Impact of Pharmacist-Led Multidisciplinary Team to Attain Targeted Vancomycin Area under the Curved Monitoring in a Tertiary Care Center in Thailand.

Vancomycin Area Under the Curve (AUC) monitoring has been recommended to ensure successful clinical outcomes and minimize the risk of nephrotoxicity, rather than traditional trough concentration. However, vancomycin AUC monitoring by a pharmacist-led multidisciplinary team (PMT) has not been well established in Southeast Asia. This study was conducted at Thammasat University Hospital. Adult patients aged ≥ 18 years who were admitted and received intravenous vancomycin ≥48 h were included. The pre-PMT period (April 2020-September 2020) was defined as a period using traditional trough concentration, while the post-PMT period (October 2020-March 2021) was defined as a period using PMT to monitor vancomycin AUC. The primary outcome was the rate of achievement of the therapeutic target of an AUC/MIC ratio of 400-600. There was a significantly higher rate of achievement of therapeutic target vancomycin AUC during post-PMT period (66.7% vs. 34.3%, p < 0.001). Furthermore, there was a significant improvement in the clinical cure rate (92.4% vs. 69.5%, p < 0.001) and reduction in 30-day ID mortality (2.9% vs. 12.4%, p = 0.017) during the post-PMT period. Our study demonstrates that PMT was effective to help attain a targeted vancomycin AUC, improve the clinical cure rate, and reduce 30-day ID mortality. This intervention should be encouraged to be implemented in Southeast Asia.

Real-life effectiveness of COVID-19 vaccine during the Omicron variant-dominant pandemic: how many booster doses do we need?

The surge in coronavirus disease 2019 (COVID-19) caused by the Omicron variants of the severe acute respiratory syndrome coronavirus 2 necessitates researches to inform vaccine effectiveness (VE) and other preventive measures to halt the pandemic. A test-negative case-control study was conducted among adults (age ≥18 years) who were at-risk for COVID-19 and presented for nasopharyngeal real-time polymerase chain reaction testing during the Omicron variant-dominant period in Thailand (1 January 2022-15 June 2022). All participants were prospectively followed up for COVID-19 development for 14 days after the enrolment. Vaccine effectiveness was estimated and adjusted for characteristics associated with COVID-19. Of the 7971 included individuals, there were 3104 cases and 4867 controls. The adjusted VE among persons receiving 2-dose, 3-dose, and 4-dose vaccine regimens for preventing infection and preventing moderate-to-critical diseases were 33%, 48%, 62% and 60%, 74%, 76%, respectively. The VE were generally higher among those receiving the last dose of vaccine within 90 days compared to those receiving the last dose more than 90 days prior to the enrolment. The highest VE were observed in individuals receiving the 4-dose regimen, CoronaVac-CoronaVac-ChAdOx1 nCoV-19-BNT162b2 for both preventing infection (65%) and preventing moderate-to-critical diseases (82%). Our study demonstrated increased VE along with an increase in number of vaccine doses received. Current vaccination programmes should focus on reducing COVID-19 severity and mandate at least one booster dose. The heterologous boosters with viral vector and mRNA vaccines were highly effective and can be used in individuals who previously received the primary series of inactivated vaccine.

Comparing real-life effectiveness of various COVID-19 vaccine regimens during the delta variant-dominant pandemic: a test-negative case-control study.

