Colistin Research Articles

Electrospun nanofibers based on carboxymethyl cellulose/polyvinyl alcohol as a potential antimicrobial wound dressing

In this work, citric acid-based quantum dots (CA-QDs) as a novel and safe crosslinked agent was applied in different feeding ratios (5–15 wt%) to synthesize carboxymethyl cellulose/polyvinyl alcohol (CMC/PVA) nanofibers (NFs) for the first time. Colistin (CL) as an antibacterial agent was also loaded (2 w/w%) during the synthesizing process of CMC/PVA electrospun NFs to trigger antimicrobial properties. The morphological, hydrophilic, and mechanical properties of the prepared NFs were fully investigated with different techniques. The electrospun NFs with crosslinking ratios of 10 wt% CA-QDs revealed appropriate mechanical properties. According to cell culture data, the prepared NFs demonstrated good cytocompatibility against HFF-1 cells (over 80% cell viability). Remarkably, CL-loaded NFs showed desired antibacterial efficacy against S. aureus, E. coli, K. pneumoniae, and P. aeruginosa with 1.0–1.4, 1.3–1.4, 0.8–1.0, and 1.3–1.5 cm inhibition zones, respectively. These outcomes suggested that the fabricated NFs can be useful as wound healing scaffolds.

Prevalence of Bacillus cereus in dairy powders focusing on its toxigenic genes and antimicrobial resistance

Bacillus cereus is a common environmental foodborne microorganism that is mainly found to harbor toxigenic genes with multiple antibiotic resistances and is linked to threatening the safety of dried milk in concern to powdered infant milk formula. In the current investigation, the mean value of B. cereus in 140 samples of powdered milk was 0.57 × 102 ± 0.182 × 102, 0.15 × 102 ± 0.027 × 102, 0.21 × 102 ± 0.035 × 102, and 0.32 × 102 ± 0.072 × 102 CFU/g in a percentage of 64.0 samples of whole milk powder, 43.3 of skim milk powder, 26.7 of powdered infant milk formula and 36.7 milk–cereal-based infant formula, respectively. The results revealed that B. cereus isolates were found to harbor toxigenic genes in the following percentages: 77.8, 2.0, 72.7, 16.2, and 67.7 for nhe, hbl, cytK, ces, and bceT, respectively. Despite all evaluated B. cereus strains were originated from dairy powders, they showed a significant difference (P < 0.05) in their harbored toxigenic cytK gene between whole and skim milk powders with powdered infant formula and milk–cereal-based infant formula, as well as between powdered infant formula and milk–cereal-based infant formula. All isolated B. cereus strains were resistant to cefoxitin, colistin sulfate, neomycin, trimethoprim–sulfamethoxazole, oxacillin, and penicillin. Based on the antimicrobial resistance of B. cereus strains to cephalothin, chloramphenicol, nalidixic acid, and tetracycline, there was a significant difference (P < 0.05) between powdered infant milk formula and whole milk powder strains. This survey is one of few studies proceeded in Egypt to determine the prevalence of toxigenic B. cereus strains in milk–cereal-based infant formula and powdered infant formula as well as skim milk powder.

Self-assembly synthesis of flower-like gold nanoparticles for photothermal treatment of cancer

Polymyxin E (PE) could be used as a soft template, because of its characteristics of self-assembly and ability of metal ions reduction. Here, PE induced gold nanoflowers (PE@AuNFs) were successfully synthesized by seed growth method. PE@AuNFs had anisotropy, large absorption cross section, and large surface plasmon resonance (LSPR) peak, resulting in high photothermal conversion efficiency of 34.9%. Moreover, the cell viability of PE@AuNFs for HeLa cells was 19% under near-infrared light irradiation, while cell viability of 15 nm citrate capped gold nanoparticles (SC@AuNPs) was 83%. PE@AuNFs showed good antibacterial effect with laser irradiation. Furthermore, the excellent inhibition efficacy of PE@AuNFs also was demonstrated in U14 tumor-bearing mice in vivo. Taken together, the flower-shaped PE@AuNFs prepared by this new method had good biocompatibility and outstanding near-infrared photothermal treatment effect, indicating their great potential in photothermal therapy.

