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Fulltext Population Pharmacokinetics of Doripenem in Critically Ill Patients with Sepsis in a Malaysian Intensive Care Unit

Abdul-Aziz MH, Abd Rahman AN, Mat-Nor MB, Sulaiman H, Wallis SC, Lipman J, et al.

Antimicrob Agents Chemother, 2016 01;60(1):206-14.
PMID: 26482304 DOI: 10.1128/AAC.01543-15

Doripenem has been recently introduced in Malaysia and is used for severe infections in the intensive care unit. However, limited data currently exist to guide optimal dosing in this scenario. We aimed to describe the population pharmacokinetics of doripenem in Malaysian critically ill patients with sepsis and use Monte Carlo dosing simulations to develop clinically relevant dosing guidelines for these patients. In this pharmacokinetic study, 12 critically ill adult patients with sepsis receiving 500 mg of doripenem every 8 h as a 1-hour infusion were enrolled. Serial blood samples were collected on 2 different days, and population pharmacokinetic analysis was performed using a nonlinear mixed-effects modeling approach. A two-compartment linear model with between-subject and between-occasion variability on clearance was adequate in describing the data. The typical volume of distribution and clearance of doripenem in this cohort were 0.47 liters/kg and 0.14 liters/kg/h, respectively. Doripenem clearance was significantly influenced by patients' creatinine clearance (CL(CR)), such that a 30-ml/min increase in the estimated CL(CR) would increase doripenem CL by 52%. Monte Carlo dosing simulations suggested that, for pathogens with a MIC of 8 mg/liter, a dose of 1,000 mg every 8 h as a 4-h infusion is optimal for patients with a CL(CR) of 30 to 100 ml/min, while a dose of 2,000 mg every 8 h as a 4-h infusion is best for patients manifesting a CL(CR) of >100 ml/min. Findings from this study suggest that, for doripenem usage in Malaysian critically ill patients, an alternative dosing approach may be meritorious, particularly when multidrug resistance pathogens are involved.

Matched MeSH terms: Gram-Negative Bacterial Infections/drug therapy*
Public Knowledge and Attitudes Regarding the Use of Antibiotics and Resistance: Findings from a Cross-Sectional Study Among Palestinian Adults

Abu Taha A, Abu-Zaydeh AH, Ardah RA, Al-Jabi SW, Sweileh WM, Awang R, et al.

Zoonoses Public Health, 2016 09;63(6):449-57.
PMID: 26752329 DOI: 10.1111/zph.12249

Antibiotics are considered to be among the most commonly sold drug classes in Palestine. Resistance to antibiotics has increased for reasons relating to the use and misuse of antibiotics. The aim of this study was to evaluate the knowledge, and attitudes regarding antibiotic use and awareness about resistance among adults visiting the emergency departments at hospitals in North Palestine. A self-administered cross-sectional questionnaire survey involving participants aged 18 or over was conducted from June 2012 to February 2013. Adults who visited the emergency departments at hospitals in North Palestine were included. Demographic characteristics, knowledge and attitudes towards antibiotic use were included in the questionnaire. Poor and good knowledge were defined as a total knowledge score of 0-7 and 8-15 of 15 questions, respectively. Attitude scores of 0-3 and 4-7 of 7 questions were considered poor and good, respectively. A total of 375 questionnaires were included in the study. A response rate of 83.3% was attained. About 55.0% of the participants had a good knowledge and 56.5% had a good attitude towards rational antibiotic use. A significant positive correlation was shown between participants' knowledge scores and participants' attitude scores towards antibiotic use (R = 0.344, P = 0.001. Participants with a high family income were more likely to be aware of appropriate antibiotic use than participants with a low family income (P-value <0.001). Participants with a higher educational level (university) had a good attitude towards rational antibiotic use than those with a lower education level (P-value <0.001). This study has documented important knowledge and attitude gaps in antibiotic use. These findings will help health policymakers in Palestine to implement intervention programmes to rationalize antibiotic use. Continuing medical education, professional development and training workshops for healthcare professionals regarding rational use of antibiotics and health risks associated with the spread of antibiotic resistance are needed. In addition, minimizing non-prescription use of antibiotics and increasing the public awareness about the health and economic hazards of antibiotic resistance are also required.

