Antimicrobial Susceptibility Among Gram-Negative Isolates in Pediatric Patients in Latin America, Africa-Middle East, and Asia From 2016-2020 Compared to 2011-2015: Results From the ATLAS Surveillance Study.

BACKGROUND: Antimicrobial resistance (AMR) data in the pediatric population are limited, particularly in developing countries. This study assessed the AMR profile and key resistance phenotypes and genotypes for Gram-negative bacteria (GNB) isolates collected as part of the Antimicrobial Testing Leadership and Surveillance program from pediatric patients in Latin America, Africa-Middle East, and Asia in 2016-2020 versus 2011-2015. METHODS: Minimum inhibitory concentrations by broth microdilution methodology were interpreted per the Clinical and Laboratory Standards Institute. European Committee on Antimicrobial Susceptibility Testing breakpoints were used for interpreting colistin activity. ß-lactamase genes were screened by polymerase chain reaction and sequencing. RESULTS: For Acinetobacter baumannii, low susceptibility (<60.0%) was observed for all antimicrobials, except colistin (≥92.9%), across regions and year periods. Ceftazidime-avibactam, amikacin, colistin, and meropenem were mostly active (78.6%-100.0%) against Enterobacter cloacae, Escherichia coli, and Klebsiella pneumoniae. For Pseudomonas aeruginosa, susceptibility to ceftazidime-avibactam, amikacin, and colistin was ≥85.9%. Among resistance phenotypes, carbapenem-resistant (CR, ≥44.8%) and difficult-to-treat resistant (DTR, ≥37.1%) rates were the highest in A. baumannii. A consistent increase in CR and DTR K. pneumoniae was noted across regions over time. Extended-spectrum ß-lactamases (ESBL)-producing K. pneumoniae (32.6%-55.6%) were more frequent than ESBL-producing E. coli (25.3%-37.1%). CTX-M was the dominant ESBL among Enterobacterales. NDM-positive Enterobacterales species and VIM-positive P. aeruginosa were identified across regions. CONCLUSIONS: This study identified high susceptibility to few agents for key GNB in pediatric patients. Continued surveillance of resistance phenotypes and genotypes at regional levels may help to guide appropriate treatment decisions.

In Vitro Activity of Ceftaroline and Comparators against Bacterial Isolates Collected Globally from Patients with Skin and Soft Tissue Infections: ATLAS Program 2019-2020.

The objective of this study was to assess the in vitro activity of ceftaroline and a panel of comparator agents against isolates causing skin and soft tissue infections (SSTIs) collected in Africa/Middle East, Asia-Pacific, Europe, and Latin America from 2019-2020. Minimum inhibitory concentrations (MIC) were determined using European Committee on Antimicrobial Susceptibility Testing criteria. All the methicillin-susceptible Staphylococcus aureus (MSSA) isolates were susceptible to ceftaroline. Across all regions, ceftaroline demonstrated potent activity against methicillin-resistant S. aureus (MRSA, susceptibility 89.5-93.7%) isolates. Susceptibility to vancomycin, daptomycin, linezolid, teicoplanin, trimethoprim sulfamethoxazole, and tigecycline was ≥94.1% in MSSA and MRSA isolates. Against ß-hemolytic streptococci isolates, ceftaroline demonstrated very potent activity (MIC90 0.008-0.03 mg/L) across all regions. All ß-hemolytic streptococci isolates were susceptible to linezolid, penicillin, and vancomycin (MIC90 0.06-2 mg/L). Among the extended-spectrum ß-lactamases (ESBL)-negative Enterobacterales tested (E. coli, K. pneumoniae, and K. oxytoca), susceptibility to ceftaroline was high (88.2-98.6%) in all regions. All ESBL-negative Enterobacterales were susceptible to aztreonam. Potent activity was observed for amikacin, cefepime, and meropenem (94.1-100%) against these isolates. Overall, ceftaroline showed potent in vitro activity against isolates of pathogens causing SSTIs. Continuous surveillance of global and regional susceptibility patterns is needed to guide appropriate treatment options against these pathogens.

