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WHAT IS KNOWN AND OBJECTIVE?: Dalbavancin is used against gram-positive pathogens such as Staphylococcus aureus in acute bacterial skin and skin-structure infections. METHODS: Our main goal was to identify the key articles sustaining the current knowledge of this drug's therapeutic possibilities through a bibliometric analysis of the available literature. RESULTS AND DISCUSSION: On 15 March 2021, we searched the Web of Science electronically for documents that contain within its title the term "dalbavancin." We found a total of 675 documents that average 20.23 citations/publication with a density of 682.60 citations per/year, yielding an h-index of 58. After ranking them by the number of times cited, we extracted the top 100 most-cited records (T100). Number of citations/publication ranged from 13 to 231, publication years were 2002-2019, with the top-cited article published in 2014. All T100 publications were written in English. JMI Laboratories was the institution with the most articles in the T100 (22 documents), and the United States was the top country (75 documents). Five authors participated in at least five of the T100, led by Jones RN with 20 articles. Positions #1, #2, #5, and #9 were clinical trials for acute bacterial skin and skin structure infections (ABSSSI), the on-label indication for dalbavancin. Only one article in the top 10 (T10) was an off-label indication that was published in 2005 with 186 citations, and occupied the third position among the T100. Using the VOSviewer© programme, we observed that the most used keywords were: dalbavancin, lipoglycopeptide, gram-positive, osteomyelitis, vancomycin, and MRSA. WHAT IS NEW AND CONCLUSIONS?: Our study identifies the most significant research on dalbavancin, including the highest impact publications, and highlights the recent trend of dalbavancin in new therapies. The T10 articles include the most important dalbavancin clinical trials, along with other studies and reviews that support the growing role of this antibiotic in clinical use. Emphasis has been on the favourable pharmacokinetic profile that allows administration once-weekly, with minimal risk of severe adverse events.

Background Teicoplanin is a glycopeptide antibiotic used for the treatment of methicillin-resistant Staphylococcus aureus infections. To ensure successful target attainment, therapeutic drug monitoring-informed dosage adjustment is recommended. However, it relies on the experience of the clinician and the frequency of drug measurements. This study aimed to design a new optimal dosing regimen of teicoplanin with a maintenance dosing strategy for neonates and children based on their physiological characteristics. Methods Data from teicoplanin-treated patients (n = 214) were collected from electronic medical records. Covariate analyses were performed using population pharmacokinetic (PK) modeling with 399 serum teicoplanin concentrations from 48 neonates and 166 children. Multiple PK simulations were conducted to explore optimal dosing regimens that would allow control of the trough concentration to the target of 15-30 mg/L quicker than the current standard regimen. Results Allometrically scaled body weight, postmenstrual age (PMA), renal function, and serum albumin were implemented as substantial covariates for teicoplanin clearance in a two-compartment PK model. Covariate analyses and comprehensive simulation assessments recommended the following modifications to the current regimen: 1) decreased dose for premature babies (PMA ≤ 28 weeks), 2) decreased dose for children with renal dysfunction, and 3) increased dose for children (0.5-11 years) with an estimated glomerular filtration rate of ≥90 mL/min/1.73 m2. Conclusions This study leverages real-world clinical information and proposes new optimal dosing regimens for teicoplanin in neonates and children through PK modeling and simulation analyses, taking into account the age, including PMA, and renal function of patients.

To describe the clinical experience with dalbavancin in the treatment of diabetic foot infection in a multidisciplinary unit of a second level hospital.A retrospective, descriptive study was made with all patients with diabetic foot infection treated with dalbavancin in the Diabetic Foot Unit of Hospital Universitario Fundación Alcorcón, covering the period from September 2016 to December 2019. Demographic parameters and comorbidities, characteristics of the infection and treatment with dalbavancin were recorded. The cure rate is estimated at 90 days after finishing the treatment.A total of 23 patients with diabetic foot infection (osteomyelitis) started treatment with dalbavancin, 19 were men and the mean age was 65 years. The microorganisms most frequently isolated for the indication of treatment with dalbavancin were Staphylococcus aureus (11) and Corynebacterium striatum (7). Dalbavancin was used as a second choice therapy in 22 cases, in 11 due to toxicity from other antibiotics. The median duration of treatment was 5 (4-7) weeks; the most frequent dose of dalbavancin (8 patients) was 1000 mg followed by 500 mg weekly for 5 weeks. 3 patients presented mild side effects (nausea and gastrointestinal discomfort). At 90 days after completion of dalbavancin therapy, 87% (20) of the patients were cured (95% CI: 65.2%-94.52%).Patients with osteomyelitis due to gram-positive microorganisms who received as part of the multidisciplinary antibiotic treatment with dalbavancin, had a high rate of cure with adequate tolerance and few side effects. Dalbavancin offers a safe alternative in treating deep diabetic foot infection.

There are few reports on the distribution of the plasma trough concentration (CData on patients treated with teicoplanin from January 2019 to January 2021 were collected retrospectively and divided into ARC (creatinine clearance rate [CCr]130 ml/min, n = 22) and non-ARC (60 ml/min ≤ CCr ≤130 ml/min, n = 24) groups. The COn the third day of the HD, CThese results suggest that it is necessary to apply a loading dose of 800 mg (but not higher) q12h three times for patients with ARC, with 800 mg needed as a maintenance dose during severe infection, and 600 mg or 400 mg for mild infection.

Teicoplanin is a glycopeptide antibiotic deployed to combat Gram-positive bacterial infection and has recently been associated with development of adverse drug reactions, particularly following previous exposure to vancomycin. In this study, we generated teicoplanin-specific monoclonal T-cell populations from healthy volunteers expressing HLA-A*32:01 and defined pathways of T-cell activation and HLA allele restriction. Teicoplanin-responsive T-cells were CD8+, HLA class I-restricted, and cross-reacted with the lipoglycopeptide daptomycin in proliferation and cytokine/cytolytic molecule (granzyme B, Perforin, and FasL) release assays. These data show that teicoplanin activates T-cells, which may play a role in the pathogenesis of teicoplanin-induced adverse events, in HLA-A*32:01 positive donors.

Introduction Because of its lower risk of renal toxicity than vancomycin, teicoplanin is the preferred treatment for methicillin-resistant Staphylococcus aureus infection in patients undergoing continuous venovenous haemodiafiltration (CVVHDF) in whom renal function is expected to recover. The dosing regimen for achieving a trough concentration (Cmin) of ≥20 μg/mL remains unclear in patients on CVVHDF using the low flow rate adopted in Japan. Methods The study was conducted in patients undergoing CVVHDF with a flow rate of Results Overall, 60 patients were eligible for study inclusion. The proportion of patients achieving the Cmin target was significantly higher for the enhanced regimen than for the high-dose regimen (52.9% versus 8.3%, p = 0.003). In multivariate analysis, the enhanced regimen (odds ratio [OR] = 39.93, 95% confidence interval [CI] = 5.03–317.17) and hypoalbuminaemia (OR = 0.04, 95% CI = 0.01–0.44) were independent predictors of the achievement of Cmin ≥ 20 μg/mL. Conclusions An enhanced teicoplanin regimen was proposed to treat complicated or invasive infections by methicillin-resistant Staphylococcus aureus in patients receiving CVVHDF even with a low flow rate.

Purpose In the present narrative review, the authors aimed to discuss the relationship between the pharmacokinetic/pharmacodynamic of antibiotics and clinical response (including efficacy and toxicity). In addition, this review describes how this relationship can be applied to define the therapeutic range of a particular antibiotic (or antibiotic class) for therapeutic drug monitoring. Methods Relevant clinical studies that examined the relationship between pharmacokinetic/pharmacodynamic of antibiotics and clinical response (efficacy and response) were reviewed. The review (performed for studies published in English up to September 2021) assessed only commonly used antibiotics (or antibiotic classes), including aminoglycosides, beta-lactam antibiotics, daptomycin, fluoroquinolones, glycopeptides (teicoplanin and vancomycin), and linezolid. The best currently available evidence was used to define the therapeutic range for these antibiotics. Results The therapeutic range associated with maximal clinical efficacy and minimal toxicity is available for commonly used antibiotics, and these values can be implemented when therapeutic drug monitoring for antibiotics is performed. Additional data are needed to clarify the relationship between pharmacokinetic/pharmacodynamic indices and the development of antibiotic resistance. Conclusion Therapeutic drug monitoring should only be regarded as a means to achieve the main goal of providing safe and effective antibiotic therapy for all patients. The next critical step is to define exposures that can prevent the development of antibiotic resistance and include these exposures as therapeutic drug monitoring targets.

