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Once-daily aminoglycoside dosing

Riley PA

JUMMEC, 1996;1:17-19.

The conventional use of aminoglycoside antibiotics has several disadvantages including the need for regular pre- and post-dose assaying and the risks of toxicity. Achieving a therapeutic and non-toxic serum concentration may be difficult in many patients especially those with severe sepsis. Correct timing of doses and assays is essential, but this is often difficult to achieve. Many of these difficulties may be remedied by the use of once daily dosing. This dosing schedule appears to be equally effective as the conventional method and i s also less toxic. There are many other advantages including the need for less assays and venepuncture resulting in reduced costs. KEYWORDS: Aminoglycosides, antibiotic therapy, toxicity, therapeutic monitoring

Matched MeSH terms: Aminoglycosides
Designing potential lead compounds targeting aminoglycoside N (6')-acetyltransferase in Serratia marcescens: A drug discovery strategy

Prabhu D, Shankari G, Rajamanikandan S, Jeyakanthan J, Velusamy P, Gopinath SCB, et al.

Int J Biol Macromol, 2024 Nov;281(Pt 1):136976.
PMID: 39490491 DOI: 10.1016/j.ijbiomac.2024.136976

Serratia marcescens is an opportunistic human pathogen that causes urinary tract infections, ocular lens infections, and respiratory tract infections. S. marcescens employs various defense mechanisms to evade antibiotics, one of which is mediated by aminoglycoside N-acetyltransferase (AAC). In this mechanism, the enzyme AAC facilitates the transfer and linkage of the acetyl moiety from the donor substrate acetyl-coenzyme A to specific positions on antibiotics. This modification alters the antibiotic's structure, leading to the inactivation of aminoglycoside antibiotics. In the current scenario, antibiotic resistance has become a global threat, and targeting the enzymes that mediate resistance is considered crucial to combat this issue. The study aimed to address the increasing global threat of antibiotic resistance in Serratia marcescens by targeting the aminoglycoside N-acetyltransferase (AAC (6')) enzyme, which inactivates aminoglycoside antibiotics through acetylation. Due to the absence of experimental structure, we constructed a homology model of aminoglycoside N (6')-acetyltransferase (AAC (6')) of S. marcescens using the atomic structure of aminoglycoside N-acetyltransferase AAC (6')-Ib (PDB ID: 1V0C) as a template. The stable architecture and integrity of the modelled AAC (6') structure were analyzed through a 100 ns simulation. Structure-guided high-throughput screening of four small molecule databases (Binding, Life Chemicals, Zinc, and Toslab) resulted in the identification of potent inhibitors against AAC (6'). The hits obtained from screening were manually clustered, and the five hit molecules were shortlisted based on the docking score, which are observed in the range of -17.09 kcal/mol to -11.95 kcal/mol. These selected five molecules displayed acceptable pharmacological properties in ADME predictions. The binding free energy calculations, and molecular dynamics simulations of ligand bound AAC (6') complexes represented higher affinity and stable binding. The selected molecules demonstrated stable binding with AAC (6'), indicating their strong potential to hamper the binding of aminoglycoside in the respective site. and thereby inhibit. This process mitigates enzyme mediated AAC (6') activity on aminoglycosides and reverse the bactericidal function of aminoglycosides, and also this method could serve as a platform for the development of potential antimicrobials.

Matched MeSH terms: Aminoglycosides/metabolism; Aminoglycosides/pharmacology; Aminoglycosides/chemistry
Fulltext Burkholderia pseudomallei isolates from Sarawak, Malaysian Borneo, are predominantly susceptible to aminoglycosides and macrolides

Podin Y, Sarovich DS, Price EP, Kaestli M, Mayo M, Hii K, et al.