Ceftazidime-avibactam and comparators against Pseudomonas aeruginosa isolates collected globally and in each geographical region between 2017-2020.

OBJECTIVES: The objective of this study was to assess the distribution and antimicrobial susceptibility of Pseudomonas aeruginosa isolates against ceftazidime-avibactam (CAZ-AVI) and a panel of comparator agents collected globally and in each region from 2017-2020 from the Antimicrobial Testing Leadership and Surveillance program. METHODS: Susceptibility and minimum inhibitory concentration of all P. aeruginosa isolates were determined using broth microdilution methodology according to the Clinical and Laboratory Standards Institute guidelines. RESULTS: Of the total 29746 isolates of P. aeruginosa collected, 20.9% were multidrug resistant (MDR), 20.7% were extremely drug resistant (XDR), 8.4% were CAZ-AVI-resistant (CAZ-AVI-R), and 3.0% were MBL-positive. Amongst the MBL-positive isolates, the proportion of VIM-positive isolates was highest (77.8%). The highest proportion of MDR (25.5%), XDR (25.0%), MBL-positive (5.7%), and CAZ-AVI-R (12.3%) isolates were in Latin America. Amongst the sources, the highest proportion of isolates were from respiratory sources (43.0%), and the majority of isolates were from non-intensive care unit wards (71.2%). Overall, all P. aeruginosa isolates (90.9%) showed high susceptibility to CAZ-AVI. However, MDR and XDR isolates were less susceptible to CAZ-AVI (≤60.7). The only comparators to which all isolates of P. aeruginosa showed good overall susceptibility were colistin (99.1%) and amikacin (90.5%). However, only colistin was active (≥98.3%) against all the resistant isolates. CONCLUSION: CAZ-AVI presents a potential treatment option against P. aeruginosa infections. However, active monitoring and surveillance, especially of the resistant phenotypes, is warranted for effective treatment of infections caused by P. aeruginosa.

Antimicrobial Activity of Ceftazidime-Avibactam and Comparators Against Fluoroquinolone-Resistant Klebsiella pneumoniae Collected Globally from Antimicrobial Testing Leadership and Surveillance: 2018-2019.

This study assessed the in vitro antimicrobial activity of ceftazidime-avibactam (CAZ-AVI) and a panel of comparator agents, including aztreonam, cefepime, ceftazidime, meropenem, imipenem, colistin, piperacillin-tazobactam, and tigecycline against isolates of fluoroquinolone-resistant (FQ-R) Klebsiella pneumoniae collected in 2018 and 2019 from the Antimicrobial Testing Leadership and Surveillance (ATLAS) program. Susceptibility and minimum inhibitory concentration were determined using broth microdilution for all antimicrobial agents by a central reference laboratory according to the Clinical and Laboratory Standards Institute guidelines and European Committee on Antimicrobial Susceptibility Testing guidelines. Of all the K. pneumoniae isolates (n = 10,906), 44.1% (4,814/10,906) were FQ-R. Of these, 71.3% (3,432/4,814) were extended-spectrum ß-lactamase (ESBL)-positive, and 10.4% (499/4,814) were CAZ-AVI-resistant. CAZ-AVI showed high susceptibility (>87%) against all the FQ-R K. pneumoniae isolates. However, metallo- ß-lactamase-positive isolates showed low susceptibility (3.8%; 18/470) to CAZ-AVI. Among the different geographical regions, CAZ-AVI showed the highest activity against isolates collected from North America (98.2%, 216/220) and lowest against those collected from Asia Pacific (APAC) (81.7%; 882/1,079). Among comparator agents, carbapenems showed a relatively lower susceptibility (<71.5%), while only tigecycline and colistin were active (>85%) across all isolates. In conclusion, CAZ-AVI may be a potential treatment option for FQ-R K. pneumoniae isolates. However, increasing CAZ-AVI resistance among ESBL-positive and metallo-ß-lactamase-positive isolates and in isolates from APAC warrants continuous surveillance.