Bacteriological profile and antibiotics sensitivity patterns among neonates admitted at Birat Medical College Teaching Hospital

Background: Neonatal sepsis still remains serious and potentially life-threatening events with a mortality rate of up to 50%. The current practice of starting empirical antibiotic therapy in all neonates showing infection-like symptoms results in their exposure to adverse drug effects, nosocomial complications, and in the emergence of resistant strains. The antibiotic sensitivity pattern of organisms is changing very rapidly over a short period which is varying from country to country, one place to another, and one institute to another. Therefore, periodic evaluation of sensitivity patterns is essential for rational and appropriate use of antibiotics. Aims and Objectives: This study aims to see bacteriological profile and their antibiotics sensitivity among the sepsis suspected neonates at the neonatal intensive care unit of Birat Medical College Teaching Hospital (BMCTH). Materials and Methods: It was a cross-sectional descriptive study from July 21, 2021, to December 21, 2021. Sample size of 138 was included in the study. Neonates were selected by non-probability consecutive sampling techniques. Neonatal sepsis suspected neonates and plan to treat with injectable antibiotics by the treating pediatrician were included in the study. All patients included were started on empirical antibiotics after drawing samples for blood cultures and CRP along with other investigations. Bacteriological profile and their sensitivity to different antibiotics were collected from blood culture reports. Data collection was done using a specifically designed questionnaire. The descriptive and inferential statistics were used for data analysis. The test of significance was done by the Chi-square test. P&lt;0.05 was considered statistically significant. Results: Among the 46 blood culture-proven sepsis, the most common organism isolated was Staphylococcus aureus which was 33 (71.7%). Among the isolated S. aureus, 100% were sensitive to colistin sulfate and injectable linezolid, 93.1% sensitive to injectable meropenem, 85.7% sensitive to injectable piperacillin and tazobactam combination, 83.3% sensitive to injectable vancomycin, and 85.7% sensitive to injectable amikacin but only 40.7% to injectable cefotaxime. Isolated Acinetobacter species were found 100% sensitive to colistin sulfate and meropenem, and 80% sensitive to cefotaxime and amikacin but only 66.7% sensitive to injectable piperacillin and tazobactam combination. Only one neonate had Klebsiella isolated in blood culture which was 100% resistant to injectable cefotaxime but was sensitive 100% to Meropenem, piperacillin-tazobactam, and amikacin. Isolated Enterococcus species were 100% sensitive to piperacillin-tazobactam combination, meropenem, and imipenem but only 66.7% sensitive to injectable cefotaxime. Conclusion: Gram-positive isolates were the predominant pathogens among enrolled neonatal sepsis suspected neonates at Birat medical college teaching hospital (BMCTH). Based on our findings, a combination of cefotaxime and amikacin can be used as first-line therapy. However, cefotaxime only had moderate sensitivity, so change to piperacillin-tazobactam and vancomycin or linezolid as second-line therapy can be considered early in case of no improvement or deterioration, or combination of vancomycin and meropenem as third line would be the appropriate empirical therapy at BMCTH. However, the use of the broad-spectrum antibiotics as empirical therapy should be evaluated in the long run and should be used cautiously and modified to narrow spectrum antibiotics, as guided by the culture and susceptibility report at the earliest possible.

