Study for Monitoring Antimicrobial Resistance Trends (SMART) in the Asia-Pacific region, 2002–2010

Multi-drug resistant Enterobacterales is a growing health threat. Imipenem/relebactam and meropenem/vaborbactam, are not clinically used in Taiwan and the susceptibility is lack from routine laboratory tests.

Broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) and interpreted according to the Clinical and Laboratory Standards Institute (CLSI) breakpoints criteria. Isolates that were not susceptible to imipenem (MIC ≥ 2 mg/L), imipenem/relebactam (MIC ≥ 2 mg/L), or ceftolozane-tazobactam (MIC ≥ 4 mg/L) were selected for further molecular testing for genes encoding extended-spectrum beta-lactamases (ESBLs), AmpC β-lactamases, and carbapenemases by multiplex PCR assays.

A total of 290 Enterobacterales isolates from 9 participating hospitals were collected in 2020. Escherichia coli (n = 135, 46.6%) and Klebsiella pneumoniae (n = 88, 30.3%) were two leading pathogens of all Enterobacterales isolates. The antimicrobial agents with susceptibility rates more than 90% included amikacin (99.3%, 288/290), ertapenem (90.0%, 261/290), meropenem (97.2%, 282/290), imipenem/relebactam (94.8%, 275/290) and meropenem/vaborbactam (99.3%, 288/290). K. pneumoniae isolates were less susceptible to ertapenem, imipenem, meropenem, piperacillin-tazobactam and ceftozolane/tazobactam than E. coli (all p < 0.05). ESBL, AmpC, and carbapenemase were detected in 40.5% (17/42), 45.2% (19/42) and 11.9% (5/42) among tested isolates, respectively. The 5 carbapenemase genes included 4 bla_KPC and 1 bla_IMP. The imipenem-non-susceptible isolates (n = 30) had higher susceptibility rates to meropenem/vaborbactam (93.3%, 28/30) than imipenem/relebactam (50%, 12/30) (p < 0.05).

Imipenem/relebactam and meropenem/vaborbactam had excellent efficacy against Enterobacterales isolates. Meropenem/vaborbactam allowed better salvage therapy for carbapenem-resistant Enterobacterales infections.

Pseudomonas aeruginosa (P. aeruginosa) is an emerging opportunistic pathogen, which can cause bacterial skin diseases such as green nail syndrome, interdigital infections and folliculitis. Curcumin-mediated antimicrobial photodynamic therapy (aPDT) has been demonstrated as a promising therapeutic option for the treatment of skin infection though its inactivation of gram-negative bacteria such as P. aeruginosa.

In the present study, we examined the adjuvant effect of polymyxin B on the antibacterial activity of curcumin-mediated aPDT against P. aeruginosa. P. aeruginosa was treated with curcumin in the presence of 0.1–0.5 mg/L polymyxin B and irradiated by blue LED light (10 J/cm²). Bacterial cultures treated with curcumin alone served as controls. Colony forming units (CFU) were counted and the viability of P. aeruginosa was calculated after aPDT treatment. The possible underlying mechanisms for the enhanced killing effects were also explored.

The killing effects of curcumin-mediated aPDT against P. aeruginosa was significantly enhanced by polymyxin B (over 2-log reductions). Moreover, it was also observed that addition of polymyxin B in the curcumin-mediated aPDT led to the apparent bacterial membrane damage with increased leakage of cytoplasmic contents and extensive DNA and protein degradation.

The photodynamic action of curcumin against P. aeruginosa could be significantly enhanced by the FDA-approved drug polymyxin B. Our results highlight the potential of introducing polymyxin B to enhance the effects of aPDT treatment against gram-negative skin infections, in particular, P. aeruginosa.

