Vancomycin flushing syndrome in orthopaedic practice:A case report

BACKGROUND Vancomycin flushing syndrome(VFS),also known as red man syndrome,is an allergic reaction to vancomycin.It typically presents as a rash on the face,neck,and upper torso after intravenous administration of vancomycin.VFS is blamed on rapid intravenous infusion of vancomycin during management and rarely happens after local use.A review of the literature showed that in the last 23 years,4 such cases have been reported.Here,we add another case of VFS developed after slow local absorption of vancomycin in cement beads.CASE SUMMARY A 44-year-old male with a known case of hypertension,no history of allergies to medications,and a history of chronic osteomyelitis of the right tibia with discharging sinus over the anterolateral aspect of the leg.The pus culture grew Staphylococcus aureus,which was sensitive to clindamycin and vancomycin.The patient underwent irrigation and debridement with the placement of vancomycin cement beads made from 4 g of vancomycin powder and 40 g of polymethyl methacrylate.Three hours postoperatively,the patient developed a pruritic,erythematous,macular rash predominantly on his face,neck,chest,and lower extremities and to a lesser extent his upper extremities.A diagnosis of VFS was made and was successfully treated with cetirizine(10 mg,oral)and methylprednisolone sodium succinate(125 mg,intravenous).The patient continued to have itching with a facial rash for 12 h with gradual improvement.A decision was made to not remove the beads as the patient continued to improve.Gradually,the rash disappeared after 96 h with no further sequela.CONCLUSION VFS can occur not only after rapid intravenous injection of vancomycin but also with local release,as in our case.As orthopaedic surgeons routinely use vancomycin with polymethyl methacrylate in chronic osteomyelitis and revision arthroplasty,they should be aware of such a complication occurring.

Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia

Objective This study aimed to evaluate the clinical benefits of a vancomycin dosage strategy based on a serum trough concentration model in elderly patients.Methods This prospective single-center, open-label, randomized controlled trial categorized 66 elderly patients with severe pneumonia into study and control groups. The control group received vancomycin using a regimen decided by the attending physician. Meanwhile, the study group received individualized vancomycin therapy with a dosing strategy based on a serum trough concentration model. The primary endpoint was the proportion of patients with serum trough concentrations reaching the target values.The secondary endpoints were clinical response, vancomycin treatment duration, and vancomycinassociated acute kidney injury(VA-AKI) occurrence.Results All patients were at least 60 years old(median age = 81 years). The proportion of patients with target trough concentration achievement(≥ 15 mg/L) with the initial vancomycin regimen was significantly higher in the study group compared to the control group(75.8% vs. 42.4%, P = 0.006).Forty-five patients(68.2%) achieved clinical success, the median duration of vancomycin therapy was10.0 days, and VA-AKI occurred in eight patients(12.1%). However, there were no significant differences in these parameters between the two groups. The model for predicting vancomycin trough concentrations was upgraded to: serum trough concentration(mg/L) = 17.194-0.104 × creatinine clearance rate(mL/min) + 0.313 × vancomycin daily dose [mg/(kg·d)].Conclusion A vancomycin dosage strategy based on a serum trough concentration model can improve the proportion of patients achieving target trough concentrations in elderly patients with severe pneumonia.

Evaluating Vancomycin Clinical Outcomes Using Area under the Curve versus Trough Based Dosing Strategies

Background: The 2020 consensus guidelines recommend AUC guided dosing as the preferred monitoring method for vancomycin. AUC based dosing has shown to reduce incidence of acute kidney injury (AKI), utilize lower daily doses in obese patients, and maintain efficacy. Several institutions have adjusted their protocols to utilize AUC guided dosing. However, there are limited studies comparing the clinical outcomes of AUC versus trough monitoring. Methods: This was a retrospective, observational, single centered study. The primary outcome was to evaluate the clinical success of AUC dosing versus trough based dosing of vancomycin for MRSA infections using a composite outcome of afebrile post treatment ( Results: Forty-seven patients were included in this study, 17 in the AUC group and 30 in the trough group. The primary composite outcome showed a significant benefit of AUC dosing (p = 0.04). The composite component culture clearance showed the largest improvement for the AUC group when compared with the trough group (p = 0.03). More patients achieved therapeutic target attainment and reached the target sooner (3 days versus 4 days, p = 0.2) in the AUC group. Over the study course, 94.1% of patients in the AUC group were considered therapeutic compared to 63.8% in the trough group (p = 0.03). Vancomycin levels were collected less frequently in the AUC group (3 versus 4, p = 0.2). Conclusion: The outcomes of this study may suggest AUC guided dosing as a beneficial alternative to trough based dosing. AUC based dosing may improve clinical success which can be further explored in larger prospective clinical trials.

