Bacteriologic profile, antibiotics resistance pattern, and outcomes of patients admitted to Lancet General Hospital from June 2022 to June 2023: A retrospective cohort study

Background Prior studies indicated increased antimicrobial resistance in Ethiopia, with related health, economic, and environmental costs. Knowing an institutions and population microbiologic profile allows for proper antibi-otic treatment, which substantially impact patients' outcomes such as healthcare related costs, morbidity, and mortality. The current study assessed the bacteriologic profile, resistance pattern, and treatment outcome in Lancet General Hospital. Method A retrospective cohort study on the bacteriologic profile, antibiotics resistance pattern, and outcome of patients was done on 128 eligible patients who were admitted to Lancet General Hospital from June 2022 to June 2023. Data from all hospitalized patients with culture-confirmed infection were analyzed. SPSS version 26.0 was used to analyze the data. Association between independent and dependent variables was analyzed using binary logistic regression model. Results Gram-negative bacteria were recovered in 77% of the cases. Extended-spectrum beta-lactamase producing Enterobacteriaceae was found in 37.5% (54) isolates and carbapenem resistant bacteria were identified in 27.8% of patients. In-hospital mortality from multidrug resistant bacterial infection was 14.8%. Age ≥ 65 years, presence of septic shock, and presence of carbapenem-resistant bacteria were independently associated with in-creased in-hospital mortality. Conclusion High number of resistant microorganisms was isolated, and increased mortality was documented from infections caused by carbapenem-resistant bacteria. Multi-center studies should be done to determine the extent of resistant organisms in health facilities throughout the country. epidemiology, and the findings should be factored into clinical decision making and program design for disease prevention, screening, and treatment. It also calls for further prospective research to learn more about the conditions in the context of additional relevant personal and clinical characteristics

Influence of augmented renal clearance on the clinical application and therapeutic effect of vancomycin in critical children / 中国小儿急救医学

Objective:To explore the effect of augmented renal clearance(ARC)on 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio(AUC 24/MIC)of vancomycin and prognosis in critical children, thus to provide proposal for individual dosage regimen. Methods:Sixty-five critical children treated with vancomycin, who suffered from sepsis/septic shock, were brought into this retrospective cohort study.According to estimate glomerular filtration rate, these children were divided into ARC group ( n=27) and normal group ( n=38). The influencing factor of AUC 24/MIC of vancomycin and therapy prognosis for two groups were detected and analyzed. Results:There were no significant differences between two groups in basic setting (age, sex, weight), scores of pediatric sequential organ failure assessment and pediatric risk of mortality Ⅲ, infection markers (C-reactive protein and procalcitonin), glutamic-pyruvic transaminase, hypoproteinemia, usage of diuretic and vasoactive agent( P>0.05). The patients from ARC group showed lower levels than those from normal group in AUC 24/MIC of vancomycin[375.2(300.8, 489.4) vs. 443.6(412.3, 593.2), Z=2.263, P=0.024] and it′s target achievement ratio (TAR)(40.7% vs. 76.3%, χ2=8.440, P=0.005). When usage of diuretic and vasoactive agent, the AUC 24/MIC of ARC group was lower than that of normal group( P<0.05). But there was no significant difference between ARC group and normal group regarding hypoproteinemia( P>0.05). The days of body temperature steady at least 48 hours[7.0(5.5, 9.0)d vs. 6.0(5.0, 8.0)d], the length of hospital stay[39.0(21.0, 58.0)d vs. 20.5(16.0, 28.0)d], the length of PICU stay[14.0(9.0, 31.5)d vs. 10.0(5.0, 15.0)d] were longer than those in normal group( P<0.05). There were no significant differences between ARC group and normal group regarding days of ventilation and infectious markers decreased at least 50%, as well as 28-days mortality( P>0.05). The multivariable analysis showed that the presence of ARC, hypoproteinemia, use of diuretics and vasoactive agent were significantly associated with AUC 24/MIC of vancomycin( P<0.05). Conclusion:ARC may down regulate levels of AUC 24/MIC and TAR of vancomycin.During ARC period, the usage of diuretic and vasoactive agent could affect the AUC 24/MIC of vancomycin.Individual dosage regimen should be employed for critical children suffered with ARC.