Drug combinations may have a crucial role in treating infections due to multidrug resistant Acinetobacter spp. One suggested combination is colistin with teicoplanin. The effect of colistin on Acinetobacter spp. outer membrane can permit teicoplanin to its target in the cell wall. The aim of this study was to evaluate the synergistic activity of colistin and teicoplanin combination against 29 multidrug resistant isolates of Acinetobacter spp. The antimicrobial activity of colistin alone and in combination with teicoplanin was assessed using MIC and time–kill assays. The combination of 1 mg/l colistin and 10 mg/l teicoplanin showed in vitro synergism against all tested Acinetobacter isolates except one (Acinetobacter lowffii). The combination of 1 mg/l colistin and 10 mg/l teicoplanin was bactericidal at 6 h against 100% of Acinetobacter baumannii isolates with no bacterial regrowth at 24 h. The same combination was bactericidal against three out of seven non-baumannii Acinetobacter isolates. The increased concentration of teicoplanin (20 mg/l) was synergistic but still not bactericidal against the four remaining isolates. The combination of colistin and teicoplanin was synergistic against all tested Acinetobacter spp It is therefore recommended that clinical trials are conducted to clarify the therapeutic potential of the combination.

The pharmacokinetics (PK) of teicoplanin differs in children as compared with adults, and especially in renally-impaired pediatric patients. Inappropriate empirical antibacterial therapy may lead to treatment-related antibacterial resistance and increased toxicity, making adjustment of the dosage regimen essential. In the present study, physiologically based pharmacokinetic (PBPK) models were developed to define the appropriate dosage regimen for pediatric patients with differing renal function. Our PBPK models accurately predicted teicoplanin exposures in both adult and pediatric subjects after single and multiple intravenous infusions, with less than a 1.36-fold error between predicted and observed data, and all observed data were within minimal and maximal data of the corresponding population simulation. The area under the plasma concentration-time curve was predicted to increase 1.25-fold, 1.95-fold, and 2.82-fold in pediatric patients with mild, moderate, and severe renal impairment (RI), respectively, relative to that of healthy children. Subsequently, the results of Monte Carlo simulations indicated that the recommended dosing of 12, 9.5, 6, and 4 mg/kg at 12-hour intervals would be appropriate in pediatric patients with normal renal function and in those with mild RI, moderate RI, and severe RI, respectively, at a susceptible MIC

Dalbavancin is a synthetic lipoglycopeptide that exerts its antimicrobial activity through two distinct modes of action, inhibition of cell wall synthesis and an anchoring mechanism. Compared with previous glycopeptide antibiotics, dalbavancin demonstrates improved antibacterial potency against Gram-positive organisms and a long half-life of approximately 1 week, which is longer in tissues (e.g., skin, bone) than plasma. These factors facilitated the development of single-dose or once-weekly dosing regimens to treat acute bacterial skin and skin structure infections (ABSSSI). Dalbavancin exhibits dose-proportional pharmacokinetics and is highly protein bound (93%). Despite being highly protein bound, it has a steady-state volume of distribution10 L and distributes widely into the skin, bone, peritoneal space, and epithelial lining fluid, but not cerebrospinal fluid. Dalbavancin elimination occurs via a combination of renal (approximately 45%) and non-renal clearance, with dose adjustments recommended only in patients with a creatinine clearance30 mL/min not receiving any form of dialysis. The established pharmacokinetic/pharmacodynamic index associated with bacterial kill is free area under the concentration-time curve over the minimum inhibitory concentration (fAUC/MIC), with a goal 24-h fAUC/MIC of at least 27.1 for Staphylococcus aureus infections. Recent data suggest usefulness in the treatment of infections beyond ABSSSI, with convenient dosing and redosing strategies for complicated infections requiring extended treatment durations. Additional studies are needed to confirm these preliminary findings.

Background: Significant changes in the pathophysiology of older critically ill patients may affect the pharmacokinetics and pharmacodynamics of teicoplanin. This study aimed to determine the optimal teicoplanin blood level in this patient population. Materials & Methods: 128 older critically ill and 86 older non-critically ill patients were involved and analyzed. Results: The target thresholds of teicoplanin blood concentrations in older critically ill patients and non-critically ill patients should be 31.4mg/L and 15.3mg/L, respectively. The dose of teicoplanin in older critically ill patients should be greater than 800 mg to achieve the target blood level. Conclusion : An individualized dosing approach of teicoplanin based on therapeutic drug monitoring is necessary for older critically ill patients.

OBJECTIVE To improve the production of A40926, a combined strategy of constructing the engineered strain and optimizing the medium was implemented. RESULTS The engineered strain lcu1 with the genetic features of dbv23 deletion and dbv3-dbv20 coexpression increased by 30.6% in the production of A40926, compared to the original strain. In addition, a combined medium called M9 was designed to be further optimized by the central composite design method. The optimized M9 medium was verified to significantly improve the A40926 yield from 257 to 332 mg l-1. CONCLUSIONS The engineered strain lcu1 could significantly promote A40926 production in the optimized M9 medium, which indicated that the polygenic genetic manipulation and the media optimization played an equally important role in increasing the A40926 yield.

Teicoplanin is a glycopeptide antibiotic against methicillin-resistant Staphylococcus aureus infections. However, the impact of clinical characteristics on nephrotoxicity associated with teicoplanin has not been determined. This meta-analysis aimed to investigate the relationship between clinical characteristics and nephrotoxicity associated with teicoplanin. We identified clinical research published from January 1975 to June 2021 using PubMed, Cochrane Library, and Scopus, which described the nephrotoxicity associated with teicoplanin. Meta-analysis determined the incidence of nephrotoxicity. Using meta-regression analysis, we evaluated the impact of clinical characteristics on outcomes. Of the 567 articles, eight articles including 634 patients were analysed. The overall incidence of nephrotoxicity associated with teicoplanin was 11.0% (95% confidence interval: 8.0-13.0) for the fixed-effect model. Additionally, patients with >65 years had a high trend for the risk of nephrotoxicity compared to those with ≤65 years (>65 years; 12.0% [95% confidence interval: 9.0-15.0] vs. ≤65 years; 7.0% [95% confidence interval: 3.0-12.0], p = 0.09) for the fixed-effect model. Meta-regression analysis demonstrated that only serum albumin level negatively correlated with the risk of nephrotoxicity (y = -17.0 x + 56.7, r = 0.74, p = 0.01). This meta-analysis ascertained that hypoalbuminemia leads to nephrotoxicity associated with teicoplanin.

BACKGROUND: Vancomycin-resistant Enterococcus faecium (VREfm) is an important agent of hospital-acquired infection. VanA phenotype is characterized by resistance to high levels of vancomycin and teicoplanin and is encoded by the vanA gene, whereas VanD phenotype is characterized by resistance to vancomycin and susceptibility or intermediate resistance to teicoplanin; however, some isolates carry a VanD phenotype with a vanA genotype, but there are many gaps in the knowledge about the genetic mechanisms behind this pattern. OBJECTIVE: To characterize the genetic structure, clonality, and mobile genetic elements of VRE isolates that display a VanD-vanA phenotype. RESULTS: All vanA VRE-fm isolates displayed minimum inhibitory concentration (MIC) for vancomycin > 32µg/mL and intermediate or susceptible MIC range for teicoplanin (8–16µg/mL). The isolates were not clonal, and whole-genome sequencing analysis showed that they belonged to five different STs (ST478, ST412, ST792, ST896, and ST1393). The absence of some van complex genes were observed in three isolates: Ef5 lacked vanY and vanZ, Ef2 lacked vanY, and Ef9 lacked orf1 and orf2; moreover, another three isolates had inverted positions of orf1, orf2, vanR, and vanS genes. IS1542 was observed in all isolates, whereas IS1216 in only five. Moreover, presence of other hypothetical protein-encoding genes located downstream the vanZ gene were observed in six isolates. CONCLUSION: VRE isolates can display some phenotypes associated to vanA genotype, including VanA and VanB, as well as VanD; however, further studies are needed to understand the exact role of genetic variability, rearrangement of the transposon Tn1546, and presence of insertion elements in isolates with this profile.

