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A physiological approach to renal clearance: From premature neonates to adults

Holford N, O'Hanlon CJ, Allegaert K, Anderson B, Falcão A, Simon N, et al.

Br J Clin Pharmacol, 2024 Apr;90(4):1066-1080.
PMID: 38031322 DOI: 10.1111/bcp.15978

AIMS: We propose using glomerular filtration rate (GFR) as the physiological basis for distinguishing components of renal clearance.
METHODS: Gentamicin, amikacin and vancomycin are thought to be predominantly excreted by the kidneys. A mixed-effects joint model of the pharmacokinetics of these drugs was developed, with a wide dispersion of weight, age and serum creatinine. A dataset created from 18 sources resulted in 27,338 drug concentrations from 9,901 patients. Body size and composition, maturation and renal function were used to describe differences in drug clearance and volume of distribution.
RESULTS: This study demonstrates that GFR is a predictor of two distinct components of renal elimination clearance: (1) GFR clearance associated with normal GFR and (2) non-GFR clearance not associated with normal GFR. All three drugs had GFR clearance estimated as a drug-specific percentage of normal GFR (gentamicin 39%, amikacin 90% and vancomycin 57%). The total clearance (sum of GFR and non-GFR clearance), standardized to 70 kg total body mass, 176 cm, male, renal function 1, was 5.58 L/h (95% confidence interval [CI] 5.50-5.69) (gentamicin), 7.77 L/h (95% CI 7.26-8.19) (amikacin) and 4.70 L/h (95% CI 4.61-4.80) (vancomycin).
CONCLUSIONS: GFR provides a physiological basis for renal drug elimination. It has been used to distinguish two elimination components. This physiological approach has been applied to describe clearance and volume of distribution from premature neonates to elderly adults with a wide dispersion of size, body composition and renal function. Dose individualization has been implemented using target concentration intervention.

Matched MeSH terms: Gentamicins/pharmacokinetics
Identification and mechanism determination of the efflux pump subunit amrB gene mutations linked to gentamicin susceptibility in clinical Burkholderia pseudomallei from Malaysian Borneo

Hussin A, Nathan S, Shahidan MA, Nor Rahim MY, Zainun MY, Khairuddin NAN, et al.

Mol Genet Genomics, 2024 Feb 21;299(1):12.
PMID: 38381232 DOI: 10.1007/s00438-024-02105-w

The bacterium Burkholderia pseudomallei is typically resistant to gentamicin but rare susceptible strains have been isolated in certain regions, such as Thailand and Sarawak, Malaysia. Recently, several amino acid substitutions have been reported in the amrB gene (a subunit of the amrAB-oprA efflux pump gene) that confer gentamicin susceptibility. However, information regarding the mechanism of the substitutions conferring the susceptibility is lacking. To understand the mechanism of amino acid substitution that confers susceptibility, this study identifies the corresponding mutations in clinical gentamicin-susceptible B. pseudomallei isolates from the Malaysian Borneo (n = 46; Sarawak: 5; Sabah: 41). Three phenotypically confirmed gentamicin-susceptible (GENs) strains from Sarawak, Malaysia, were screened for mutations in the amrB gene using gene sequences of gentamicin-resistant (GENr) strains (QEH 56, QEH 57, QEH20, and QEH26) and publicly available sequences (AF072887.1 and BX571965.1) as the comparator. The effect of missense mutations on the stability of the AmrB protein was determined by calculating the average energy change value (ΔΔG). Mutagenesis analysis identified a polymorphism-associated mutation, g.1056 T > G, a possible susceptible-associated in-frame deletion, Delta V412, and a previously confirmed susceptible-associated amino acid substitution, T368R, in each of the three GENs isolates. The contribution of Delta V412 needs further confirmation by experimental mutagenesis analysis. The mechanism by which T368R confers susceptibility, as elucidated by in silico mutagenesis analysis using AmrB-modeled protein structures, is proposed to be due to the location of T368R in a highly conserved region, rather than destabilization of the AmrB protein structure.

Matched MeSH terms: Gentamicins/pharmacology
Pharmaceutical Development of Intraperitoneal Arachis hypogaea as a Renal Protective Agent

Gul A, Khan H, Shah SI, Alsharif KF, Qahl SH, Rehman IU, et al.