Early appropriate diagnostics and treatment of MDR Gram-negative infections.

The term difficult-to-treat resistance has been recently coined to identify Gram-negative bacteria exhibiting resistance to all fluoroquinolones and all ß-lactam categories, including carbapenems. Such bacteria are posing serious challenges to clinicians trying to identify the best therapeutic option for any given patient. Delayed appropriate therapy has been associated with worse outcomes including increase in length of stay, increase in total in-hospital costs and ∼20% increase in the risk of in-hospital mortality. In addition, time to appropriate antibiotic therapy has been shown to be an independent predictor of 30 day mortality in patients with resistant organisms. Improving and anticipating aetiological diagnosis through optimizing not only the identification of phenotypic resistance to antibiotic classes/agents, but also the identification of specific resistance mechanisms, would have a major impact on reducing the frequency and duration of inappropriate early antibiotic therapy. In light of these considerations, the present paper reviews the increasing need for rapid diagnosis of bacterial infections and efficient laboratory workflows to confirm diagnoses and facilitate prompt de-escalation to targeted therapy, in line with antimicrobial stewardship principles. Rapid diagnostic tests currently available and future perspectives for their use are discussed. Early appropriate diagnostics and treatment of MDR Gram-negative infections require a multidisciplinary approach that includes multiple different diagnostic methods and further consensus of algorithms, protocols and guidelines to select the optimal antibiotic therapy.

Strain Specific Variations in Acinetobacter baumannii Complement Sensitivity.

The complement system is required for innate immunity against Acinetobacter baumannii, an important cause of antibiotic resistant systemic infections. A. baumannii strains differ in their susceptibility to the membrane attack complex (MAC) formed from terminal complement pathway proteins, but the reasons for this variation remain poorly understood. We have characterized in detail the complement sensitivity phenotypes of nine A. baumannii clinical strains and some of the factors that might influence differences between strains. Using A. baumannii laboratory strains and flow cytometry assays, we first reconfirmed that both opsonization with the complement proteins C3b/iC3b and MAC formation were inhibited by the capsule. There were marked differences in C3b/iC3b and MAC binding between the nine clinical A. baumannii strains, but this variation was partially independent of capsule composition or size. Opsonization with C3b/iC3b improved neutrophil phagocytosis of most strains. Importantly, although C3b/iC3b binding and MAC formation on the bacterial surface correlated closely, MAC formation did not correlate with variations between A. baumannii strains in their levels of serum resistance. Genomic analysis identified only limited differences between strains in the distribution of genes required for serum resistance, but RNAseq data identified three complement-resistance genes that were differentially regulated between a MAC resistant and two MAC intermediate resistant strains when cultured in serum. These data demonstrate that clinical A. baumannii strains vary in their sensitivity to different aspects of the complement system, and that the serum resistance phenotype was influenced by factors in addition to the amount of MAC forming on the bacterial surface.

Clinical data from studies involving novel antibiotics to treat multidrug-resistant Gram-negative bacterial infections.