Matched MeSH terms: Bacterial Infections/drug therapy
Impact of a training intervention on use of antimicrobials in teaching hospitals

Akter SF, Heller RD, Smith AJ, Milly AF

J Infect Dev Ctries, 2009 Jul 01;3(6):447-51.
PMID: 19762958

BACKGROUND: Antimicrobials are often used inappropriately in paediatric wards of medical college hospitals in Bangladesh. Most of the antimicrobials are prescribed based on clinical grounds-signs and symptoms. This intervention study assessed the effectiveness of a training intervention on antimicrobials prescribing by physicians in paediatric wards of tertiary care level hospitals.
METHODOLOGY: This study was conducted at medical college hospitals in Bangladesh during the period from 1998 through 2000. The pre-intervention survey of antimicrobial use was conducted during 1998 in five hospitals. The post-intervention survey was conducted after the interactive training during the succeeding year in three of the original five hospitals, of which one was the intervention hospital and two control hospitals. A total of 3,466 admitted paediatric patients' treatment charts (2,171 in the pre-intervention and 1,295 in the post-intervention surveys) were reviewed.
RESULTS: The most commonly used antimicrobials were ampicillin, gentamicin, amoxicillin, cloxacillin and ceftriaxone. Appropriate antimicrobial therapy for the most common infectious diseases, pneumonia and diarrhoea, increased by 16.4% and 56.8% respectively in the intervention hospital compared with the two control hospitals and these improvements were significant (p = < 0.001 and p = 0.002, for pneumonia and diarrhoea respectively).
CONCLUSIONS: An interactive, focussed educational intervention, targeted at physicians, appears to have been effective in improving appropriate antimicrobial prescribing for the most common paediatric infectious diseases in a medical college hospital in Bangladesh.

Matched MeSH terms: Bacterial Infections/drug therapy
Bioassay-Guided Isolation and in Silico Study of Antibacterial Compounds From Petroleum Ether Extract of Peperomia blanda (Jacq.) Kunth

Al-Madhagi WM, Hashim NM, Awadh Ali NA, Taha H, Alhadi AA, Abdullah AA, et al.

J Chem Inf Model, 2019 05 28;59(5):1858-1872.
PMID: 31117526 DOI: 10.1021/acs.jcim.8b00969

Bioassay-guided isolation protocol was performed on petroleum ether extract of Peperomia blanda (Jacq.) Kunth using column chromatographic techniques. Five compounds were isolated and their structures were elucidated via one-dimensional (1D) and two-dimensional (2D) NMR, gas chromatography mass sectroscopy (GCMS), liquid chromatography mass spectroscopy (LCMS), and ultraviolet (UV) and infrared (IR) analyses. Dindygulerione E (a new compound), and two compounds isolated from P. blanda for the first time-namely, dindygulerione A and flavokawain A-are reported herein. Antimicrobial activity was screened against selected pathogenic microbes, and minimum inhibitory concentrations (MIC) were recorded within the range of 62-250 μg/mL. Assessment of the pharmacotherapeutic potential has also been done for the isolated compounds, using the Prediction of Activity spectra for Substances (PASS) software, and different activities of compounds were predicted. Molecular docking, molecular dynamics simulation and molecular mechanics/Poisson-Boltzmann Surface Area (MM-PBSA) calculations have proposed the binding affinity of these compounds toward methylthioadenosine phosphorylase enzyme, which may explain their inhibitory actions.

Matched MeSH terms: Bacterial Infections/drug therapy
Fulltext Genotypic variations of virulent genes in Enterococcus faecium and Enterococcus faecalis isolated from three hospitals in Malaysia

Al-Talib H, Zuraina N, Kamarudin B, Yean CY

Adv Clin Exp Med, 2015 Jan-Feb;24(1):121-7.
PMID: 25923096 DOI: 10.17219/acem/38162

The genus Enterococcus is of increasing significance as a cause of nosocomial infections, and this trend is exacerbated by the development of antibiotic resistance.

Matched MeSH terms: Gram-Positive Bacterial Infections/drug therapy
Detection of mobile colistin-resistance gene variants (mcr-1 and mcr-2) in urinary tract pathogens in Bangladesh: the last resort of infectious disease management colistin efficacy is under threat

Ara B, Urmi UL, Haque TA, Nahar S, Rumnaz A, Ali T, et al.