Front Biosci (Landmark Ed), 2023 Jan 17;28(1):14.
PMID: 36722262 DOI: 10.31083/j.fbl2801014

BACKGROUND: Kidneys are among the vital organs of the human body; therefore, damage from any exogenous/endogenous agent may put human life at risk. Arachis hypogaea (AH) contains different free radical scavenging flavonoids, stilbenes, and tannins. This research aimed to elucidate the possible nephroprotective mechanism of AH methanolic crude extract (AHcr) and n-hexane oil fraction (AHO) against gentamycin-induced nephrotoxicity.
METHODS: After the extraction of the crude oil of the plant, they were tested against a Gentamycin (GM)-treated group of Swiss Albino mice for their nephroprotective action. Animals were divided into six (6) equal groups with five (5) animals in each group. These groups were: control group (0.5 mL normal saline via intraperitoneal -i.p), gentamycin group (gentamycin 100 mg/kg i.p), Silymarin + gentamycin group (Silymarin 50 mg/kg and gentamycin 100 mg/kg i.p), plant extract (AHcr1) and gentamycin group (AHcr1 250 mg/kg and gentamycin 100 mg/kg i.p), AHcr2 + gentamycin group (AHcr2; 500 mg/kg and gentamycin 100 mg/kg i.p) and the hexane oil fraction (AHO) + gentamycin (AHO 1 mL/kg and GM 100 mg/kg i.p). After completion of doses, animals were sacrificed for the collection of blood to further investigate biochemical changes and histopathological changes in kidney tissues.
RESULTS: Serum creatinine, urea, and blood urea nitrogen significantly increased (p < 0.001) in the gentamycin-treated group as compared to the control group. The elevated level of serum creatinine, urea, and blood urea nitrogen was decreased significantly (p < 0.001) in groups treated with AHcr and AHO compared to the gentamycin group. Similarly, the histopathological study of kidney tissues from the gentamycin group showed tubular necrosis, vacuolation, and fibrosis.
CONCLUSIONS: The effect of crude extract and hexane soluble fraction of AH caused a significant reversal of gentamycin-induced nephrotoxicity.

Matched MeSH terms: Gentamicins
Mutations in atpG2 may confer resistance to gentamicin in Listeria monocytogenes

Ng JML, Ngeow YF, Saw SH, Ng HF, Zin T

J Med Microbiol, 2022 Dec;71(12).
PMID: 36748567 DOI: 10.1099/jmm.0.001618

Introduction Listeriosis, a foodborne infection caused by Listeria monocytogenes, could lead to febrile listerial gastroenteritis and a more invasive form which is often associated with a high mortality and hospitalisation rate. Gentamicin, used as an adjunct therapy with ampicillin, remains the treatment of choice for this life-threatening and invasive infection.Gap statement Nevertheless, there is little data on gentamicin resistance determinants in L. monocytogenes.Aim In this study, we selected and characterised B2b, a gentamicin-resistant mutant derived from L. monocytogenes ATCC 19115 to determine the target(s) of resistance in L. monocytogenes after exposure to gentamicin.Methodology Whole-genome sequencing was carried out to identify the mutation site(s) and possible mechanism(s) of resistance. The mutant was characterised using antimicrobial susceptibility testing and PCR. For biological verifications, complementation and allelic exchange mutagenesis were carried out.Results We found that the gentamicin resistance in B2b was caused by a 10 bp deletion in atpG2 which encodes a gamma subunit of the ATP synthase in L. monocytogenes. Using atpG2 PCR, various other mutations were identified in other gentamicin resistant mutants derived from ATCC 19115. In addition, the mutation from B2b, when introduced into L. ivanovii, also caused gentamicin resistance in this Listeria species.Conclusion Hence, atpG2 mutations appear to be important determinants of gentamicin resistance not only in L. monocytogenes but possibly also in other Listeria species.

Matched MeSH terms: Gentamicins/pharmacology
Fulltext Enterococcus faecalis Endophthalmitis: Clinical Settings, Antibiotic Susceptibility, and Management Outcomes

Chen KJ, Lai CC, Chen HC, Chong YJ, Sun MH, Chen YP, et al.