Plasma concentrations of Colistin sulfate in a patient with septic shock on extracorporeal membrane oxygenation and continuous renal replacement therapy: a case report

BackgroundPolymyxins antibiotics have become the first-line clinical drugs in the treatment of refractory gram-negative bacterial infections. Currently, there is a lack of clinical studies on the effect of extracorporeal membrane oxygenation (ECMO) combined with continuous renal replacement therapy (CRRT) on polymyxin concentrations. The purpose of this report was to investigate the changes in the plasma concentrations of Colistin sulfate during ECMO and CRRT and to provide drug administration programs for critically ill patients receiving ECMO and CRRT.Case DescriptionIn this case report, a patient with septic shock caused by severe acute pancreatitis, with abdominal pain and dyspnea as the main manifestations, was treated with ECMO combined with CRRT for life support and multiple anti-infective drugs. However, the symptoms of infection had not got improved, the inflammatory indicators remain high and the body temperature fluctuates repeatedly 36.7–38.5 ℃, was considered as carbapenem-resistant organisms (CROs) infection, and was empirically given Colistin sulfate for anti-infection treatment. Finally, the patient’s condition improved and ECMO and CRRT were gradually withdrawn. At the same time, the plasma concentrations of Colistin sulfate before and after ECMO combined with CRRT, was monitored to determine the changes in the plasma concentrations of Colistin sulfate during ECMO and CRRT. Trough and peak concentrations on the 4th day of venovenous ECMO (VV-ECMO) combined with CRRT were 0.36 and 0.98 mg/L, respectively. After withdrawal of ECMO and CRRT, the concentrations were, respectively, 0.27 and 0.34 mg/L for trough concentrations, and 0.82 and 0.98 mg/L for peak concentrations. The data showed that there were no significant differences in the trough and peak concentrations of Colistin sulfate before and after ECMO and CRRT. No adverse effects occurred during follow-up.ConclusionsThere were no significant differences in the trough and peak concentrations of Colistin sulfate before and after ECMO and CRRT. Therefore, no dose modification is required for Colistin sulfate in patients receiving ECMO with CRRT.

Colistimethate sodium

Colistimethate sodium

Colistin Therapy, Survival and Renal Replacement Therapy in Burn Patients: A 10-Year Single-Center Cohort Study.

PurposeColistin is still a therapeutic cornerstone against multidrug-resistant gram-negative bacteria (MDRGN), mostly when other antibiotics do not gain adequate activity on these strains. In the present study, we evaluated in a cohort of burn patients the relationship between colistin therapy, survival and requirement of renal replacement therapy (CRRT).Patients and MethodsRetrospective study of 133 burn patients treated with iv colistimethate sodium (loading dose 9.0 × 106 IU, maintenance dose 4.5 × 106 IU BID) and 35 treated with other antibiotics for MDRGN infection including Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae between January 2008 and December 2017. Multivariate analysis with logistic regression was used to determine the effect of the predictors such as age, total body surface area (TBSA), third-degree burn areas, Revised Baux score, Charlson comorbidity score, length of stay, colistin dose and duration of treatment, mechanical ventilation, and need of CRRT on in-hospital mortality. To investigate the relationship between colistin and renal function, we focused on survivor patients as the completion of the therapeutic course of colistin represented the basic requirement to analyze its impact on the kidney.ResultsOut of 133 colistin- and 35 other antibiotics-treated patients, 83 (62.4%) and 31 (88.6%) survived, and 53 (39.8%) and 3 (9.7%) required CRRT, respectively. The severity of burns, as well as CRRT requirement and mortality, was significantly higher in colistin-treated patients than in other antibiotics-treated patients. Age and TBSA% were the significant predictors of mortality. Out of 83 colistin-treated survivors, 19 (22.9%) required CRRT (9 before and 10 after the start of colistin), and 64 (77.1%) had a normal renal function. No difference about the colistin dose and baseline characteristics, but the revised Baux score was found between the 9 patients requiring CRRT before the colistin course and the 10 patients after. Similarly, among the 64 patients not undergoing CRRT, no difference was found between the patients treated with the cumulative dose of colistin <99.0 × 106 IU (n = 33, median daily dose of 4.0 × 106 IU) and >99.0 × 106 IU (n = 31, median daily dose of 9.0 × 106 IU) about the baseline characteristics and the daily median plasma creatinine over 24 days of therapy.ConclusionColistin therapy was associated with more severe burns, mortality, and CRRT requirement. A short course therapy, at appropriate cumulative dosage, can lead to clinical success without a significant association with severe renal impairment.

