Fluconazole and echinocandin resistance of Candida species in invasive candidiasis at a university hospital during pre-COVID-19 and the COVID-19 outbreak.

Antifungal susceptibility of Candida species is decreasing. Successful treatment for antifungal-resistant candida infection is challenging and associated with significant mortality. We performed a prospective observational study to identify the species and antifungal susceptibilities of invasive isolates of Candida species over a 5-year period at a university hospital in southern Thailand. Between 2017 and 2021, the species distribution was 39.1% Candida tropicalis, 24.8% Candida albicans, 20.3% Candida parapsilosis complex, 10.5% Candida glabrata, and 5.2% miscellaneous Candida spp. Notable observations include elevated minimal inhibitory concentration (MIC) and decrease susceptibility of C. tropicalis and C. glabrata to echinocandin and all tested triazoles. A shift of MIC90 value in the COVID-19 era was seen in C. albicans and C. tropicalis with azoles and echinocandins. Azole resistance increased among C. tropicalis isolates, and echinocandin resistance also increased among C. parapsilosis and C. glabrata isolates. Novel alterations in FKS1 HS1 and HS2 were detected in both isolates of anidulafungin-resistant C. parapsilosis. As Candida species have become more resistant to azoles and less susceptible to echinocandin development, the need arose to observe the emergence of resistance to both antifungal classes in candida clinical isolates, for a more effective infection control in the hospital.

Suspected Cat-to-Human Transmission of SARS-CoV-2, Thailand, July-September 2021.

A veterinarian in Thailand was diagnosed with COVID-19 after being sneezed on by an infected cat owned by an infected patient. Genetic study supported the hypothesis of SARS-CoV-2 transmission from the owner to the cat, and then from the cat to the veterinarian.

Adjunctive therapy of intravenous colistin to intravenous tigecycline for adult patients with non-bacteremic post-surgical intra-abdominal infection due to carbapenem-resistant Acinetobacter baumannii.

Post-surgical intra-abdominal infections (IAIs) due to carbapenem-resistant Acinetobacter baumannii (CRAB) are difficult to treat due to suboptimal peritoneal penetrations of several antimicrobial agents. Tigecycline has favorable outcomes of treating IAIs due to multidrug-resistant organisms but occurrence of breakthrough bacteremia has been observed because this agent has low serum level. Colistin has in vitro activity against CRAB but data on treatment of IAIs is limited due to poor peritoneal penetration. The purpose of this retrospective study is to explore the outcomes of adjunctive intravenous (IV) colistin to IV tigecycline in the treatment of IAIs caused by CRAB. Of 28 patients with non-bacteremic post-surgical IAIs due to CRAB, 14 patients received IV tigecycline alone and 14 patients received IV tigecycline with IV colistin. The 14-day, 30-day, in-hospital mortality rates, the rate of breakthrough bacteremia and the rate of bacterial eradication were not significantly different. The adjunctive therapy of IV colistin was associated with significantly higher rates of renal complications (10/14) than those receiving IV tigecycline alone (3/14) (P value = 0.023). In addition, the patients receiving adjunctive IV colistin had significantly more unfavorable non-clinical outcomes including longer length of hospital stay (P value = 0.049) and higher antimicrobial cost (P value = 0.008) and non-antimicrobial costs (P value = 0.037). In this study, adjunctive IV colistin to conventional IV tigecycline in the treatment of non-bacteremic post-surgical IAIs caused by CRAB did not yield clinical benefit but caused higher renal complication and unfavorable non-clinical outcomes.

Comparative immunogenicity and neutralizing antibody responses post heterologous vaccination with CoronaVac (Sinovac) and Vaxzevria (AstraZeneca) in HIV-infected patients with varying CD4+ T lymphocyte counts.

The immune response to heterologous coronavirus disease (COVID-19) vaccination in people living with HIV (PLWH) is still unclear. Herein, our prospective cohort study aimed to compare the immune response of heterologous vaccination with CoronaVac (Sinovac) and Vaxzevria (AstraZeneca) between PLWH having CD4 counts ≤ 200 cells/µL (low CD4+) and > 200 cells/µL (high CD4+). Anti-receptor-binding domain (RBD) immunoglobulin G (IgG) levels and the percentage inhibition of neutralizing antibodies (nAbs) were analyzed at 2 and 12 weeks after immunization. Participants in the low and high CD4+ groups had mean CD4+ counts of 139 and 575 cell/µL, respectively. Two and 12 weeks after immunization, in the low CD4 group, the median anti-RBD-IgG levels were 159 IU/mL and 143 IU/mL, respectively, whereas the nAb level was 71% and decreased to 47.2%, respectively. Contrarily, the median anti-RBD-IgG levels in the high CD4+ group were 273 IU/mL and 294 IU/mL, respectively, whereas the nAb levels were 89.3% and relatively stable at 81.6%. However, although immune responses between the two study groups were not significantly different, a decline in nAb levels was observed at 12 weeks in the low CD4+ group. Therefore, a COVID-19 booster vaccine dose is suggested for immunoprotection.