Antimicrob Agents Chemother, 2014;58(1):162-6.
PMID: 24145517 DOI: 10.1128/AAC.01842-13

Melioidosis is a potentially fatal disease caused by the saprophytic bacterium Burkholderia pseudomallei. Resistance to gentamicin is generally a hallmark of B. pseudomallei, and gentamicin is a selective agent in media used for diagnosis of melioidosis. In this study, we determined the prevalence and mechanism of gentamicin susceptibility found in B. pseudomallei isolates from Sarawak, Malaysian Borneo. We performed multilocus sequence typing and antibiotic susceptibility testing on 44 B. pseudomallei clinical isolates from melioidosis patients in Sarawak district hospitals. Whole-genome sequencing was used to identify the mechanism of gentamicin susceptibility. A novel allelic-specific PCR was designed to differentiate gentamicin-sensitive isolates from wild-type B. pseudomallei. A reversion assay was performed to confirm the involvement of this mechanism in gentamicin susceptibility. A substantial proportion (86%) of B. pseudomallei clinical isolates in Sarawak, Malaysian Borneo, were found to be susceptible to the aminoglycoside gentamicin, a rare occurrence in other regions where B. pseudomallei is endemic. Gentamicin sensitivity was restricted to genetically related strains belonging to sequence type 881 or its single-locus variant, sequence type 997. Whole-genome sequencing identified a novel nonsynonymous mutation within amrB, encoding an essential component of the AmrAB-OprA multidrug efflux pump. We confirmed the role of this mutation in conferring aminoglycoside and macrolide sensitivity by reversion of this mutation to the wild-type sequence. Our study demonstrates that alternative B. pseudomallei selective media without gentamicin are needed for accurate melioidosis laboratory diagnosis in Sarawak. This finding may also have implications for environmental sampling of other locations to test for B. pseudomallei endemicity.

Matched MeSH terms: Aminoglycosides/pharmacology*
Central composite design for optimizing istamycin production by Streptomyces tenjimariensis

Gomaa FAM, Selim HMRM, Alshahrani MY, Aboshanab KM

World J Microbiol Biotechnol, 2024 Sep 09;40(10):316.
PMID: 39249607 DOI: 10.1007/s11274-024-04118-4

Istamycins (ISMs) are 2-deoxyfortamine-containing aminoglycoside antibiotics (AGAs) produced by Streptomyces tenjimariensis ATCC 31603 with broad-spectrum bactericidal activities against most of the clinically relevant pathogens. Therefore, this study aimed to statistically optimize the environmental conditions affecting ISMs production using the central composite design (CCD). Both the effect of culture media composition and incubation time and agitation rate were studied as one factor at the time (OFAT). The results showed that both the aminoglycoside production medium and the protoplast regeneration medium gave the highest specific productivity. Results also showed that 6 days incubation time and 200 rpm agitation were optimum for their production. A CCD quadratic model of 17 runs was employed to test three key variables: initial pH, incubation temperature, and concentration of calcium carbonate. A significant statistical model was obtained including, an initial pH of 6.38, incubation temperature of 30 ˚C, and 5.3% CaCO3 concentration. This model was verified experimentally in the lab and resulted in a 31-fold increase as compared to the unoptimized conditions and a threefold increase to that generated by using the optimized culture media. To our knowledge, this is the first report about studying environmental conditions affecting ISM production as OFAT and through CCD design of the response surface methodology (RSM) employed for statistical optimization. In conclusion, the CCD design is an effective tool for optimizing ISMs at the shake flask level. However, the optimized conditions generated using the CCD model in this study should be scaled up in a fermenter for industrial production of ISMs by S. tenjimariensis ATCC 31603 considering the studied environmental conditions that significantly influence the production proces.

Matched MeSH terms: Aminoglycosides/pharmacology
Clinical pharmacokinetics, toxicity and cost effectiveness analysis of aminoglycosides and aminoglycoside dosing services

Mathews A, Bailie GR

J Clin Pharm Ther, 1987 Oct;12(5):273-91.
PMID: 3119606

This article reviews the clinical pharmacokinetics, clinical toxicity and cost-effectiveness analysis of aminoglycosides and of dosing services for aminoglycosides. The reader is referred elsewhere for a review of the pharmacology, antimicrobial spectrum of activity and clinical use of these drugs. A critique of the more commonly used methods of aminoglycoside dosage determinations is included, based on the inter-individual variation in aminoglycoside disposition parameters. The advantages and disadvantages of arbitrary, predictive, and pharmacokinetic methods of dosing determination are summarized. Justification for the routine determination of serum aminoglycoside concentrations is reviewed. We review the lack of standardization of definitions for aminoglycoside-associated nephrotoxicity in published studies, and studies which illustrate these differences are highlighted. Evidence for the association between serum aminoglycoside concentrations and nephrotoxicity is examined. Ototoxicity is similarly reviewed. The concept of cost-effectiveness analysis is examined extensively in this review. We discuss the literature concerning the cost benefit analysis of drug dosing services.