Mucoid phenotype is an important adaptive defense response for Acinetobacter baumannii (A. baumannii). The aim of this study was to analyze the impact of mucoid phenotype for the molecular characteristics and virulence of A. baumannii. We observed that the colonies of mucoid A. baumannii were moist, with an elevated surface, and the wire drawing result was positive. Transmission electron microscopy data showed that the outer wall of the mucoid colonies was not smooth, had protruding pseudopodia, and was surrounded by a layer of unknown material. Antibiotic susceptibility testing showed that the mucoid strains were multidrug resistant. Notably, the mucoid phenotype and antibiotic resistance were not correlated with the amount of biofilm produced by A. baumannii. MLST data demonstrated that the mucoid A. baumannii strains belonged to type ST2. Most (82.6 %, 38/46) of the multidrug-resistant nonmucoid strains also belonged to the molecular type ST2 and to other types, including ST129, ST158, ST195, ST80 and ST3. Moreover, mucoid A. baumannii strains were more virulent than nonmucoid isolates in a mouse model. The comparative transcriptomic data indicated that 15 genes, especially IX87_RS16955 (acnA), IX87_RS10800 (XanP), IX87_RS12875 (GlmM), IX87_RS00885 and IX87_RS12395 (bfr), were possibly associated with the phenotype and virulence of mucoid A. baumannii. In conclusions, the study comprehensively describes the molecular characteristics and virulence regulatory mechanism of mucoid A. baumannii, and provides novel insights for the prevention and treatment of infections associated with these strains.

Levofloxacin is commonly prescribed to treat varied community-acquired gram-negative infections; knowledge of the therapeutic efficacies of high-dose (HD) administration is helpful to improve patient care.

In this 6-year cohort, adults with community-onset Enterobacteriaceae bacteremia were retrospectively studied in 2 hospitals. To overcome the confounding factors in the dosage choice of empiric administration, patients receiving empiric intravenous HD (750 mg/d) therapy were matched with those receiving the conventional dose (CD; 500 mg/d) by using individual propensity scores, calculated by the independent predictors of 30-day crude mortality.

Initially, more patients with critical illness (Pitt bacteremia score [PBS] ≥4) at bacteremia onset and comorbid malignancies and the higher 15- and 30-day mortality rate were recorded in 136 patients receiving HD therapy, compared to 103 receiving CD therapy. After appropriate matching, differences in patient demographic and clinical characteristics between the HD (n = 103) and CD (n = 103) groups were nonsignificant. Consequently, crude mortality rates at 3, 15, or 30 days after onset of bacteremia did not differ. However, the period of time to defervescence, total intravenous antimicrobial administration, and hospital stay was shorter in the HD group than in the CD group. Similarly, regardless if patients had more critical illness (PBS ≥2) or stabilized illness (PBS <2), the advantage of empiric HD therapy on defervescence remained significant. Within 60 days after discontinuation of intravenous levofloxacin therapy, the proportion of recurrent bacteremia, posttreatment overall infections, and posttreatment crude mortality was similar between the HD and CD groups.

For adults with community-onset Enterobacteriaceae bacteremia, empiric administration of HD levofloxacin was as effective as CD levofloxacin in reducing mortality and, notably, led to more rapid defervescence compared with CD administration.

Treating infections of Gram-negative pathogens, in particular Pseudomonas aeruginosa, is a challenge for clinicians in the Asia-Pacific region owing to inherent and acquired antimicrobial resistance. This systematic review and meta-analysis provides updated information on risk factors for P. aeruginosa infection in Asia-Pacific as well as the consequences (e.g. mortality, costs) of initial inappropriate antimicrobial therapy (IIAT).

Embase and MEDLINE databases were searched for Asia-Pacific studies reporting the consequences of IIAT versus initial appropriate antimicrobial therapy (IAAT) in Gram-negative bacterial infections as well as risk factors for serious P. aeruginosa infection. A meta-analysis of unadjusted mortality was performed using a random-effects model.

A total of 22 studies reporting mortality and 13 reporting risk factors were identified. The meta-analysis demonstrated that mortality was significantly lower in patients receiving IAAT versus IIAT, with a 67% reduction observed for 28- or 30-day all-cause mortality (odds ratio = 0.33, 95% confidence interval 0.20–0.55; P < 0.001). Risk factors for serious P. aeruginosa infection include previous exposure to antimicrobials, mechanical ventilation and previous hospitalisation.

High rates of antimicrobial resistance in Asia-Pacific as well as the increased mortality associated with IIAT and the presence of risk factors for serious infection highlight the importance of access to newer and appropriate antimicrobials.