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.

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.

Composition of the intestinal microbiota in extended-spectrum ß-lactamase-producing Enterobacteriaceae carriers and non-carriers in Thailand.

There is increasing recognition that the intestinal microbiota govern human well-being and prevent diseases. Intestinal colonization by antibiotic-resistant pathogens, however, can lead to the spread of resistance as well as serious infections. Extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-E) represent particularly dangerous pathogens, which are known to asymptomatically colonize the intestinal tract in the community. Here, we performed a 16S rRNA metagenomics sequence analysis to analyse differences in the microbiota composition between ESBL-E carriers and non-carriers in Thailand, where ESBL-E carriage rates are notoriously high. The most notable difference detected was that the phylum Bacteroidetes, and in particular, the species Bacteroides uniformis, were significantly more abundant in ESBL-E non-carriers than carriers. The Shannon diversity index in non-carriers (5.10 ± 0.69) was also lower than that in ESBL-E carriers (5.39 ± 0.48) without statistical significance (P=0.13). The overall beta diversity difference of the intestinal microbiota of ESBL-E carriers as compared to non-carriers was statistically significant (Adonis on weighted unifrac: R2=0.14, P=0.005). Furthermore, ESBL-E carriage was significantly lower in farmers than in those with other occupations. Our findings suggest that a dynamic interaction exists between microbiota diversity and ESBL-E carriage, which is possibly driven by dietary composition and may be exploited using probiotic approaches to control the spread of ESBL-E.

Application of Pharmacodynamic Profiling for the Selection of Optimal ß-lactam Regimens in a Large University Hospital.

BACKGROUND: Infections caused by drug-resistant Gram-negative bacteria (GNB) are increasing worldwide and as a result, the selection of appropriate empiric antibiotics (ATBs) has been made increasingly difficult. The present study aimed to identify optimized dosing regimens of intravenous (IV) ATBs, defined by cumulative fraction response (CFR), against E. coli (EC), K. pneumoniae (KP), P. aeruginosa (PA), and A. baumannii (AB) at 2,300-bed University Hospital. MATERIALS AND METHODS: The minimum inhibitory concentrations (MIC) of EC, KP, PA, and AB from clinical specimens, 250 each, were determined. Pharmacodynamic profiling using Monte Carlo Simulation was performed for standard, high dosage, and prolonged infusions (PI) of ceftriaxone, cefepime, ceftazidime, imipenem, meropenem, and doripenem. A CFR of ≥90% was targeted as providing a sufficiently high ATB exposure. RESULTS: When considering the Enterobacteriaceae, the % susceptible for the cephalosporins ranged from 60% for ceftriaxone to 86% for cefepime, as a result only the 2g q8h regimens of ceftazidime and cefepime provided high CFRs. In contrast, all the carbapenems had % susceptible and CFRs ≥90% for EC and KP. While cefepime and ceftazidime demonstrated higher % susceptibility (82-83%) for PA relative to that of the carbapenems (61-69%) only doripenem 2g q8h (4h PI) achieved an optimal CFR (92%) against this organism. Due to the MIC profiles and dismal susceptibilities of AB (16-22%), none of the regimens studied achieved CFRs > 65%. CONCLUSIONS: The pharmacodynamic profiling undertaken in the current study provides insights that allow prescribers to select more appropriate empirical antibiotic regimens for the treatment of infection caused by these common GNB pathogens at this Thai hospital. While higher doses and PI of ß-lactams improve exposures against EC, KP and PA, this approach will not sufficiently enhance their potency against AB, thus alternative therapies should be considered for this organism.

Francisella novicida bacteremia, Thailand.

We report isolation of Francisella novicida-causing bacteremia in a woman from Thailand who was receiving chemotherapy for ovarian cancer. The organism was isolated from blood cultures and identified by 16S rDNA and PPIase gene analyses. Diagnosis and treatment were delayed due to unawareness of the disease in this region.

Bacterial study of autopsy specimens.

Autopsy reports were reviewed for the detection of infectious diseases at autopsy and to determine what extent an infectious process was involved in the patient's death. The present study was performed to analyze bacterial data of autopsy specimens in Siriraj Hospital during 1992-1999. Various autopsy specimens were cultured including heart blood, bronchus, lung, brain, cerebro-spinal fluid, pleural fluid, ascitic fluid, peritoneal fluid, liver, kidney, pericardial fluid, spleen and gall bladder From 781 autopsy specimens 502 (64.28%) were positive for bacterial pathogens. The five most common bacterial pathogens isolated from the present study were nonfermentative gram-negative rods followed by Klebsiella pneumoniae, Salmonella serogroup E, Escerichia coli and Acinetobacter anitratus, respectively. The ante mortem diagnosis by clinicians was correct 56% regarding to retrospectively analysis of septicemia/septic shock versus autopsy culture from heart blood

Respiratory tract infection caused by bacteria (non-Mycobacterium) and their antibiogram in HIV-positive patients.