Multidrug-resistant (MDR) Gram-negative bacteria (GNB) pose a critical threat to global healthcare, worsening outcomes and increasing mortality among infected patients. Carbapenemase- and extended-spectrum ß-lactamase-producing Enterobacterales, as well as carbapenemase-producing Pseudomonas and Acinetobacter spp., are common MDR pathogens. New antibiotics and combinations have been developed to address this threat. Clinical trial findings support several combinations, notably ceftazidime-avibactam (CZA, a cephalosporin-ß-lactamase inhibitor combination), which is effective in treating complicated urinary tract infections (cUTI), complicated intra-abdominal infections and hospital-acquired and ventilator-associated pneumonia caused by GNBs. Other clinically effective combinations include meropenem-vaborbactam (MVB), ceftolozane-tazobactam (C/T) and imipenem-relebactam (I-R). Cefiderocol is a recent siderophore ß-lactam antibiotic that is useful against cUTIs caused by carbapenem-resistant Enterobacterales (CRE) and is stable against many ß-lactamases. Carbapenem-resistant Enterobacterales are a genetically heterogeneous group that vary in different world regions and are a substantial cause of infections, among which Klebsiella pneumoniae are the most common. Susceptible CRE infections can be treated with fluoroquinolones, aminoglycosides or fosfomycin, but alternatives include CZA, MVB, I-R, cefiderocol, tigecycline and eravacycline. Multidrug-resistant Acinetobacter baumannii and Pseudomonas aeruginosa are increasingly common pathogens producing a range of different carbapenemases, and infections are challenging to treat, often requiring novel antibiotics or combinations. Currently, no single agent can treat all MDR-GNB infections, but new ß-lactam-ß-lactamase inhibitor combinations are often effective for different infection sites and, when used appropriately, have the potential to improve outcomes. This article reviews clinical studies investigating novel ß-lactam approaches for treatment of MDR-GNB infections.

In Vitro Activity of Ceftolozane-Tazobactam and Other Antibiotics against Pseudomonas aeruginosa Infection-Isolates from an Academic Medical Center in Thailand.

(1) Background: Resistant Pseudomonas aeruginosa (PA) infections have limited treatment options. Data on the activity of ceftolozane-tazobactam (C-T) against PA in Thailand are limited. Objectives: The objective of this study was to identify the in vitro activity of C-T against general and resistant PA isolates from patients with real clinical infections from the HRH Princess Maha Chakri Sirindhorn Medical Center (MSMC) compared to other antibiotics and to study the resistant molecular patterns of those PA strains which were resistant to C-T. (2) Materials and Methods: This was an in vitro susceptibility study of 100 PA isolates plus an additional seven resistant PA isolates collected from MSMC patients. All PA isolates were tested with susceptibility broth (Sensititre™) and C-T minimal inhibitory concentration (MIC) test strips (Liofilchem, Roseto degli, Abruzzi, Italy). The C-T-resistant PA isolates were analyzed for six ß-lactamase genes (blaCTX-M, blaNDM, blaIMP, blaVIM, blaOXA-23 and blaOXA-48) and the mcr-1 gene. (3) Results: A total of 100 PA isolates were collected between January 2020 and January 2021 and between February 2021 and September 2021 for the additional 7 resistant isolates. There were 18 resistant PA isolates (6 MDR, 11 XDR and 1 pan-drug resistant isolate). The overall susceptibility of the initial 100 PA isolates and the 18 resistant PA isolates was 94% and 44.5%, respectively, for C-T. The C-T susceptibility rates for isolates non-susceptible to ceftazidime, piperacillin-tazobactam, carbapenems and antipseudomonal ß-lactams were 65.5%, 69.7%, 50% and 44.5%, respectively. Among the 10 isolates which were resistant to C-T, there were only 3 isolates found to have the resistant gene, which included 1 for blaIMP, 1 for blaVIM and 1 for blaNDM. (4) Conclusions: Although C-T was the best susceptibility antibiotic overall for PA isolates and MDR PA isolates at the MSMC, most of the XDR PA isolates and the PDR PA isolate were not susceptible to C-T. The mechanisms for C-T resistance involved multiple factors including the presence of blaIMP, blaVIM and blaNDM.

Antimicrobial-resistant Bacteroides fragilis in Thailand and their inhibitory effect in vitro on the growth of Clostridioides difficile.

