Locally produced colistin appears to be safe and effective for the treatment of infections caused by MDR P. aeruginosa and A. baumannii in Thai adult patients.
Tigecycline efficacy in this murine ACB pneumonia model was well predicted by fAUC/MIC. Requisite tigecycline exposures for efficacy appear to be higher for ACB pneumonia than for other pathogens reported of non-respiratory infections.
BackgroundRecent guidelines have recommended vancomycin trough levels of 15–20 mg/L for treatment of serious infections caused by methicillin-resistant Staphylococcus aureus (MRSA). However, high trough levels may increase risk of nephrotoxicity and mortality, and high vancomycin trough levels have not been well studied. This study was designed to combine safety and efficacy results from independent studies and to compare between high and low vancomycin trough levels in the treatment of MRSA-infected patients using meta-analysis.MethodsFrom 19 eligible studies, 9 studies were included in meta-analysis to compare clinical success between high and low vancomycin trough levels, while 10 and 11 studies met criteria for comparing trough levels and nephrotoxicity and trough levels and mortality, respectively. The PubMed/Medline, Web of Science, and Scopus databases, and hand searching were used to identify eligible studies dated up to March 2016. Of 2344 subjects with MRSA infection, 1036 were assigned to trough levels ≥15 mg/L and 1308 to trough levels <15 mg/L.ResultsHigh vancomycin trough levels were found to be associated with risk of nephrotoxicity (odds ratio [OR] 2.14, 95 % confidence interval [CI] 1.42–3.23 and adjusted OR 3.33, 95 % CI 1.91–5.79). There was no evidence of difference between high and low vancomycin trough levels for mortality (OR; 1.09; 95 % CI 0.75–1.60) or clinical success (OR 1.07; 95 % CI 0.68–1.68).ConclusionIn this study, high vancomycin trough levels were identified as an independent factor associated with risk of nephrotoxicity in MRSA-infected patients. Association between vancomycin trough levels and both adverse effects and clinical outcomes requires further study.Electronic supplementary materialThe online version of this article (doi:10.1186/s13104-016-2252-7) contains supplementary material, which is available to authorized users.
Tigecycline (TGC) is an extended-spectrum antibiotic with activity against Staphylococcus aureus, including methicillin (meticillin)-resistant S. aureus strains, which are well-recognized pathogens in nosocomial pneumonia. The objective of this study was to characterize the exposure-response relationship for TGC against S. aureus in an immunocompromised BALB/c murine pneumonia model. Six S. aureus isolates were studied, and the TGC MICs for those isolates ranged from 0.125 to 0.5 mg/liter. The pharmacokinetics (PK) of TGC in serum and bronchoalveolar lavage (BAL) fluid were evaluated, as was the level of protein binding of the compound in this murine species. Administration of TGC at 1.56 to 150 mg/kg of body weight/day in single or two to three divided doses was used in the efficacy studies. TGC displayed linear PK and had a mean half-life of 10.9 ؎ 2.5 h. Efficacy was highly correlated with the area under the free concentration-time curve (fAUC)/ MIC (r 2 ؍ 0.93). The 80% and 50% effective exposure indexes and the stasis exposure index were similar between the isolates (means ؎ standard deviations, 3.04 ؎ 1.12, 1.84 ؎ 1.3, and 1.9 ؎ 1.5, respectively). Maximal efficacy was predicted at a 2.85-log 10 -CFU reduction. TGC appeared to accumulate in the interstitial space, as the ratios of the fAUC from 0 to 8 h of epithelial lining fluid to plasma were 7.02, 15.11, and 23.95 for doses of 12.5, 25, and 50 mg/kg, respectively. TGC was highly effective in this murine pneumonia model. In light of current MIC distributions, the fAUC/MIC targets that we defined against S. aureus are readily achievable in humans given conventional doses of TGC.Staphylococcus aureus has long been recognized as an important cause of infection, and the emergence of S. aureus strains with the methicillin (meticillin)-resistant phenotype (methicillin-resistant S. aureus [MRSA]) has further complicated management. Both community-acquired MRSA (CA-MRSA) and hospital-acquired MRSA (HA-MRSA) strains have been associated with severe and difficult-to-treat infections. While the most common site of staphylococcal infection is the skin and skin structures, the surveillance of 8,792 invasive MRSA cases in the United States showed that pneumonia is the second most common clinical manifestation of MRSA infection (13.3% overall; 14% of the strains were CA-MRSA and 28% were HA-MRSA) (9).Tigecycline (TGC) is a broad-spectrum glycylcycline with efficacy against gram-positive and gram-negative bacteria, including drug-resistant bacteria such as MRSA. The MIC 90 of TGC against methicillin-susceptible S. aureus (MSSA) and MRSA strains is reported to be Յ0.25 mg/liter (6). TGC is approved by the FDA for use for the treatment of complicated skin and skin structure infections and complicated intra-abdominal infections. Pneumonia is an important clinical manifestation of infection with drug-resistant bacteria; therefore, many in vivo and in vitro studies of TGC for the treatment of lower respiratory infection are ongoing (data available at http://www.clinicaltri...
