Carbapenemase-producing Enterobacterales infections: recent advances in diagnosis and treatment.

Increasing carbapenem resistance in Enterobacterales poses a threat to public health. In recent decades, this increase in carbapenem resistance has been caused by the global dissemination of carbapenemase-producing Enterobacterales (CPE). Carbapenemases are members of the ß-lactamases that are divided into classes A, B and D based on their molecular structures. Although certain traditionally used antibiotics, such as amikacin, polymyxins, tigecycline and fosfomycin, may remain effective against some CPE, their clinical use is limited owing to adverse effects, including renal toxicity, tissue penetration or the requirement for combination treatment. Recently, several novel agents have been approved for clinical use, such as ceftazidime/avibactam, ceftolozane/tazobactam, cefiderocol, eravacycline, omadacycline, meropenem/vaborbactam, imipenem/cilastatin/relebactam and plazomicin. However, the spectrum of antimicrobial activities and efficacies of novel agents vary depending on the mechanisms associated with carbapenem resistance in Enterobacterales. Therefore, it is of utmost importance to enable accurate and rapid diagnosis of CPE infection, including the determination of their antimicrobial resistance mechanisms. Here, recent advances in methods for the identification of CPE have been reviewed, including phenotypic methods (carbapenemase inactivation methods), biochemical methods [Carbapenemase Nordmann-Poirel (Carba NP) test and modified Carba NP test], immunochromatographic methods, proteomic methods [matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF/MS)] and molecular-based methods [nucleic acid amplification technologies, hybridisation techniques (microarray) and whole-genome sequencing]. Both precise diagnosis and adequate treatment are important to combat the emerging CPE crisis.

Efficacy of induction regimens for cryptococcal meningitis in HIV-infected adults: a systematic review and network meta-analysis.

Cryptococcal meningitis (CM) is the most fatal adult meningitis in patients with human immunodeficiency virus (HIV). There is no conclusive evidence for the superiority of 1-week amphotericin B deoxycholate (AmphB) + flucytosine (5-FC) regimen over other antifungals in the management of HIV patients with CM (HIV-CM patients). We aimed to evaluate the differences in efficacy and tolerability of different antifungal agents in HIV-CM patients by conducting a current network meta-analysis NMA. Overall, 19 randomized controlled trials were included with 2642 participants. A regimen indicated a possibly lower early mortality rate, namely, AmphB + 5-FC + Azole (OR = 1.1E-12, 95% CIs = 1.3E-41 to 0.06) comparing to AmphB + 5-FC. The current NMA provides evidence that AmphB + 5-FC + Azole are superior to all the investigated treatments for induction regimen in HIV-CM patients.

Recommendations and guidelines for the treatment of Clostridioides difficile infection in Taiwan.

Clostridioides difficile infection (CDI) is a major enteric disease associated with antibiotic use and a leading cause of hospital-acquired infections worldwide. This is the first guideline for treatment of CDI in Taiwan, aiming to optimize medical care for patients with CDI. The target audience of this document includes all healthcare personnel who are involved in the medical care of patients with CDI. The 2018 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group was formed, comprising of infectious disease specialists from 13 medical centers in Taiwan, to review the evidence and draft recommendations using the grading of recommendations assessment, development, and evaluation (GRADE) methodology. A nationwide expert panel reviewed the recommendations during a consensus meeting in March 2019. The recommendation is endorsed by the Infectious Diseases Society of Taiwan (IDST). This guideline describes the epidemiology and risk factors of CDI, and provides recommendations for treatment of CDI in both adults and children. Recommendations for treatment of the first episode of CDI, first recurrence, second and subsequent recurrences of CDI, severe CDI, fulminant CDI, and pediatric CDI are provided.

Recommendations and guidelines for the treatment of pneumonia in Taiwan.

Pneumonia is a leading cause of death worldwide, ranking third both globally and in Taiwan. This guideline was prepared by the 2017 Guidelines Recommendations for Evidence-based Antimicrobial agents use in Taiwan (GREAT) working group, formed under the auspices of the Infectious Diseases Society of Taiwan (IDST). A consensus meeting was held jointly by the IDST, Taiwan Society of Pulmonary and Critical Care Medicine (TSPCCM), the Medical Foundation in Memory of Dr. Deh-Lin Cheng, the Foundation of Professor Wei-Chuan Hsieh for Infectious Diseases Research and Education and CY Lee's Research Foundation for Pediatric Infectious Diseases and Vaccines. The final guideline was endorsed by the IDST and TSPCCM. The major differences between this guideline and the 2007 version include the following: the use of GRADE methodology for the evaluation of available evidence whenever applicable, the specific inclusion of healthcare-associated pneumonia as a category due to the unique medical system in Taiwan and inclusion of recommendations for treatment of pediatric pneumonia. This guideline includes the epidemiology and recommendations of antimicrobial treatment of community-acquired pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, healthcare-associated pneumonia in adults and pediatric pneumonia.

The experience of intramuscular benzathine penicillin for prophylaxis of recurrent cellulitis: A cohort study.

BACKGROUND/PURPOSE: Recurrent cellulitis is an important clinical issue but the optimal strategy for prophylaxis is not determined. Intramuscular benzathine penicillin at a 4-week interval had been adopted in our hospital and the study was conducted to evaluate the efficacy. METHODS: From January 1, 2009 to May 31, 2013, all patients aged ≥ 18 year, with a history of recurrent cellulitis and having received at least three shots of intramuscular benzathine penicillin for prophylaxis were retrospectively recruited for analysis. Two treatment periods (prophylaxis period and nonprophylaxis period) were defined. The effects of benzathine penicillin prophylaxis and patient characteristics on the incidence rate of recurrent cellulitis were analyzed using Poisson regression model. RESULTS: A total of 72 patients were enrolled, including 26 (36.1%) men. The most common underlying conditions were past surgery at the proximal side of the affected limb (38, 52.8%), malignancy (31, 43.1%), and diabetes mellitus (24, 33.3%). The incidence rate of recurrent cellulitis in the prophylaxis period was 0.73 episode/patient-year, significantly lower than that of 1.25 episodes/patient-year in the nonprophylaxis period (p < 0.001). Tinea pedis was a significant factor associated with increasing incidence of recurrent cellulitis in our cohort. CONCLUSION: Intramuscular benzathine penicillin at a 4-week interval may be an effective prophylactic strategy to reduce the incidence of cellulitis. Further studies are necessary to determine the factors associated with failure of prophylaxis as well as optimal individualized dosage and dosing interval of the prophylactic agent.