Expert Rev Clin Pharmacol, 2021 Apr;14(4):513-522.
PMID: 33691556 DOI: 10.1080/17512433.2021.1901577

Background: Currently, colistin-resistant pathogens emerged has become a global health concern. This study assessed the distribution of mcr-1 to mcr-5 variants with the phenotypic colistin-resistance in bacterial isolates from urinary tract infection (UTI) patients in Bangladesh.Methods: A cross-sectional study was conducted between April 2017 and March 2018 to enroll uncomplicated UTI patients, and 142 urine samples were analyzed. Uropathogens were identified using the API-20E biochemical panel and 16s rRNA gene sequencing. Polymerase chain reactions detected the mcr gene variants in the UTI isolates. The phenotypic colistin-susceptibility was determined by the Kirby-Bauer disc-diffusion method and the minimal inhibitory concentration (MIC) measurement.Results: The combined carriage of mcr-1 and mcr-2 genes in 11.4% (14/123) of urinary tract pathogens. The mcr-positive pathogens include five Escherichia coli, three Klebsiella pneumoniae, three Pseudomonas putida, two Enterobacter cloacae, and one Enterobacter hormaechei. The mcr-positive variant showed significantly higher phenotypic colistin resistance with MIC between >16 µg/mL and >128 µg/mL (pdrug may lead to a lack of treatment options for the infectious diseases and spread of infection to the unaffected cohorts.

Matched MeSH terms: Gram-Negative Bacterial Infections/drug therapy*
Septicaemia in paediatric cancer patients: a 5-year surveillance study in university hospital, Kuala Lumpur, Malaysia

Ariffin H, Ariffin W, Peng LH, Parasakthi N

J Trop Pediatr, 1997 10;43(5):279-81.
PMID: 9364125 DOI: 10.1093/tropej/43.5.279

Infectious complications are the major cause of morbidity and mortality in children with malignancy. Empirical antimicrobial therapy in the management of fever of unknown origin should be tailored to local bacteriological data and antibiotic sensitivity patterns. Five-hundred-and-fifty-nine cases of culture-proven septicaemia occurring in pediatric cancer patients between 1990 and 1994 were retrospectively analysed and compared with a similar study done in our centre between 1976 and 1979. A wide spectrum of organisms was isolated. Staphylococcus epidermidis, Staphylococcus aureus, and Klebsiella pneumoniae were the most common and consistent bacteria isolated during the 5 year period. More than 70 per cent of the staphylococci were sensitive to methicillin and universally sensitive to vancomycin. However, a worrying trend of ceftazidime-resistance amongst gram-negative organisms was found. In these situations, the use of imipenem is recommended as resistance to this antimicrobial agent was exceedingly rare.

Matched MeSH terms: Bacterial Infections/drug therapy
Antibiotic resistance patterns in nosocomial gram-negative bacterial infections in units with heavy antibiotic usage

Ariffin H, Navaratnam P, Kee TK, Balan G

J Trop Pediatr, 2004 Feb;50(1):26-31.
PMID: 14984166

The pattern of antibiotic resistance amongst gram-negative bacteria (GNB) in paediatric units, which have heavy empirical usage of broad-spectrum antibiotics, was studied prospectively over a 6-month period. A total of 200 consecutive, non-duplicate gram-negative isolates were obtained from 109 patients admitted to intensive care and oncology units in two hospitals. The commonest isolates were Klebsiella spp (36.5 per cent) and Pseudomonas (20.0 per cent). The isolates showed lower susceptibility rates to the third-generation cephalosporins (47-62 per cent) compared with cefepime (91 per cent), imipenem (90 per cent) and ciprofloxacin (99 per cent). Fifty-four (52.8 per cent) Klebsiella and Escherichia coli isolates were determined to be extended-spectrum beta-lactamase (ESBL) producing strains. Antibiotics found to be effective against ESBL-producers were imipenem and ciprofloxacin. The high resistance rate amongst GNB to third-generation cephalosporins is a likely consequence of heavy empirical usage of this group of antibiotics. The carbapenems and quinolones remain useful agents in the management of patients admitted to these units.

Matched MeSH terms: Gram-Negative Bacterial Infections/drug therapy*
Fulltext A scaffolded approach to unearth potential antibacterial components from epicarp of Malaysian Nephelium lappaceum L

Asghar A, Tan YC, Zahoor M, Zainal Abidin SA, Yow YY, Khan E, et al.