Outcomes of Adjunctive Therapy with Open Arthrotomy for Patients with Septic Arthritis Due to Melioidosis: A Retrospective Study.

Melioidosis is a potentially fatal infection caused by the bacterium Burkholderia pseudomallei. Septic arthritis caused by this infection is uncommon and difficult to treat. The role of adjunctive open arthrotomy in this type of infection has not yet been elucidated. We conducted a retrospective study of patients with microbiologically confirmed melioidosis between January 2002 and December 2022. Patients with a clinical condition of septic arthritis and positive cultures for B. pseudomallei were included. Comparisons were made between patients who received adjunctive therapy with open arthrotomy with conventional standard treatment and those who did not in terms of clinical outcomes and hospital expenditures. Of the 478 patients diagnosed with melioidosis microbiological confirmation, 81 patients had septic arthritis, accounting for 17% of cases. Among these patients, only 36 (44%) underwent adjunctive therapy with open arthrotomy. The 14-day and 30-day in-hospital mortality and length of hospital stays of patients who underwent adjunctive therapy with open arthrotomy were more favorable than those of patients who did not receive adjunctive therapy with open arthrotomy; however, the difference was not statistically significant. Patients who underwent adjunctive therapy with open arthrotomy had lower hospital expenditures (antimicrobial and non-antimicrobial costs) than those who did not undergo open arthrotomy. Adjunctive therapy with open arthrotomy for patients with septic arthritis due to melioidosis was associated with favorable clinical outcomes and significantly lower hospital expenditures.

Pharmacodynamics of meropenem in critically ill patients with ventilator-associated pneumonia.

BACKGROUND: Pharmacokinetic changes have been found in critically ill patients, including ventilator-associated pneumonia (VAP) when compared with healthy volunteers leading to fluctuation of plasma concentrations. OBJECTIVE: To compare the probability of target attainment (PTA) and cumulative fraction of response (CFR) for meropenem between administration by a bolus injection and a 3-hour infusion. MATERIAL AND METHOD: The study was a randomized three-way crossover in nine patients with VAP. Each patient received meropenem in three regimens consecutively: (i) a bolus injection of 1 g every eight hours (q8h) for 24 hours; (ii) a 3-hour infusion of 1 g q8h for 24 hours; and (iii) a 3-hour infusion of 2 g q8h for 24 hours. The pharmacodynamic analysis of meropenem was performed to determine the PTA by using the Monte Carlo simulation and the study used susceptibility patterns obtained from EUCAST and MYSTIC for assessment of CFR. RESULTS: For an MIC of 4 microg/ml, the PTAs achieving 40% T > MIC following a bolus injection of 1 g q8h, a 3-hour infusion of 1 g q8h, and a 3-hour infusion of 2 g q8h were 87.71%, 98.80%, and 99.90%, respectively. Only the 3-hour infusion regimens were predicted to achieve a CFR > or = 90% against E. coli, Klebsiella spp., P. aeruginosa, and Acinetobacter spp. CONCLUSION: A 3-hour infusion of 2 g of meropenem regimen was predicted to have the highest PTA rates. Only the prolonged infusion regimens achieved a high CFR against E. coli, Klebsiella spp., P. aeruginosa, and Acinetobacter spp.

Characteristics, Outcomes, and Factors Affecting Mortality in Hospitalized Patients with CAP Due to Different Variants of SARS-CoV-2 and Non-COVID-19 CAP.