Data on real-life vaccine effectiveness (VE), against the delta variant (B.1.617.2) of the severe acute respiratory syndrome coronavirus 2 among various coronavirus disease 2019 (COVID-19) vaccine regimens are urgently needed to impede the COVID-19 pandemic. We conducted a test-negative case-control study to assess the VE of various vaccine regimens for preventing COVID-19 during the period when the delta variant was the dominant causative virus (≥ 95%) in Thailand (25 July 2021-23 Oct 2021). All individuals (age ≥18 years) at-risk for COVID-19, presented for nasopharyngeal real-time polymerase chain reaction (RT-PCR) testing, were prospectively enrolled and followed up for disease development. Vaccine effectiveness was estimated with adjustment for individual demographic and clinical characteristics. Of 3353 included individuals, there were 1118 cases and 2235 controls. The adjusted VE among persons receiving two-dose CoronaVac plus one BNT162b2 booster was highest (98%; 95% confidence interval [CI] 87-100), followed by those receiving two-dose CoronaVac plus one ChAdOx1 nCoV-19 booster (86%; 95% CI 74-93), two-dose ChAdOx1 nCoV-19 (83%; 95% CI 70-90), one CoronaVac dose and one ChAdOx1 nCoV-19 dose (74%; 95% CI 43-88) and two-dose CoronaVac (60%; 95% CI 49-69). One dose of CoronaVac or ChAdOx1 nCoV-19 had a VE of less than 50%. Our study demonstrated the incremental VE with the increase in the number of vaccine doses received. The two-dose CoronaVac plus one BNT162b2 or ChAdOx1 nCoV-19 booster regimens was highly effective in preventing COVID-19 during the rise of delta variant.

Effectiveness of a vancomycin dosing protocol guided by area under the concentration-time curve to minimal inhibitory concentration (AUC/MIC) with multidisciplinary team support to improve hospital-wide adherence to a vancomycin dosing protocol: A pilot study.

BACKGROUND: Limited data are available on the implementation of an area under the concentration-time curve (AUC)-based dosing protocol with multidisciplinary team (MT) support to improve adherence with vancomycin dosing protocol. OBJECTIVE: To evaluate the effectiveness of an AUC-based dosing protocol with MT support intervention with adherence to a hospital-wide vancomycin dosing protocol at Thammasat University Hospital. METHOD: We conducted a quasi-experimental study in patients who were prescribed intravenous vancomycin. The study was divided into 2 periods; (1) the preintervention period when the vancomycin dosing protocol was already applied in routine practice and (2) the post-intervention period when the implementation of an AUC-based dosing protocol with MT support was added to the existing vancomycin dosing protocol. The primary outcome was the rate of adherence, and the secondary outcomes included acute kidney injury events, vancomycin-related adverse events, and 30-day mortality rate. RESULTS: In total, 240 patients were enrolled. The most common infections were skin and soft-tissue infections (24.6%) and bacteremia (24.6%). The most common pathogens were coagulase-negative staphylococci (19.6%) and Enterococcus spp (15.4%). Adherence with the vancomycin dosing protocol was significantly higher in the postintervention period (90.8% vs 55%; P ≤ .001). By multivariate analysis, an AUC-based dosing protocol with MT support was the sole predictor for adherence with the vancomycin dosing protocol (adjusted odds ratio, 10.31; 95% confidence interval, 4.54-23.45; P ≤ .001). The 30-day mortality rate was significantly lower during the postintervention period (8.3% vs 20%; P = .015). CONCLUSIONS: AUC-based dosing protocol with MT support significantly improved adherence with vancomycin dosing protocol and was associated with a lower 30-day mortality rate.

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.

The higher prevalence of extended spectrum beta-lactamases among Escherichia coli ST131 in Southeast Asia is driven by expansion of a single, locally prevalent subclone.

The ST131 multilocus sequence type (MLST) of Escherichia coli is a globally successful pathogen whose dissemination is increasing rates of antibiotic resistance. Numerous global surveys have demonstrated the pervasiveness of this clone; in some regions ST131 accounts for up to 30% of all E. coli isolates. However, many regions are underrepresented in these published surveys, including Africa, South America, and Asia. We collected consecutive bloodstream E. coli isolates from three countries in Southeast Asia; ST131 was the most common MLST type. As in other studies, the C2/H30Rx clade accounted for the majority of ST131 strains. Clinical risk factors were similar to other reported studies. However, we found that nearly all of the C2 strains in this study were closely related, forming what we denote the SEA-C2 clone. The SEA-C2 clone is enriched for strains from Asia, particularly Southeast Asia and Singapore. The SEA-C2 clone accounts for all of the excess resistance and virulence of ST131 relative to non-ST131 E. coli. The SEA-C2 strains appear to be locally circulating and dominant in Southeast Asia, despite the intuition that high international connectivity and travel would enable frequent opportunities for other strains to establish themselves.