Matched MeSH terms: Aminoglycosides/administration & dosage*; Aminoglycosides/adverse effects; Aminoglycosides/pharmacokinetics
Analytical and Non-Analytical Variation May Lead to Inappropriate Antimicrobial Dosing in Neonates: An In Silico Study

Nguyen TA, Kirubakaran R, Schultz HB, Wong S, Reuter SE, McMullan B, et al.

Clin Chem, 2023 Jun 01;69(6):637-648.
PMID: 37116191 DOI: 10.1093/clinchem/hvad036

BACKGROUND: Therapeutic drug monitoring (TDM) of aminoglycosides and vancomycin is used to prevent oto- and nephrotoxicity in neonates. Analytical and nonanalytical factors potentially influence dosing recommendations. This study aimed to determine the impact of analytical variation (imprecision and bias) and nonanalytical factors (accuracy of drug administration time, use of non-trough concentrations, biological variation, and dosing errors) on neonatal antimicrobial dosing recommendations.
METHODS: Published population pharmacokinetic models and the Australasian Neonatal Medicines Formulary were used to simulate antimicrobial concentration-time profiles in a virtual neonate population. Laboratory quality assurance data were used to quantify analytical variation in antimicrobial measurement methods used in clinical practice. Guideline-informed dosing recommendations based on drug concentrations were applied to compare the impact of analytical variation and nonanalytical factors on antimicrobial dosing.
RESULTS: Analytical variation caused differences in subsequent guideline-informed dosing recommendations in 9.3-12.1% (amikacin), 16.2-19.0% (tobramycin), 12.2-45.8% (gentamicin), and 9.6-19.5% (vancomycin) of neonates. For vancomycin, inaccuracies in drug administration time (45.6%), use of non-trough concentrations (44.7%), within-subject biological variation (38.2%), and dosing errors (27.5%) were predicted to result in more dosing discrepancies than analytical variation (12.5%). Using current analytical performance specifications, tolerated dosing discrepancies would be up to 14.8% (aminoglycosides) and 23.7% (vancomycin).
CONCLUSIONS: Although analytical variation can influence neonatal antimicrobial dosing recommendations, nonanalytical factors are more influential. These result in substantial variation in subsequent dosing of antimicrobials, risking inadvertent under- or overexposure. Harmonization of measurement methods and improved patient management systems may reduce the impact of analytical and nonanalytical factors on neonatal antimicrobial dosing.

Matched MeSH terms: Aminoglycosides
Fulltext In vitro activity of aminoglycosides, ureidopenicillins and cephalosporins against P. aeruginosa isolated in Kuala Lumpur

Ngeow YS, Puthucheary SD, Lai PS

Med J Malaysia, 1985 Sep;40(3):196-201.
PMID: 3939567

170 clinical isolates of Pseudomonas aeruginosa were tested for in vitro susceptibility to gentamicin, amikacin, tobramycin, netilmicin, kanamycin, streptomycin, cefotaxime, ceftriaxone, cefoperazone, ceftazidime, moxalactam, azlocillin, piperacillin and ticarcillin. Against 93 gentamicin-sensitive strains, the most active antibiotics were in descending order, ceftazidime, tobramycin, gentamicin, amikacin, and the ureidopenicillins. Against 77 gentamicin-resistant strains, only ceftazidime, amikacin and moxalactam had mode minimum inhibitory concentrations within achievable peak serum levels after standard therapeutic dosage. There was no correlation between cephalosporin resistance and aminoglycoside resistance except for cefoperazone, which, together with the ureidopenicillins and ticarcillin, showed marked decrease in activity against gentamicin-resistant strains.