Use of topical vancomycin powder in total joint arthroplasty:Why the current literature is inconsistent?

Periprosthetic joint infection(PJI)is a rare but terrible complication in hip and knee arthroplasty,and the use of topical vancomycin powder(VP)has been investigated as a tool to potentially reduce its incidence.However,there remains no consensus on its efficacy.Therefore,the aim of this review is to provide an overview on the application of topical vancomycin in orthopaedic surgery focusing on the recent evidence and results in total joint arthroplasty.Several systematic reviews and meta-analyses on topical VP in hip and knee arthroplasty have been recently published reporting sometimes conflicting results.Apart from all being limited by the quality of the included studies(mostly level III and IV),confounding variables are often included potentially leading to biased conclusions.If taken into consideration the exclusive use of VP in isolation,the available data,although very limited,suggest that it does not reduce the infection rate in routine primary hip and knee arthroplasty.Therefore,we still cannot advise for a routinary application.A properly powered randomized-controlled trial would be necessary to clarify the role of VP in hip and knee arthroplasty.Based on the analysis of the current evidence,the use of topical VP appears to be safe when used locally in terms of systemic adverse reactions,hence,if proven to be effective,it could bring great benefits due to its low cost and accessibility.

Treatment of methicillin-resistant Staphylococcus aureus infections:Importance of high vancomycin minumum inhibitory concentrations

Staphylococcus aureus(SA) infections remain a major cause of morbidity and mortality despite the availability of numerous effective anti-staphylococcal antibiotics.This organism is responsible for both nosocomial and community-acquired infections ranging from relatively minor skin and soft tissue infections to life-threateningsystemic infections.The increasing incidence of methicillin-resistant strains has granted an increasing use of vancomycin causing a covert progressive increase of its minimum inhibitory concentration(MIC)(dubbed the MIC "creep").In this way,the emergence of vancomycinintermediate SA(VISA) strains and heteroresistantVISA has raised concern for the scarcity of alternative treatment options.Equally alarming,though fortunately less frequent,is the emergence of vancomycin-resistant SA.These strains show different mechanisms of resistance but have similar problems in terms of therapeutic approach.Ultimately,various debate issues have arisen regarding the emergence of SA strains with a minimum inhibitory concentration sitting on the superior limit of the sensitivity range(i.e.,MIC = 2 μg/mL).These strains have shown certain resilience to vancomycin and a different clinical behaviour regardless of vancomycin use,both in methicillin-resistant SA and in methicillin-sensitive SA.The aim of this text is to revise the clinical impact and consequences of the emergence of reduced vancomycin susceptibility SA strains,and the different optimal treatment options known.

Nitric oxide mediated Staphylococcus aureus pathogenesis and protective role of nanoconjugated vancomycin

Objective:To investigate the relation between fruit seeds,plants residuals and appendicitis. Methods:Among cases that underwent appendectomy,the appendicitis cases having fruit seeds and undigested plant residuals in their etiology were examined retrospectively.Also, histopathological features,age,sex,and parameters of morbidity and mortality were used. Results:Fruit seed was found in one case(0.05%) with presence of pus in appendix lumen, undigested plant residuals in 7 cases(0.35%).It was determined that there were appendix inflammation in 2 of the plant residuals cases,while there were obstruction and lymphoid hyperplasia in the appendix lumen of 5 cases.No mortality was observed.Conclusions:The ratio of acute appendicitis caused by plants is minimal among all appendectomised patients, but avoidence of eating undigested fruit seeds and chewing plants well may help to prevent appendicitis.