Nocardia intracranial mycotic aneurysm associated with proteasome inhibitor.

We report a case of Nocardia farcinica ruptured intracranial mycotic aneurysm associated with bortezomib and corticosteroid treatment in a multiple myeloma patient. The patient was treated with trimethoprim-sulfamethoxazole and moxifloxacin together with surgical repairment of intracranial mycotic aneurysm.

Differentiating Streptococcus pseudoporcinus from GBS: could this have implications in pregnancy?

BACKGROUND: Streptococcus agalactiae (GBS) is a common pathogen known to cause neonatal and maternal infectious morbidity. Streptococcus pseudoporcinus (S pseudoporcinus) is a separate, recently identified ß-hemolytic gram-positive coccus that can cause false-positive results on standard GBS agglutination testing assays. OBJECTIVE: To determine the prevalence and clinical implications of Streptococcus pseudoporcinus colonization in pregnancy. MATERIALS AND METHODS: This is a 2-year retrospective cohort study comparing pregnant women colonized with GBS to those colonized with S. pseudoporcinus. A proteomics method of identification, namely, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, was used to distinguish between S. pseudoporcinus and GBS colonization. Antibiotic susceptibility testing was carried out on all specimens. Maternal and neonatal chart reviews were conducted to identify predictors of S. pseudoporcinus colonization and to compare maternal and neonatal outcomes. RESULTS: S. pseudoporcinus colonization occurred in 1.6% of all pregnancies. A total of 2.5% of all GBS-positive results by agglutination assay were false positive, instead reflecting S. pseudoporcinus colonization. Clindamycin resistance among S. pseudoporcinus isolates is uncommon. S. pseudoporcinus colonization in pregnancy is independently associated with African American race, tobacco use, and body mass index ≥35. Preterm premature rupture of membranes or spontaneous preterm birth was more common in patients colonized with S. pseudoporcinus. CONCLUSION: Although the prevalence of S. pseudoporcinus colonization is low, it primarily occurs in African American women and is associated with preterm premature rupture of membranes or spontaneous preterm birth when compared to individuals colonized with GBS.

The impact of chlorhexidine gluconate bathing on skin bacterial burden of neonates admitted to the Neonatal Intensive Care Unit.

OBJECTIVE: To assess the impact of chlorhexidine gluconate (CHG) bathing on skin bacterial burden in neonates. STUDY DESIGN: In this prospective observational study, arm and groin skin bacterial growth was measured in 40 CHG-exposed and nonexposed neonates admitted to the NICU. Exposed neonates received 2% CHG baths per protocol for central line-associated bloodstream infection (CLABSI) prevention or Staphylococcus aureus decolonization. RESULTS: Forty neonates were enrolled, 18 of whom were CHG-exposed. Mean baseline Gram-positive (GP) bacterial burden was 2.19 log CFU/ml on the arm and 1.81 log CFU/ml on the groin. Bacterial burden decreased after the first bath, but returned to baseline by 72 h. Residual skin CHG concentration declined over time, with a corresponding increase in GP bacterial burden. CONCLUSIONS: CHG bathing reduces skin bacterial burden, but burden returns to baseline after 72 h. Twice weekly CHG bathing may be inadequate to suppress skin bacterial growth in hospitalized neonates.

A case of secondary syphilis with pulmonary involvement and review of the literature.

Syphilis is a sexually transmitted systemic infection caused by Treponema pallidum. We report a case of a heterosexual, HIV-positive man who presented with secondary syphilis and a lung abscess. A bacterial lung abscess was suspected and a computed tomography-guided percutaneous needle aspiration of the lung abscess was performed. Direct pulmonary involvement by T. pallidum was suggested by a positive PCR result on the aspirated fluid specimen. The clinical signs of secondary syphilis improved, and the lung abscess was resolved after treatment with benzathine penicillin G and amoxicillin-clavulanate. The final diagnosis was secondary pulmonary syphilis. Few reports of secondary syphilis with pulmonary involvement have been reported to date.