OBJECTIVES: The aim of this study was to investigate antimicrobial-resistant Bacteroides fragilis in Thailand and possible effects of such strains on human health and disease. METHODS: Phenotypic antimicrobial susceptibility testing was performed on 17 clinical B. fragilis isolates. The genome of one isolate was sequenced and analysed to explore its resistance genotype. An in vitro growth assay was conducted to evaluate the inhibitory effect of B. fragilis on Clostridioides difficile. RESULTS: There was a high prevalence of clindamycin (71%), meropenem (47%) and moxifloxacin (29%) resistance. Most strains remained susceptible to metronidazole, but one had high-level metronidazole resistance conferred by a nimD-containing plasmid. B. fragilis displayed an in vitro inhibitory effect on the growth of C. difficile and a drug-resistant strain retained this inhibition in the presence of clindamycin. CONCLUSIONS: Antimicrobial resistance was seen in Thai B. fragils isolates, which may help protect the host against C. difficile infection.

In vitro activity of ceftazidime/avibactam and comparators against carbapenemase-producing Enterobacterales and Pseudomonas aeruginosa isolates collected globally between 2016 and 2018.

OBJECTIVES: This study reports the antimicrobial activity of ceftazidime/avibactam (CZA) and comparators against carbapenemase-producing Enterobacterales (N = 1992) and carbapenemase-producing Pseudomonas aeruginosa (N = 784) collected in Africa/Middle East, Asia/South Pacific, Europe and Latin America (2016-2018). METHODS: Minimum inhibitory concentrations (MICs) and susceptibility were determined using broth microdilution methodology and EUCAST breakpoints. Carbapenemase-encoding genes were detected using multiplex PCR. RESULTS: No isolates of carbapenemase-producing, metallo-ß-lactamase (MBL)-negative Enterobacterales from Africa/Middle East or Latin America were resistant to CZA; resistance rates in Europe and Asia/South Pacific were ≤4.5%. Colistin had the lowest resistance rate among MBL-positive isolates (6.0-11.4%). Enterobacterales isolates collected in Latin America predominantly carried a KPC carbapenemase (77.6%), whereas in Africa/Middle East OXA-48-like carbapenemases were most frequently detected (55.9%), and in Asia/South Pacific most isolates carried NDM carbapenemases (56.2%). Among all Enterobacterales carrying KPC carbapenemases, the lowest rate of resistance was to CZA (1.5%), and among isolates carrying NDM carbapenemases it was to colistin (10.8%). Among carbapenemase-producing, MBL-negative P. aeruginosa, resistance rates to CZA were 8.6% for isolates collected in Europe and 53.2% in Latin America. Isolates in each region most frequently carried VIM carbapenemases, ranging from 41.7% of isolates in Asia/South Pacific to 86.2% in Africa/Middle East. No P. aeruginosa carrying KPC or NDM carbapenemases and 1.0% of isolates carrying GES carbapenemases were resistant to colistin. CONCLUSION: Given the limited therapeutic options to treat infections caused by carbapenemase-positive Enterobacterales and P. aeruginosa, continued surveillance of CZA activity as well as agents such as colistin is crucial.

Sequential Vaccination With Heterologous Acinetobacter baumannii Strains Induces Broadly Reactive Antibody Responses.

Antibody therapy may be an alternative treatment option for infections caused by the multi-drug resistant (MDR) bacterium Acinetobacter baumannii. As A. baumannii has multiple capsular serotypes, a universal antibody therapy would need to target conserved protein antigens rather than the capsular polysaccharides. We have immunized mice with single or multiple A. baumannii strains to induce antibody responses to protein antigens, and then assessed whether these responses provide cross-protection against a collection of genetically diverse clinical A. baumannii isolates. Immunized mice developed antibody responses to multiple protein antigens. Flow cytometry IgG binding assays and immunoblots demonstrated improved recognition of both homologous and heterologous clinical strains in sera from mice immunized with multiple strains compared to a single strain. The capsule partially inhibited bacterial recognition by IgG and the promotion of phagocytosis by human neutrophils. However, after immunization with multiple strains, serum antibodies to protein antigens promoted neutrophil phagocytosis of heterologous A. baumannii strains. In an infection model, mice immunized with multiple strains had lower bacterial counts in the spleen and liver following challenge with a heterologous strain. These data demonstrate that antibodies targeting protein antigens can improve immune recognition and protection against diverse A. baumannii strains, providing support for their use as an antibody therapy.