The purpose of the study: to compare the activity of vancomycin, teicoplanin and linezolid and to determine their place in the current treatment of nosocomial infections caused by gram-positive microflora.Material and Methods. 640 gram-positive microorganisms (S. aureus, E. faecium, E. faecalis) isolated in 2018 from various pathological materials from cancer patients treated at N.N. Blokhin National Medical Research Center of Oncology were studied. Literature data from 1982 to 2019, concerning efficacy of glycopeptides (vancomycin, teicoplanin) and linezolid against these pathogens were analyzed.Results. Data analysis showed that percentage of methicillin-resistant Staphylococcus aureus (MRSA) was 89 % and percentage of vancomycinresistant enterococci (VRE) was 5.1 % among Enterococcus faecalis and 16.4 % among Enterococcus faecium. The susceptibility of the studied gram-positive microorganisms to teicoplanin, vancomycin and linezolid ranged from 83.3 to 98.8 % (p>0.5). In general, teicoplanin, vancomycin, and linezolid had equally high microbiological activity against nosocomial strains of S. aureus and Enterococcus spp. Also, according to the literature data, a comparative assessment of the clinical effectiveness and cost-effectiveness of glycopeptides and linezolid was assessed.Conclusion. Vancomycin and teicoplanin are still the main drugs for the treatment of various infections caused by resistant gram-positive microflora. However, teicoplanin, with an efficacy equal to that of vancomycin, has a number of significant advantages over the latter: better tolerability, lower frequency of adverse reactions, and pharmacokinetic features that make it possible to use it once a day both intravenously and intramuscularly. Both drugs, along with linezolid, can be used to treat infections caused by gram-positive microorganisms in cancer patients.

Gram-negative bacteria possess intrinsic resistance to glycopeptide antibiotics so these important antibacterial medications are only suitable for the treatment of Gram-positive bacterial infections. At the same time, polymyxins are peptide antibiotics, structurally related to glycopeptides, with remarkable activity against Gram-negative bacteria. With the aim of breaking the intrinsic resistance of Gram-negative bacteria against glycopeptides, a polycationic vancomycin aglycone derivative carrying an n-decanoyl side chain and five aminoethyl groups, which resembles the structure of polymyxins, was prepared. Although the compound by itself was not active against the Gram-negative bacteria tested, it synergized with teicoplanin against Escherichia coli, Pseudomonas aeruginosa and Acinetobacter baumannii, and it was able to potentiate vancomycin against these Gram-negative strains. Moreover, it proved to be active against vancomycin- and teicoplanin-resistant Gram-positive bacteria.

Glycopeptide antibiotics (GPAs) are among the most clinically successful antimicrobials. GPAs inhibit cell-wall biosynthesis in Gram-positive bacteria via binding to lipid II. Natural GPAs are produced by various actinobacteria. Being themselves Gram-positives, the GPA producers evolved sophisticated mechanisms of self-resistance to avoid suicide during antibiotic production. These self-resistance genes are considered the primary source of GPA resistance genes actually spreading among pathogenic enterococci and staphylococci. The GPA-resistance mechanism in

BACKGROUND Mycobacterium tuberculosis (M. tuberculosis) is usually treated by oral antimycobacterial agents, including rifampicin, ethambutol, and pyrazinamide, but the treatment regimen with intravenous and/or intramuscular antimycobacterial agents for patients who cannot take medications orally remains unclear. CASE REPORT A 77-year-old man with chronic renal failure had an esophageal-skin fistula after he had surgeries for removal of esophageal and gastric cancers and reconstruction using jejunum, and he showed a cavity, tree-in-bud formation, and pleural effusions in his left upper lung fields on his chest X-ray after treatment of cellulitis and bacteremia/candidemia by meropenem, teicoplanin, and micafungin. M. tuberculosis was isolated from his sputum and exudate fluid from the reconstructed esophageal-skin fistula. Although he could not take antimycobacterial agents orally, treatment was started with intravenous agents combining levofloxacin (LVFX) every other day, isoniazid (INH), and linezolid (LZD). However, his platelets were decreased 21 days after treatment started, and it was thought to be an adverse effect of LZD and/or INH. After changing LZD to tedizolid (TZD), in addition to changing from INH to intramuscular streptomycin twice per week, his platelet counts increased. Intravenous TZD could be continued, and it maintained his condition without exacerbations of thrombocytopenia and renal failure. The M. tuberculosis disappeared, and the abnormal chest X-ray shadows were improved 2 months after the start of treatment. CONCLUSIONS Administration of intravenous TZD, in addition to intravenous LVFX and intramuscular SM in combination, might be a candidate regimen for M. tuberculosis patients who cannot take oral medications.

Background and Rationale: Enterococci have long been recognised as low virulence bacteria occurring as commensals in the human intestine. However in the last two decades they emerged as one of the leading causes of nosocomial infections with the development of resistance to antibiotics. So appropriate identification and characterization and antimicrobial susceptibility testing of Enterococcal species is necessary for management and prevention of these infections. Materials and Methods: 150 isolates of Enterococcal species were obtained from various clinical samples. Characterisation was done by standard Microbiological methods and antibiotic susceptibility testing was done by Kirby- Bauer disc diffusion method and Vancomycin MIC tested by E- test. Results: Out of 150 isolates from various clinical samples like urine 93(62%), pus 45(30%), blood 7(4.6%) and other body fluids 5(3%), E.faecalis 131(87.3%) was the predominant isolate followed by E.faecium 14(9.3%), E.avium 2(1.3%), E.raffinosus 2(1.3%) and E.durans 1(0.6%). All isolates were sensitive to Vancomycin, Teicoplanin and Linezolid. Sensitivity to High level Gentamicin was 92%. Rate of resistance to Penicillin 150(100%), Tetracycline 95(63.3%), Ciprofloxacin 103(68.6%) and Ampicillin 67(44.6%). Conclusions: Even though no Vancomycin resistant strains were isolated from our study, there is incidence of Vancomycin resistant Enterococci are emerging as potent pathogen. So methods for characterization, antimicrobial susceptibility testing and MIC of Vancomycin should be done routinely for Enterococcal species. Keywords: Enterococcus, Efaecalis, Efaecium, High level Gentamicin, Vancomycinresistant Enterococci

This study reports the distribution of enterotoxigenic determinants among staphylococci and the susceptibility of staphylococci to various classes of antibiotics. We observed all the isolates as resistant to beta-lactam antibiotics and a few as resistant to non-beta-lactam antibiotics such as clindamycin (47.4%), erythromycin (44.7%), gentamicin (23.7%), norfloxacin (34.2%), tetracycline (26.3%), trimethoprim-sulfamethoxazole (15.8%) etc. The resistance of S. sciuri (n = 1) and S. haemolyticus (n = 1) to rifampicin and intermediate resistance of S. gallinarum (n = 2) to teicoplanin, a high-end antibiotic, are also observed in this study. The multidrug-resistance (≥ 3 classes of antibiotics) was recorded in 23 (60.5%) isolates. The virulomes such as sea, seb, seg and sei were identified predominantly in S. haemolyticus. Surprisingly, certain isolates which were phenotypically confirmed as biofilm-producers by Congo red agar (CRA) test did not harbor biofilm-associated loci. This implies the protein-mediated mechanism of biofilm formation as an alternative to polysaccharide intercellular adhesin (PIA) in staphylococci. However, icaAD locus which encodes PIA was identified in 10 (26.3%) isolates and the eno locus, encoding elastin-binding protein which can accelerate the biofilm production, is identified in all the isolates. The possession of type V SCCmec elements by the S. haemolyticus (15.8%) raised the concern about the rapid dissemination of mecA gene to other species of staphylococci including the virulent S. aureus. In short, this study acknowledges the toxigenicity of coagulase-negative staphylococci (CoNS). Through this study, surveillance of antimicrobial resistance and transference of virulomes in staphylococci is warranted.