Analysis of a case of pancytopenia complicated with delayed drug fever induced by vancomycin infusion in a child / 中国药房

OBJECTIVE To accurately identify the rare adverse drug reactions （ADR） of vancomycin-pancytopenia in order to promote its safe use. METHODS Through a case report of a child with suppurative hip arthritis who developed pancytopenia combined with delayed drug fever caused by intravenous infusion of vancomycin，Naranjo score method and related literature were used to summarize the association between the ADR and vancomycin and its possible mechanism， and suggestions for rational use of vancomycin in pediatric patients were put forward. RESULTS & CONCLUSIONS The association of pancytopenia combined with delayed drug fever and vancomycin in this child is “very likely”. In clinical practice， it is difficult to distinguish between pancytopenia combined with delayed drug fever from fever and hematopenia caused by aggravation of infection. Medical staff should increase their awareness of vancomycin rare ADR such as pancytopenia， and pharmacists should assist medical staff in timely screening for ADR. The initial dose of vancomycin infusion for children should start from 60 mg/（kg·d），and the blood concentration should be monitored 48 h after the first infusion and the dose should be adjusted in time to maintain the valley concentration of vancomycin at 5-15 mg/L to prevent the occurrence of ADR caused by excessive blood concentration. For children who have been using vancomycin for more than one week，the blood routine should be rechecked regularly. Once pancytopenia occurs，the drug should be stopped immediately，and symptomatic treatment should be given according to the situation.

Pharmacokinetics and therapeutic target attainment of vancomycin in pediatric post-liver transplant patients

Abstract Introduction Vancomycin is widely prescribed to treat or prevent Gram-positive infections in pediatric liver transplant recipients. The objective of this prospective cohort study is to describe vancomycin pharmacokinetics and to evaluate the therapeutic target attainment after initial dose regimen. Materials and methods Patients with previous renal injury were excluded. Vancomycin therapy started with 40‒60 mg/kg/day. The pharmacokinetic parameters were assessed using two steady-state blood samples and the first-order kinetic equations. Therapeutic target was defined as vancomycin 24-hour Area Under the Curve/Minimum Inhibitory Concentration (AUC/MIC) ≥ 400 and < 600. Results Sixteen patients were included. The found vancomycin clearance, half-life, and volume of distribution were, respectively: 2.1 (1.3‒2.8) mL/kg/min, 3.3 (2.7‒4.4) hours, and 0.7 (0.5‒0.9) L/kg. With the initial dose, only 6 (37 %) patients reached the therapeutic target against Gram-positive pathogens with MIC 1 mg/L. After individual dose adjustments, all patients reached the target. The correlation between trough levels and AUC was low (R2= 0.5). Conclusions Pediatric patients with preserved renal function after liver transplantation have an increased volume of distribution for vancomycin, and most patients present subtherapeutic levels after the standard initial dosing regimen. With the vancomycin AUC-guided monitoring and dosing, it is possible to improve therapeutic target attainment.

Agranulocitosis secundaria a uso de vancomicina en pediatría. reporte de caso

La vancomicina es un antibiótico de uso común en pacientes hospitalizados. Se han descrito múltiples efectos adversos relacionados a este fármaco, de los cuales la agranulocitosis es una entidad poco frecuente pero potencial mente grave. Este caso muestra una consecuencia médica secundaria al uso prolongado de este antibiótico, generando una neutropenia profunda posterior a 24 días de tratamiento, presentándose clínicamente con un pico febril aislado. Se asume que esta situación es consecuencia de una respuesta inmunológica inadecuada del huésped, por lo que la suspensión del agente etiológico es la clave del tratamiento. Existen pocos reportes de estos casos en la población pediátrica y debe considerarse un efecto secundario que requiere vigilancia estrecha para evitar repercusiones clínicas.