Synergistic efficacy of meropenem, ciprofloxacin and colistin antibiotics against planktonic and biofilm forms of Myroides odoratimimus bacterial isolates

PurposeIn this study, it was aimed to investigate the combined synergistic efficacy of colistin (CT), meropenem (MEM), and ciprofloxacin (CIP) antibiotics on planktonic and biofilm forms in Myroidesodoratimimus strains isolated from various clinical specimens. MethodsAntibiotic susceptibility was determined by the Kirby-Bauer disk diffusion method. In addition, minimum inhibitory concentrations (MIC) of CIP, MEM, and CT were studied using the standardized broth microdilution method. In vitro synergistic activity of antibiotics against M. odoratimimus planktonic bacteria strains was studied by the Micro Broth Checkerboard method. The microtiter plate (MtP) method was used to determine the effectiveness of antibiotics on M. odoratimimus biofilm formation. ResultsA zone of inhibition was not observed against other antibiotics used except amikacin and linezolid in all strains. While CT/MEM and CT/CIP combinations have a synergistic effect on all strains, the combination CIP/MEM has an additive effect. According to the biofilm inhibition results, all three antibiotics inhibited biofilm formation. However, the efficacy of MEM (60.3–76.5%) and CIP (60.2–77.8%) was approximately two times higher than that of CT (25.4–34.5%). In addition, the effectiveness of combinations of antibiotics on biofilm formation was examined and the percentage of inhibition was 30.8% when CT was used alone, while the biofilm inhibition rates of CT/MEM and CT/CIP were 92.4% and 91.7%, respectively. MEM/CIP combination was inhibited biofilm formation by 75.7%. ConclusionsThis study is the first report showing the efficacy of CT, MEM and CIP antibiotics, which are frequently used in clinical practice, in combination on M. odoratimimus planktonic and biofilm forms. The findings of our study are particularly guiding for combined antibiotic treatment options in immunosuppressed patients admitted to an intensive care unit (ICU). The CT/MEM combination is currently used frequently. In addition, these results are important in terms of supporting in vitro that CT/CIP and MEM/CIP combinations can also be used as a treatment option in M. odoratimimus related infections.

Evaluation of In Vitro Efficacy of Ceftazidime-Avibactam, Meropenem, and Colistin Single and Binary Combinations Against Carbapenem Resistant Klebsiella pneumoniae Strains Isolated from Various Clinical Specimens

It has been reported that many antibiotics used today, including the carbapenem group, fail to treat Klebsiella pneumoniae infections effectively. Despite many studies in recent years, the definitive treatment for carbapenem-resistant Klebsiella pneumoniae (CRKP) infections is still uncertain. In this study, it was aimed to investigate in vitro activities of colistin (COL) and meropenem (MEM), which are frequently used in the treatment of CRKP infections, and ceftazidime-avibactam (CZA), which is recently used in our country, alone or in combination against different CRKP isolates having different carbapenem resistance mechanisms andto analyze whether the presence of colistin resistance, which is an important problem in CRKP strains, influences the drug interaction results. This study was carried out in 42 K.pneumoniae isolates, which were isolated from various clinical samples as an infectious agent in Süleyman Demirel University Faculty of Medicine, Department of Medical Microbiology, Bacteriology Laboratory and whose carbapenem resistance was confirmed by carbapenemase inactivation test. The carbapenemase genes of the isolates were determined by the polymerase chain reaction (PCR) method. Antimicrobial susceptibilities of CRKP strains to CZA, MEM, and COL were determined by the broth microdilution method and in vitro synergy activities of dual combinations of these drugs were evaluated by checkerboard and time-kill methods. Statistical evaluation of categorical data was performed using Fisher's exact test, and p-value of less than 0.05 was considered statistically significant in terms of difference between the groups. Of the 42 CRKP isolates 34 (81%) were only OXA-48 positive, 5 (11.9%) were OXA-48+NDM and 3 (7.1%) were OXA-48+KPC positive. In the checkerboard test, synergy was detected against 97.6% of the isolates both with CZA+MEM and CZA+COL combinations, whereas this rate was 50% with MEM+COL. In the time-kill test, synergy was detected with CZA+MEM and CZA+COL combinations in the OXA-48 positive isolate and OXA-48+KPC positive isolate, while synergy was detected with CZA+COL and MEM+COL combinations in the OXA-48+NDM positive isolate. There was no significant relationship between whether the isolates were resistant to colistin or not and the checkerboard test results of antibiotic combinations (pCZA+MEM= 0.33, pCZA+COL= 0.11, pMEM+COL= 0.61). Results of our study revealed that the most common carbapenemase type in CRKP isolates was OXA-48 in our hospital, and the combinations of CZA with MEM and COL had high potential for synergism against these isolates.