Sci Rep, 2021 Jul 05;11(1):13859.
PMID: 34226594 DOI: 10.1038/s41598-021-92622-0

The emergence and spread of antimicrobial resistance have been of serious concern to human health and the management of bacterial infectious diseases. Effective treatment of these diseases requires the development of novel therapeutics, preferably free of side effects. In this regard, natural products are frequently conceived to be potential alternative sources for novel antibacterial compounds. Herein, we have evaluated the antibacterial activity of the epicarp extracts of the Malaysian cultivar of yellow rambutan fruit (Nephelium lappaceum L.) against six pathogens namely, Bacillus subtilis, methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes, Pseudomonas aeruginosa, Klebsiella pneumoniae and Salmonella enterica. Among a series of solvent extracts, fractions of ethyl acetate and acetone have revealed significant activity towards all tested strains. Chemical profiling of these fractions, via HPLC, LC-MS and GC-MS, has generated a library of potentially bioactive compounds. Downstream virtual screening, pharmacological prediction, and receptor-ligand molecular dynamics simulation have eventually unveiled novel potential antibacterial compounds, which can be extracted for medicinal use. We report compounds like catechin, eplerenone and oritin-4-beta-ol to be computationally inhibiting the ATP-binding domain of the chaperone, DnaK of P. aeruginosa and MRSA. Thus, our work follows the objective to propose new antimicrobials capable of perforating the barrier of resistance posed by both the gram positives and the negatives.

Matched MeSH terms: Bacterial Infections/drug therapy*
Short cationic lipopeptides as effective antibacterial agents: Design, physicochemical properties and biological evaluation

Azmi F, Elliott AG, Marasini N, Ramu S, Ziora Z, Kavanagh AM, et al.

Bioorg Med Chem, 2016 05 15;24(10):2235-41.
PMID: 27048775 DOI: 10.1016/j.bmc.2016.03.053

The spread of drug-resistant bacteria has imparted a sense of urgency in the search for new antibiotics. In an effort to develop a new generation of antibacterial agents, we have designed de novo charged lipopeptides inspired by natural antimicrobial peptides. These short lipopeptides are composed of cationic lysine and hydrophobic lipoamino acids that replicate the amphiphilic properties of natural antimicrobial peptides. The resultant lipopeptides were found to self-assemble into nanoparticles. Some were effective against a variety of Gram-positive bacteria, including strains resistant to methicillin, daptomycin and/or vancomycin. The lipopeptides were not toxic to human kidney and liver cell lines and were highly resistant to tryptic degradation. Transmission electron microscopy analysis of bacteria cells treated with lipopeptide showed membrane-damage and lysis with extrusion of cytosolic contents. With such properties in mind, these lipopeptides have the potential to be developed as new antibacterial agents against drug-resistant Gram-positive bacteria.

Matched MeSH terms: Gram-Positive Bacterial Infections/drug therapy
Applying the Multinational Association for Supportive Care in Cancer risk scoring in predicting outcome of febrile neutropenia patients in a cohort of patients

Baskaran ND, Gan GG, Adeeba K

Ann Hematol, 2008 Jul;87(7):563-9.
PMID: 18437382 DOI: 10.1007/s00277-008-0487-7

The purpose of this study was to determine if the Multinational Association for Supportive Care in Cancer (MASCC) risk-index score is able to predict the outcome of febrile neutropenia in patients with underlying hematological malignancy and to look at the other possible predictors of outcome. A retrospective study of 116 episodes of febrile neutropenia in patients who were admitted to the hematology ward of a local medical center in Malaysia between January 1st 2004 and January 31st 2005. Patient characteristics and the MASCC score were compared with outcome. The MASCC score predicted the outcome of febrile neutropenic episodes with a positive predictive value of 82.9%, a sensitivity of 93%, and specificity of 67%. Other predictors of a favorable outcome were those patients who had lymphomas versus leukemias, duration of neutropenia of less than 7 days, low burden of illness characterized by the absence of an infective focus and absence of lower respiratory tract infection, a serum albumin of >25 g/l, and the absence of gram-negative bacteremia on univariate analysis but only serum albumin level, low burden of illness, and presence of respiratory infection were significantly associated with unfavorable outcome after multivariate analysis. The MASCC score is a useful predictor of outcome in patients with febrile neutropenia with underlying hematological malignancies. This scoring system may be adapted for use in local settings to guide the clinical management of patients with this condition.