Vancomycin is a commonly used antibiotic in hospitalized patients. Multiple adverse effects related to this drug have been described, of which agranulocytosis is a rare but potentially serious entity. This case shows a medical consequence secondary to the prolonged use of this antibiotic, generating profound neutropenia after 24 days of treatment, presenting clinically with an isolated feverish peak. It is assumed that this situation is the consequence of an inadequate immunological response of the host, for which reason the suspension of the etiological agent is the key to treatment. There are few reports of these effects in the pediatric population and should be considered a side effect that requires close monitoring to avoid clinical repercussions.

Clinical Evaluation of a Vancomycin Dosage Strategy Based on a Serum Trough Concentration Model in Elderly Patients with Severe Pneumonia / 生物医学与环境科学（英文）

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 vancomycin-associated 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 was 10.0 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.

Effects of individualized dosing regimen on blood trough concentration of vancomycin and renal function in critically ill patients / 中国药房

OBJECTIVE To investigate the effects of individualized dosing regimen on blood trough concentration of vancomycin and renal function in critically ill patients. METHODS According to relevant guidelines and the results of Vancomycin Calculator， clinical pharmacists formulated an individualized dosing regimen of vancomycin including loading dose and maintenance dose for critically ill patients based on the two independent variables of body weight and creatinine clearance rate. Using the method of retrospective study， patients who were admitted to the department of intensive care unit （ICU） of the Second Affiliated Hospital of Guangzhou Medical University and used the regimen from July 2018 to December 2021 were selected as the trial group， and patients who were treated with vancomycin and received blood drug concentration monitoring in ICU from January 2015 to June 2018 were recruited in the control group. The difference in trough concentration distribution and the incidence of acute kidney injury （AKI） after medication were compared between the two groups， the change of serum creatinine before and after medication in the trial group was analyzed. RESULTS Totally 197 patients were included in the trial group and 144 patients were in the control group. There was no significant difference between the two groups in the clinical information （gender， age， body weight， acute physiology and chronic health evaluation Ⅱ score， the proportion of patients with renal insufficiency， etc.） （P＞0.05）. The proportions of major infection sites （including lung， urinary， abdominal， blood and central nervous system） and treatment type （target or empirical treatment） also had no significant difference between the two groups （P＞0.05）. There was no significant difference in the attainment rate of ideal trough concentration （15-20 μg/mL） and the proportion of patients with trough concentration　＞20 μg/mL between the two groups （P＞0.05）， while the attainment rate of target trough concentration （10-20 μg/mL） and the proportion of patients with trough concentration ＜10 μg/mL were significantly different between the two groups （P＜0.05）. The attainment rate of target trough concentration in patients with chronic renal insufficiency in trial group was significantly higher than that in control group （P＜0.05）. There was no significant difference in the incidence of AKI and vancomycin-associated AKI between the two groups （P＞0.05）. In the trial group with medication duration ≥7 days ， the level of serum creatinine on the 7th day of treatment was increased significantly， compared with that on the 3rd day of treatment （P＜0.05）. CONCLUSIONS This individualized dosing regimen can improve the attainment rate of target trough concentration of vancomycin in critically ill patients， especially those with chronic renal insufficiency， during the first standardized monitoring， and not increase the risk of renal injury compared with previous empirical medication.

Clinical treatment and observation of the endophthalmitis caused by Bacillus cereus / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To analyze the clinical characteristics and antibiotic sensitivity of traumatic endophthalmitis caused by Bacillus cereus and discuss the early diagnosis and treatment measures.METHODS: The data of 15 patients(15 eyes)with Bacillus cereus endophthalmitis admitted to the Eye Trauma Center of Shaanxi Provincial Eye Hospital from January 2019 to December 2021 were collected. The injury time, injury condition, preoperative visual acuity, corrected visual acuity in the last follow-up, operation method, bacterial culture and drug sensitivity test results were recorded.RESULTS: Among the 15 patients(15 eyes), 5 eyes with simple corneal perforating wound were treated with wound debridement and suture combined with intraocular antibiotic injection. And another 10 eyes with penetrating injuries combined with traumatic cataract and intraocular foreign bodies were treated with debridement, cataract extraction, removal of intraocular foreign bodies, vitrectomy combined with silicone oil tamponade and intraocular antibiotic injection. Among the 15 patients, 11 patients(73%)were treated effectively and the eyeball was preserved, and 4 patients(27%)were treated ineffectively and ocular evisceration was performed. Among the 11 patients with eyeball retention, 1(9%)had decreased vision, 1(9%)had unchanged vision, 4(36%)had improved vision by 1 level, and 5(45%)had improved vision by 2 levels, and the postoperative visual acuity was significantly improved. Correlation analysis showed that the course of disease was negatively correlated with corrected visual acuity(rs=-0.762, P=0.001). The cultures of vitreous humor and aqueous humor samples of patients were all grown in Bacillus cereus, and susceptibility tests were sensitive to vancomycin.CONCLUSIONS: Vancomycin is an effective drug for the treatment of Bacillus cereus endophthalmitis. Vitrectomy combined with silicone oil tamponade and intravitreal injection of vancomycin are effective method for the treatment of Bacillus cereus endophthalmitis.