Matched MeSH terms: Aminoglycosides/pharmacology*
Fulltext Management and treatment of contact lens-related Pseudomonas keratitis

Willcox MD

Clin Ophthalmol, 2012;6:919-24.
PMID: 22791973 DOI: 10.2147/OPTH.S25168

Pubmed and Medline were searched for articles referring to Pseudomonas keratitis between the years 2007 and 2012 to obtain an overview of the current state of this disease. Keyword searches used the terms "Pseudomonas" + "Keratitis" limit to "2007-2012", and ["Ulcerative" or "Microbial"] + "Keratitis" + "Contact lenses" limit to "2007-2012". These articles were then reviewed for information on the percentage of microbial keratitis cases associated with contact lens wear, the frequency of Pseudomonas sp. as a causative agent of microbial keratitis around the world, the most common therapies to treat Pseudomonas keratitis, and the sensitivity of isolates of Pseudomonas to commonly prescribed antibiotics. The percentage of microbial keratitis associated with contact lens wear ranged from 0% in a study from Nepal to 54.5% from Japan. These differences may be due in part to different frequencies of contact lens wear. The frequency of Pseudomonas sp. as a causative agent of keratitis ranged from 1% in Japan to over 50% in studies from India, Malaysia, and Thailand. The most commonly reported agents used to treat Pseudomonas keratitis were either aminoglycoside (usually gentamicin) fortified with a cephalosporin, or monotherapy with a fluoroquinolone (usually ciprofloxacin). In most geographical areas, most strains of Pseudomonas sp. (≥95%) were sensitive to ciprofloxacin, but reports from India, Nigeria, and Thailand reported sensitivity to this antibiotic and similar fluoroquinolones of between 76% and 90%.

Matched MeSH terms: Aminoglycosides
Antimicrobial resistance in aquaculture: Occurrence and strategies in Southeast Asia

Suyamud B, Chen Y, Quyen DTT, Dong Z, Zhao C, Hu J

Sci Total Environ, 2024 Jan 10;907:167942.
PMID: 37863226 DOI: 10.1016/j.scitotenv.2023.167942

Aquaculture is a highly important and expanding industry in Southeast Asia (SEA). An upcoming problem is the emergence of antibiotic resistant pathogens due to the unchecked use of antibiotics and human clinical practices. This review focused insight into the occurrence of antimicrobial resistance (AMR) and strategies from SEA aquaculture based on the original research publication over the period 2002 to 2023. Amongst the 11 SEA countries, the most AMR report has come from Vietnam, Malaysia, and Thailand, respectively. The AMR found in SEA aquaculture were classified into 17 drug classes. The most reported AMR are aminoglycosides, beta-lactams, (fluoro)quinolones, tetracycline, sulpha group and multi-drug. Beta-lactams, tetracycline, sulpha group are reported in each country with the reported frequencies higher than 40 %. Escherichia coli, Aeromonas and Vibrio are the most widely and frequently reported ARB in SEA aquaculture. Multiple antibiotic resistance (MAR) indexes for the sample containing multiple bacterial isolates were generally low, while the medium numbers of MAR indexes for the typical bacteria species were higher than 0.2 and showed higher MAR levels than the global mean. Most of the detected ARGs are related to beta-lactams, tetracycline, sulpha group, and aminoglycosides. Amongst the beta-lactam resistance genes, blaTEM, and blaSHV are the most frequently detected. Almost all the available information of antibiotics, ARB and ARGs in SEA aquaculture was consistent with the global scale analysis. In addition, factors that contribute to the development and spread of AMR in SEA aquaculture were discussed. Moreover, the national action plan to combat AMR in SEA countries and the available technologies that already applied in the SEA aquaculture are also included in this review. Such findings underline the need for synergistic efforts from scientists, engineers, policy makers, government managers, entrepreneurs, and communities to manage and reduce the burden of AMR in aquaculture of SEA countries.

Matched MeSH terms: Aminoglycosides
Fulltext 4'-O-substitutions determine selectivity of aminoglycoside antibiotics

Perez-Fernandez D, Shcherbakov D, Matt T, Leong NC, Kudyba I, Duscha S, et al.

