULTS: At TOC visit, the clinical cure rate was 89.2% (58/65) in sitafloxacin group and 97.1% (68/70) in levofloxacin group for the patients with acute uncomplicated UTI corresponding to the bacterial eradication rate of 97.1% (34/35) and 97.6% (41/42) (all p > .05), respectively. For the patients with complicated UTI, the clinical cure rate was 81.8% (27/33) in sitafloxacin group and 76.9% (20/26) in levofloxacin group corresponding to the bacterial eradication rate of 93.3% (14/15) and 63.6% (7/11) (all p > .05), respectively. Sitafloxacin and levofloxacin showed similar incidence of drug-related adverse events. CONCLUSIONS: Oral sitafloxacin is as effective and safe as levofloxacin in treating acute uncomplicated and complicated UTI. KEY MESSAGE: Oral sitafloxacin showed similar clinical cure rate and bacterial eradication rate as levofloxacin for treatment of complicated and uncomplicated urinary tract infections (UTIs) in a randomized, active-controlled, multicentre clinical trial. Oral sitafloxacin is safe and well-tolerated in treating acute uncomplicated and complicated UTIs in Chinese adults. Sitafloxacin is a promising alternative treatment option for UTIs in adults.

Synergistic Antibacterial Activity of Combined Antimicrobials and the Clinical Outcome of Patients With Carbapenemase-Producing Acinetobacter baumannii Infection.

This study aimed to explore the activity of combined antimicrobials in vitro, and the relationship among resistance mechanisms, antimicrobial regimens, and the clinical outcome of patients with carbapenem-resistant Acinetobacter baumannii (CRAB) infections in western China. A total of 89 CRAB strains were collected from patients with CRAB infection from January 2018 to June 2018. The checkerboard assay was used to study the combined effects in vitro. Carbapenemase-encoding genes were detected by polymerase chain reaction (PCR) or multiplex PCR technique. The clinical data of 86 patients were collected. CRAB showed high susceptibility to tigecycline (91.01% inhibition) and polymyxin (83.15% inhibition). Polymyxin plus sulbactam exhibited the highest synergistic effect at a rate of 82.35%. Production of carbapenemase (bla OXA-23) was the main resistance mechanism of CRAB to carbapenem (95.35%). Excessive expression of active efflux pump genes (adeB, adeJ, and abeM) and deletion of the CarO protein accounted for 13.95% (12/86) and 84.88% (73/86), respectively. The synergistic effect of the sulbactam-based combination was higher than that of the polymyxin B-tigecycline combination for carbapenemase-producing CRAB (P < 0.05). The clinical outcome was not affected by the resistance mechanisms (P > 0.05). Advanced age, multiple organ dysfunction syndromes (MODS), and admission to the intensive care unit (ICU) were associated with treatment failure (P < 0.05). Appropriate antibiotic therapy did not improve the clinical outcome of critically ill patients. Higher minimum inhibitory concentrations (MICs) of tigecycline were associated with treatment failure (P < 0.05). A multivariate analysis showed that ICU stay (OR = 15.123, 95% CI: 2.600-87.951, P = 0.002) and procalcitonin ≥2 ng/ml (OR = 2.636, 95% CI: 1.173-5.924, P = 0.019) were the risk factors for treatment failure. In conclusion, this study demonstrated that the sulbactam-based combination exhibited a synergistic effect in vitro. The clinical outcome of patients was not associated with resistance mechanisms. This indicates that the early control of the progression from infection to severe disease may be important.

Clinical characteristics and outcomes of patients with multidrug-resistant Gram-negative bacterial infections treated with ceftazidime/avibactam.

OBJECTIVES: The aim of this study was to investigate the clinical characteristics and outcomes of patients with infections caused by multidrug-resistant Gram-negative bacteria (MDR-GNB) treated with ceftazidime/avibactam (CAZ/AVI) during the period September 2019 to June 2020 since CAZ/AVI had been marketed in China. METHODS: A total of 20 MDR-GNB-infected patients were retrospectively identified using the electronic medical record system in West China Hospital. RESULTS: The mean age of the 20 patients 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 (55% 18/33) was the predominant pathogen. The 14-day clinical cure rate was 45%. The 14-day and 30-day mortality rates were 25% and 55%, respectively. No significant difference was found in 30-day mortality between treatment with CAZ/AVI monotherapy and combination regimens (P > 0.05). Three patients suffered from adverse drug reactions such as diarrhoea. CONCLUSION: No significant difference was found between the effectiveness of CAZ/AVI in the clinical failure and cure groups as salvage treatment of MDR-GNB infection.