Liposomes for systematic delivery of vancomycin hydrochloride to decrease nephrotoxicity:Characterization and evaluation

Vancomycin hydrochloride(VANH),the first glycopeptide antibiotic,is a water-soluble drug for the treatment of acute osteomyelitis.Liposomal formulations of VANH have already been manipulated and characterized,which was a mean of increasing their therapeutic index,reducing their toxicity and altering drug biodistribution.One of the challenges for preparing VANH-Lips is their low encapsulation efficiency(EE).In the present study,we aim to improve the liposomal formulation of VANH for higher EE,longer systemic circulation,reduced nephrotoxicity and enhanced antimicrobial activities.Vancomycin hydrochloride-loaded liposomes(VANH-Lips)were formulated by the method of modified reverse phase evaporation.Based on the optimization of formulation with orthogonal experimental design,the average drug encapsulation efficiency and the mean particle size of VANH-Lips were found to be 40.78±2.56%and 188.4±2.77 nm.In vitro drug release of VANH-Lips possessed a sustained release characteristic and their release behavior was in accordance with the Weibull equation.After intravenous injection to mice,the mean residence time(MRT)of VANH-Lips group was significantly prolonged in vivo and the AUC value was improved as well compared with the vancomycin hydrochloride solution(VANH-Sol)group.Furthermore,the biodistribution results in mice showed that VANH-Lips decreased the accumulation of VANH in kidney after intravenous injection.In conclusion,VANH-Lips may be a potential delivery system for VANH to decrease nephrotoxicity in the treatment of osteomyelitis.

Mass spectrometry detection of basic drugs in fast chiral analyses with vancomycin stationary phases

Current trends in chiral analysis of pharmaceutical drugs are focused on faster separations and higher separation efficiencies, Core-shell or superficially porous particles （SPP） based chiral stationary phases （CSPs） provide reduced analysis times while maintaining high column efficiencies and sensitivity. In this study, mobile phase conditions suitable for chiral analyses with electrospray ionization LC-MS were systematically investigated using vancomycin as a representative CSP. The performance of a 2.7 μm SPP based vancomycin CSP （SPP-V） 10 cm ×0.21 cm column was compared to that of a corresponding 5 μm fully porous particles based analogue column. The results demonstrated that the SPP-V column provides higher efficiencies, 2-5 time greater sensitivity and shorter analysis time for a set of 22 basic pharma- ceutical drugs. The SPP-V was successfully applied for the analysis of the degradation products of racemic citalopram whose enantiomers could be selectively identified by MS.

Incidence and risk factors for potentially suboptimal serum concentrations of vancomycin during cardiac surgery

AIMTo investigate the incidence and risk factors for van-comycin concentrations less than 10 mg/L during cardiac surgery.METHODSIn this prospective study, patients undergoing cardiac surgery received a single dose of 1000 mg of van-comycin. Multiple arterial samples were drawn during surgery. Exclusion criteria were hepatic dysfunction; renal dysfunction; ongoing infectious diseases; solid or hematologic tumors; severe insulin-dependent diabetes; body mass index of 〈 17 or 〉 40 kg/m2; pregnancy or lactation; antibiotic, corticosteroid, orother immunosuppressive therapy; vancomycin or non-steroidal anti-inflammatory drug therapy in the previous2 wk; chemotherapy or radiation therapy in the previous 6 mo; allergy to vancomycin or cefazolin; drug abuse; cardiac surgery in the previous 6 mo; previous or scheduled organ transplantation; preoperative stay in the intensive care unit for more than 24 h; emergency procedure or lack of adequate preparation for surgery; and participation in another trial.RESULTSOver a 1-year period, 236 patients were enrolled, and a total of 1682 serum vancomycin concentrations （median 7/patient） were measured. No vancomycin levels under 10 mg/L were recorded in 122 out of 236 patients （52%）, and 114 out of 236 patients （48%） were found to have at least 1 serum sample with a vancomycin level 〈 10 mg/L; 54 out of 236 patients （22.9%） had at least 5 serum samples with a vancomycin level lower than 10 mg/L. Vancomycin infusion was administered for 60 min in 97 out of 236 patients （41%）. In 47 patients （20%）, the duration of infusion was longer than 60 min, and in 92 patients （39%） the duration of infusion was shorter than 60 min. The maximum concentration and area under the concentration-time curve were significantly higher in patients with no vancomycin levels less than 10 mg/L （ P 〈 0.001）. The multivariate analysis identifiedfemale gender, body mass index （BMI） 〉 25 kg/m , and creatinine clearance above 70 mL/min as risk factors for vancomycin levels less than 10 mg/L.CONCLUSIONResults of this study identified female gender, BMI 〉 25 kg/m2, and creatinine clearance above 70 mL/min as risk factors for suboptimal vancomycin serum concentration during cardiac surgery; no relationship was found bet-ween infusion duration and vancomycin levels less than 10 mg/L. These findings call attention to the risk of facilitating the emergence of vancomycin-resistant methicillin-resistant Staphylococcus aureus strains.