Nationwide Surveillance and Molecular Characterization of Critically Drug-Resistant Gram-Negative Bacteria: Results of the Research University Network Thailand Study.

A large-scale surveillance is an important measure to monitor the regional spread of antimicrobial resistance. We prospectively studied the prevalence and molecular characteristics of clinically important Gram-negative bacilli, including Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii complex (ABC), and Pseudomonas aeruginosa, from blood, respiratory tract, urine, and sterile sites at 47 hospitals across Thailand. Among 187,619 isolates, 93,810 isolates (50.0%) were critically drug resistant, of which 12,915 isolates (13.8%) were randomly selected for molecular characterization. E. coli was most commonly isolated from all specimens, except the respiratory tract, in which ABC was predominant. Prevalence of extended-spectrum cephalosporin resistance (ESCR) was higher in E. coli (42.5%) than K. pneumoniae (32.0%), but carbapenem-resistant (CR)-K. pneumoniae (17.2%) was 4.5-fold higher than CR-E. coli (3.8%). The majority of ESCR/CR-E. coli and K. pneumoniae isolates carried blaCTX-M (64.6% to 82.1%). blaNDM and blaOXA-48-like were the most prevalent carbapenemase genes in CR-E. coli/CR-K. pneumoniae (74.9%/52.9% and 22.4%/54.1%, respectively). In addition, 12.9%/23.0% of CR-E. coli/CR-K. pneumoniae cocarried blaNDM and blaOXA-48-like. Among ABC isolates, 41.9% were extensively drug resistant (XDR) and 35.7% were multidrug resistant (MDR), while P. aeruginosa showed XDR/MDR at 6.3%/16.5%. A. baumannii was the most common species among ABC isolates. The major carbapenemase gene in MDR-A. baumannii/XDR-A. baumannii was blaOXA-23-like (85.8%/93.0%), which had much higher rates than other ABC species. blaIMP, blaVIM, blaOXA-40-like, and blaOXA-58-like were also detected in ABC at lower rates. The most common carbapenemase gene in MDR/XDR-P. aeruginosa was blaIMP (29.0%/30.6%), followed by blaVIM (9.5%/25.3%). The findings reiterate an alarming situation of drug resistance that requires serious control measures.

Molecular Characterization of, and Antimicrobial Resistance in, Clostridioides difficile from Thailand, 2017-2018.

Antimicrobial resistance (AMR) plays an important role in the pathogenesis and spread of Clostridioides difficile infection (CDI). Many antimicrobials, such as fluoroquinolones, have been associated with outbreaks of CDI globally. This study characterized AMR among clinical C. difficile strains in Thailand, where antimicrobial use remains inadequately regulated. Stool samples were screened for tcdB and positives were cultured. C. difficile isolates were characterized by toxin profiling and PCR ribotyping. Antimicrobial susceptibility testing was performed by agar incorporation, and whole-genome sequencing and AMR genotyping were performed on a subset of strains. There were 321 C. difficile strains isolated from 326 stool samples. The most common toxigenic ribotype (RT) was RT 017 (18%), followed by RTs 014 (12%) and 020 (7%). Resistance to clindamycin, erythromycin, moxifloxacin, and rifaximin was common, especially among RT 017 strains. AMR genotyping revealed a strong correlation between resistance genotype and phenotype for moxifloxacin and rifaximin. The presence of erm-class genes was associated with high-level clindamycin and erythromycin resistance. Point substitutions in the penicillin-binding proteins were not sufficient to confer meropenem resistance, but a Y721S substitution in PBP3 was associated with a 4.37-fold increase in meropenem minimal inhibitory concentration. No resistance to metronidazole, vancomycin, or fidaxomicin was observed.

First characterization of Tn1546-like structures of vancomycin-resistant Enterococcus faecium Thai isolates.