Microorganisms, 2021 Apr 24;9(5).
PMID: 33923356 DOI: 10.3390/microorganisms9050918

Enterococcus faecalis is known to cause severe acute endophthalmitis and often leads to poor visual outcomes in most ophthalmic infections. This retrospective study is to report the clinical settings, antimicrobial susceptibility patterns, and visual outcome of E. faecalis endophthalmitis at a tertiary referral institution in Taoyuan, Taiwan. E. faecalis endophthalmitis was diagnosed in 37 eyes of 37 patients. Post-cataract surgery was the most common cause (n = 27, 73%), followed by bleb-associated (n = 3, 8%), endogenous (n = 2, 5%), corneal ulcer-related (n = 2, 5%), post-vitrectomy (n = 1, 3%), post-pterygium excision (n = 1, 3%), and trauma (n = 1, 3%). Visual acuities upon presentation ranged from counting fingers to no light perception. Pars plana vitrectomy with intravitreal antibiotics were performed in 23 eyes (76%) as primary or secondary treatment. All isolates (37/37, 100%) were sensitive to vancomycin, penicillin, ampicillin, and teicoplanin. Six of 22 eyes (27%) were resistant to high-level gentamicin (minimum inhibitory concentration > 500 mg/L). Final visual acuities were better than 20/400 in 11 eyes (30%), 5/200 to hand motions in 4 eyes (11%), and light perception to no light perception in 22 eyes (59%). Three eyes were treated with evisceration. Compared with non-cataract subgroups, the post-cataract subgroup showed a significant difference of better visual prognosis (p = 0.016).

Matched MeSH terms: Gentamicins
Liver functions in combined models of the gentamicin induced nephrotoxicity and metabolic syndrome induced by high fat or fructose diets: a comparative study

Ibraheem ZO, Farhan SS, Al Sumaidaee A, Al Sufi L, Bashir A, Balwa A, et al.

Toxicol Res, 2021 Apr;37(2):221-235.
PMID: 33868979 DOI: 10.1007/s43188-020-00059-w

Metabolic syndrome is one of the major risk factors that lead to various serious complications like cardiovascular abnormalities, hyperlipidemia and diabetes. Its co-incidence with other organs dysfunction results in further deterioration of the condition or precipitation of other dysfunctions. This study aimed at studying the changes in the hepatic functions after the co-incidence of the high fat or fructose diets induced metabolic syndrome along with the gentamicin induced nephrotoxicity. Briefly, six groups of male Sprague Daley rats (n = 10-12) were fed with different feeding protocols; viz; standard rodent's chow, an experimental high fat or high fructose diets feedings. For each, two groups were allocated that one of them was injected with normal saline and the other with 80 mg/kg/day I.P gentamicin during the last 24 days of the feeding period. The rats were monitored for changes in the metabolic data, glycemic control, lipid profile, renal and hepatic functions, oxidative stress and the inflammatory response. The study revealed stronger hepatic changes in the renal failure groups fed with the high fat diet rather than that in the groups fed with the high fructose diet. Although, the latter experienced a stronger deterioration in the glycemic control. The study suggests that the incidence of the hepatic changes is more linked to the incidence of the deterioration in the lipids profile that was observed after the high fat diet feeding. Overall, the co-incidence of the high fat diet induced metabolic syndrome along with the renal failure constitutes a risk factor for the hepatic dysfunction.

Matched MeSH terms: Gentamicins
Fulltext Phenotypic Antimicrobial Susceptibility of Escherichia coli from Raw Meats, Ready-to-Eat Meats, and Their Related Samples in One Health Context

Adzitey F, Huda N, Shariff AHM

Microorganisms, 2021 Feb 05;9(2).
PMID: 33562804 DOI: 10.3390/microorganisms9020326

Meat is an important food source that can provide a significant amount of protein for human development. The occurrence of bacteria that are resistant to antimicrobials in meat poses a public health risk. This study evaluated the occurrence and antimicrobial resistance of E. coli (Escherichia coli) isolated from raw meats, ready-to-eat (RTE) meats and their related samples in Ghana. E. coli was isolated using the USA-FDA Bacteriological Analytical Manual and phenotypic antimicrobial susceptibility test was performed by the disk diffusion method. Of the 200 examined meats and their related samples, 38% were positive for E. coli. Notably, E. coli was highest in raw beef (80%) and lowest in RTE pork (0%). The 45 E. coli isolates were resistant ≥ 50% to amoxicillin, trimethoprim and tetracycline. They were susceptible to azithromycin (87.1%), chloramphenicol (81.3%), imipenem (74.8%), gentamicin (72.0%) and ciprofloxacin (69.5%). A relatively high intermediate resistance of 33.0% was observed for ceftriaxone. E. coli from raw meats, RTE meats, hands of meat sellers and working tools showed some differences and similarities in their phenotypic antimicrobial resistance patterns. Half (51.1%) of the E. coli isolates exhibited multidrug resistance. The E. coli isolates showed twenty-two different resistant patterns, with a multiple antibiotic resistance index of 0.0 to 0.7. The resistant pattern amoxicillin (A, n = 6 isolates) and amoxicillin-trimethoprim (A-TM, n = 6 isolates) were the most common. This study documents that raw meats, RTE meats and their related samples in Ghana are potential sources of antimicrobial-resistant E. coli and pose a risk for the transfer of resistant bacteria to the food chain, environment and humans.