Teicoplanin combined with conventional vancomycin therapy for the treatment of pulmonary methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis infections

BACKGROUND Vancomycin and teicoplanin are both antibiotics that have significant antimicrobial effects on Gram-positive cocci.AIM To explore the value of teicoplanin combined with conventional(vancomycin only)anti-infective therapy for the treatment of methicillin-resistant Staphylococcus aureus and Staphylococcus epidermidis pulmonary infections.METHODS A total of 86 patients with methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis pulmonary infections,treated in our hospital between January 2018 and February 2020,were assigned to the study and control groups using a random number table method,with 43 patients in each group.The control group received conventional treatment(vancomycin),and the study group received both teicoplanin and conventional treatment.The following indicators were assessed in both groups:the time required for symptom relief,treatment effectiveness,serum levels of inflammatory factors(procalcitonin,interleukin-1β,tumor necrosis factor-α,C-reactive protein),clinical pulmonary infection scores before and after treatment,and the incidence of adverse reactions.RESULTS Patients in the study group were observed to have faster cough and expectoration resolution,white blood cell count normalization,body temperature normalization,and rales disappearance than patients in the control group(all P<0.05);the total rate of effectiveness was 93.02%in the study group,higher than the 76.74%in the control group(P<0.05).The pre-treatment serum levels of procalcitonin,interleukin-1β,tumor necrosis factor-α,and C-reactive protein as well as the clinical pulmonary infection scores were similar among the patients in both groups.However,the post-treatment serum levels of procalcitonin,interleukin-1β,tumor necrosis factor-α,and C-reactive protein as well as the clinical pulmonary infection scores were significantly lower in the study group than in the control group(P<0.05).There was no significant difference in the incidence of adverse reactions between the groups.CONCLUSION Compared with conventional(vancomycin only)therapy,teicoplanin and vancomycin combination therapy for patients with pulmonary methicillinresistant Staphylococcus aureus and methicillin-resistant Staphylococcus epidermidis infections can improve patient clinical symptoms,modulate serum inflammatory factor levels,and improve treatment efficacy,without increasing the risk of adverse reactions.

Vancomycin-induced thrombocytopenia in endocarditis:A case report and review of literature

BACKGROUND Thrombocytopenia is a serious complication in the medical practice of numerous drugs.Vancomycin is frequently used for the prophylaxis and treatment of suspected or identified methicillin-resistant positive infections.Several cases with vancomycin-induced thrombocytopenia(VIT)have been reported.However,these have rarely been extensively reviewed.The present report describes a case of VIT in endocarditis,and reviews all VIT cases reported in the literature.CASE SUMMARY A 26-year-old male diagnosed with infective endocarditis was admitted.The patient was treated with multiple drugs,including vancomycin,which was initially intravenously given at 1000 mg every 12 h and subsequently at 500 mg every 8 h on day 3.On day 11,the platelet count decreased to 51×10^(9)/L,vancomycin was switched to 500 mg every 12 h,and platelet transfusion was given.On day 17,the platelet count dropped to 27×10^(9)/L,and platelet transfusion was administered again.On day 23,vancomycin was adjusted to 500 mg every 8 h as the trough concentration dropped to the minimum effective concentration.On day 33,the platelet count declined to approximately 40×10^(9)/L.After platelet transfusion,the platelet count rebounded to 90×10^(9)/L on day 35 but dropped again to 42×10^(9)/L on day 43.Based on the time-to-platelet count curve and Naranjo’s Adverse Drug Reaction Probability Scale score,VIT was suspected.After vancomycin discontinuation and platelet transfusion,the platelet count gradually normalized.CONCLUSION The diagnosis of VIT can be achieved through the time-to-platelet count curve and Naranjo’s Adverse Drug Reaction Probability Scale score.The platelet count cannot be normalized simply by platelet transfusion alone,and vancomycin discontinuation is essential.