Few pieces of research have focused on Micrococcus luteus bloodstream infection (BSI) because of its low incidence; hence data is needed to illustrate this uncommon infection. This study aimed to explore the clinical characteristics of patients with M. luteus BSI. From January 2010 to December 2019, inpatients that met the criteria for M. luteus BSI were included in this study. Data was collected by reviewing electronic records. Ninety-seven patients were enrolled in this study. Sixty-three percent of the patients have a higher neutrophil percentage (NEUT%). The average blood C-reactive protein (CRP) concentration was 5.5 ± 6.4 mg/dl. 48.5% of the patients had malignancy, and 40.2% underwent invasive surgeries. Linezolid was found to have the largest average diameter of the inhibition zone (36 mm), while erythromycin was found to have the smallest average zone diameter (15 mm). However, some M. luteus strains had a potentially broad antimicrobial resistance spectrum. Cephalosporins (59.2%) and quinolones (21.4%) were the most commonly used antibiotics for empirical therapies. In conclusion, M. luteus BSI mainly happens in immunocompromised patients or those with former invasive surgeries or indwelling catheters. M. luteus strains are less responsive to erythromycin. Cephalosporins and quinolones are effective empirical antibiotics for M. luteus BSI; however, vancomycin and teicoplanin should be considered for potentially broadly drug-resistant M. luteus strains.

Therapeutic drug monitoring and target concentration intervention based on population pharmacokinetic and pharmacodynamic models has been strongly recommended for anti-methicillin-resistant Staphylococcus aureus (MRSA) agents in order to provide appropriate antimicrobial chemotherapy to each individual patient, and pharmacokinetic and pharmacodynamic analyses in hospitalized patients have been actively conducted, as evidenced with vancomycin. Teicoplanin, daptomycin, and linezolid have been the most studied antibiotics, using population pharmacokinetics of patients with MRSA. Infections caused by MRSA have higher severity and fatality rates than other antimicrobial-susceptible infections. Therefore, many medical facilities have been implementing infection control programs based on antimicrobial stewardship to prevent nosocomial infections and drug-resistant strains. Studies detailing pharmacometrics for these antibiotics have been reported to elucidate the pharmacokinetic and pharmacodynamic properties, to determine significant factors influencing variabilities between individuals, and to develop target concentration interventions and dosing regimens for adults, the elderly, patients with renal insufficiency including those on continuous renal replacement therapies, patients with low body weight, obese patients, and pediatric patients. This review presents the details of our recent research on the optimal dosing design of antimicrobial agents for the treatment of MRSA infection based on hospital pharmacometrics. In addition, the prospect of using modeling and simulation has shown major advantages in supporting dosing regimen selection.

Objectives Long-acting lipoglycopeptides are promising therapeutic options in Staphylococcus aureus bone and joint infections (BJIs). This study evaluated the ability of dalbavancin to eradicate the intraosteoblastic reservoir of S. aureus, associated with BJI chronicity. Methods Osteoblastic cells were infected with a standardized inoculum of the S. aureus reference strain HG001 and incubated for 24 h with dalbavancin, vancomycin or rifampicin using the MIC, 10×MIC, 100×MIC and/or the intraosseous concentrations reached using standard therapeutic doses (i.e. vancomycin, 10 mg/L; rifampicin, 2 mg/L; and dalbavancin, 6 mg/L). The remaining intracellular bacteria were quantified by plating cell lysates. Results MICs of dalbavancin, vancomycin and rifampicin were 0.125, 1 and 0.004 mg/L, respectively. Dalbavancin significantly reduced the intracellular inoculum of S. aureus starting at a concentration equal to the MIC, with a significant dose effect, ranging from a reduction of 31.4% (95% CI = 17.6%–45.2%) at MIC to 51.6% (95% CI = 39.8%–63.4%) at 100×MIC compared with untreated cells. Of note, dalbavancin was the only molecule to significantly reduce the intraosteoblastic inoculum at low concentration (MIC). At intraosseous concentrations, dalbavancin reduced the intracellular inoculum by 49.6% (95% CI = 45.1%–54.1%) compared with untreated cells (P Conclusions Dalbavancin was able to decrease the intraosteoblastic S. aureus inoculum by 50% at intraosseous concentrations reached during standard human therapeutic dosing, with no difference compared with vancomycin, and remained less efficient than rifampicin. However, it was the only molecule significantly active at low concentration.

Teicoplanin is a glycopeptide and is a mixture of related glycopeptides. Teicoplanin inhibits the synthesis of the cell wall in sensitive bacteria by binding with high affinity to the D-alanyl-D-alanine terminus of cell wall precursor units. Because of its large molecular size, teicoplanin is unable to penetrate the outer membrane of gram-negative bacteria. The intravenous dosage of teicoplanin consists in a loading dose of 16 mg/kg followed by a maintenance dose of 8 mg/kg once-daily to infants aged < one month and in older infants the dosage of teicoplanin consists in a loading dose of 12 mg/kg twice-daily followed by a maintenance dose of 10 mg/kg once daily. In children, the oral dose is 100 to 200 mg twice-daily and the intravenous dosage consists in 12 mg/kg twice-daily followed by 12 mg/kg once-daily. Teicoplanin has been found efficacy and safe in infants and children. The elimination half-life of teicoplanin is 73.9 hours in infants and children and teicoplanin is cleared from the body by renal and extra-renal routes. The total body clearance of teicoplanin is 0.09 L/h in children aged < 12 months and 0.29 L/h in older children. The treatment and the prophylaxis with teicoplanin have been described in infants and children. Teicoplanin administered intravenously and/or intraventricularly treats the cerebral infections caused by staphylococci and enterococci. The aim of this study is to review the published data on teicoplanin dosing, efficacy and safety, pharmacokinetics, drug-interactions, treatment, prophylaxis, and penetrates into the cerebrospinal fluid in infants and children.

Introduction An increase in recent years in the isolation of Vagococcus spp. is suggestive of emerging infection by this pathogen in our hospital. Methods Prospective, descriptive study. Period: July 2014–January 2019. Phenotypic identification of 15 isolates of Vagococcus spp. was performed by conventional biochemical tests, automated methodology and mass spectrometry (MALDI-TOF MS). Molecular identification was achieved by sequencing the 16S rRNA gene. The Vitek™ 2C automated system was used to test antibiotic susceptibility. Results The molecular method identified 11 Vagococcus fluvialis, one Vagococcus lutrae and three Vagococcus spp. MALDI-TOF MS facilitated the rapid recognition of the genus. The most active antibiotics were ampicillin, trimethoprim/sulfamethoxazole, vancomycin, teicoplanin and linezolid. Most of the cases of isolation were associated with skin and soft tissue or osteoarticular infections in patients with diabetes. Conclusion This article is the most extensive review of cases of Vagococcus spp. infection reported in the literature and highlights the microbiological and clinical aspects of this pathogen.

The symptomatology and severity of covid-19 ranges widely depending on stage of infection. Most of the patients with mild to moderate disease can be managed without hospitalization. The patients with risk factors are likely to progress to severe disease. Patients developing secondary blood stream infections require longer hospital stay and are likely to develop fatal disease. The antibiotic selection is key to successful treatment of secondary BSI. This is cross-sectional study of 166 COVID 19 patients admitted to ICU of Parul Sevashram Hospital who developed sepsis like syndrome and were subjected to blood culture.Blood cultures were performed of all the patients developing sepsis like syndrome. IDSA guidelines were followed during blood collection for culture. Blood cultures were monitored on automated blood culture system. ID and susceptibility of all the isolates were performed on automated system (VITEK 2).A total of 1915 patients were reported RT-PCR positive for SARS nCoV2 during the period of 1st March2020 to 30 October 2020. 452 patients needed hospitalization based on their Oxygen saturation and co-morbidities. Out of 452, 166 patients developed sepsis like syndrome and were subjected to blood culture. The Blood culture positivity was 37/166 (22.28%). Gram positive bacteria were found in 48.64% while gram negative bacteria were 43.24%. The Enterococcus was the most common Gram positive bacterial isolates in patients. Candida was isolated in 2/37 positive blood cultures. Gram negative bacteria were isolated mostly amongst those patients who were on Ventilator. Most of the Gram positive bacteria were sensitive to Clindamycin, Linezolid, Vancomycin, Daptomycin and Teicoplanin.The incidence rate of BSI was high. Early secondary blood stream infections were mostly endogenous. Enterococcus was the most common amongst Gram positive bacteria. Gram negative secondary bacterial infections were more common with patients on ventilator. The susceptibility pattern would help in decision making of empiric antibiotic therapy. Interestingly as described by some authors earlier the relationship between SARS nCoV 2 and Enterococci needs to be studied further.