Nat Commun, 2014;5:3112.
PMID: 24473108 DOI: 10.1038/ncomms4112

Clinical use of 2-deoxystreptamine aminoglycoside antibiotics, which target the bacterial ribosome, is compromised by adverse effects related to limited drug selectivity. Here we present a series of 4',6'-O-acetal and 4'-O-ether modifications on glucopyranosyl ring I of aminoglycosides. Chemical modifications were guided by measuring interactions between the compounds synthesized and ribosomes harbouring single point mutations in the drug-binding site, resulting in aminoglycosides that interact poorly with the drug-binding pocket of eukaryotic mitochondrial or cytosolic ribosomes. Yet, these compounds largely retain their inhibitory activity for bacterial ribosomes and show antibacterial activity. Our data indicate that 4'-O-substituted aminoglycosides possess increased selectivity towards bacterial ribosomes and little activity for any of the human drug-binding pockets.

Matched MeSH terms: Aminoglycosides/pharmacology*; Aminoglycosides/therapeutic use; Aminoglycosides/chemistry*
Fulltext Antimicrobial susceptibility of clinical isolates of Pseudomonas aeruginosa from a Malaysian Hospital

Pathmanathan SG, Samat NA, Mohamed R

Malays J Med Sci, 2009 Apr;16(2):27-32.
PMID: 22589655 MyJurnal

Ongoing surveillance of Pseudomonas aeruginosa resistance against antimicrobial agents is fundamental to monitor trends in susceptibility patterns and to appropriately guide clinicians in choosing empirical or directed therapy. The in vitro activity level of eight antimicrobial drugs was assessed against 97 clinical isolates of P. aeruginosa collected consecutively for three months in 2007 from a Malaysian hospital. Antimicrobial susceptibility was determined using the E-test method in addition to the hospital's routine diagnostic testing by the disk diffusion method. Respiratory and wound swab isolates were the most frequently encountered isolates. The E-test and disk diffusion methods showed high concordance in determining the in vitro activity of the antimicrobial agents against the E isolates. Piperacillin-tazobactam was the most active antimicrobial agent with 91.8% susceptibility, followed by the aminoglycosides (amikacin, 86.6% and gentamicin, 84.5%), the quinolone (ciprofloxacin, 83.5%) and the beta-lactams (cefepime, 80.4%, ceftazidime, 80.4%, imipenem, 79.4% and meropenem, 77.3%). Incidence of multidrug resistance was 19.6% (19 out of 97 isolates). Periodic antibiotic resistance surveillance is fundamental to monitor changes in susceptibility patterns in a hospital setting.

Study site: Hospital Kuala Lumpur

Matched MeSH terms: Aminoglycosides
High-level aminoglycoside resistance and virulence characteristics among Enterococci isolated from recreational beaches in Malaysia

Dada AC, Ahmad A, Usup G, Heng LY, Hamid R

Environ Monit Assess, 2013 Sep;185(9):7427-43.
PMID: 23417753 DOI: 10.1007/s10661-013-3110-x

We report the first study on the occurrence of high-level aminoglycoside-resistant (HLAR) Enterococci in coastal bathing waters and beach sand in Malaysia. None of the encountered isolates were resistant to high levels of gentamicin (500 μg/mL). However, high-level resistance to kanamycin (2,000 μg/mL) was observed in 14.2 % of tested isolates, the highest proportions observed being among beach sand isolates. High-level resistance to kanamycin was higher among Enterococcus faecalis and Enterococcus faecium than Enterococcus spp. Chi-square analysis showed no significant association between responses to tested antibiotics and the species allocation or source of isolation of all tested Enterococci. The species classification of encountered Enterococci resistance to vancomycin was highest among Enterococcus spp. (5.89 %) followed by E. faecium (4.785) and least among E. faecalis. A total of 160 isolates were also tested for virulence characteristics. On the whole, caseinase production was profoundly highest (15.01 %) while the least prevalent virulence characteristic observed among tested beach Enterococci was haemolysis of rabbit blood (3.65 %). A strong association was observed between the source of isolation and responses for each of caseinase (C = 0.47, V = 0.53) and slime (C = 0.50, V = 0.58) assays. Analysis of obtained spearman's coefficient showed a strong correlation between caseinase and each of the slime production (p = 0.04), gelatinase (p = 0.0035) and haemolytic activity on horse blood (p = 0.004), respectively. Suggestively, these are the main virulent characteristics of the studied beach Enterococci. Our findings suggest that recreational beaches may contribute to the dissemination of Enterococci with HLAR and virulence characteristics.