A Protocol for Developing a Clinical Practice Guideline for Therapeutic Drug Monitoring of Vancomycin

This study aimed to develop a guideline for therapeutic drug monitoring（TDM） of vancomycin. We adopted the new guideline definition from the Institute of Medicine（IOM）, adhered closely to the six domains of the Appraisal of Guidelines for Research ＆ Evaluation Ⅱ（AGREE Ⅱ）, and made recommendations based on systematic reviews. We established a Guideline Steering Group and a Guideline Development Group, formulated 12 questions in the form of Population, Intervention, Comparison, Outcome（PICO） and completed a literature search. As far as we know, we will develop the first evidenced-based guideline for vancomycin TDM under the framework of the Grade of Recommendations Assessment, Development and Evaluation（GRADE）.

Vancomycin pretreatment attenuates acetaminophen-induced liver injury through 2-hydroxybutyric acid

Liver injury caused by acetaminophen(AP)overdose is a leading public health problem.Although APinduced liver injury is well recognized as the formation of N-acetyl-p-benzoquinone(NAPQI),a toxic metabolite of AP,resulting in cell damage,emerging evidence indicates that AP-induced liver injury is also associated with gut microbiota.However,the gut microbiota-involved mechanism remains largely unknown.In our study,we found that vancomycin(Vac)pretreatment(100 mg/kg,twice a day for 4 days)attenuated AP-induced liver injury,altered the composition of gut microbiota,and changed serum metabolic profile.Moreover,we identified Vac pretreatment elevated cecum and serum 2-hydroxybutyric acid(2-HB),which ameliorated AP-induced cell damage and liver injury in mice by reducing AP bioavailability and elevating GSH levels.Our current results revealed the novel role of 2-HB in protecting AP-induced liver injury and add new evidence for gut microbiota in affecting AP toxicity.

Vancomycin lavage for the incidence of acute surgical site infection following primary total hip arthroplasty and total knee arthroplasty

BACKGROUND Surgical site infection is a rare but serious complication associated with total joint arthroplasty(TJA).There are limited data on the effectiveness of intrawound irrigation with vancomycin solution(1000 mg/L;2 L)before wound closure for preventing acute surgical site infection following primary total hip arthroplasty(THA)and total knee arthroplasty(TKA).AIM To investigate the effectiveness of prophylactic intraoperative application of vancomycin(1000 mg/L;2 L)solution vs.plain irrigation in reducing the incidence of acute surgical site infection following primary THA and TKA.METHODS A retrospective review of 2725 consecutive patients undergoing THA or TKA from January 2012–December 2019 was performed.These patients received either intrawound irrigation with normal saline before wound closure between January 2012 and December 2015(group 1,1018 patients;453 undergoing THA and 565 undergoing TKA)or intrawound irrigation with vancomycin solution(1000 mg/L)before wound closure between January 2016 and December 2019(group 2,1175 patients;512 undergoing THA and 663 undergoing TKA).The outcomes were the incidences of postoperative surgical site infection and wound healing complications within 3 mo of primary TJA.RESULTS There were no significant demographic differences between the 2 groups.There was a significantly higher incidence of acute infection at the surgical site in patients who received intrawound irrigation with normal saline before wound closure than in those who received intrawound irrigation with vancomycin solution(1000 mg/L;2 L)before wound closure(overall incidence of infection:group 1,2.46%vs group 2,0.09%,P<0.001).There was no significant difference in the incidence of wound healing complications between the two groups.CONCLUSION Prophylactic irrigation with vancomycin solution(1000 mg/L;2 L)significantly decreases the incidence of acute surgical site infection after primary TJA.This strategy is a safe,efficacious,and inexpensive method for reducing the incidence of acute surgical site infection after TJA.

