Normal skin is the first line of defense in the human body. A burn injury makes the skin susceptible to bacterial infection, thereby delaying wound healing and ultimately leading to sepsis. The chances of biofilm formation are high in burn wounds due to the presence of avascular necrotic tissue. The most common pathogen to cause burn infection and biofilm is Pseudomonas aeruginosa. The purpose of this study was to create a microemulsion (ME) formulation for topical application to treat bacterial burn infection. In the present study, tea tree oil was used as the oil phase, Tween 80 and transcutol were used as surfactants, and water served as the aqueous phase. Pseudo ternary phase diagrams were used to determine the design space. The ranges of components as suggested by the design were chosen, optimization of the microemulsion was performed, and in vitro drug release was assessed. Based on the characterization studies performed, it was found that the microemulsion were formulated properly, and the particle size obtained was within the desired microemulsion range of 10 to 300 nm. The I release study showed that the microemulsion followed an immediate release profile. The formulation was further tested based on its ability to inhibit biofilm formation and bacterial growth. The prepared microemulsion was capable of inhibiting biofilm formation.

Gentamicin (Genta)-induced nephrotoxicity poses a significant clinical challenge due to its detrimental effects on kidney function. Clopidogrel (Clop), an antiplatelet drug known for its ability to prevent blood clots by inhibiting platelet aggregation, also has potential effects on oxidative stress and cell death. This study investigates Clop\'s protective role against Genta-induced nephrotoxicity, emphasizing the importance of the coagulation cascade. The 32 adult male albino rats were randomly assigned to four groups of eight (n = 8). The first group received only the vehicle. Genta was injected intraperitoneally at 100 mg/kg/day for 8 days in the second group. Groups 3 and 4 received oral Clop at 10 and 20 mg/kg/day for 1 week before Genta delivery and throughout the experiment. Renal tissue showed renal function tests, oxidative stress, pro-inflammatory cytokines, apoptotic markers, coagulation profile, and fibrin expression. Clop improved Genta-induced kidney function and histopathology. Clop substantially reduced pro-inflammatory cytokines, oxidative stress indicators, pro-apoptotic proteins, and fibrin protein. Clop also significantly boosted renal tissue anti-inflammatory and anti-apoptotic protein expression. Genta-induced nephrotoxicity involves oxidative stress, apoptosis, and coagulation system activation, according to studies. This study underscores that Genta-induced nephrotoxicity is associated with oxidative stress, apoptosis, and activation of the coagulation system. Clop\'s protective effects on nephrons are attributed to its anticoagulant, antioxidant, anti-inflammatory, and anti-apoptotic properties, presenting it as a promising therapeutic strategy against Genta-induced kidney damage.

It seems that gentamicin\'s toxicity to the liver is caused by reactive oxygen species production. The antioxidant and anti-inflammatory properties of Acacia nilotica extract (AN) have been demonstrated in recent studies. This research focused on how AN\'s extract affected gentamicin-induced liver damage in rats. Twenty-four Wister rats of male type were divided into four groups: first group received saline as a control, second group received AN (5%) for fifteen days, group three received daily intraperitoneal injections of gentamicin (100 mg/kg) for fifteen days, and group four, as mentioned in groups 2 and 3, also received gentamicin injections and AN extraction (5%) for fifteen days. In order to conduct biochemical analysis, serum was extracted. Histopathology, immunohistochemistry analyses for hepatic toxicity were all performed on the collected tissue samples. Serum levels of ALT, AST, total bilirubin, and GGT were all elevated after using gentamicin. The inflammatory cytokines)IL-1, TNF-α and IL-6(, all were increased in gentamycin-injected group. There were showing deformity of bile duct, hepatocellular necrosis and infiltration of inflammatory cells congestion of portal vein, and hepatic sinusoids besides fibrosis of portal area (white arrows), hypertrophy in gentamycin-injected group compared to AN plus gentamycin administered rats. There were upregulation in the immunoreactivity of COX-2, IFNkB and TGF-beta1 (TGF-β1) in gentamycin intoxicated rats. When gentamicin and AN were administered together, hepatic biomarkers, inflammatory cytokines, histological, and immunohistochemical markers were all ameliorated by AN administration.