Efficacy of local application of colistimethate sodium in non-healing wounds infected by multidrug resistant bacteria

Efficacy of local application of colistimethate sodium in non-healing wounds infected by multidrug resistant bacteria

Salvage parenteral antibiotics for multidrug-resistant (MDR) Gram-negative bacteria; a fluorescamine-based technique for ultrasensitive spectrofluorimetric measurement of Polymyxins; human plasma application.

Polymyxins (PMS), namely Colistin (CS) and polymyxin B (poly B), are antimicrobial drugs that have been recently used to treat multiresistant Gram-negative bacteria infections and their resurgence, owing to a lack of new antibiotics. A speedy, simple, and ultrasensitive spectrofluorimetric screening of PMS in pharmaceutical formulations and biological fluids was urgently required from this point forwards. A reaction between fluorescamine and the aliphatic amino moiety found in both drugs was performed in a slightly alkaline borate buffer (pH 8.5) resulted in highly fluorescent products measured at λem 460 (after λex 390.5 nm). Linear calibration curves were constructed over the concentration range 70-1800 ng ml-1 and 100 to 1400 ng ml-1 , with slope values of 0.273 and 0.286, correlation coefficients of 0.9998 and 0.9997, and determination coefficient of 0.9997 and 0.9994 for poly B and CS, respectively. The ultrasensitivity of the proposed method was demonstrated by the very low limit of quantification values of 67.56 ng ml-1 and 94.89 ng ml-1 for poly B and CS, respectively. The cited drugs were successfully determined in their intravenous market preparations by the prescribed method. Moreover, due to the high sensitivity, the suggested method was used to assay the investigated drugs in biological fluids.

Dosing Colistimethate Every 8 h Results in Higher Plasma Concentrations of Active Colistin Than Every 12-Hourly Dosing without Increase in Nephrotoxicity: A Phase 1 Pharmacokinetics Trial in Healthy Adult Volunteers.

Despite its use for decades, pharmacokinetic (PK) and safety studies on colistin are limited. We conducted a phase l, open-label trial to evaluate the safety and PK of multiple doses of intravenous (IV) and aerosolized colistimethate sodium (CMS) administered separately and in combination. In total, 31 healthy adults were enrolled into three cohorts of 9, 10, and 12 participants, respectively. Each cohort received increasing doses of CMS over three dosing periods as follows: Period 1 (IV only), 2.5 mg/kg every 12 h (q12h) to 3.3 mg/kg every 8 h (q8h); Period 2 (aerosolized only), 75 mg 2–4 doses, and Period 3 (combined IV aerosolized), in which was Periods 1 and 2 combined. Safety assessments, serum and lung concentrations of colistin analytes (colistin A, colistin B, CMS A, and CMS B), and kidney biomarkers were measured at specified time points. Increasing the CMS dose from 2.5 mg/kg q12h to q8h resulted in a 33% increase in serum colistin A concentrations from 3.9 μg/mL to 5.3 μg/mL—well above the accepted target of 2 μg/mL for 6 h after dosing, without evidence of nephrotoxicity. However, there was an increase in neurotoxicity, primarily perioral and lingual paresthesias, and self-limited ataxia. IV administration did not increase the lung concentrations of colistin.