The study was conducted from October 2020 to March 2022 in a province in southern Thailand. The inpatients with community-acquired pneumonia (CAP) and more than 18 years old were enrolled. Of the 1511 inpatients with CAP, COVID-19 was the leading cause, accounting for 27%. Among the patients with COVID-19 CAP, mortalities, mechanical ventilators, ICU admissions, ICU stay, and hospital costs were significantly higher than of those with non-COVID-19 CAP. Household and workplace contact with COVID-19, co-morbidities, lymphocytopenia and peripheral infiltration in chest imaging were associated with CAP due to COVID-19. The delta variant yielded the most unfavorable clinical and non-clinical outcomes. While COVID-19 CAP due to B.1.113, Alpha and Omicron variants had relatively similar outcomes. Among those with CAP, COVID-19 infection as well as obesity, a higher Charlson comorbidity index (CCI) and APACHE II score were associated with in-hospital mortality. Among those with COVID-19 CAP, obesity, infection due to the Delta variant, a higher CCI and higher APACHE II score were associated with in-hospital mortality. COVID-19 had a great impact on the epidemiology and outcomes of CAP.

Prevalence of carbapenemase genes among multidrug-resistant Pseudomonas aeruginosa isolates from tertiary care centers in Southern Thailand.

OBJECTIVES: To assess the prevalence of carbapenemase genes among multidrug-resistant Pseudomonas aeruginosa (P. aeruginosa) isolates from tertiary care centers in Southern Thailand. METHODS: The prevalence of carbapenemase genes in P. aeruginosa isolates collected from patients hospitalized between 2015-2017 in 2 tertiary care hospitals in Songkhla Province, Southern Thailand, was investigated. Standard laboratory procedures were followed and disk diffusion test was used for bacterial identification and susceptibility evaluations. Carbapenemase genes were detected using multiplex polymerase chain reaction (PCR) and genotyping by pulsed field gel electrophoresis. RESULTS: Among the 289 P. aeruginosa isolates, 55% was from sputum, 19.4% was from urine, and 8% was from secretions. The prevalence was 55.7% in carbapenem-resistant multidrug-resistant P. aeruginosa (CR-MDR-PA) and 39.4% in multidrug-resistant P. aeruginosa (MDR-PA). Resistance to imipenem, meropenem, gentamicin, and ceftazidime ranged from 50-60%, and amikacin was the most effective antibiotic (38.4%). The carbapenemase genes bla VIM (27.7%), bla IMP (23.9%), and bla OXA48 (4.8%) were detected; however, bla SPM and bla BIC were not detected in any of the isolates. Pulsed field gel electrophoresis analysis revealed clonal diversity among 17 CR-MDR-PA strains. CONCLUSION: A high percentage of CR-MDR-PA carries carbapenemase genes in our area; therefore, more emphasis on and application of molecular techniques for infection prevention and control may provide useful insights on disease epidemiology.

Clinical Characteristics, Outcomes, and Risk Factors for Mortality in Patients with Stenotrophomonas maltophilia Bacteremia.

This study aimed to establish the clinical features, outcomes, and factors associated with mortality in patients with Stenotrophomonas maltophilia (S. maltophilia) septicemia. The characteristics and outcome data used in this retrospective study were collected from medical records at Songklanagarind Hospital. Risk factors for survival were analyzed using χ2-tests, Kaplan−Meier curves, and Cox regression. A total of 117 patients with S. maltophilia bacteremia were analyzed. The patients' median age was 45 years, 77 (70%) were male, 105 (90%) had comorbidities, 112 (96%) had previously undergone carbapenem therapy, and over half of the patients were on invasive medical devices. Trimethoprim-sulfamethoxazole (TMP-SMX) and fluoroquinolone showed high susceptibility rates to S. maltophilia, with 93% and 88% susceptibility, respectively. Patients who received appropriate empirical antibiotic treatment had significantly reduced 14-day, 30-day, and in-hospital mortality rates than those who did not (p < 0.001). The days of hospital stay and costs for those who received appropriate and inappropriate empirical antimicrobial treatment were 21 and 34 days (p < 0.001) and 142,463 and 185,663 baht, respectively (p < 0.002). Our results suggest that an appropriate empirical antibiotic(s) is significantly associated with lower 30-day mortality in hospitalized patients with S. maltophilia septicemia.

Outcomes of early oseltamivir treatment for hospitalized adult patients with community-acquired influenza pneumonia.