Matched MeSH terms: Aminoglycosides/toxicity*
Low prevalence of vancomycin- and bifunctional aminoglycoside-resistant enterococci isolated from poultry farms in Malaysia

Chan YY, Abd Nasir MH, Yahaya MA, Salleh NM, Md Dan AD, Musa AM, et al.

Int J Food Microbiol, 2008 Feb 29;122(1-2):221-6.
PMID: 18187222 DOI: 10.1016/j.ijfoodmicro.2007.11.063

A total of 225 samples from poultry farms and the surrounding environment were screened for vancomycin-resistant enterococci (VRE) and bifunctional aminoglycoside-resistant enterococci using conventional microbiological tests and a nanoplex polymerase chain reaction (PCR) assay. Three (1.3%) of the samples were found to contain vancomycin-resistant isolates (MIC>256 microg/mL) that had a vanA genotype. The three vanA positive VRE isolates were identified as different species. Only one isolate (Enterococcus faecium F 4/13_54) was sensitive to teicoplanin (MIC<0. 12-0.35 microg/mL); the other two VRE (E. faecalis A 21_35 and E. gallinarum F 5/10_1) were resistant to teicoplanin (MIC 3.6-->16 microg/mL). The vanC genotype was observed in nine (4%) of the samples collected. High-level gentamicin-resistant (HLGR) enterococci (with MIC ranging between 100 and 500 microg/mL) were detected in 44 samples. However, only 40 of these were found to possess the aac(6')-aph(2'') gene. The overall prevalence of VRE among the samples from the poultry farms and environment was 5.3%, but the prevalence of the clinically significant vanA VRE was 1.3%, and the prevalence of bifunctional aminoglycoside-resistant enterococci was slightly higher, at 19.5%.

Matched MeSH terms: Aminoglycosides/pharmacology*
Detection of methicillin- and aminoglycoside-resistant genes and simultaneous identification of S. aureus using triplex real-time PCR Taqman assay

Sabet NS, Subramaniam G, Navaratnam P, Sekaran SD

J Microbiol Methods, 2007 Jan;68(1):157-62.
PMID: 16935372

In this study we describe a triplex real-time PCR assay that enables the identification of S. aureus and detection of two important antibiotic resistant genes simultaneously using real-time PCR technology in a single assay. In this triplex real-time PCR assay, the mecA (methicillin resistant), femA (species specific S. aureus) and aacA-aphD (aminoglycoside resistant) genes were detected in a single test using dual-labeled Taqman probes. The assay gives simultaneous information for the identification of S. aureus and detection of methicillin and aminoglycoside resistance in staphylococcal isolates. 152 clinical isolates were subjected to this triplex real-time PCR assay. The results of the triplex real-time PCR assay correlated with the results of the phenotypic antibiotic susceptibility testing. The results obtained from triplex real-time PCR assay shows that the primer and probe sets were specific for the identification of S. aureus and were able to detect methicillin- and aminoglycoside-resistant genes. The entire assay can be performed within 3 h which is a very rapid method that can give simultaneous information for the identification of S. aureus and antibiotic resistance pattern of a staphylococcal isolate. The application of this rapid method in microbiology laboratories would be a valuable tool for the rapid identification of the S. aureus isolates and determination of their antibiotic resistance pattern with regards to methicillin and aminoglycosides.