Colistin A Last Resort Antibiotic

Colistin is an antibiotic of last resort, works as a last line of defense against illness caused by the multiple drug resistant (MDR) gram negative bacteria. Polimixins consist of aqua phobic acyl tail, linear tripeptide part, and heptapeptide ring. Chemical formula of colistin is C52H98N16O13. Colistin is given in two forms, colistin methane sulfonate (CMS) and colistin sulfate.&#x0D; Findings: Colistin disturbs or destroys the outer membrane of bacteria, or stops the respiratory enzymes of the inner membrane of bacteria. Colistin also works as an antiendotoxin. Colistin has great bactericidal activity against gram negative rods. Colistin resistance is a serious concern of present time. High rate of the spread of MDR gram negative bacterial infections is leading to high use of colistin for treatment, due to which prevalence of colistin resistance is increasing worldwide. As bacterial outer membrane is the main target of colistin, resistance against it develop by modification of outer membrane LPS. There are several mechanisms of colistin resistance. Intrinsic mechanism involves expression of arnBCADTEF operon and eptB gene. Acquired non-transferable resistance involves pmrAB, PhoPQ, and CrrAB two component systems (TCSs), mgrB gene and ramA. Transferable resistance is more serious concern as it can be spread in population by horizontal gene transfer. Mcr genes are responsible for transferable or plasmid-mediated colistin resistance.&#x0D; Conclusion: This review focuses on the chemistry of colistin, mechanism of action, spectrum of action, colistin resistance and different mechanisms behind it.

Colistin sulfate for decontamination of preservation fluid in kidney transplantation to decrease the incidence of donor-derived infections caused by multidrug-resistant Gram-negative bacteria.

Preservation fluid (PF) contamination, especially by multidrug-resistant (MDR) Gram-negative bacteria (GNB), poses a high risk of donor-derived infection (DDI) and severe clinical outcomes. We sought to determine whether the use of colistin sulfate to decontaminate PF in kidney transplantation can decrease the incidence of probable DDI (p-DDI) caused by MDR GNB. In a retrospective study of 916 recipients who received deceased donation, 864 PF samples were collected and cultured, and microbiological contaminants were recorded with the recipients' clinical data and outcomes. From March 2016 to May 2019, 624 samples were decontaminated with ceftizoxime, and from June 2019 to March 2021, 240 samples were decontaminated with colistin sulfate. Between-group comparisons were performed to assess the ability of the two decontamination regimens to decrease the incidence of p-DDI, especially MDR GNB-related infection. The overall PF contamination rate was 54.51% (471/864), and 80 samples were positive for MDR GNB contamination. All p-DDIs occurred in the ceftizoxime group (p<0.001), and 67.65% of p-DDIs were MDR GNB-related. In the ceftizoxime group, 23 of 61 cases of MDR GNB contamination led to related p-DDIs, while none occurred in the colistin sulfate group (p=0.002). Among the 23 patients with p-DDIs, 5 died due to severe infection, and 2 experienced graft loss. The goal of decontamination should be to decrease the risk of MDR GNB-related p-DDI, and colistin sulfate could be an effective and feasible option.

Ceftolozane/tazobactam versus colistin in the treatment of ventilator-associated pneumonia due to extensively drug-resistant Pseudomonas aeruginosa

Resistant strains of Pseudomonas aeruginosa are common pathogens in the intensive care unit (ICU), limiting available therapeutic options. We aimed to compare ceftolozane/tazobactam (C/T) with colistimethate sodium (CMS) in the treatment of ventilator-associated pneumonia (VAP) due to extensively drug-resistant (XDR) Pseudomonas aeruginosa. A retrospective, observational study was performed at a tertiary care ICU. Clinical and microbiological success rate, 28-day all-cause mortality, and adverse events were compared in patients who received C/T with those treated with systemic CMS. A total of 51 patients were included (18 in the C/T and 33 in the CMS group). Clinical success rates in the C/T and CMS groups were 13 (72.2%) and 10 (30.3%), respectively. On multivariate regression analysis, treatment with C/T was independently associated with clinical success (odds ratio 4.47, 95% CI 1.17–17.08). There was no difference in 28-day all-cause mortality (27.8% and 33.3% in the C/T and CMS group, p = 0.76). Acute kidney injury was more common in patients who received CMS (48.5% vs 11.1%, p = 0.01). In our study, ceftolozane/tazobactam was more efficacious in the treatment of XDR Pseudomonas aeruginosa VAP and showed a better safety profile compared to CMS.