Matched MeSH terms: Gentamicins
Fulltext High Levels of Antibiotic Resistance in Isolates From Diseased Livestock

Haulisah NA, Hassan L, Bejo SK, Jajere SM, Ahmad NI

Front Vet Sci, 2021;8:652351.
PMID: 33869326 DOI: 10.3389/fvets.2021.652351

Overuse of antimicrobials in livestock health and production beyond therapeutic needs has been highlighted in recent years as one of the major risk factors for the acceleration of antimicrobial resistance (AMR) of bacteria in both humans and animals. While there is an abundance of reports on AMR in clinical isolates from humans, information regarding the patterns of resistance in clinical isolates from animals is scarce. Hence, a situational analysis of AMR based on clinical isolates from a veterinary diagnostic laboratory was performed to examine the extent and patterns of resistance demonstrated by isolates from diseased food animals. Between 2015 and 2017, 241 cases of diseased livestock were received. Clinical specimens from ruminants (cattle, goats and sheep), and non-ruminants (pigs and chicken) were received for culture and sensitivity testing. A total of 701 isolates were recovered from these specimens. From ruminants, Escherichia coli (n = 77, 19.3%) predominated, followed by Staphylococcus aureus (n = 73, 18.3%). Antibiotic sensitivity testing (AST) revealed that E. coli resistance was highest for penicillin, streptomycin, and neomycin (77-93%). In addition, S. aureus was highly resistant to neomycin, followed by streptomycin and ampicillin (68-82%). More than 67% of E. coli isolates were multi-drug resistant (MDR) and only 2.6% were susceptible to all the tested antibiotics. Similarly, 65.6% of S. aureus isolates were MDR and only 5.5% were susceptible to all tested antibiotics. From non-ruminants, a total of 301 isolates were recovered. Escherichia coli (n = 108, 35.9%) and Staphylococcus spp. (n = 27, 9%) were the most frequent isolates obtained. For E. coli, the highest resistance was against amoxicillin, erythromycin, tetracycline, and neomycin (95-100%). Staphylococcus spp. had a high level of resistance to streptomycin, trimethoprim/sulfamethoxazole, tetracycline and gentamicin (80-100%). The MDR levels of E. coli and Staphylococcus spp. isolates from non-ruminants were 72.2 and 74.1%, respectively. Significantly higher resistance level were observed among isolates from non-ruminants compared to ruminants for tetracycline, amoxicillin, enrofloxacin, and trimethoprim/sulfamethoxazole.

Matched MeSH terms: Gentamicins
Fulltext Antibacterial-Integrated Collagen Wound Dressing for Diabetes-Related Foot Ulcers: An Evidence-Based Review of Clinical Studies

N Amirrah I, Mohd Razip Wee MF, Tabata Y, Bt Hj Idrus R, Nordin A, Fauzi MB

Polymers (Basel), 2020 Sep 22;12(9).
PMID: 32972012 DOI: 10.3390/polym12092168

Diabetic foot ulcer (DFU) is a chronic wound frequently delayed from severe infection. Wound dressing provides an essential barrier between the ulcer and the external environment. This review aimed to analyse the effectiveness of antibacterial collagen-based dressing for DFU treatment in a clinical setting. An electronic search in four databases, namely, Scopus, PubMed, Ovid MEDLINE(R), and ISI Web of Science, was performed to obtain relevant articles published within the last ten years. The published studies were included if they reported evidence of (1) collagen-based antibacterial dressing or (2) wound healing for diabetic ulcers, and (3) were written in English. Both randomised and non-randomised clinical trials were included. The search for relevant clinical studies (n) identified eight related references discussing the effectiveness of collagen-based antibacterial wound dressings for DFU comprising collagen impregnated with polyhexamethylene biguanide (n = 2), gentamicin (n = 3), combined-cellulose and silver (n = 1), gentian violet/methylene blue mixed (n = 1), and silver (n = 1). The clinical data were limited by small sample sizes and multiple aetiologies of chronic wounds. The evidence was not robust enough for a conclusive statement, although most of the studies reported positive outcomes for the use of collagen dressings loaded with antibacterial properties for DFU wound healing. This study emphasises the importance of having standardised clinical trials, larger sample sizes, and accurate reporting for reliable statistical evidence confirming DFU treatment efficiency.