Early initiation of oseltamivir within 48 h to 5 days from illness onset has been associated with improved survival among patients with community-acquired influenza pneumonia. Delay of hospitalization limits early treatment and the survival of patients. To date, the effects of early oseltamivir initiation within 24 hours from admission on patient mortality has remained unknown. This retrospective study reviewed and analyzed the clinical and non-clinical outcomes of 143 patients, with community-acquired influenza pneumonia, who received oseltamivir within 24 h (group A) and after 24 h (group B) from admission. Among the patients, 82 (57.3%) received oseltamivir within 24 h while 61 (42.7%) received oseltamivir after 24 h. The median time from symptom onset to admission for group A and group B was not statistically significant (P < 0.001). The 14-day mortality rate was 9% and 23% for group A and B, respectively (P = 0.03), while the 30-day mortality were 15% and 30% for group A and B, respectively (P = 0.05). Administration of oseltamivir within 24 h significantly affected 30-day mortality rates (adjust OR: 0.14, 95% CI: 0.47-0.04, P < 0.01), particularly among patients with respiratory failure at admission (adjust OR: 0.08, 95% CI: 0+.30-0.06, P < 0.01). Survival analysis of patient with influenza pneumonia and respiratory failure at admission demonstrated significant difference between those who received oseltamivir within and after 24 h (P = 0.002). The results indicated that early oseltamivir initiation within 24 h improved the survival outcome mainly among those with respiratory failure at admission.

Outcomes of Adjunctive Therapy with Intravenous Cefoperazone-Sulbactam for Ventilator-Associated Pneumonia Due to Carbapenem-Resistant Acinetobacter baumannii.

INTRODUCTION: The efficacy of adjunctive therapy with cefoperazone-sulbactam (CEP-SUL) for ventilator-associated pneumonia (VAP) due to carbapenem-resistant A. baumannii (CRAB) is unclear. METHODS: We retrospectively analyzed the therapeutic effect of adding CEP-SUL to standard regimens for VAP due to CRAB. Patients with VAP due to CRAB strains that were susceptible to CEP-SUL were enrolled into the study. The patients were divided into two groups: those who receive cefoperazone-sulbactam (CEP-SUL+), and those who did not receive cefoperazone-sulbactam (CEP-SUL). Mortality rates and resource utilization of these two groups were compared. Factors associated with mortality were explored. RESULTS: Eighty patients were enrolled into the study, 52 CEP-SUL+ and 28 CEP-SUL-. The baseline characteristics of the two groups were comparable, except for median Acute Physiology and Chronic Health Evaluation (APACHE) II score which was significantly higher for CEP-SUL+. Thirty-day, and in-hospital mortality rates for CEP-SUL+ were significantly lower than CEP-SUL- with values of 35%, 39% and 61%, 68%, for CEP-SUL+ and CEP-SUL-, respectively. The survival rate for CEP-SUL+ was significantly higher compared with CEP-SUL- (P < 0.001). The number of hospital days, ventilator days since diagnosis of VAP and hospital costs were lower for CEP-SUL+. CONCLUSION: Overall results suggested that patients with VAP due to CRAB strains who received adjunctive therapy with CEP-SUL had lower mortality rates and resource utilization compared with CEP-SUL-.

Necrotizing skin and soft-tissue infections associated with septicemia: 7 cases report and review.

The authors report seven cases of necrotizing skin and soft-tissue infections, with clinical presenting as hemorrhagic bullae, gangrenous cellulitis or necrotizing fasciitis, in association with septicemia, between January 2003 and January 2007 in Hat Yai Hospital. Six were male and the majority of the lesions, six cases, occurred in the lower extremities. The average age of the patients was 50.0 +/- 11.019 years old. All patients presented with watery diarrhea, severe abdominal pain, high fever and sepsis. The skin lesions were begun with erythema, tender and swelling with formation of hemorrhagic bullae, gangrene and necrosis within 24-48 hours. Three of them were caused by Streptococcus spp., another three by Halophilic Vibrios, and only one by Aeromonas hydrophila. Furthermore, the literatures related with clinical manifestations of necrotizing skin and soft-tissue infections, etiologic pathogens, histological finding, management in setting of sepsis, comorbid conditions, complications and patients' outcome were reviewed.

Outcomes of adjunctive therapy with intrathecal or intraventricular administration of colistin for post-neurosurgical meningitis and ventriculitis due to carbapenem-resistant acinetobacter baumannii.