INTRODUCTION: Vancomycin-resistant Enterococcus faecium (VREfm) carrying vanA was first isolated from patient at Siriraj Hospital, Thailand in 2004. Since then, VREfm isolates have been detected increasingly in this 2500-bed university hospital. To understand the epidemiology of vanA VREfm in this setting, the isolates collected during 2004-2013 were characterized. METHODS: A total of 49 vanA VREfm isolates previously confirmed by multiplex PCR were characterized by determining resistance phenotypes to vancomycin, teicoplanin, ampicillin and ciprofloxacin by broth microdilution method. Multilocus sequence typing (MLST) and virulence genes of those isolates were investigated. The Tn1546 structure diversity was studied by long-range overlapping PCR and primer walking sequencing. RESULTS: Of all isolates studied, 9 sequence types (ST17, ST80, ST78, ST730, ST203, ST18, ST280, ST64, ST323) in clonal complex 17 and a novel ST1051 were revealed. The esp-positive isolates were 73.5%. Of all vanA operons characterized, at least 9 types of Tn1546-like structures were detected. All of vanA determinants contained 5'-end different from the Tn1546 prototype. Approximately 47% of them also carried the insertion sequence IS1251 at the intergenic region between vanS and vanH. Interestingly, another IS (ISEfa4) was found to be inside the sequence of IS1251 in ST17 isolate. CONCLUSION: Heterogeneity of vanA VREfm was observed. Nearly all of isolates studied belonged to CC17. One novel ST1051 strain was detected. Isolates in the initial period carried vanA operon similar to the prototype. The diversity of vanA determinants has been increased in the recent isolates. A novel vanA operon structure was detected.

Prevalence of nasal carriage of Staphylococcus aureus in allergic rhinitis patients and healthy controls in Thailand.

BACKGROUND: Staphylococcus aureus has been proposed as a disease modifier of allergic rhinitis (AR) severity. Although several studies have investigated the prevalence of nasal carriage of S. aureus in healthy controls and AR patients, data from Thailand is scarce. OBJECTIVE: The aim of this study was to determine the prevalence of nasal carriage of S. aureus in AR patients compared with healthy controls in Thailand. METHODS: This prospective study enrolled non-AR healthy controls and confirmed AR aged 18-60 years who attended the Department of Otorhinolaryngology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand during June 2013 and December 2013. To detect nasal carriage of S. aureus, nasal swab was used for specimen collection from the nasal vestibule. S. aureus prevalence was compared between groups. All AR patients were assessed for disease severity and quality of life. RESULTS: The 200 enrolled participants were evenly divided between the AR and healthy control groups. Nasal swab cultures were positive for S. aureus in 20 of 100 subjects in the healthy control group, and in 21 of 100 subjects in the AR group (p = 0.86). Nasal carriage of S. aureus was significantly more prevalent in males than in females (p = 0.01). None of the investigated factors were found to be significantly associated with AR severity among S. aureus-positive AR subjects. CONCLUSIONS: The 20% prevalence of S. aureus in AR patients is not different from that of healthy controls in Thailand, and is similar to other reported rates. No significant associations with AR severity were identified.

Genomic basis of antimicrobial resistance in non-toxigenic Clostridium difficile in Southeast Asia.

Despite being incapable of causing Clostridium difficile infection, non-toxigenic C. difficile (NTCD) may still be relevant. This study explored the role of NTCD as a reservoir of accessory antimicrobial resistance (AMR) genes in NTCD from Southeast Asia. This region has high rates of antimicrobial use, a high prevalence of NTCD and phenotypic AMR in such strains. More than half of the 28 NTCD strains investigated had at least one accessory AMR gene on mobile genetic elements (MGEs) which were similar to the elements found in other bacteria, including Erysipelothrix rhusiopathiae and Streptococcus suis, both of which are found in the pig gut. Thus, C. difficile may facilitate the movement of AMR genes between different hosts within a wide range of pathogenic bacteria. C. difficile ß-lactamases were not located on MGEs and were unlikely to be transferred. Concordance between the MLSB resistance genotype and phenotype was low, suggesting multiple resistance mechanisms, many of which remain unknown. On the contrary, there was a high concordance between resistance genotype and phenotype for both fluoroquinolones and rifaximin. From an epidemiological perspective, NTCD populations in Southeast Asia comprised members of evolutionary clades 1 and 4, which are thought to have originated from Europe and Asia, respectively. This population structure reflects the close relationship between the people of the two regions.