A bacterial biofilm is one of the main reasons that many diseases are difficult to cure. Herein, a teicoplanin (TPN)-loaded self-adapting chitosan-based hydrogel (CPH) system, called TPN-CPH, was prepared by encapsulating antibacterial TPN into CPH. This TPN-CPH can effectively combat preformed biofilms

Background: Misuse of antibiotics is the leading factor promoting emergence of bacterial resistance, a situation that has become a serious public health challenge. Among the leading bacteria that have developed resistance to antibiotics are Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae and Pseudomonas aeruginosa, which have caused infections in patients, resulting in considerable mortality. The objective of this retrospective study was to assess antibiotic resistance rates of bacterial pathogens isolated from clinical specimens in two Lebanese hospitals between the years 2018 and 2019. Methodology: Bacteria isolated from routine clinical specimens collected from hospitalized patients in two hospitals, Haroun and Bekaa, in Lebanon for 2018 and 2019, were analyzed. Bacteria isolation and identification were carried out at the laboratory of each hospital using conventional microbiological methods. Antimicrobial susceptibility testings (AST) of each bacterial isolate to antibiotics were performed by the disc diffusion test and interpreted using EUCAST, CLSI or WHO/AST guidelines. Comparisons of the mean resistance rates of each isolate to individual antibiotics by year of isolation were done using the Z-test and p< 0.05 was considered statistically significant. Results: There were a total of 1698 bacteria isolates recovered from hospitalized patients in the two hospitals for 2018 and 2019, of which 87.5% were Gram-negative and 12.5% were Gram-positive bacteria. The most frequent among the Gram-negative isolates was E. coli (66.1%) followed by P. aeruginosa (13.3%), K. pneumoniae (7.7%), Proteus mirabilis (6.7%) and Enterobacter spp (6.3%), while coagulase positive staphylococci CoPS (68.4%) and E. faecalis (31.6%) were the two Gram positive isolates. Of the Gram-negative isolates over the two-year period, 72.2% of E. coli and 76.3% of K. pneumoniae were resistant to ceftazidime, 93% of P. mirabilis to colistin, and 98% of Enterobacter to cefoxitin, but low resistance rates were demonstrated by E. coli to imipenem (1%), K. pneumoniae to tigecycline and amikacin (0.9%), P. mirabilis to imipinem (2%), and Enterobacter to amikacin, ertapenem and tigecycline (3%). Resistance of P. aeruginosa varied between 2% to colistin and 24% to levofloxacin. For the Gram-positive bacteria, 79.1% of E. faecalis were resistant to erythromycin while 70% of CoPS were resistant to cefoxitin, but no isolate was resistant (0%) to linezolid, and only 1% to teicoplanin. Except for Enterobacter spp that showed significant increase in resistance rates (by 250%) to piperacillin/tazobactam in 2019 over 2018, resistance rates of other Gram-negative isolates significantly decreased in 2019 compared to 2018 (p

Introduction Vancomycin-resistant Enterococcus faecium (VREfm) carrying vanA was first isolated from patient at Siriraj Hospital, Thailand in 2004. Since then, VREfm isolates have been detected increasingly in this 2500-bed university hospital. To understand the epidemiology of vanA VREfm in this setting, the isolates collected during 2004–2013 were characterized. Methods A total of 49 vanA VREfm isolates previously confirmed by multiplex PCR were characterized by determining resistance phenotypes to vancomycin, teicoplanin, ampicillin and ciprofloxacin by broth microdilution method. Multilocus sequence typing (MLST) and virulence genes of those isolates were investigated. The Tn1546 structure diversity was studied by long-range overlapping PCR and primer walking sequencing. Results Of all isolates studied, 9 sequence types (ST17, ST80, ST78, ST730, ST203, ST18, ST280, ST64, ST323) in clonal complex 17 and a novel ST1051 were revealed. The esp-positive isolates were 73.5%. Of all vanA operons characterized, at least 9 types of Tn1546-like structures were detected. All of vanA determinants contained 5′-end different from the Tn1546 prototype. Approximately 47% of them also carried the insertion sequence IS1251 at the intergenic region between vanS and vanH. Interestingly, another IS (ISEfa4) was found to be inside the sequence of IS1251 in ST17 isolate. Conclusion Heterogeneity of vanA VREfm was observed. Nearly all of isolates studied belonged to CC17. One novel ST1051 strain was detected. Isolates in the initial period carried vanA operon similar to the prototype. The diversity of vanA determinants has been increased in the recent isolates. A novel vanA operon structure was detected.

Infections caused by vancomycin-resistant Enterococci are difficult to treat given the limited therapeutic alternatives. Different gene clusters are known to confer vancomycin resistance. vanA and vanB genes are transferable and are clinically relevant. This cross-sectional study aimed to identify the vancomycin-resistant genotypes in the strains causing urinary tract infection and also to test the in vitro efficacy of linezolid and pristinamycin against the vancomycin-resistant isolates.Antimicrobial resistance profile of 118 enterococcal isolates was evaluated. Minimum inhibitory concentration of vancomycin, teicoplanin and high-level gentamicin (HLG) was determined by micro broth dilution. The vancomycin-resistant isolates were tested against linezolid and pristinamycin by micro-broth dilution and E strip method. The presence of vancomycin-resistant genes was detected by multiplex polymerase chain reaction and was sequenced and analyzed.Most commonly isolated species were Enterococcus faecalis (76.9%) and Enterococcus faecium (16.9%). It was found that 43 per cent of the isolates were resistant to HLG and 16.9 per cent to vancomycin. Higher resistance was seen against fluoroquinolones, erythromycin, tetracycline and β-lactam drugs. However, 5.08 per cent strains were resistant to tigecycline. All vancomycin-resistant strains were sensitive to pristinamycin and one was resistant to linezolid. vanA and vanB gene were found in 15 and five isolates, respectively. The gene sequences were submitted to NCBI gene bank and accession numbers were obtained.The present study showed prevalence of vanA and vanB genes carrying Enterococcus in a tertiary care centre in north India. The emergence of resistance against drugs such as tigecycline and linezolid is a topic of concern as it will be a therapeutic challenge for physicians.

Chiral carbon nanoparticles (CNPs) represent a rapidly evolving area of research for optical and biomedical technologies. Similar to small molecules, applications of CNPs as well as fundamental relationships between their optical activity and structural asymmetry would greatly benefit from their enantioselective separations by chromatography. However, this technique remains in its infancy for chiral carbon and other nanoparticles. The possibility of effective separations using high performance liquid chromatography (HPLC) with chiral stationary phases remains an open question whose answer can also shed light on the components of multiscale chirality of the nanoparticles. Herein, we report a detailed methodology of HPLC for successful separation of chiral CNPs and establish a path for its future optimization. A mobile phase of water/acetonitrile was able to achieve chiral separation of CNPs derived from L- and D-cysteine denoted as L-CNPs and D-CNPs. Molecular dynamics simulations show that the teicoplanin-based stationary phase has a higher affinity for L-CNPs than for D-CNPs, in agreement with experiments. The experimental and computational findings jointly indicate that chiral centers of chiral CNPs are present at their surface, which is essential for the multiple applications of these chiral nanostructures and equally essential for interactions with biomolecules and circularly polarized photons.