Study of the Interactive Effect between Tylosin Tartrate and Colistin for its Use in the Therapy and Prevention of Poultry Diseases in Veterinary Medicine

The pharmacological interaction of antibiotic combinations of tylosin and colistin was studied. For this purpose, an in vitro challenge method was used. The results were used to calculate their interaction using the graphic representation known as ISOBOLOGRAM. The pure salts of tylosin tartrate and colistin sulfate were obtained from the manufacturer of the product, Laboratorios Ecozoo SA de CV Mexico. The bioassay method was used in agar wells and to quantify the results, the following criteria were used: A synergistic effect was defined when the real/theoretical effect (SMF) was greater than 1. The additive effect was defined when the SMF was equal to 1. The area between the antagonism and additive effect was defined as the zone of indifference. When studying the interaction between tylosin and colistin it was observed that the best SMF of this antibiotic combination was 3 to 2 and 2 : 4 (tylosin colistin respectively). It was cocluded that the combination of tylosin with colistin exerts a synergistic effect and can be recommended for oral administration in poultry for the treatment of infections by disease producing germs sensitive to the formula.

The Value of Neutrophil-To-Lymphocyte Ratio for Evaluating Blood Stream Infection Caused by Carbapenem-Resistant Klebsiella pneumoniae: A Retrospective Cohort Study.

BackgroundThe neutrophil-to-lymphocyte ratio (NLR) is a useful marker of inflammation. However, the prognostic function of the NLR in patients with carbapenem-resistant Klebsiella pneumoniae (CRKP) blood stream infection (BSI) remains largely unknown. The aim of this study was to explore the potential relationship between the NLR and mortality in these patients.MethodsWe performed a retrospective cohort study based on data retrieved from the computerized patient record system in a tertiary hospital from 1 January 2017 to 31 October, 2020. A total of 134 inpatients with CRKP BSI were enrolled in this study, including 54 fatal cases and 80 survival cases, 28 days after the onset of CRKP BSI. A logistic analysis was performed to assess the association between the NLR on the 4th day and 28-day mortality. Multivariate analyses were used to control for the confounders.ResultsThe overall 28-day mortality rate of patients with a CRKP BSI episode was 40.3% (54/134). We conducted a multivariate analysis of the data of 134 patients and found that the NLR on the 4th day [odds ratio (OR) 1.148, 95% confidence interval (CI) 1.076–1.225, p < 0.001] and antibiotic exposure before BSI onset (OR 3.847, 95% CI 1.322–11.196, p = 0.013) were independent risk factors for 28-day mortality of patients with CRKP BSI, while appropriate initial therapy (AIT, OR 0.073, 95% CI 0.017–0.307, p < 0.001) was an independent protective factor. Among patients treated with AITs, the Cox proportional hazards regression analysis revealed a significant difference in prognosis (p = 0.006) between the ceftazidime/avibactam contained (CAZ) group and non CAZ-AVI groups. After dividing the non CAZ-AVI group into the tigecycline (TGC), colistin (COL), and TGC + COL groups, there were no differences between the CAZ-AVI group and the TGC group (p = 0.093), but CAZ-AVI group showed lower 28-day mortality than COL (p = 0.002) and TGC + COL (p = 0.002) groups. Meanwhile, there was no difference in NLR on the 1st day (p = 0.958) of patients in different groups but significant difference in NLR on the 4th day (p = 0.047).ConclusionsThe NLR on the 4th day is a readily available and independent prognostic biomarker for patients with CRKP BSI. This marker may have the potential for use in evaluating the efficacy of different anti-infection therapy strategies at an early stage.