Matched MeSH terms: Aminoglycosides/pharmacology*
Extra-intestinal non-typhoidal Salmonella infections in children

Lee WS, Puthucheary SD, Parasakthi N

Ann Trop Paediatr, 2000 Jun;20(2):125-9.
PMID: 10945063

Extra-intestinal non-typhoidal Salmonella (NTS) infections are uncommon in developed countries but common in developing ones. The risk factors, clinical features and outcome of children admitted to the Department of Paediatrics, University of Malaya Medical Center, Kuala Lumpur from 1978 to 1998 with extra-intestinal NTS infections were reviewed. All positive cultures of NTS, blood, cerebrospinal fluid, urine, synovial, pericardial and other body secretions (except stools), were included. Of the 98 cases reviewed, 56 were boys and 42 girls. The mean age was 2.1 years (range: newborn to 14 years). Twenty-seven children were severely immunocompromised and 21 had underlying chronic medical disorders. Bacteraemia was the most commonly detected type of infection and meningitis the commonest focal infection. The overall mortality rate was 15%. An immunocompromised state or underlying chronic medical disorder was associated with increased mortality. The three serotypes most commonly isolated were S. enteritidis, S. paratyphi B and S. typhimurium. Most isolates were sensitive to antibiotics commonly used in salmonellosis.

Matched MeSH terms: Aminoglycosides/therapeutic use
In vivo assessment of reversing aminoglycoside antibiotics nephrotoxicity using Jatropha mollissima crude extract

Iqbal MO, Yahya EB

Tissue Cell, 2021 Oct;72:101525.
PMID: 33780659 DOI: 10.1016/j.tice.2021.101525

Aminoglycoside antibiotics are widely employed clinically due to their powerful bactericidal activities, less bacterial resistance compared to beta lactam group and low cost. However, their use has been limited in recent years due to their potential induction of nephrotoxicity. Here we investigate the possibility of reversing nephrotoxicity caused by gentamicin in rat models by using ethanolic crude extract of the medicinal plant Jatropha Mollissima. Nephrotoxic male Wistar rats was obtained by gentamicin antibiotic, which then treated with two doses of J. mollissima crude extract for 3 weeks with monitoring their parameter in weekly base. Our results indicate that J. mollissima crude extract at both doses has strong protection ability against gentamicin nephrotoxicity, most of tested parameters backed to normal values after few days from the administration of the crude extract, which could be due to the antagonized the biochemical action of gentamicin on the proximal tubules of the kidney. The results of histopathologic analysis showed observable improvement in J. mollissima treated groups compared with untreated groups. Our findings suggests the J. mollissima has exceptional nephron protection potentials able to reverse the nephrotoxicity caused by gentamicin antibiotic.

Matched MeSH terms: Aminoglycosides/toxicity*
Fulltext Diverse and abundant multi-drug resistant E. coli in Matang mangrove estuaries, Malaysia

Ghaderpour A, Ho WS, Chew LL, Bong CW, Chong VC, Thong KL, et al.

Front Microbiol, 2015;6:977.
PMID: 26483759 DOI: 10.3389/fmicb.2015.00977

E.coli, an important vector distributing antimicrobial resistance in the environment, was found to be multi-drug resistant, abundant, and genetically diverse in the Matang mangrove estuaries, Malaysia. One-third (34%) of the estuarine E. coli was multi-drug resistant. The highest antibiotic resistance prevalence was observed for aminoglycosides (83%) and beta-lactams (37%). Phylogenetic groups A and B1, being the most predominant E. coli, demonstrated the highest antibiotic resistant level and prevalence of integrons (integron I, 21%; integron II, 3%). Detection of phylogenetic group B23 downstream of fishing villages indicates human fecal contamination as a source of E. coli pollution. Enteroaggregative E. coli (1%) were also detected immediately downstream of the fishing village. The results indicated multi-drug resistance among E. coli circulating in Matang estuaries, which could be reflective of anthropogenic activities and aggravated by bacterial and antibiotic discharges from village lack of a sewerage system, aquaculture farms and upstream animal husbandry.

Matched MeSH terms: Aminoglycosides
Fulltext Post meningitic sensori-neural hearing loss in children--alterations in hearing level