Matched MeSH terms: Bacterial Infections/drug therapy
Synthesis and biological evaluation of novel substituted 1,3,4-thiadiazole and 2,6-di aryl substituted imidazo [2,1-b] [1,3,4] thiadiazole derivatives

Chandrakantha B, Isloor AM, Shetty P, Fun HK, Hegde G

Eur J Med Chem, 2014 Jan;71:316-23.
PMID: 24321835 DOI: 10.1016/j.ejmech.2013.10.056

A new series of N-[5-(4-(alkyl/aryl)-3-nitro-phenyl)-[1,3,4-thiadiazol-2-yl]-2,2-dimethyl-propionamide 4 (a-l) and 6-(4-Methoxy-phenyl)-2-(4-alkyl/aryl)-3-nitro-phenyl)-Imidazo [2,1-b] [1,3,4] thiadiazole 6 (a-l) were synthesized starting from 5-(4-Fluoro-3-nitro-phenyl)-[1,3,4] thiadiazole-2-ylamine. The synthesized compounds were characterized by IR, NMR, mass spectral and elemental analysis. All the compounds were tested for antibacterial and antifungal activities. The antimicrobial activities of the compounds were assessed by well plate method (zone of inhibition). Compounds 4a, 4c and 6e, 6g displayed appreciable activity at the concentration 0.5-1.0 mg/mL.

Matched MeSH terms: Bacterial Infections/drug therapy
Chromobacterium violaceum infection in Taiwan: a case report and literature review

Chang CY, Lee YT, Liu KS, Wang YL, Tsao SM

J Microbiol Immunol Infect, 2007 Jun;40(3):272-5.
PMID: 17639170

Chromobacterium violaceum is a facultative anaerobic, Gram-negative bacillus which inhabits stagnant water in tropical and subtropical regions. We describe the case of an 80-year-old female patient with C. violaceum bacteremia due to traumatic wound infected by contaminated water and soil. She had persistent fever, hypotension and neutrophilic leukocytosis on admission. Two sets of blood cultures yielded C. violaceum. The patient was successfully treated with levofloxacin. Since the first case from Malaysia in 1927, about 150 cases have been reported in the world literature. To our knowledge, six other cases have been reported previously from Taiwan, including two children and four adults. Of the total of seven patients from Taiwan, four had a fatal outcome within several days, while the three survivors were apparently free of vital organ involvement. Although human infections caused by C. violaceum are rare, clinicians should be aware of this potentially fatal infection as part of the differential diagnosis of sepsis associated with a history of exposure to stagnant water.

Matched MeSH terms: Gram-Negative Bacterial Infections/drug therapy
Fulltext Underestimation of co-infections in COVID-19 due to non-discriminatory use of antibiotics

Chang CY, Chan KG

J Infect, 2020 Sep;81(3):e29-e30.
PMID: 32628960 DOI: 10.1016/j.jinf.2020.06.077
Matched MeSH terms: Bacterial Infections/drug therapy
Fulltext Antimicrobial resistance pattern of bacteria isolated from patients seen by private practitioners in the Klang Valley

Cheong YM, Fairuz A, Jegathesan M

Singapore Med J, 1995 Feb;36(1):43-6.
PMID: 7570134

Data on bacterial resistance in patients seen by general practitioners are usually not readily available. The objective of this paper is to present the antimicrobial resistance pattern of bacteria isolated from patients seen by private practitioners in the Klang Valley. A total of 18 clinics participated in this study. From mid August 1991 to end of June 1993, 2,823 specimens were received. Throat swabs and urine specimens constituted 56% of all the specimens. A large proportion of the specimens (55%) yielded no growth or just normal flora. The common bacteria encountered were Staphylococcus aureus (18.4%), Escherichia coli (16.2%), Klebsiella spp (13.7%) and Neisseria gonorrhoeae (9.3%). The S. aureus strains were mainly isolated from wound, pus and ear swabs. Not one out of the 218 strains tested was resistant to methicillin. In vitro susceptibility tests showed that 91% were resistant to penicillin while 23% were resistant to tetracycline and 13% to erythromycin. Eighty-two percent of the E. coli were isolated from urine. It was also the most common isolate from urine. Fifty percent of these strains were resistant to ampicillin, 33% to cotrimoxazole, 17% to cephalothin, 21% to ampicillin-sulbactam, 18% to amoxycillin-clavulanic acid while only 2.3% were resistant to nalidixic acid and nitrofurantoin and none to cefuroxime. Generally the gram negative bacilli encountered in general practice are less resistant to the third generation cephalosporins and aminoglycosides when compared to the hospital strains.