A Study of Scanning Electron Microscope of Vancomycin Resistant <i>Enterococcus faecalis</i>from Clinical Isolates

Vancomycin-resistant Enterococcus faecalis pose an emerging health risk, but little is known about the precise epidemiology for vancomycin resistance. The glycopeptide resistant was studied using different techniques such as broth macrodilution, agar dilution combined with agar diffusion, morphology cell changes by scanning electron microscopy. Eight VREF isolated from different clinical samples were used. Results showed low level and high level resistant to vancomycin antibiotic at concentration of 64 to 128 μg/ml, but antibacterial activity was reduced to 256 μg/ml, the SEM revaled increased in the cell size with the antibiotic compared to control and standard culture. The technique constitutes simple method for the detection of organism.

Using sensitive surface plasmon resonance to detect binding of peptide molecules and immobilized vancomycin

To perform the mechanism study of special association for vancomycin and D-Ala-D-Ala-containing peptides on the interface of solution and self-assemble monolayer, the binding between vancomycin and pentapeptide （Lys-Lys-Gly-D-Ala-D-Ala） was investigated by flow injection surface plasmon resonance （FI-SPR） and flow injection quartz crystal microbalance （FI-QCM）. To facilitate the formation of a compact vancomycin adsorbates layer with a uniform surface orientation, vancomycin molecules were attached onto a preformed alkanethiol self-assembled monolayer. By optimizing the conditions for the binding between Lys-Lys-Gly-D-Ala-D-Ala and vancomycin on the assembled chip, the detecting limit of Lys-Lys-Gly-D-Ala-D-Ala was greatly improved （reaching 0.5 ×10^- 6 mol/L or 7.5 × 10^-12 mol）. The equilibrium constant of the association of Lys-Lys-Gly-D-Ala-D-Ala with vancomycin was also obtained （KAds=5.0×10^4 L/tool）.

Vancomycin dosing in an obese patient with acute renal failure:A case report and review of literature

BACKGROUND Vancomycin is the most commonly used drug for methicillin-resistant Staphylococcus aureus.The empirical clinical doses of vancomycin based on non-obese patients may not be optimal for obese ones.CASE SUMMARY This study reports a case of vancomycin dosing adjustment in an obese patient(body mass index 78.4 kg/m2)with necrotizing fasciitis of the scrotum and left lower extremity accompanied with acute renal failure.Dosing adjustment was performed based on literature review and factors that influence pharmacokinetic parameters are analyzed.The results of the blood drug concentration monitoring confirmed the successful application of our dosing adjustment strategy in this obese patient.Total body weight is an important consideration for vancomycin administration in obese patients,which affects the volume of distribution and clearance of vancomycin.The alterations of pharmacokinetic parameters dictate that vancomycin should be dose-adjusted when applied to obese patients.At the same time,the pathophysiological status of patients,such as renal function,which also affects the dose adjustment of the patient,should be considered.CONCLUSION Monitoring vancomycin blood levels in obese patients is critical to help adjust the dosing regimen to ensure that vancomycin concentrations are within the effective therapeutic range and to reduce the incidence of renal injury.

Vancomycin-related convulsion in a pediatric patient with neuroblastoma:A case report and review of the literature

BACKGROUND Vancomycin is often used as an anti-infective drug in patients receiving antitumor chemotherapy.There are concerns about its adverse drug reactions during treatment,such as nephrotoxicity,ototoxicity,hypersensitivity reactions,etc.However,potential convulsion related to high plasma concentrations of vancomycin in children receiving chemotherapy has not been reported.CASE SUMMARY A 3.9-year-old pediatric patient with neuroblastoma receiving vancomycin to treat post-chemotherapy infection developed an unexpected convulsion.No other potential disease conditions could explain the occurrence of the convulsion.The subsequently measured overly high plasma concentrations of vancomycin could possibly provide a clue to the occurrence of this convulsion.The peak and trough plasma concentrations of vancomycin were 59.5 mg/L and 38.6 mg/L,respectively,which were much higher than the safe range.Simulation with the Bayesian approach using MwPharm software showed that the area under the concentration-time curve over 24 h was 1086.6 mg·h/L.Therefore,vancomycin was immediately stopped and teicoplanin was administered instead combined with meropenem and fluconazole as the anti-infective treatment strategy.CONCLUSION Unexpected convulsion occurring in a patient after chemotherapy is probably due to toxicity caused by abnormal pharmacokinetics of vancomycin.Overall evaluation and close therapeutic drug monitoring should be conducted to determine the underlying etiology and to take the necessary action as soon as possible.