Matched MeSH terms: Gentamicins
Fulltext Improving the appropriateness of therapeutic drug monitoring sampling in Hospital Sultanah Nur Zahirah, Kuala Terengganu

Lukman Nul Hakim Md Khairi, Farah Syakirah Ahmad, Aimi Shazana Muhammad Anuar, Nurul Ain Wan Omar, Nurul Najmi Muhammad, Nurulhayati Abd. Jamal, et al.

Q Bulletin, 2020;1(29):28-35.
MyJurnal

Therapeutic drug monitoring (TDM) is a valuable clinical tool in optimisation of drug regimens. However, improper utilisation of TDM may lead to significant resource wastage and expose patients to avoidable trauma, toxicity, therapeutic failure and prolonged hospitalisation. This study aimed to reduce the percentage of inappropriate TDM sampling to our proposed standard of less than 20% within a four-month intervention period. A cross-sectional study was undertaken from January to December 2015 at the inpatient setting of Hospital Sultanah Nur Zahirah. Gentamicin and Vancomycin analytes were studied because these analytes accounted for 69.2% of total samples received in 2014. TDM Monitoring Form was used to collect sampling and dosage information to assess sampling appropriateness. A closed-ended self-administered questionnaire was distributed to a group of medical doctors to assess their knowledge on appropriate Gentamicin and Vancomycin TDM sampling method pre- and post-intervention. Prior to the intervention phase in October to December 2014, 79.4% of TDM were inappropriately sampled. The main contributing factors were inadequate knowledge among medical doctors, lack of sampling reminders for new TDM requests, and misunderstanding on sampling information for repeated TDM requests. 60-minute face-to-face educational sessions on TDM sampling method were conducted specifically for staff at the General Medical and Paediatric Departments, and two continuing medical education (CME) slots were held at the hospital level. Guidelines on TDM sampling was initiated and laminated copies were distributed to all wards. Implementation of TDM Alert System which consisted of digital reminders and physical stickers was also introduced. The interventions were able to reduce the inappropriate sampling percentage from 79.4% to 41.8% post-intervention, and to 19.1% in the recent monitoring phase of January until June 2019. Continuous close monitoring and sustainable implementation of the measures are vital as TDM sampling appropriateness may affect clinical interpretation of the results.

Matched MeSH terms: Gentamicins
Fulltext Antibiotic susceptibility of staphylococcus epidermidis among undergraduate students in malaysia public university health campus

Abu Zarrin, A.M., Nor Munirah, M.A., Mohammad Izwan, E.O., Abdullah, A.S., Hanani, A.Y.

Medicine & Health, 2020;15(1):166-176.
MyJurnal

Staphylococcus epidermidis (S. epidermidis) menjadi salah satu keprihatinan utama dalam pengurusan hospital berikutan kebolehannya menyebabkan jangkitan perolehan hospital terutamanya daripada alatan perubatan yang tercemar. Pengurusan jangkitan S. epidermidis semakin mencabar dengan peningkatan kes kerintangan terhadap antibiotik sejak kebelakangan ini. Laporan terhad mengenai kerintangan terhadap antibiotik oleh S. epidermidis di kalangan kumpulan komuniti yang sihat meninggalkan satu persoalan mengenai tahap penyebaran bakteria rintang antibiotik di kalangan komuniti. Oleh itu, kajian ini bertujuan untuk mengenalpasti corak rentan antibiotik oleh S. epidermidis yang dipencilkan daripada pelajar-pelajar sihat di salah satu kampus kesihatan di universiti awam. Sebanyak 96 sampel sapuan telapak tangan telah diambil dan melalui beberapa ujikaji termasuk ujian pengenalpastian secara mikroskopik, biokimia dan juga ujian rentan antiobiotik untuk eryhtromycin, oxacillin, gentamicin, penicillin dan tetracycline menerusi ujian Kirby Bauer. Sejumlah 43 sampel menunjukkan kehadiran S. epidermidis (44.8%), di mana 72.1% daripada jumlah pencilan bakteria ini menunjukkan kerintangan terhadap sekurang-kurangnya satu jenis antibiotik. Tahap kerintangan tertinggi dan terendah masing-masing didapati pada penicillin dan gentamicin. Walaupun tiada perbezaan yang signifikan antara corak rentan antibiotik antara kumpulan jantina, tahap kerintangan antibiotik yang tinggi di kalangan komuniti sihat menunjukkan terdapat keperluan terhadap kajian lanjut kerana penyebaran strain bakteria rintang antibiotik boleh berlaku kepada populasi komuniti lain dengan lebih meluas dan tanpa disedari.