Matched MeSH terms: Bacterial Infections/drug therapy
Fulltext Francisella philomiragia bacteremia in an immunocompromised patient: a rare case report

Chua HS, Soh YH, Loong SK, AbuBakar S

Ann Clin Microbiol Antimicrob, 2021 Oct 03;20(1):72.
PMID: 34602092 DOI: 10.1186/s12941-021-00475-2

BACKGROUND: Francisella philomiragia is a very rare opportunistic pathogen of humans which causes protean diseases such as pneumonia and other systemic infections. Subsequent failure of prompt treatment may result in poor prognosis with mortality among infected patients.
CASE PRESENTATION: The present report describes a case of F. philomiragia bacteraemia first reported in Malaysia and Asian in a 60-year-old patient with underlying end-stage renal disease (ESRF) and diabetes mellitus. He presented with Acute Pulmonary Oedema with Non-ST-Elevation Myocardial Infarction (NSTEMI) in our hospital. He was intubated in view of persistent type I respiratory failure and persistent desaturation despite post haemodialysis. Blood investigation indicated the presence of ongoing infection and inflammation. The aerobic blood culture growth of F. philomiragia was identified using the matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) mass spectrometry (Score value: 2.16) and confirmed by 16S Ribosomal DNA (16S rDNA) sequencing. He was discharged well on day 26 of admission, after completing one week of piperacillin/tazobactam and two weeks of doxycycline.
CONCLUSION: Clinical suspicion should be raised if patients with known risk factors are presenting with pneumonia or pulmonary nodules especially as these are the most common manifestations of F. philomiragia infection. Early diagnosis via accurate laboratory identification of the organism through MALDI-TOF mass spectrometry and molecular technique such as 16S rDNA sequencing are vital for prompt treatment that results in better outcomes for the afflicted patients.

Matched MeSH terms: Gram-Negative Bacterial Infections/drug therapy
Current Technology in the Discovery and Development of Novel Antibacterials

Chung PY

Curr Drug Targets, 2018;19(7):832-840.
PMID: 28891454 DOI: 10.2174/1389450118666170911114604

BACKGROUND: Bacterial resistance to antibiotics is one of the most serious challenge to global public health. The introduction of new antibiotics in clinical settings, i.e. agents that belong to a new class of antibacterials, act on new targets or has a novel mechanisms of action, may not be sufficient to cope with the emergence of multidrug-resistant pathogens such as Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii and Escherichia coli, which are increasingly prevalent in healthcare settings in Europe, the USA and Asia. Hence, coordinated efforts in minimizing the risk of spread of resistant bacteria and renewing research efforts in the search for novel antibacterial agents are urgently needed to manage this global crisis.
OBJECTIVE: This review highlights the challenges and potential in using current technologies in the discovery and development of novel antibacterial agents to keep up with the constantly evolving resistance in bacteria.
CONCLUSION: With the explosion of bacterial genomic data and rapid development of new sequencing technologies, the understanding of bacterial pathogenesis and identification of novel antibiotic targets have significantly improved.

Matched MeSH terms: Bacterial Infections/drug therapy*
Antimicrobial effects of Caulerpa sertularioides extract on foodborne diarrhea-caused bacteria

Darah I, Tong WY, Nor-Afifah S, Nurul-Aili Z, Lim SH

Eur Rev Med Pharmacol Sci, 2014;18(2):171-8.
PMID: 24488904

Caulerpa (C.) sertularioides has many therapeutic uses in the practice of traditional medicine in Malaysia. Crude methanolic, diethyl ether extract, ethyl acetate extract and butanolic extract from C. sertularioides were subjected to antimicrobial screening including the three Gram-positive and three Gram-negative diarrhea-caused bacteria.