Frequency of small-colony variants and antimicrobial susceptibility of methicillin-resistant Staphylococcus aureus in cystic fibrosis patients.

BACKGROUND: Small-colony variants (SCVs) are a distinct phenotype of Staphylococcus aureus, known for their role in chronic, difficult to treat infections, including cystic fibrosis (CF) lung disease. The goal of this study was to characterize SCV MRSA infection in an adult and pediatric CF population and to identify antibiotic susceptibility patterns unique to SCV MRSA. METHODS: We recovered methicillin-resistant S. aureus (MRSA) from respiratory culture samples from CF patients at the Johns Hopkins Hospital during a 6month study period. RESULTS: Of 1161 samples, 200 isolates (17%) were identified as MRSA, and 37 isolates from 28 patients were identified as SCV MRSA. A higher proportion of MRSA was found among SCV isolates (37/66, 56%) compared to normal colony variant (NCV) isolates (163/417, 39%), p=0.02. All SCV MRSA isolates from individual patients were susceptible to vancomycin and ceftaroline, but they demonstrated higher rates of antibiotic resistance to trimethoprim/sulfamethoxazole, moxifloxacin, and erythromycin, compared to NCV MRSA isolates. Additionally, individuals with SCV MRSA had lower lung function, higher rates of persistent MRSA infection, and higher rates of previous antibiotic use, compared to individuals with NCV MRSA. CONCLUSIONS: A significant proportion of MRSA isolates recovered from patients with CF have the SCV morphology. Compared to individuals with NCV MRSA, those with SCV MRSA have higher rates of persistent MRSA infection and lower lung function. SCV MRSA isolates were more resistant than NCV, but they are highly susceptible to vancomycin, linezolid and ceftaroline.

Quantitative assessment of interactions between hospitalized patients and portable medical equipment and other fomites.

In an observational study, we demonstrated that hospitalized patients frequently had direct or indirect interactions with medical equipment and other fomites that are shared among patients, and these items were often contaminated with health care-associated pathogens. There is a need for protocols to ensure routine cleaning of shared portable equipment.

2015 Epidemic of Severe Streptococcus agalactiae Sequence Type 283 Infections in Singapore Associated With the Consumption of Raw Freshwater Fish: A Detailed Analysis of Clinical, Epidemiological, and Bacterial Sequencing Data.

BACKGROUND: Streptococcus agalactiae (group B Streptococcus [GBS]) has not been described as a foodborne pathogen. However, in 2015, a large outbreak of severe invasive sequence type (ST) 283 GBS infections in adults epidemiologically linked to the consumption of raw freshwater fish occurred in Singapore. We attempted to determine the scale of the outbreak, define the clinical spectrum of disease, and link the outbreak to contaminated fish. METHODS: Time-series analysis was performed on microbiology laboratory data. Food handlers and fishmongers were screened for enteric carriage of GBS. A retrospective cohort study was conducted to assess differences in demographic and clinical characteristics of patients with invasive ST283 and non-ST283 infections. Whole-genome sequencing was performed on human and fish ST283 isolates from Singapore, Thailand, and Hong Kong. RESULTS: The outbreak was estimated to have started in late January 2015. Within the study cohort of 408 patients, ST283 accounted for 35.8% of cases. Patients with ST283 infection were younger and had fewer comorbidities but were more likely to develop meningoencephalitis, septic arthritis, and spinal infection. Of 82 food handlers and fishmongers screened, none carried ST283. Culture of 43 fish samples yielded 13 ST283-positive samples. Phylogenomic analysis of 161 ST283 isolates from humans and fish revealed they formed a tight clade distinguished by 93 single-nucleotide polymorphisms. CONCLUSIONS: ST283 is a zoonotic GBS clone associated with farmed freshwater fish, capable of causing severe disease in humans. It caused a large foodborne outbreak in Singapore and poses both a regional and potentially more widespread threat.