Matched MeSH terms: Gentamicins
Fulltext Paediatric oropharyngeal tularaemia requiring surgical intervention

Nemmour A, Bakri A, Fischer CA, Brand Y

BMJ Case Rep, 2019 Sep 06;12(9).
PMID: 31494583 DOI: 10.1136/bcr-2019-229754

Tularaemia is a rare infectious disease endemic in most European countries caused by the bacterium Francisella tularensis 1 Patients often show acute non-specific symptoms, which causes a delay in diagnosis and proper treatment, potentially resulting in significant morbidities such as deep neck abscess, meningitis, endocarditis and septic shock. The authors present a case of a 5-year old boy with a 4-day history of fever, sore throat and painful cervical lymphadenopathy, whose clinical progression worsened despite being treated with recommended antibiotics as per WHO guidelines once the diagnosis of Tularaemia was confirmed by serologic tests. He developed a parapharyngeal abscess and a persistent left necrotic cervical lymph node, which both were surgically drained and excised, respectively, and an extended course of antibiotic was given. Subsequently, the patient fully recovered from the illness and the follow-up was negative for relapse.

Matched MeSH terms: Gentamicins/therapeutic use
Comparative evaluation of bioburden and sterility of indigenously prepared bone allograft with and without gentamicin

Makker K, Lamba AK, Faraz F, Tandon S, Sheikh Ab Hamid S, Aggarwal K, et al.

Cell Tissue Bank, 2019 Jun;20(2):243-253.
PMID: 30903410 DOI: 10.1007/s10561-019-09763-w

During bone allograft processing, despite stringent donor screening and use of aseptic techniques, microbial invasion may occur due to the porous nature of the graft and cause potentially fatal infections. The aim of the present study was to prepare bone allograft with and without gentamicin and to compare bioburden and sterility in the obtained grafts to evaluate the role of antibiotic in enhancing graft safety. Fifty samples of demineralized freeze-dried bone allograft were prepared from suitable donors according to international standards. Randomly selected 25 samples were placed in 8 mg gentamicin/gram bone solution for 1 h. Packaging and sealing was done to ensure no microbial ingress during transportation. 40 samples were selected for bioburden testing. Remaining 10 were subjected to 25 kGy gamma radiation and tested for sterility. Microbiological evaluation revealed no evidence of colony forming units in all the samples of both the groups (Bioburden = 0). Post-radiation sterility testing also revealed no bacterial colony in the tested samples from both the groups. Favorable results validate the processing protocol while comparable results in both groups indicate no additive benefit of gentamicin addition. Nil bioburden may be used in further studies to determine a lower radiation dose to achieve adequate sterility and minimize the disadvantages of radiation like collagen cross-linking and decreased osteoinductive capacity.

Matched MeSH terms: Gentamicins/therapeutic use*
Fulltext Clinical and Antibacterial Effects of Tualang Honey on Pseudomonas-induced Keratitis in Rabbit Eyes

Punitan R, Sulaiman SA, Hasan HB, Shatriah I

Cureus, 2019 Mar 27;11(3):e4332.
PMID: 31186997 DOI: 10.7759/cureus.4332

Introduction Pseudomonas aeruginosa is a common cause of microbial keratitis that can cause a significant loss of visual acuity. Antibiotics, including fluoroquinolones and aminoglycosides, are clinically effective against Pseudomonas-induced keratitis, but their effectiveness has been conspicuously reduced as resistant pathogens have become more potent. This study sought to evaluate the clinical and antibacterial effects of tualang honey as an alternative therapeutic agent against Pseudomonas-induced keratitis. Methods We conducted a randomized control trial in which 30 rabbits were injected intrastromally with 1,000 colony-forming units (CFU) of Pseudomonas aeruginosa in the right eye of each rabbit (n = 30). The rabbits were then randomized into three groups of 10 rabbits each. Group A was treated with topical gentamicin 0.3%, group B was treated with topical tualang honey 30%, and group C received both treatments. The specified treatments were administered every two hours from 24 to 48 hours post injection, and subsequently every four hours for six days. Clinical examinations were performed on days one, two, three, five, and seven, and the mean results of slit lamp examinations (SLEs) were documented. On day seven after pseudomonas induction, the rabbits were euthanized and their corneas were harvested to determine the median CFU per cornea. Results There were no statistically significant differences (p > 0.05) in mean SLE scores (p = 0.209) or median CFU values (p = 0.820) between the three groups. Conclusion Topical gentamicin, topical tualang honey, and the combination of the two all showed similar clinical and antimicrobial effects in treating Pseudomonas-induced keratitis in rabbits. These findings should be verified in further studies with larger sample sizes and the addition of a control group.