The efficacy and safety of intrathecal (ITH) or intraventricular (IVT) colistin in addition to intravenous (IV) colistin for meningitis and ventriculitis due to carbapenem-resistant Acinetobacter baumannii (CRAB) is unclear. In this retrospective observational study of 40 patients with post-neurosurgical meningitis and ventriculitis due to CRAB, 33 patients without concomitant infection received appropriate dosage regimens of IV colistin. Of the 33 patients, 17 received additional ITH/IVT colistin and 16 received only IV colistin. The 14-day, 30-day and in-hospital mortality rates were nominally lower for patients who received ITH/IVT colistin adjunctive therapy versus patients who received only IV colistin (24% vs. 38%, 29% vs. 56% and 29% vs. 56%, respectively). The costs of treatment were significantly lower, the lengths of hospital and intensive care unit (ICU) stay were significantly shorter, and the number of ventilator days was significantly less among patients who received ITH/IVT colistin compared with patients who did not receive ITH/IVT colistin. The initial Acute Physiology and Chronic Health Evaluation (APACHE) II and Glasgow Coma Scale (GCS) scores were associated with 30-day mortality with odds ratios (95% confidence intervals) of 1.21 (1.08-1.46) and 0.77 (0.44-0.85), respectively. Chemical meningitis from ITH/IVT colistin was mild and resolved spontaneously. Treatment of post-neurosurgical CRAB meningitis and ventriculitis with ITH/IVT colistin as an adjunct to IV colistin was associated with shorter lengths of hospital and ICU stay and a trend to lower mortality, especially among severely ill patients.

Peripheral facial paralysis associated with HIV infection: A case series and literature review.

OBJECTIVE: The association between peripheral facial paralysis (PFP) and HIV infection has been scarcely explained. The authors aimed to describe the association between PFP and HIV infection status, along with the related co-morbidities and the outcomes of PFP, as well as the literature review on this topic. PATIENTS AND METHODS: All HIV-infected patients who experienced PFP, both before and after a positive HIV serology test, between January 2002 and June 2015 were retrospectively reviewed. The patients' demographic data, clinical characteristics, HIV co-morbidities and outcomes of PFP were summarized. A literature review of PFP in HIV infection was also performed. Descriptive statistics were used in the data analysis. The Mann-Whitney U test was performed to compare the parameters between the current case series and cases from literature review to determine statistical significant differences (p <  0.05). RESULTS: Sixteen patients (6 males and 10 females) were enrolled. Their median age was significantly higher than that of the cases in the literature review [46 (38, 49.75) vs. 33 (26, 41) years (p =  0.004)]. Nonetheless, a non-significant lower median CD4 count was observed [274 (134.5, 425.5) vs. 373 (265, 718) cells/µL (p =  0.058)]. In our series, unilateral PFP (UFP) was the most frequent, and it typically occurred long after a positive HIV serology test. However, bilateral PFP (BFP) was commonly found in the literature, and a simultaneous positive HIV serology test was reported in almost all cases. Consequently, most of our cases, except for those with HIV-related complications or co-morbidities, experienced a satisfactory recovery from PFP regardless of treatments received. CONCLUSIONS: Most of the cases in our series were UPF with a higher median age and a lower median CD4 count. Moreover, facial paralysis presented later in our series than in the previously reported cases in the literature. Most of our cases experienced satisfactory recovery of facial weakness.

Pharmacodynamics of doripenem in critically ill patients with ventilator-associated Gram-negative bacilli pneumonia.

Several pathophysiological changes in critically ill patients are important in determining the therapeutic success of ß-lactam antibiotics. The aim of this study was to assess the population pharmacokinetics and probabilities of target attainment (PTAs) of doripenem in patients with ventilator-associated pneumonia, comparing administration by 1-h and 4-h infusion. Patients were randomised into two groups: Group I received a 1-h infusion of 0.5 g every 8 h (q8h) for seven doses; and Group II received a 4-h infusion of 0.5 g q8h for seven doses. A Monte Carlo simulation was performed to determine the PTAs. PTAs of achieving 40% T(>MIC) [exposure time during which the free drug concentration remains above the minimum inhibitory concentration (MIC)] and 75% T(>MIC) are required for effective bactericidal activity of this agent in immunocompetent and immunocompromised hosts, respectively. Values of volume of distribution and total clearance of doripenem in these patients were 17.26±1.83 L and 24.89±1.63 L/h, respectively. For pathogens with a MIC of 1 µg/mL, the PTAs of achieving 40% T(>MIC) following administration of doripenem by a 1-h and 4-h infusion of 0.5 g q8h were 92.95% and 98.32%, respectively. For pathogens with a MIC of 2 µg/mL in immunocompromised hosts, the PTAs of achieving 80% T(>MIC) following administration of doripenem by 1-h and 4-h infusion of 2 g q8h were 56.57% and 91.21%, respectively. In conclusion, these findings indicated that higher than recommended doses in this patient population, particularly neutropenic patients, would be necessary to optimise the pharmacokinetics of doripenem.