BACKGROUND To investigate the incidence, risk factors, pathogen distribution, and drug resistance patterns in continuous ambulatory peritoneal dialysis-associated peritonitis (CAPDP). MATERIAL AND METHODS Clinical data for 248 patients who underwent continuous ambulatory peritoneal dialysis (CAPD) treatment in a single center in China from March 2018 to January 2021 were retrospectively collected. The patients were divided into the CAPDP group (n=40) and the non-CAPDP group (n=208) according to whether peritonitis occurred. The incidence rate, risk factors, bacterial distribution, and drug sensitivity of CAPDP were analyzed. RESULTS The incidence of CAPDP was 16.13%, and 87.5% of patients with CAPDP continued CAPDP treatment after anti-infection treatment. Patients with and without CAPDP were clearly distinguished, on the basis of their clinical characteristics, by using principal component analysis (PCA) methods. Logistic regression analysis found that body mass index (BMI; P=0.0095), albumin (P=0.016), albumin/globulin ratio (P=0.018), C-reactive protein (P=0.0001), and rapid transport (P=0.034) were independent risk factors for CAPDP. The main pathogens causing the CAPDP were Staphylococcus epidermidis (50.00%), Staphylococcus capitis (13.33%), and Escherichia coli (10.00%). Among the pathogenic bacteria, the main drugs to which gram-negative cocci were sensitive were imipenem, meropenem, piperacillin/tazobactam, cefoperazone/sulbactam, ceftazidime, and tigecycline. The main drugs to which gram-positive cocci were sensitive were vancomycin, teicoplanin, and linezolid. The drug resistance rate of pathogenic bacteria to penicillin G, ampicillin, compound trimethoprim, cefepime, ceftriaxone, and amoxicillin-clavulanic acid drugs was 36.26-100%. CONCLUSIONS BMI, albumin, albumin/globulin ratio, C-reactive protein, and rapid transport are independent risk factors for CAPDP. Gram-positive bacteria are the main pathogens of CAPDP and are sensitive to vancomycin, teicoplanin, and linezolid.

Aims Bacterial response to temperature changes can influence their pathogenicity to plants and humans. Changes in temperature can affect cellular and physiological responses in bacteria that can in turn affect the evolution and prevalence of antibiotic-resistance genes. Yet, how antibiotic-resistance genes influence microbial temperature response is poorly understood. Methods and Results We examined growth rates and physiological responses to temperature in two species—E. coli and Staph. epidermidis—after evolved resistance to 13 antibiotics. We found that evolved resistance results in species-, strain- and antibiotic-specific shifts in optimal temperature. When E. coli evolves resistance to nucleic acid and cell wall inhibitors, their optimal growth temperature decreases, and when Staph. epidermidis and E. coli evolve resistance to protein synthesis and their optimal temperature increases. Intriguingly, when Staph. epidermidis evolves resistance to Teicoplanin, fitness also increases in drug-free environments, independent of temperature response. Conclusion Our results highlight how the complexity of antibiotic resistance is amplified when considering physiological responses to temperature. Significance Bacteria continuously respond to changing temperatures—whether through increased body temperature during fever, climate change or other factors. It is crucial to understand the interactions between antibiotic resistance and temperature.

Background Dalbavancin is a semisynthetic lipoglycopeptide antimicrobial agent with activity against Gram-positive bacteria including anaerobes. Research design and methods Meta-analysis of randomized control trials and large case series (more than 20 patients), were identified by searching Pubmed and Cochrane databases through December 14, 2020. Results 3,073 patients from 6 RCTs met the inclusion criteria in acute bacterial skin and skin-structure infections, catheter-related infections and osteomyelitis. Treatment emergent adverse effects were described in 30.6% dalbavancin patients, and 38.1% patients with other treatments. Our meta-analysis supports favorable results for dalbavancin treatment (OR 0.79; 95%CI 0.66-0.94; p = 0.01). 2.74% dalbavancin patients had to discontinue treatment versus 2.49% patients on other antibiotics. 4.80% dalbavancin patients versus 5.30% patients with other treatments had severe adverse events. 0.31% in the dalbavancin group and 0.95% receiving other antibiotics died. There was no statistically significant difference in severe adverse effects with OR 0.77; 95% CI 0.52-1.14; p=0.19. Dalbavancin therapy was shown to have statistically significant lower mortality rate (OR 0.26; 95% CI 0.07-0.90; p = 0.03). Observational studies reported few side effects but included a heterogeneous population of patients concerning their diagnosis and the duration of antibiotic treatment. Conclusions Dalbavancin has comparable safety profile relative to other antibiotics and is well-tolerated.

The objective of this study was to evaluate the efficacy of various dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin against methicillin-resistant Staphylococcus aureus (MRSA) in neutropenic patients with cancer. Monte Carlo simulations were conducted using pharmacokinetic parameters and pharmacodynamic data to determine cumulative fraction of response (CFRs) in terms of area under the concentration-time curve/minimum inhibition concentration target. Currently clinical standard dosing regimens of vancomycin, teicoplanin, linezolid and daptomycin were insufficient to provide expected CFRs against MRSA for neutropenic patients with cancer. The high dosing regimens of vancomycin (3500 mg/d), teicoplanin (800 mg/d) and daptomycin (8 mg/kg/d) could provide CFRs of ≥ 80%, showing a higher treatment success. However, the majority of CFRs with linezolid simulated dosing regimens reached < 80% against MRSA. Therefore, a strategy of high dosages of vancomycin, teicoplanin and daptomycin may be needed to attain optimal therapeutic efficacy against MRSA in neutropenic patients with cancer.

Non-union infected bone is a chronic impairment disorder that causes severe complications for surgeons. In Pakistan a very limited literature was produced in recent years to evaluate the role of antibiotic impregnated cemented nail in infected non-union of tibia. To fill this gap this prospective study was designed to investigate the role of antibiotic Cement Coated Nailing in Infected Nonunion of Tibia in the Orthopedic Department of Liaqat University of medical and health science, Jamshoro, Pakistan, from February 2019 to February 2020. A total of 30 patients with infected "nonunion of the tibia" was enrolled during the research period. Patients within the age range of 22-61 years were part of this research. For surgery, polymer beads were added into the 40 gm cement which was prepared by adding 2 gm vancomycin and 2 gm teicoplanin. After that endotracheal tube was cut by a surgical knife to recover antibiotic and cement coated k nail. The nail was then inserted into the tibia. Resuts demonstrate that in 28 patients 93% utilization of antibodies cement coated nails helped to eradicate the infection. 24 patients achieved complete bone unification without any need for further procedure. The overall ratio of single-time antibiotic cement coated nail was observed as 70%. The infected nonunion tibia can be effectively treated if the protocol of debridement is correctly followed. Results demonstrate that bone stability can be regained with 22 to 44 weeks. We concluded that antibiotic-impregnated cemented nail is an ideal procedure to control the postoperative infection and achieve reunion.

Introduction: Enterococci from being intestinal commensals have evolved in becoming pathogens and are associated with significant morbidity and mortality Aims & Objectives: This study was done to speciate the uropathogenic Enterococci using the chromogenic medium and to determine the antibiogram also to detect virulence factors phenotypically. Materials and methods: The study included a total of 30 uropathogenic Enterococci isolated over 6 months. Speciation was done using HiCrome Enterococcus faecium agar base. Antibiotic sensitivity was done by the Kirby Bauer Disc Diffusion method as per Clinical and Laboratory Standards Institute (CLSI) guidelines. Among the virulence factors hemolysin, haemagglutination, and gelatin liquefaction tests were done. Results: Amongst the 30 enterococci isolates, 17 were Enterococcus faecalis (E. faecalis) (56.66%) & 13 were Enterococcus faecium (E. faecium) (43.33 %). 100% of the Enterococcus species were sensitive to Vancomycin & Teicoplanin. 66.67% of the Enterococci showed hemolysis, 10% haemagglutination, and 43.33% gelatinase property. Conclusion: Most common isolated species were Enterococcus faecalis. The changing patterns of antibiotic sensitivity to Enterococci in patients with urinary tract infection possess difficulty in selection of the antibiotics. Failure to synergistic therapy is seen in cases of resistance to High-level Gentamicin. Therefore, speciation and antibiotic sensitivity patterns will help in setting up an empirical therapy and thereby help in the reduction of morbidity and mortality. Key words: Antibiotic susceptibility, Chrome agar, Enterococcus species, virulence factors.