Matched MeSH terms: Gentamicins
Fulltext Melioidosis: an unusual cause of infective endocarditis: a case report

Sia T, Podin Y, Chuah TB, Wong JS

Eur Heart J Case Rep, 2018 Jun;2(2):yty055.
PMID: 31020134 DOI: 10.1093/ehjcr/yty055

Introduction: As a causal organism in infective endocarditis, Burkholderia pseudomallei is rare. Burkholderia pseudomallei is intrinsically resistant to aminoglycosides but a gentamicin-susceptible strain was discovered in Sarawak, Malaysian Borneo in 2010. We report the first occurrence of infective endocarditis due to the gentamicin-susceptible strain of B. pseudomallei.
Case presentation: A 29-year-old man presented with pneumonia and melioidosis septicaemia. His condition was complicated with infective endocarditis and septic emboli to the brain. Despite difficulties in reaching a diagnosis, the patient was successfully treated using intravenous gentamicin and ceftazidime and was discharged well.
Discussion: The role of gentamicin in the treatment of the gentamicin-susceptible strain of B. pseudomallei remains unclear.

Matched MeSH terms: Gentamicins
Fulltext Encapsulation and Characterization of Gentamicin Sulfate in the Collagen Added Electrospun Nanofibers for Skin Regeneration

Abdul Khodir WKW, Abdul Razak AH, Ng MH, Guarino V, Susanti D

J Funct Biomater, 2018 May 18;9(2).
PMID: 29783681 DOI: 10.3390/jfb9020036

In the current practice, the clinical use of conventional skin substitutes such as autogenous skin grafts have shown several problems, mainly with respect to limited sources and donor site morbidity. In order to overcome these limitations, the use of smart synthetic biomaterials is tremendously diffusing as skin substitutes. Indeed, engineered skin grafts or analogues frequently play an important role in the treatment of chronic skin wounds, by supporting the regeneration of newly formed tissue, and at the same time preventing infections during the long-term treatment. In this context, natural proteins such as collagen-natively present in the skin tissue-embedded in synthetic polymers (i.e., PCL) allow the development of micro-structured matrices able to mimic the functions and to structure of the surrounding extracellular matrix. Moreover, the encapsulation of drugs, such as gentamicin sulfate, also improves the bioactivity of nanofibers, due to the efficient loading and a controlled drug release towards the site of interest. Herein, we have done a preliminary investigation on the capability of gentamicin sulfate, loaded into collagen-added nanofibers, for the controlled release in local infection treatments. Experimental studies have demonstrated that collagen added fibers can be efficaciously used to administrate gentamicin for 72 h without any toxic in vitro response, thus emerging as a valid candidate for the therapeutic treatment of infected wounds.

Matched MeSH terms: Gentamicins
Potential action of Rumex vesicarius (L.) against potassium dichromate and gentamicin induced nephrotoxicity in experimental rats

Subramaniyan V, Shaik S, Bag A, Manavalan G, Chandiran S

Pak J Pharm Sci, 2018 Mar;31(2):509-516.
PMID: 29618442

To determine the ameliorative potential of the active fraction from different extracts of Rumex vesicarius against potassium dichromate and gentamicin induced nephrotoxicity in experimental rats and its possible mechanism of action. Both sex wistar rats were divided into 6 groups (n=6/group) were fed with a control, potassium dichromate and gentamicin supplemented with different extracts at the doses of 200 and 400mg/kg respectively. Oral administration of EERV offered a significant (p<0.01 and p<0.001) dose dependent protection against PD and GN induced nephrotoxicity. Potassium dichromate and gentamicin nephrotoxicity assessed in terms of body weight, kidney weight, creatinine, urea, uric acid, BUN, albumin and total protein. Thus the present study revealed that EERV phytochemical constituents play an important role in protection against kidney damage.

Matched MeSH terms: Gentamicins/adverse effects*
Fulltext Atypical contact lens related corneal ulcer caused by pasteurella multocida

Fatin Hanisah, F., Umi Kalthum, M. N., Rona Asnida, N., Jemaima, C. H.