Matched MeSH terms: Gram-Negative Bacterial Infections/drug therapy; Gram-Positive Bacterial Infections/drug therapy
Oritavancin - a new semisynthetic lipoglycopeptide agent to tackle the challenge of resistant gram positive pathogens

Das B, Sarkar C, Schachter J

Pak J Pharm Sci, 2013 Sep;26(5):1045-55.
PMID: 24035967

Natural glycopeptide antibiotics like vancomycin and teicoplanin have played a significant role in countering the threat posed by Gram-positive bacterial infections. The emergence of resistance to glycopeptides among enterococci and staphylococci has prompted the search for second-generation drugs of this class and semi-synthetic derivatives are currently under clinical trials. Antimicrobial resistance among Gram-positive organisms has been increasing steadily during the past several decades and the current development of antibiotics falls short of meeting the needs. Oritavancin (LY-333328 diphosphate), a promising novel second-generation semisynthetic lipoglycopeptide, has a mechanism of action similar to that of other glycopeptides. It has concentration-dependent activity against a variety of Gram-positive organisms specially methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-intermediate resistant Staphylococcus aureus (VISA), Streptococcus pneumoniae and vancomycin-resistant enterococcus. It is rapidly bactericidal against many species and in particular for enterococci where vancomycin and teicoplanin are only bacteriostatic even against susceptible strains. The pharmacokinetic profile of oritavancin has not been fully described; however, oritavancin has a long half-life of about 195.4 hours and is slowly eliminated by renal means. Oritavancin is not metabolized by the liver in animals. Oritavancin will most probably be prescribed as a once-daily dose and it demonstrates concentration-dependent bactericidal activity. Oritavancin has demonstrated preliminary safety and efficacy in Phase I and II clinical trials. In a Phase III clinical trial, oritavancin has achieved the primary efficacy end point in the treatment of complicated Gram-positive skin and skin-structure infections. To date, adverse events have been mild and limited; the most common being administration site complaints, headache, rhinitis, dry skin, pain, increases in liver transaminases and accumulation of free cholesterol and phospholipids in phagocytic (macrophages) and nonphagocytic (fibroblast) cells. Oritavancin appears to be a promising antimicrobial alternative to vancomycin (with additional activity against Staphylococcus and Enterococcus resistant to vancomycin) for the treatment of complicated Gram-positive skin and skin-structure infections. Additional clinical data are required to fully explore its use.

Matched MeSH terms: Gram-Negative Bacterial Infections/drug therapy*
Review: dalbavancin--a novel lipoglycopeptide antimicrobial for gram positive pathogens

Das B, Sarkar C, Biswas R, Pandey S

Pak J Pharm Sci, 2008 Jan;21(1):78-87.
PMID: 18166524

Glycopeptide antibiotics represent an important class of microbial compounds produced by several genera of actinomycetes. The emergence of resistance to glycopeptides among enterococci and staphylococci has prompted the search for second-generation drugs of this class and semi-synthetic derivatives are currently under clinical trials. Antimicrobial resistance among gram-positive organisms has been increasing steadily during the past several decades. Dalbavancin, a novel lipoglycopeptide, has a mechanism of action similar to that of other glycopeptides. It has in vitro activity against a variety of Gram-positive organisms specially multidrug resistant Staphylococcus aureus, but no activity against Gram-negative or vancomycin-resistant enterococci that possess vanA gene. Due to its prolonged half-life (6-10 days), dalbavancin can be administered intravenously once weekly. In Phase II and III clinical trials, dalbavancin was effective and well-tolerated for the treatment of skin and soft-tissue infections, catheter-related bloodstream infections, and skin and skin-structure infections. To date, adverse events have been mild and limited; the most common being pyrexia, headache, diarrhea. Dalbavancin appears to be a promising antimicrobial agent for the treatment of Gram-positive infections. Additional clinical data are required to fully assess its use. Despite the remarkable and favorable pharmacokinetic and pharmacodynamic properties, the use of this potent agent should be restricted to severe infections due to multidrug resistant organisms to limit the risk of selection of resistance. It is active against Gram-positive aerobes and anerobes, including resistant pathogens, with the exception of strains producing vanA-mediated resistance. Its approval by the FDA is expected soon. The extent to which dalbavancin will supplant vancomycin and whether it will be preferred over other newer agents such as linezolid in the next decade remains to be seen.

Matched MeSH terms: Gram-Positive Bacterial Infections/drug therapy*

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