PURPOSE: To compare the in vitro elution characteristics of CMW1 and Palacos R bone cement loaded with gentamicin, teicoplanin, or in combination. METHODS: Four bone cement discs were prepared for each cement type. Disc 1 contained no antibiotics; disc 2 contained 0.5 g gentamicin; disc 3 contained 2 g teicoplanin; disc 4 contained 0.5 g gentamicin and 2 g teicoplanin. Elution studies were conducted using a fluorescence polarisation immunoassay technique and performed at intervals of 6 weeks. RESULTS: For CMW1, gentamicin and teicoplanin elution levels in combination discs were higher than those in the single antibiotic discs (p

Background/Aim: The frequency and severity of respiratory tract infections increase with aging. The aim of this study was to determine the bacterial profile of respiratory tract samples in geriatric patients and evaluate the antibiotic susceptibility patterns of the pathogens. Methods: In this cross-sectional study, a total of 509 clinical samples which were obtained from 302 geriatric patients over 65 years of age and sent to the microbiology laboratory between June 2019-January 2021 were investigated retrospectively. The identification and antibiotic susceptibilities of strains were evaluated with BD-Phoenix-100 fully automated microbiology system. Results: Of the 302 geriatric patients, 166 (%55) were males and 136 (%45) were females. The most isolated pathogens were Klebsiella pneumoniae (25.3%) Pseudomonas aeruginosa (22.5%) and Acinetobacter baumannii (10.2%), Corynebacterium striatum (7.3%), Escherichia coli (6.4%), Staphylococcus aureus (6.4%) and coagulase-negative staphylococci (4.2%). The production of ESBL in Klebsiella pneumoniae strains (52.3%) was higher than in Escherichia coli (41%) strains. All Corynebacterium striatum samples were resistant to ciprofloxacin, tetracycline, rifampin, and penicillin. Methicillin resistance among Staphylococcus aureus (MRSA) isolates was 22.7% and they were 100% susceptible to vancomycin and teicoplanin. Above 90% of K. pneumoniae, P. aeruginosa and A. baumannii positive patients were hospitalized in intensive care units (P

Introduction: The spread of multidrug resistant bacteria has added a new angel to the problem of wound infections which are a major cause of morbidity. To avoid difficulty in treatment of such infections it is mandatory for every pus sample to undergo Culture and sensitivity. Aim: To isolate and study the antibiogram of the aerobic bacteria from pus samples. Materials and Methods: A total of 426 pus samples received from various wards in the Microbiology department. Andhra Medical College, Visakhapatnam were processed as per standard guidelines in the laboratory. All the aerobic bacterial isolates obtained were kept for antibiogram by Kirby Bauer’s disc diffusion method as per CLSI Guidelines. Results: Out of 426 samples 394 (92.4%) were culture positive. Among culture positive samples 90.6% were pure cultures and 9.4% were mixed isolates. Gram negative bacilli were 72.8% of the total isolates and 27.2% were Gram positive cocci. Escherichia coli and Klebsiella pneumonia were the predominant isolates (30.3% and 28.9%) followed by Pseudomonas aeruginosa (24%), Proteus species (9.7%) and Acinetobacter species (6.9%). Among Gram positive cocci Staphylococcus aureus (62.6%), Enterococci (20.5%) and Coagulase Negative Staphylococcus (11.2%) and Streptococci (3.7%). GNB were more sensitive to Colistin (92%), Amikacin (86%), Imipenem and Meropenem (86% and 84.4%), Piperacillin Tazobactam (84%), Gentamycin (78%), Cefaperazone Sulbactam (76.2%) and Ciprofloxacin (56%). Gram positive cocci were sensitive to Linezolid and Teicoplanin (98% each), Vancomycin (96.2%), Clindamycin (84%), Gentamycin (79%), Azithromycin (76.4%), Ciprofloxacin (66%) and Amoxiclav (54%) out of 62.6% Staphylococcus aureus isolates 31.4% were MRSA and out of 72.8% of Gram negative bacilli 38.2% were ESBLS. Conclusion: As multidrug resistant bacterial strains are emerging in various infectious and pyogenic wound infection is most important cause of morbidity, it is important for a clinician to send all pus samples for microbiological analysis and their antibiogram before putting cases on antibiotics. Keywords: Pus samples, Multidrug resistance, Gram negative bacilli, Gram positive cocci, Antimicrobial sensitivity.

We compared the rates of acute kidney injury (AKI), 7-day and 30-day mortalities, and resolution of AKI at discharge in combination therapies involving either teicoplanin (TEI) or vancomycin (VAN) with piperacillin-tazobactam (TZP) or meropenem (MER). In a single-center, retrospective cohort study, adult patients (>18 years) who had a baseline serum creatinine level within 24 h of admission and who received study antibiotics for at least 48 h were included. The primary outcome was AKI incidence after therapy per RIFLE criteria. Multivariate logistic regression and propensity score match analyses were employed for statistical comparisons. Data from 379 patients were evaluated. In multivariate analysis (MVA) of the whole cohort, TZP-VAN combination was associated with significantly higher rate of AKI as compared with TZP-TEI (aOR: 3.21, 95% CI, 1.36-7.57; p = 0.008) or with MER-VAN (aOR: 2.28, 95% CI, 1.008-5.18; p = 0.048). In MVA of the matched cohorts, TZP-VAN as compared with TZP-TEI and MER-VAN was associated with 3.96 times (95% CI, 1.48-10.63, p = 0.006) and 3.11 times (95% CI, 1.12-8.62; p = 0.028) increased risk of AKI, respectively. No differences between MER-TEI and MER-VAN combinations were detected. Seven-day and 30-day mortalities and resolution rates of AKI were similar in all comparisons. Teicoplanin can be preferred instead of VAN when combination with TZP is used particularly for patients with high AKI risk.

The rise in Pantone-Valentine leucocidin (PVL) and gAMMA-haemolysin (Hlg) producing Enterococcus spp., among the people is a serious concern on evolution of antibiotic resistance. Recent reports suggested that the synergistic association of PVL toxin and necrotic lesions that lead to infections in skin and mucosa. To study the prevalence of Enterococcus isolated from the various clinical samples from both inpatient and out - patient department at a Tertiary care hospital. The resistance to Pantone-Valentine leucocidin (PVL) and gAMMA-haemolysin (Hlg) is further tested by using E-test strips for gentamicin test showed 26.8% of isolated populations had resistance to cell wall active agents. In our study all the intermediately sensitive to vancomycin isolates were found to be vancomycin sensitive by both the Epsilometer test and automated Vitek 2 system. The minimum inhibitory concentration ranging from 0.5 - 4 ug/ml. Hence my study confirmed good activity of the vancomycin, linezolid and Teicoplanin against isolated Enterococci spp.

We prepared a polyclonal antibody against a teicoplanin (TEIC)-bovine serum albumin conjugate that was specific to both conjugated and free forms of TEIC. We demonstrated that this antibody could be used to detect the time-dependent localization of TEIC in rat kidneys. Immunohistochemistry revealed immunoreactivity specifically in the microvilli and apical cytoplasm of epithelial cells in proximal tubule segments S1 and S2, 1 h after intravenous TEIC injection, with higher staining intensity in the S2 segments. The epithelial cells of S3 segments showed moderate immunostaining with a few cells exhibiting nuclear staining. Furthermore, we found that the distal tubules and collecting ducts contained both TEIC-positive and -negative cells. TEIC immunoreactivity decreased rapidly over time; only weak staining remained in the S3 segments, distal tubules, and collecting ducts 24 h after administration. No staining was detected 7 days after injection. These results were significantly different from those of our previous study obtained using vancomycin, which showed moderate staining in the proximal tubule segments S1 and S2, distal tubules, and the collecting ducts 8 days after administration. The lower TEIC accumulation in tissues may account for a lower risk of adverse events compared to that using vancomycin.