A novel model of dermatomyositis induced by membrane antigen and calciphylaxis in rats.

Dermatomyositis (DM) is a severe autoimmune disease of the connective tissue characterized by inflammatory and degenerative changes in the skin and muscle. However, the lack of experimental models of DM represents a challenge for the development of effective drugs. The aim of the present study was to establish a pharmacodynamic rat model of DM that would recapitulate the clinical manifestation seen in patients. The DM model was established using membrane antigen-induced autoimmune injury, followed by toxin-induced subcutaneous calciphylaxis. The rats were divided into five groups and were subcutaneously injected with membrane antigen. Of these, four antigen-immunized groups then received dihydrotestosterone (DHT), iron-dextrin (Fe-Dex), polymyxin (PMX) either individually or in combination to induce cutaneous calciphylaxis. The clinical manifestation score, ratio of infiltrated lymphocytes, ratio of arteriole calcified nodules in skeletal muscles, serum antibody levels [anti-histidyl tRNA synthetase (Jo-1) and anti-melanoma differentiation-associated protein 5 (MDA5)] and serum cytokine levels [tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ)] were then detected. The results demonstrated that all five autoimmune groups displayed local cutaneous swelling and weakness, increased serum antibody and cytokine levels, and T lymphocyte infiltration in perimysial and perivascular sites. Moreover, pathological changes indicative of calciphylaxis were observed in the PMX and DHT + Fe-Dex + PMX. Among all groups, the rats in the PMX and DHT + Fe-Dex + PMX displayed characteristics most closely resembling those of DM pathogenesis in patients. In conclusion, membrane antigen immunization combined with toxin-induced calciphylaxis can be used as a DM model in rats. This model may be used for the development of effective drugs for DM treatment.

Antimicrobial efficacy of Terminalia chebula (Haritaki) ethanol extracts against Escherichia coli and Salmonella isolated from commercial broiler

Antimicrobial resistance is one of the most concerning issues globally for public health. To tackle this problem, elucidation of folk medicine could be an option to treat infectious diseases and reduce the risk of antimicrobial resistance in both human and veterinary medicine. Escherichia coli and Salmonella are two common bacterial pathogens of poultry in Bangladesh. Therefore, the present study aimed to investigate the efficacy of ethanolic extract of Terminalia chebula (Haritaki) fruits against these two organisms and some other commercial antimicrobials, including ciprofloxacin, enrofloxacin, colistin sulfate, tetracycline, and trimethoprim. For this purpose, a total of 90 commercial broiler chickens were purchased from local markets, sacrificed, and liver samples were collected for isolation of E. coli and Salmonella spp. A total of three concentrations (1mg/µL, 0.5mg/µL, and 0.25mg/µL) of the ethanolic extract of Terminalia chebula fruit were tested against these organisms. The Terminalia chebula extracts showed a zone of inhibition at 1mg/µL dose soaked the disc with 20 µl extracts against E. coli (12-13 mm) and Salmonella spp. (10-11 mm), which are similar to the intermediary zone sensitivity of colistin sulfate, tetracycline, and trimethoprim. In summary, we may conclude that ethanolic extracts of the Terminalia chebula fruits would be a potential source as antimicrobial agents

Preparation of Veterinary Premix with Dual Active Ingredients in Granular Form

The aim of the study was to investigate the preparation of granular veterinary premix containing two different antibiotics by fluid bed granulation process. The particle size and density of the active ingredients were investigated for the proper selection of the filler material. The used antibiotics were tylosin tartarate and colistin sulfate, while isomalt sugar alcohol and cellulose materials were selected as filler and binder, respectively. The colistin sulfate was fed together with the binder solution because of its low density, fine particle size and relatively low (1.2%) concentration in the product. The type and concentration of the binder in its solution, the feeding rate and the total amount of added binder solution were optimized for obtaining dust free granules with desirable abrasion resistance and good flowability. The active ingredient content for both antibiotics was preserved even at the elevated temperature applied during the fluid granulation process.