Due to the extensive removal of CMS by dialysis, HD should be conducted at the end of a dosing interval and a supplemental dose should be administered.
Background
The epidemiology and outcomes of COVID-19 patients in Thailand are scarce.
Methods
This retrospective cohort study included adult hospitalized patients who were diagnosed with COVID-19 at Siriraj Hospital during February 2020 to April 2020.
Results
The prevalence of COVID-19 was 7.5% (107 COVID-19 patients) among 1409 patients who underwent RT-PCR for SARS-CoV-2 detection at our hospital during the outbreak period. Patients with COVID-19 presented with symptoms in 94.4%. Among the 104 patients who were treated with antiviral medications, 78 (75%) received 2-drug regimen (lopinavir/ritonavir or darunavir/ritonavir plus chloroquine or hydroxychloroquine), and 26 (25%) received a 3-drug regimen with favipiravir added to the 2-drug regimen. Disease progression was observed in 18 patients (16.8%). All patients with COVID-19 were discharged alive.
Conclusions
The prevalence of COVID-19 was 7.5% among patients who underwent RT-PCR testing, and 10% among those having risk factors for COVID-19 acquisition. Combination antiviral therapies for COVID-19 patients were well-tolerated and produced a favorable outcome.
The safety and efficacy of ivermectin for the prevention and treatment of COVID-19 are still controversial topics. From August to November 2021, we conducted a double-blinded, randomized controlled trial at Siriraj Hospital, Thailand. Eligible participants were adults ≥ 18 years with suspected COVID-19 who underwent a SARS-CoV-2 RT-PCR test. After enrollment, the participants were randomized to receive either ivermectin (400–600 µg/kg/d) or placebo once daily for 3 days. Among 983 participants, 536 (54.5%) with a negative RT-PCR result were enrolled in the prevention study, and 447 (45.5%) with a positive RT-PCR result were enrolled in the treatment study. In the prevention study, the incidence of COVID-19 on Day 14 was similar between the ivermectin and the placebo group (4.7% vs. 5.2%; p = 0.844; Δ = −0.4%; 95% CI; −4.3–3.5%). In the treatment study, there was no significant difference between the ivermectin and placebo group for any Day 14 treatment outcome: proportion with oxygen desaturation (2.7% vs. 1.9%; p = 0.75), change in WHO score from baseline (1 [−5, 1] vs. 1 [−5, 1]; p = 0.50), and symptom resolution (76% vs. 82.2%; p = 0.13). The ivermectin group had a significantly higher proportion of transient blurred vision (5.6% vs. 0.6%; p < 0.001). Our study failed to demonstrate the efficacy of a 3-day once daily of ivermectin for the prevention and treatment of COVID-19. The given regimen of ivermectin should not be used for either prevention or treatment of COVID-19 in populations with a high rate of COVID-19 vaccination.
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