Objective: to determine antimicrobial resistance of Enterococcus faecium and Enterococcus faecalis isolated from blood culture of hematological patients during different study periods.Materials and methods. Antimicrobial susceptibility of Enterococcus spp., collected as part of the multicenter study was tested by the broth microdilution method (USA Clinical and Laboratory Standards Institute (CLSI), 2018), to daptomycin by Etest (bioMeriéux, France). High-level gentamicin resistance (HLGR) and high-level streptomycin resistance (HLSR) was performed by the agar dilution method (CLSI (Oxoid, UK), 2018).Results. The susceptibility of 366 E. faecium (157 in 2002-2009 and 209 in 2010-2017) and 86 E. faecalis (44 in 20022009 and 42 in 2010-2017) was studied. In the second study period (2010-2017) the rise of vancomycin-resistant E. faecium (VREF) increased from 8.3 % to 23.4 % (p = 0.0001), and two linezolid-resistant (LREF) were identified. All VREF and LREF remained susceptible to daptomycin and tigecycline. The rate of susceptible to tetracycline E. faecium remained the same (73.9 and 74.6 %), and an increase in susceptibility to chloramphenicol (74.5 and 82.3 %) was observed. Susceptibility of E. faecium to tetracycline was detected with almost the same rate and in a part of isolates, the increase of susceptibility to chloramphenicol was registered during the analyzed periods. The rise of E. faecium susceptible to HLGR and HLSR has increased significantly in 2010-2017 compared to 2002-2009. Erythromycin, levofloxacin, ampicillin and penicillin had the least activity against E. faecium (less than 5 %).All E. faecalis were susceptible to tigecycline, linezolid, and teicoplanin. Only one of E. faecalis had intermediate resistance to vancomycin. High susceptibility to ampicillin in E. faecalis remained unchanged (97.7 and 97.6 %, respectively). In the second period of the study the rise of susceptible E. faecalis decreased significantly to penicillin (from 97.7 % to 76.2 %), to levofloxacin (from 59.1 % to 31 %), to HLSR (from 52.3 % до 31 %), and to HLGR (from 47.7 % to 26.2 %), remained unchanged to chloramphenicol (52.3 % and 50 %) and was minimal to erythromycin and tetracycline.Conclusion. The study demonstrated higher rates of antibiotic resistance among E. faecium, which consisted of an increase in VREF and the appearance of linezolid-resistant strains. High susceptibility to ampicillin remained in E. faecalis, but there was an increase in resistance to penicillin and aminoglycosides.

Background: Staphylococcus aureus is a common health problem occuring as an important nosocomial pathogen, causing urinary tract infection, surgical site, blood stream and soft tissue infection. The aim of this research was conducted to determine MRSA and VRSA from the pus samples of admitted patients. Aim & Objective: The aim and objective of study was to isolate the resistance pattern of Staphylococcus aureus in pus samples and their AST. Materials and Methods: A total of 158 positive culture Staph aureus were taken from pus samples for the study during December 2019 - October 2020. Samples were cultured on Blood and MacConkey agar then incubated at 37C for 24 hours. The modified Kirby Bauer's disc diffusion method was used to test antibiotic sensitivity of staphylococcus isolates. Result: In total of 158 positive culture of Staphylococcus aureus, 66 (41.7%) were found to be MRSA and 4 (2.5%) were found to be VRSA. Out of 158 Staph aureus, 146 (92.4%) were resistant to Penicillin, followed by Amoxycillin 140 (88.6%), Ampicillin 139 (87.9%), Erythromycin 91 (57.5%), Cefoxitin 66 (41.7%), Gentamycin 56 (35.4%), Amikacin 52 (32.9%) and Teicoplanin 37 (23.4%). Conclusion : An antibiotic policy and screening of susceptibility patterns of MRSA may help in reducing the prevalence rate of MRSA and antibiotic resistance. To stop its spread to the population, it is very important to eliminate MRSA colonization in patients and health care workers. Accurate treatment helps to reduce the rate of morbidity and improvement of patient’s outcome. Keywords: Staphylococcus aureus, MRSA, VRSA

To determine the frequency and antibiotic susceptibility pattern of CA-MRSA in patients with uncomplicated skin and soft tissue infections reporting to the dermatology outpatient of a tertiary health care hospital.A descriptive study.Dermatology outpatient of a tertiary care hospital in Punjab province of Pakistan, from September 2020 to August 2021.Patients of all age groups and both genders reporting during the study period with community-associated uncomplicated bacterial skin and soft tissue infections were enrolled in the study. Samples were collected from skin lesions and cultured on blood agar and MacConkey agar plates. Antimicrobial susceptibility testing using the modified Kirby Baur disc diffusion technique was performed.A total of 157 patients were included in the study. Impetigo was most common infection (n=80, 51%), followed by Furunculosis (n=47, 29.9%). The frequency of MRSA isolates was 54.1% (n=85). MRSA was significantly more frequently isolated from patients with furunculous, carbuncle and cutaneous abscesses as compared to impetigo. All MRSA isolates were sensitive to linezolid, teicoplanin, and vancomycin. 97.6%, 84.7%, and 72.9% of MRSA isolates were sensitive to rifampicin, minocycline, and fusidic acid respectively. 89.4% of MRSA were sensitive to amikacin and clindamycin. 63.5% were sensitive to doxycycline and 58.8% were sensitive to co-trimoxazole. Only 20% of MRSA were sensitive to ciprofloxacin.The antibiotics active against CA-MRSA including rifampicin, minocycline, amikacin, and clindamycin may be used empirically in patients with furunculosis, cutaneous abscess, and carbuncles. Linezolid, teicoplanin, and vancomycin should be reserved for severe infections.Uncomplicated skin and soft tissue infections, Community-associated Methicillin-resistant staphylococcus aureus (CA-MRSA), Antibiotic susceptibility pattern.

The long-acting lipoglycopeptides (LGPs) dalbavancin and oritavancin are semisynthetic antimicrobials with broad and potent activity against Gram-positive bacterial pathogens. While they are approved by the Food and Drug Administration for acute bacterial skin and soft tissue infections, their pharmacological properties suggest a potential role of these agents for the treatment of deep-seated and severe infections, such as bloodstream and bone and joint infections. The use of these antimicrobials is particularly appealing when prolonged therapy, early discharge, and avoidance of long-term intravascular catheter access are desirable or when multidrug-resistant bacteria are suspected. This review describes the current evidence for the use of oritavancin and dalbavancin in the treatment of invasive infections, as well as the hurdles that are preventing their optimal use. Moreover, this review discusses the current knowledge gaps that need to be filled to understand the potential role of LGPs in highly needed clinical scenarios and the ongoing clinical studies that aim to address these voids in the upcoming years.

Antibacterial bone biomaterial coatings appeal to orthopaedics, dentistry and veterinary medicine. Achieving the successful, stable conjugation of suitable compounds to biomaterial surfaces is a major challenge. A pragmatic starting point is to make use of existing, approved antibiotics which are known to remain functional in a stationary, immobilised state. This includes the macrocyclic glycopeptide, teicoplanin, following the discovery, in the 1990’s, that it could be used as a chiral selector in chromatographic enantiomeric separations. Importantly teicoplanin works at the level of the bacterial cell wall making it a potential candidate for biomaterial functionalisations. We initially sought to functionalise titanium (Ti) with polydopamine and use this platform to capture teicoplanin, however we were unable to avoid the natural affinity of the antibiotic to the oxide surface of the metal. Whilst the interaction between teicoplanin and Ti was robust, we found that phosphate resulted in antibiotic loss. Before contemplating the covalent attachment of teicoplanin to Ti we examined whether a commercial teicoplanin stationary phase could kill staphylococci. Whilst this commercially available material could bind N-Acetyl-L-Lys-D-Ala-D-Ala it was unable to kill bacteria. We therefore strongly discourage attempts at covalently immobilising teicoplanin and/or other glycopeptide antibiotics in the pursuit of novel antibacterial bone biomaterials.