Inappropriate Empirical Treatment of Uncomplicated Cystitis in Thai Women: Lessons Learned.

A prospective study conducted in a Thai general practice clinic demonstrated a high prevalence (91.3%) of inappropriate empirical antibiotic use in women with uncomplicated cystitis and 42.6% Escherichia coli fluoroquinolone resistance. An annual update of antimicrobial resistance surveillance data of uropathogens may permit targeted treatment of patients in hospital care.

Carbapenem-Resistant Acinetobacter baumannii and Enterobacteriaceae in South and Southeast Asia.

Carbapenem-resistant Gram-negative bacteria, in particular the Acinetobacter baumannii-calcoaceticus complex and Enterobacteriaceae, are escalating global public health threats. We review the epidemiology and prevalence of these carbapenem-resistant Gram-negative bacteria among countries in South and Southeast Asia, where the rates of resistance are some of the highest in the world. These countries house more than a third of the world's population, and several are also major medical tourism destinations. There are significant data gaps, and the almost universal lack of comprehensive surveillance programs that include molecular epidemiologic testing has made it difficult to understand the origins and extent of the problem in depth. A complex combination of factors such as inappropriate prescription of antibiotics, overstretched health systems, and international travel (including the phenomenon of medical tourism) probably led to the rapid rise and spread of these bacteria in hospitals in South and Southeast Asia. In India, Pakistan, and Vietnam, carbapenem-resistant Enterobacteriaceae have also been found in the environment and community, likely as a consequence of poor environmental hygiene and sanitation. Considerable political will and effort, including from countries outside these regions, are vital in order to reduce the prevalence of such bacteria in South and Southeast Asia and prevent their global spread.

Fluoroquinolone-Resistant Escherichia coli Infections After Transrectal Biopsy of the Prostate in the Veterans Affairs Healthcare System.

BACKGROUND: Recent reports suggest that infections due to fluoroquinolone-resistant Escherichia coli (E. coli) are an increasingly common complication of transrectal biopsy of the prostate (TBP) in the United States. A better understanding of the magnitude and scope of these infections is needed to guide prevention efforts. Our objective is to determine whether the incidence of infections due to fluoroquinolone-resistant E. coli after TBP has increased nationwide in the Veterans Affairs Health Care System and to identify risk factors for infection. METHODS: We performed a retrospective, observational cohort study and a nested case-control study within the US Deparment of Veterans Affairs Healthcare System. The primary outcomes were the incidence of urinary tract infection (UTI) and bacteremia with E. coli and with fluoroquinolone- resistant E. coli strains within 30 days after TBP. Secondary endpoints focused on the correlation between fluoroquinolone-resistance in all urinary E. coli isolates and post-TBP infection and risk factors for infection due to fluoroquinolone-resistant E. coli infection. RESULTS: 245 618 patients undergoing 302 168 TBP procedures from 2000 through 2013 were included in the cohort study, and 59 469 patients undergoing TBP from 2011 through 2013 were included in the nested case-control study. Between 2000 and 2013, there was a 5-fold increase in the incidence of E. coli UTI (0.18%-0.93%) and a 4-fold increase in the incidence of E. coli bacteremia (0.04%-0.18%) after TBP that was attributable to an increase in the incidence of fluoroquinolone- resistant E. coli UTI (0.03%-0.75%) and bacteremia (0.01%-0.14%). The increasing incidence of fluoroquinolone-resistant E. coli infections after TBP occurred in parallel with increasing rates of fluoroquinolone-resistance in all urinary E. coli isolates. By multivariable logistic regression analysis, independent risk factors for fluoroquinolone-resistant E. coli UTI after TBP included diabetes mellitus, fluoroquinolone exposure, prior hospitalization, and prior cultures with fluoroquinolone-resistant gram-negative bacilli. CONCLUSION: In the Veterans Affairs Healthcare System, the incidence of E. coli infection after TBP has increased significantly since 2000 due to a dramatic rise in infections with fluoroquinolone- resistant E. coli.