Stenotrophomonas maltophilia Infections: Clinical Characteristics and Factors Associated with Mortality of Hospitalized Patients.

PURPOSE: To study the clinical characteristics and factors associated with mortality of patients who had Stenotrophomonas maltophilia infections. PATIENTS AND METHODS: We conducted a retrospective study to determine the clinical characteristics and factors associated with mortality for S. maltophilia infections among hospitalized adult patients at Siriraj Hospital. The clinical and microbiological data were collected from medical records December 2013-December 2016. RESULTS: Of 1221 subjects whose clinical samples grew S. maltophilia, 213 were randomly selected for chart review. One hundred patients with a true infection were analyzed. Their median age was 66 years; 47 were males; 46 were critically ill with a median APACHE II score of 18 (2-32); and 91 received antibiotic treatment, mainly with carbapenems (56%), before being diagnosed with a S. maltophilia infection. Pulmonary (53%) and bloodstream infections (25%) were the most common infections. The median length of hospitalization was 19 days before infection onset. The in-hospital mortality rate was 54%. The following factors were associated with mortality: a pre-existing respiratory infection (OR 6.28, 1.33-29.78; p.021); critical illness (OR 3.33, 1.45-7.62; p.005); multi-organ dysfunction (OR 2.44, 1.05-5.70; p.039); being on mechanical ventilation (OR 4.44, 1.90-10.39; p.001); concurrent immunosuppressive therapy (OR 2.67, 1.10-6.47; p.029); intravascular (OR 4.43, 1.79-10.92; p.001) and urinary catheterization (OR 4.83, 1.87-12.47; p.001); and serum albumin <3 g/dL (OR 4.13, 1.05-16.33; p.043). A multivariate analysis identified two independent factors associated with mortality: being on mechanical ventilation (OR 4.43, 1.86-10.59; p 0.001) and receiving concurrent immunosuppressive therapy (OR 2.26, 1.04-6.82; p 0.042). CONCLUSION: S. maltophilia can cause nosocomial infections with high mortality, particularly in patients with a prolonged hospitalization. Concurrent immunosuppressive therapy and being on mechanical ventilation are the independent factors associated with a fatal outcome.

Mild or Malign: Clinical Characteristics and Outcomes of Clostridium difficile Infection in Thailand.

Little is known about the clinical characteristics of Clostridium difficile infection (CDI) in Asia in general, and Thailand specifically, with a few studies suggesting that the disease may be milder than elsewhere. This study aimed to describe CDI in Thailand, evaluate treatment options and their outcomes, and explore possible protective factors responsible for any unique disease characteristics. From 2015 to 2018, 469 patients were included in the study. All patients had their stools tested for the tcdB gene by direct PCR and detection of toxigenic C. difficile by culture. C. difficile isolates were subjected to toxin gene profiling and ribotyping, and patient medical records were reviewed retrospectively. There were 248 and 221 patients included in CDI and control groups, respectively. The CDI group had a higher overall 30-day mortality rate than the control group (21% versus 14%, P = 0.046), but only 2 deaths (1%) were directly attributable to CDI. Metronidazole treatment was not inferior to vancomycin in this population, and vancomycin was associated with a higher 30-day mortality rate (P = 0.047). The prevalence of severe CDI and disease outcomes were not different between patients infected with A-B+ C. difficile and A+B+ C. difficile strains or between patients with and without colonization by nontoxigenic C. difficile Besides C. difficile-specific tests, neither a single laboratory result nor a combination of results was predictive of CDI. In conclusion, CDI in Thailand was relatively mild, and metronidazole remained an effective treatment option for these mild infections.