In Vitro Activity of Plazomicin Against Carbapenem Resistant Klebsiella pneumoniae Strains.

BACKGROUND: In our study, we evaluated the in vitro activities of plazomicin, amikacin, gentamicin, and tobramycin among fifty carbapenem resistant Klebsiella pneumoniae (CR-Kp) isolates. Aminoglycoside resistance genes in selected CR-Kp strains were also examined. METHODS: Minimum inhibitory concentration (MIC) of meropenem, plazomicin, tobramycin, gentamicin, and amikacin were determined by gradient test (G-test) method. In all strains carbapenemase activity was assessed by polymerase chain reaction (PCR). Aminoglycoside modifying enzyme (AME) genes in 14 CR-Kp strains that are resistant to at least one of tobramycin, gentamicin, and amikacin among fifty CR-Kp isolates, and 16S ribosomal methylase genes in 6 CR-Kp strains with plazomicin MIC ≥ 128 mg/L were investigated by PCR method. RESULTS: The most frequently detected carbapenemase enzyme in the strains in our study was OXA-48 (88%). Aminoglycoside susceptibilities of all isolates were determined; plazomicin 84%, amikacin 66%, gentamicin 50%, tobramycin 18%. The most common AME gene positivities were found, 93% (n = 13) ant(3')-I, 78% (n = 11) aac(6')-Ib, 57% (n = 8) aac(3')-IV, 42% (n = 6) aac(3')-IIa, and 29% (n = 4) aph(3')-VI. Most of the isolates examined for the presence of AME carry at least two or more AME genes. The most common 16S ribosomal methylase gene was rmtH. In our study, MIC values of ≥ 256 µg/mL were found in 6 (12%) of 50 isolates against amikacin, tobramycin, and gentamicin, including plazomicin. At least two 16S ribosomal methylase gene positivity has been shown in these 6 strains. CONCLUSIONS: In our study, increased in vitro efficacy of plazomicin was shown in CR-Kp isolates comparing to other aminoglycosides. Plazomicin is an effective treatment option against CR-Kp isolates and needs to be sup-ported by clinical studies.

Prognostic Value of Serial Measurement of Serum Des-Arg(9)-Bradykinin Levels in Severe COVID-19 Patients.

BACKGROUND: Excessive inflammatory immune response during SARS-CoV-2 infection contributes to severe disease in COVID-19 patients. Recently, some researchers hypothesized that dysregulation of the bradykinin (BK) system may also play a role in the pathogenesis of severe disease. Des-Arg(9)-bradykinin (DABK), an active metabolite of BK, is responsible for vasodilatation and increased permeability in the lungs and regulated by angiotensin converting enzyme 2 (ACE-2). Viral inhibition of ACE-2 by SARS-CoV-2 increases DABK levels. Serum levels of this metabolite may be linked to disease severity in COVID-19 patients. In this study, it is aimed to investigate the prognostic value of serial measurement of serum DABK levels in severe COVID-19 patients. METHODS: This prospective cohort study was conducted in hospitalized severe COVID-19 patients. Serum DABK levels of patients were serially measured on day 0, day 3 and day 5. Patients were categorized as cases with poor or good prognosis and critical or non-critical cases. Serum DABK levels of these patient groups were compared with paired sample t-test. Serum DABK levels on different days in the same patients were compared with repeated measures ANOVA tests. RESULTS: There was no statistically significant difference in serum DABK levels measured at day 0, day 3, and day 5 between good and poor prognosis groups. DABK levels in critical and non-critical COVID-19 patients also did not show any significant difference. CONCLUSIONS: According to our results serially measured serum DABK levels did not correlate with outcome of severe COVID-19 and do not have prognostic value in severe COVID-19 patients.

Evaluation of the risk factors on time to phlebitis- and nonphlebitis-related failure when peripheral venous catheters were replaced as clinically indicated.

BACKGROUND: This study aimed to determine the frequency of peripheral venous catheter-related complications and the risk factors that have an impact on the time of peripheral venous catheter failure when they were replaced as clinically indicated. METHODS: This was a prospective observational study. The demographic and clinical characteristics of the patients, as well as the catheter specifications, were recorded. All the catheters were followed-up at 12-h intervals for the development of complications. Two different peripheral venous catheters were used in the study. The catheter dwell times were estimated using Kaplan-Meier analysis. The logrank test was utilized to investigate the catheter dwell times by univariate analyses. Variables with a significance level of less than 0.20 were taken into Cox regression analysis. RESULTS: Our results revealed that phlebitis and nonphlebitis complications occurred more frequently within the first 96 h. No significant difference was observed in the occurrence time of phlebitis, nonphlebitis, and composite failures. The use of a locally manufactured catheter, unsuccessful first attempt, poor skin integrity, after-hours' insertion, the use of sterile gauze dressing were all associated with shorter catheter survival rates. CONCLUSION: We observed no difference on the time to phlebitis or nonphlebitis symptoms with clinically indicated replacement of peripheral venous catheters. We found a significant difference in survival rates between locally manufactured and imported peripheral venous catheters. Our identified risk factors should be taken into account to reduce peripheral venous catheter-related complications and to increase dwell time.

In vitro activity of eravacycline in combination with colistin against carbapenem-resistant A. baumannii isolates.

The synergistic activity of eravacycline in combination with colistin on carbapenem-resistant A. baumannii (CRAB) isolates was evaluated in this study. Minimum inhibitory concentrations (MICs) of eravacycline and colistin were determined by the broth microdilution method. MICs values ranged between 1 to 4 mg and 0.5 to 256 mg l-1 for eravacycline and colistin, respectively. In vitro synergy between eravacycline and colistin was evaluated by using the chequerboard methodology. Synergistic activity was found in 10% of the strains, and additive effect in 30%. No antagonism was detected. Similar activity was also observed in colistin-resistant CRAB isolates. The result of this study indicates that eravacycline and colistin combination may be a potential therapeutic option for the treatment of CRAB related infections.