Ototoxicity of vancomycin in guinea pigs

Objective: To study the effect of vancomycin (V) with multiple intravenous injections on the inner ear of albino guinea pigs. Methods: Three groups of animals were injected with vancomycin hydrochloride (54, 108, 216 mg/kg respectively once a day for 14 d). Two groups were treated with gentamycin (GM) (80 mg·kg -1 ·d -1 ) and saline respectively as control groups. Auditory brainstem responses (ABR) and the duration of post-rotatory nystagmus (PRN) were measured before and after administration. Surface preparation and scanning electron microscopy (SEM) of the cochlea were performed for histological examination. Results: In V 54, 108 mg/kg group, similar to saline control, there was 0-1.1 dB of threshold shift. In V 216 mg/kg group, average hearing loss was 1.0-5.7 dB immediately after administration and 1.3-3.8 dB after 14 d, which was significantly lower than those in GM control group. As the saline control, no significant difference was found in PRN in all V groups before and after treatment; while in the GM group, PRN decreased significantly after treatment. Morphological evaluation demonstrated that in all V and saline animals there was no obvious missing of outer and inner hair cells and SEM showed normal surface morphology. In the GM group, there was 10%-30% of outer and inner hair cells lost in the basal turn. Conclusion: The ototoxicity of vancomycin is absent or minimal after multiple introvenous administration within this dose range.

Methicillin-Resistant Staphylococcus aureus May Also Be Resistant to Clindamycin and Vancomycin

Objectives: Methicillin-resistant Staphylococcus aureus (MRSA) is a global superbug widely distributed in hospitals, communities and livestock settings. This study investigated the presence and molecular characterization of MRSA co-resistance to clindamycin and vancomycin in the southeastern region of Nigeria. The susceptibility of these organisms to other selected antibiotics was also investigated. Method: Biological samples were obtained from consenting patients from three establishments in Enugu, Nigeria and cultured for isolation and purification. The pure isolates were subjected to antimicrobial susceptibility profiling using conventional antibiotics. The genomic DNAs of the pure isolates were isolated using the Promega genomic DNA purification kit while the antibiotic resistance genes (mecA) genes were identified using a multiplex polymerase chain reaction. Also, the minimum inhibitory concentration of the clindamycin and vancomycin antibiotics was determined as well as their combined activity on the MRSA isolates. Results: A large proportion (71%) of the MRSA isolates was from urine samples and then from the High Vaginal Swab (19%). All the isolates were resistant to cloxacillin while 95% were resistant to ciprofloxacin. MRSA isolates demonstrated resistance to clindamycin (with MIC of 23.44 - 250 μg/ml) and to vancomycin (with MIC of 62.5 - 250 μg/ml). The isolated MRSA also demonstrated multidrug-resistant traits. The combined effects of vancomycin and clindamycin against different species of MRSA exhibited additive, antagonistic and indifferent effects and none had a synergistic effect. Multiplex Polymerase Chain Reaction revealed that the majority of the strains were positive for the 162-bp internal fragment of the mecA gene of MRSA and basically displayed SCCmec type III, indicating that they were multidrug-resistant and hospital-acquired. Conclusion: Clindamycin and vancomycin-resistant MRSA infections are also within the Eastern region of Nigeria as found in other countries of the world. This superbug, therefore, may require drastic and urgent measures to curtail its spread and attendant healthcare challenges like outbreaks of infections. In addition, strict adherence to antibiotic policy and continuous surveillance is highly advocated.