Journal of Surgical Academia, 2018;8(1):43-46.
MyJurnal

A 55-year-old healthy lady with history of regular contact lens (CL) use presented with 10 days history of
progressive left eye blurring of vision, redness and pain. There was good CL hygiene practiced with no history of
swimming, trauma or contact with domestic pets. Left eye vision was hand movement and right eye was 1/60,
pinhole 6/18. On the left eye, there was a central, oval-shaped corneal infiltrate with an overlying large epithelial
defect and stromal oedema, with significant anterior chamber cells and fibrin. B-mode ultrasound showed no vitritis.
Intensive topical benzylpenicillin 10000iu/ml and topical gentamycin 1.4% hourly, homatropine 2% three times
daily, oral doxycycline and oral ascorbic acid were started. The gram stain results showed gram positive cocci
growth. Her ulcer improved with the treatment and preservative-free dexamethasone 0.1% once daily was
commenced to reduce inflammation and scarring. Interestingly, culture was reported as Pasteurella maltocida, a
gram negative bacilli sensitive to penicillin, and so treatment was continued until the ulcer completely healed. She
had central corneal scarring with best corrected vision of 6/24 in the left eye but was not keen on further surgery to
improve her vision. Although it has not been previously reported, Pasteurella multocida can cause CL related
corneal ulcer with severe anterior chamber inflammation. This diagnosis should be considered even if there is trivial
contact or no history of exposure to domestic animals.

Matched MeSH terms: Gentamicins
Fulltext A rare complication of MRSA lid abscess and orbital abscess following strabismus surgery in a child

Kenneth Teow, K. L., Nor Akmal, B., Jamalia, R., Safinaz, M. K.

Journal of Surgical Academia, 2018;8(1):32-35.
MyJurnal

Strabismus is one of the most common ocular problems affecting the preschool population and the aim of strabismus surgery is to correct abnormal alignment of the eyes. A 5-year-old girl with strabismus underwent an uneventful surgery and was discharged on the same day with topical medications. Two days later, she returned with a painful right lower eyelid swelling, eye discharge and fever which started 1 day post-surgery. She was admitted for intravenous (IV) antibiotic. Symptoms initially improved after 24 hours of treatment, but later she had worsening eyelid swelling. An urgent CT scan of the orbit showed a right lower lid abscess with orbital cellulitis. Subsequently an examination under anaesthesia (EUA) and incision and drainage (I&D) of the lower lid abscess were performed. Culture from the pus grew Community Acquired Methicillin-resistant Staphylococcus aureus (CA-MRSA), sensitive to Vancomycin. At day 2 post I&D she subsequently developed another episode of localised right lower lid swelling. Another EUA was done but showed the lower lid and wound was free of pus. She was later found to have a toxic reaction to topical Gentamicin and hence this medication was stopped. She responded well to treatment and was discharged after completing her IV antibiotics. At 14 months outpatient follow up, she was well and orthophoric in primary gaze. While treating a disease, we should be opened to all possibilities and not to treat with multiple antibiotics once susceptibility is known

Matched MeSH terms: Gentamicins
Fulltext A pilot study to Assess Serum Potassium Levels and Haemolysis in Red Cell Units

Nurimatussolehah Sarijan, Sabariah Md Noor, Tun Maizura Mohd Fathullah, Malina Osman, Zainina Seman

Malaysian Journal of Medicine and Health Sciences, 2018;14(103):1-5.
MyJurnal

Percentage of haemolysis is widely used as a quality parameter to assess red blood cell viability in blood banking. In certain blood banks, serum potassium level is used due to the unavailability of the former test. The relationship between these two tests, however, is still unclear. The objective of this study is to determine the association between haemolysis measured using two different methods for quality control. Methods: A total of forty-four samples of packed red cell in citrate-phosphate-dextrose with optisol were randomly selected from donation drives. Nine millilitres of blood was collected weekly starting from day-2 of storage, followed by day-7, 14, 21, 28, 35 and 42 for assessment of red blood cell haemolysis by measuring serum potassium level and percentage of haemolysis.Results: These two parameters were correlated significantly with a positive moderate linear relationship on day 7, 21 and 28 with r = 0.393, 0.448 and 0.425, respectively and p-values less than 0.01. The linear regression analysis showed there was a significant regression equation which could be used to predict the serum potassium level from the percentage of haemolysis. Conclusion: There were significant increases in the percentage of haemolysis and serum potassium level in the packed red cell units with storage. The serum potassium level would be able to be predicted from the percentage of haemolysis using the regression equations on day 7, 21 and 28. The serum potassium measurement could be used as an alternative test to the percentage of haemolysis before issuing blood.

Matched MeSH terms: Gentamicins

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