Yeat SW, Mukari SZ, Said H, Motilal R

Med J Malaysia, 1997 Sep;52(3):285-90.
PMID: 10968099

Post meningitic sensori-neural hearing loss was studied in forty new cases of bacterial meningitis and ten cases of viral meningitis treated at the Pediatric Institute, Kuala Lumpur Hospital from April 1991 to March 1992. Hearing assessment at 2 weeks, 3 months and 6 months following the diagnosis of meningitis using Brain Stem Evoked Response Audiometry showed that hearing loss was prevalent only in patients with bacterial meningitis. Hearing loss was detected in 32.5% of these patients during the acute phase of the disease, 22.8% after 3 months and 24.2% after 6 months. In 63.6% of the affected cases, hearing loss was bilateral. In 61.5% of the patients who had hearing loss during the acute phase of the disease, it was permanent, 16.7% had either partial or complete recovery and, 15.4% had deterioration in hearing level. In 2 cases the subsequent hearing level was unknown. The risk of developing sensori neural hearing loss was found to be significantly higher in patients who developed other neurological sequelae. The study highlights the importance of performing repeated hearing assessment in children with bacterial meningitis and the difficulty in appropriate selection of hearing aids in the early stages.

Matched MeSH terms: Aminoglycosides
Risks and burdens of third-generation cephalosporin resistant Enterobacteriaceae in neonatal sepsis

Thatrimontrichai A, Premprat N, Janjindamai W, Dissaneevate S, Maneenil G

Trop Biomed, 2020 Sep 01;37(3):663-670.
PMID: 33612780 DOI: 10.47665/tb.37.3.663

Third-generation cephalosporin resistant Enterobacteriaceae (TCRE) is a global concern especially in neonatal sepsis. We performed a secondary data analysis in a Thai neonatal intensive care unit to identify the risk factors for acquisition of TCRE sepsis and mortality of Enterobacteriaceae sepsis between 1991 and 2017. Multivariate logistic and Cox proportional regression were used for analysis. Numbers of neonates with TCRE and nonTCRE sepsis were 100 and 41 patients, respectively. Medians (interquartile ranges) of gestational age, birthweight, onset of sepsis and total hospital stay of neonates with Enterobacteriaceae sepsis were 32 (28, 38) weeks, 1670 (1025, 2750) grams, 11 (6, 25) days and 41 (22, 74) days, respectively. Univariate and multivariate analysis, neonates with TCRE sepsis were more likely to have birth asphyxia (adjusted odds ratio [aOR] = 2.6; 95% confidence interval [CI] 1.1-6.0; p = 0.02) and history of aminoglycoside exposure (aOR = 2.9; 95% CI 1.3- 6.7; p = 0.01). In-hospital case fatality rate from Enterobacteriaceae sepsis was 26% (36/141). In Cox regression, neonates with TCRE sepsis was not an independent risk of non-survivors, but septic shock (adjusted hazard ratio = 9.9; 95% CI 5.0-19.7, p < 0.001) increased 30-day mortality in the final model. Asphyxia and previous aminoglycoside consumption were risks of acquisition for neonatal TCRE sepsis while the burden was not a significant difference. Infection prevention and control must be strictly implemented in high multidrug-resistant area.

Matched MeSH terms: Aminoglycosides
Fulltext Enterobacter gergoviae peritonitis in a patient on chronic ambulatory peritoneal dialysis - first reported case

Anna Misya’il Abdul Rashid, Lim, Christopher Thiam Seong

Malaysian Journal of Medicine and Health Sciences, 2017;13(2):67-69.
MyJurnal

Enterobacter gergoviae is a gram negative rod-shaped opportunistic organism reported to cause urinary and respiratory tract infections, but peritonitis caused by this organism is unknown. We report a case of 50-year-old patient on peritoneal dialysis (PD) presented with Enterobacter gergoviae peritonitis with septic shock. Despite Intraperitoneal (IP) cloxacillin 250mg qid and IP ceftazidime 1gram q24h and subsequent escalation with IP amikacin 2mg/kg q24h and IP vancomycin 15mg/kg q24h within the next 48 hours, his peritonitis remained refractory and required catheter removal. Although Enterobacter gergoviae is naturally sensitive to aminoglycosides, carbapenems and quinolones, it reacts differently to the beta lactam antibiotics. Their resistance to third-generation cephalosporins is fast emerging and treatment with third-generation cephalosporins may cause AmpC-overproducing mutants. The majority of
Enterobacteriaceae, including Extended-spectrum beta-lactamases producers, remain susceptible to carbapenems. Our report provides an unfavourable course of E. gergoviae peritonitis likely due to acquired secondary drug resistance during the therapy period.

Matched MeSH terms: Aminoglycosides

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