Abstract. This study was undertaken from 1995-2000 to investigate the cause of respiratory tract infection among 481 patients with human immunodeficiency virus (HIV) at Siriraj Hospital, Bangkok, Thailand. The positive rate of bacterial pathogens was 38.46%. Pseudomonas aeruginosa appeared to be the most common pathogen (32.97%), followed by Staphylococcus aureus (18.92%), Klebsiella pneumoniae (10.81 %), Haemophilus influenzae (7.57%), and Acinetobacter baumannii (5.95%). P. aeruginosa was sensitive to netilmycin, amikacin, imipenem, meropenem, cefoperazone/sulbactam, piperacillin/tazobactam, and gentamicin (67-84%). S. aureus was sensitive to vancomycin and teicoplanin (100%).

Salmonella meningitis and antimicrobial susceptibilities.

Meningitis caused by Salmonella species is not uncommon in many developing countries. Patients suspected of bacterial meningitis who were admitted to Siriraj Hospital were enrolled in this study during 1986-2001. There were only 19 cases of Salmonella meningitis. Salmonella serogroup D ranked first, followed by serogroup C, serogroup B and then serogroup H. Most patients were children under 1 year of age. The antimicrobial susceptibility pattern for Salmonella meningitis may provide a guideline for the selection of appropriate drug treatment.

Bacteremia and antimicrobial susceptibilities in HIV-infected patients at Siriraj Hospital.

Bacterial infections in human immunodeficiency virus (HIV) infected patients may frequently develop into septicemia. Our study evaluated the bacterial pathogens isolated from hemocultures of HIV-infected patients at Siriraj Hospital and their antimicrobial susceptibility tests. The percentages of positive hemocultures were 24.64, 21.38, 23.88, and 28.46% in 1996, 1997, 1998, and 1999, respectively. Salmonella spp was the most pathogen isolated, followed by Escherichia coil (10.93%), Staphylococcus aureus (8.2%), coagulase-negative staphylococci (6.56%), nonfermentative gram-negative rods (6.01%), Pseudomonas aeruginosa (5.46%), Klebsiella pneumoniae (4.37%), and Enterobacter spp (4.37%). Salmonella, serogroup C was the most frequently isolated serogroup. It was sensitive to amoxicillin/clavulanate in 100%, ampicillin/sulbactam in 89%, cefazolin, cefuroxime, cefotaxime, ceftriaxone, ceftazidime, imipenem, gentamicin, amikacin, netilmycin, ofloxacin, and ciprofloxacin in 100%. The changing spectrum of bacteria and antimicrobial susceptibility patterns in HIV-1 infected patients may provide a guideline for the selection of appropriate drugs for treatment.

Bacterial isolation and antimicrobial susceptibilities in patients with infective endocarditis.

Infective endocarditis is life-threatening and urgent treatment is needed. We review here 6217 patients with infective endocarditis admitted to Siriraj Hospital during a 20 year period, 1982-2001. In this retrospective study, we obtained our data from hemoculture results. Bacterial pathogens were found in only 834 patients (13.41%). Of the five most common pathogens, nonfermentative gram-negative rods (N.F.) ranked first (20.94%), followed by coagulase-negative staphylococci (12.47%), viridans streptococci (10.23%), Staphylococcus aureus (9.29%), and Escherichia coli (8.59%). Of the N.F., the sensitivities were: cefoperazone/sulbactam (86%), piperacillin/tazobactam (86%), meropenem (84%), imipenem (83%), ceftazidime (78%), ofloxacin (85%), ciprofloxacin (71%), and co-trimoxazole (71%).

Prevalence and antimicrobial susceptibility of Pseudomonas aeruginosa mucoid and non-mucoid type.

Pseudomonas aeruginosa is a leading cause of nosocomial infections. One thousand two hundred and twenty strains of mucoid and non-mucoid types of P. aeruginosa isolated from different patients were examined at Siriraj Hospital from January 2001-October 2003. The prevalences of P. aeruginosa mucoid type and non-mucoid type were 3.6% and 96.4%, respectively. Susceptibility testing was performed by Kirby-Bauer disk diffusion method as recommended by NCCLS. The isolates with mucoid phenotypes were more susceptible than the non-mucoid isolates. The antimicrobial susceptibility pattern of both types should provide guidelines for the selection of appropriate drugs for treatment.