Published data on the molecular mechanisms underlying antimicrobial resistance in Group B Streptococcus (GBS) isolates from Saudi Arabia are lacking. Here, we aimed to determine the genetic basis of resistance to relevant antibiotics in a collection of GBS clinical isolates (n = 204) recovered from colonized adults or infected patients and expressing serotypes Ia, Ib, II, III, V, and VI. Initial susceptibility testing revealed resistance to tetracycline (76.47%, n = 156/204), erythromycin (36.76%, n = 75/204), clindamycin (25.49%, n = 52/204), levofloxacin (6.37%, n = 13/204), and gentamicin (2.45%, n = 5/204). Primers designed for the detection of known resistance determinants in GBS identified the presence of erm(A), erm(B), mef(A), and/or lsa(C) genes at the origin of resistance to macrolides and/or clindamycin. Of these, erm(B) and erm(A) were associated with the cMLSB (n = 46) and iMLSB (n = 28) phenotypes, respectively, while mef(A) was linked to the M phenotype (n = 1) and lsa(C) was present in isolates with the L phenotype (n = 8). Resistance to tetracycline was mainly mediated by tet(M) alone (n = 112) or in combination with tet(O) (n = 10); the remaining isolates carried tet(O) (n = 29), tet(L) (n = 2), or both (n = 3). Isolates resistant to gentamicin (n = 5) carried aac(6\')-Ie-aph(2\')-Ia, and those exhibiting resistance to levofloxacin (n = 13) had alterations in GyrA and/or ParC. Most isolates with the erm gene (93.24%, n = 69/74) also had the tet gene and were therefore resistant to erythromycin, clindamycin, and tetracycline. Overall, there were no clear associations between serotypes and resistance genotypes except for the presence of erm(B) in serotype Ib isolates. Dissemination of antibiotic resistance genes across different serotypes represents a public health concern that requires further surveillance and appropriate antibiotic use in clinical practice.

BACKGROUND: Otitis externa (OE) is one of the most frequently diagnosed dermatological diseases in dogs, having a multifactorial aetiology. Among the bacterial agents associated with canine OE, Pseudomonas aeruginosa is of special concern owing to its frequent multidrug resistance profile and ability to form biofilms related to the infection\'s chronicity and recurrence.
OBJECTIVE: The main objective of this study was to evaluate and compare the antibiofilm activity of two innovative antimicrobials-an otological gel containing a synthetic antimicrobial peptide and Lavandula angustifolia essential oil-with gentamicin (a conventional antibiotic) using biofilm-producing P. aeruginosa isolates obtained from dogs with OE.
METHODS: The biofilm eradication capacity of gentamicin, otological gel and lavender oil was determined against a collection of 12 P. aeruginosa biofilm-producers among 35 clinical isolates obtained from the ear canals of dogs with OE. Also, the antimicrobial activity of the otological gel against P. aeruginosa biofilms was assessed in an in vitro model of dog cerumen.
RESULTS: Lavender oil showed the best effectiveness after 30 min of contact, eradicating 58.3% (seven of 12) of the isolates, and gentamicin showed full eradication (12 of 12) after 24 h. The otological gel acted more slowly than the lavender oil; yet at 24 h, the antibiofilm capacity of both compounds was similar, with no significant difference between them. It also was found that triglycerides from synthetic cerumen earwax had antipseudomonal activity and, when combined with the otological gel, led to the full eradication of P. aeruginosa.
CONCLUSIONS: The results of this in vitro study indicate that lavender oil and the otological gel may be effective topical treatments for canine OE promoted by P. aeruginosa biofilm-producers, as alternatives to gentamicin.

The increasing numbers of total joint replacements and related implant-associated infections demand solutions, which can provide a high-dose local delivery of antibiotics. Antibiotic-loaded bone cement (ALBC) is an accepted treatment method for infected joint arthroplasties. The mechanical properties of low-dose gentamicin-loaded bone cement (BC) in medium- and high-viscosity versions were compared to unloaded BC using a vacuum mixing system. As an additional control group, manual mixed unloaded BC was used. In a uniaxial compression test, ultimate compressive strength, compressive yield strength, and compression modulus of elasticity, as well as ultimate and yield strain, were determined according to ISO 5833-2022 guidelines. All groups exceeded the minimum compressive strength (70 MPa) specified in the ISO 5833 guidelines. Both ALBC groups showed a similar ultimate compressive and yield strength to the unloaded BC. The results showed that vacuum mixing increased the compression strength of BC. ALBC showed similar compressive strength to their non-antibiotic counterparts when vacuum mixing was performed. Added low-dose gentamicin acted as a plasticizer on bone cement. From a biomechanical point of view, the usage of gentamicin-based ALBC formulations is viable.

(1) Background: Gentamicin is known to be nephrotoxic and ototoxic. Although gentamicin dosage guidelines have been established for preterm and term neonates, reports do show attainment of recommended peak concentrations but toxic gentamicin concentrations are common in this age group. (2) Methods: This was a prospective, observational study conducted in Namibia with 52 neonates. A dose of 5 mg/kg gentamicin was administered over 3-5 s every 24 h in combination with benzylpenicillin 100,000 IU/kg/12 h or ampicillin 50 mg/kg/8 h. Two blood samples were collected from each participant using a truncated pharmacokinetic sampling schedule. (3) Results: The one-compartment linear pharmacokinetic model best described the data. Birthweight, postnatal age, and white blood cell count were predictive of clearance (CL), while birthweight was predictive of volume (V). For the typical neonate (median weight 1.57 kg, median postnatal age 4 days (0.011 years), median log-transformed WBC of 2.39), predicted CL and V were 0.069 L/h and 0.417 L, respectively-similar to literature values. Simulated gentamicin concentrations varied with respect to postnatal age and bodyweight. (4) Conclusions: A 5 mg/kg/24 h dosage regimen yielded simulated gentamicin concentrations with respect to age and birthweight similar to those previously reported in the literature to be safe and efficacious, confirming its appropriateness.

(1) Background: There is an ongoing discussion on the elution efficacy of antibiotic-impregnated cements. Our experiments were intended to clarify if there are differences in the antibiotic elution of HPLC compared with inhibition zone testing using eluates or PMMA discs. (2) Materials and Methods: Two cement brands with different concentrations of the active ingredient were tested in antimicrobial Kirby-Bauer (disc diffusion) assays. Cement platelets were directly applied on the agar plates and their zone of inhibition was measured. In parallel, the platelets were incubated in phosphate buffered saline (PBS) and at distinct points of time transferred into new buffer. At these time points, 50 µL of the bone cement eluates was used for zone of inhibition testing. Standard gentamicin sulfate solutions served as a control in the same test setup. To verify the microbiological investigations, the antibiotic content of the eluates was also measured via high-performance liquid chromatography (HPLC). (3) Results: The experiments with cement eluates showed better differentiable results than the direct application of the cement discs. The results were also comparable to investigations with HPLC and gentamicin sulfate standard solutions. (4) Conclusions: The results of elution rates are influenced by the test system and the period of observation chosen. The microbial test systems reflect the results of HPLC to the same degree and give evidence of the efficacy of the antibiotics. The HPLC tests on eluates were more suitable in representing differences in release characteristics.

We investigated the effect of combination aminoglycoside and vancomycin local antibiotic treatment compared to aminoglycoside alone in the surgical management of bone infection. Data including patient demographics, type of surgery, microbiological characteristics, BACH score, duration of antibiotic treatment and clinical outcomes were collected. Failure of therapy was a composite of recurrence of infection, continued or new antimicrobial therapy, or reoperation with suspected or confirmed infection at one year after index surgery. A total of 266 patients met the inclusion criteria. 252 patients reached the final follow-up and were included in the final analysis. 113 patients had treatment with aminoglycoside alone and 139 patients had combination aminoglycoside and vancomycin. There was no difference in the failure rate between groups; 10/113 (8.8%) in the aminoglycoside alone and 12/139 (8.6%) in the combination group, p = 0.934. Multivariate analysis showed that there was no added benefit of combination therapy (OR 1.54: 95% CI 0.59-4.04, p = 0.38). BACH score and low BMI were associated with increased risk of failure (BACH OR 3.49: 95% CI 1.13-10.76, p = 0.03; Low BMI OR 0.91: 95% CI 0.84-0.99, p = 0.037). The form of the carrier material (pellets or injectable paste) had no effect on failure rate (p = 0.163). The presence of aminoglycoside resistance had no effect on failure rate (OR 0.39: 95% CI 0.05-3.01, p = 0.37). Clinical outcome was not improved by the addition of vancomycin to aminoglycoside alone as local therapy for the management of bone infection.

Bone and soft tissue infections caused by biofilm-forming bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), remain a significant clinical challenge. While the control of local infection is necessary, systemic treatment is also required, and biofilm eradication is a critical target for successful management. Topical antibiotic treatments, such as antibiotic-loaded bone cement (ALBC), have been used for some time, and continuous local antibiotic perfusion therapy, a less invasive method, has been developed by our group. However, the optimal antibiotics and concentrations for biofilms of clinical isolates are still not well understood. We examined the efficacy of high concentrations of gentamicin against MRSA biofilms and the role of gentamicin resistance genes in biofilm eradication. We collected 101 MRSA samples from a hospital in Japan and analyzed their gene properties, including methicillin and gentamicin resistance, and their minimum biofilm eradication concentration (MBEC) values. Our results showed that high concentrations of gentamicin are effective against MRSA biofilms and that even concentrations lower than the MBEC value could eliminate biofilms after prolonged exposure. We also identified three aminoglycoside/gentamicin resistance genes [aac(6\')-aph(2″), aph(3\')-III, and ant(4\')-IA] and found that the presence or absence of these genes may inform the selection of treatments. It was also found that possession of the aac(6\')-aph(2″) gene correlated with the minimum inhibitory concentration/MBEC values of gentamicin. Although this study provides insight into the efficacy of gentamicin against MRSA biofilms and the role of gentamicin resistance genes, careful selection of the optimal treatment strategy is needed for clinical application.
OBJECTIVE: Our analysis of 101 MRSA clinical isolates has provided valuable insights that could enhance treatment selection for biofilm infections in orthopedics. We found that high concentrations of gentamicin were effective against MRSA biofilms, and even prolonged exposure to concentrations lower than the minimum biofilm eradication concentration (MBEC) value could eliminate biofilms. The presence of the aac(6\')-aph(2″) gene, an aminoglycoside resistance gene, was found to correlate with the minimum inhibitory concentration (MIC) and MBEC values of gentamicin, providing a potential predictive tool for treatment susceptibility. These results suggest that extended high concentrations of local gentamicin treatment could effectively eliminate MRSA biofilms in orthopedic infections. Furthermore, testing for gentamicin MIC or the possession of the aac(6\')-aph(2″) gene could help select treatment, including topical gentamicin administration and surgical debridement.