Development of a LC-MS/MS method for the determination of vancomycin in human serum and validation of its clinical value / 中华检验医学杂志

Objective:The aim of our study is to develop an LC-MS/MS method using isotope internal standard for the determination of vancomycin in human blood serum and to validate its clinical value.Method:We conducted a methodological evaluation study using serum samples from 221 hospitalized patients (142 males and 79 females; mean age (59.31±15.32) years) who received treatments of vancomycin at the Sir Run Run Shaw Hospital of Zhejiang University between March 2021 and June 2022. In addition, thirty clinical residual serum samples from healthy individuals (15 males and 15 females; mean age (35.65±9.86) years) undergoing physical examination were used for methodological evaluation. The method was established using AB Sciex Triple Quad 4500 MD liquid chromatography-tandem mass spectrometer and chromatographic separation was carried out using a Phenyl-Hexyl column with gradient elution. The mobile phase was composed of 0.1% formic acid in water and methanol; the column temperature was 40℃; Vancomycin-[d12] TFA salt was used as the internal standard (IS). The sensitivity, specificity, linearity, accuracy, imprecision, matrix effect, and carry-over of the method were evaluated.Results:The detection limit of vancomycin was 0.2 mg/L and the lowest limit of quantification was 0.5 mg/L. It showed good linearity ( R2=0.998 4) in the 1 to 50 mg/L concentration range. Accuracy (recovery rate 87.45%-112.69%), intra-day and inter-day imprecision ( CV 4.91%-7.69%), internal standard standardized matrix factor (90.22%-104.29%). Carryover pollution was negligible. Of the 221 patients, the mean trough concentrations of vancomycin in serum was (13.15±8.56) mg/L. Conclusion:The LC-MS/MS method for the detection of serum vancomycin established in our laboratory meets the requirements of the reference method, and can be used for the monitoring of clinical therapeutic drugs.

A calf tissue flap combined with antibiotic-loaded calcium sulfate for foot and ankle osteomyelitis / 中华创伤骨科杂志

Objective:To evaluate the efficacy of a calf tissue flap combined with antibiotic-loaded calcium sulfate (artificial bone or mixed iliac bone graft) in the treatment of foot and ankle osteomyelitis.Methods:A retrospective study was conducted to analyze the 11 cases of foot and ankle osteomyelitis which had been treated at Department of Hand and Microsurgery, The Third Hospital of Baoji from October 2018 to October 2021. There were 8 males and 3 females, aged (42.3±23.7) years. The chronic hypotoxic osteomyelitis was repaired and reconstructed after thorough debridement at one stage with a calf tissue flap combined with antibiotic-loaded calcium sulfate artificial bone to fill the cavity and cover the wound. The acute infected trauma was repaired and reconstructed after thorough debridement at the second stage with a calf tissue flap combined with antibiotic-loaded calcium sulfate artificial bone to fill the cavity and cover the wound only after the acute infection was controlled by local dressing, drainage or negative pressure therapy and systemic anti-infection treatment at the primary stage. The flap size ranged from 3.5 cm × 2.0 cm to 12.0 cm × 6.0 cm. Four cases were treated by a peroneal artery perforator flap combined with antibiotic-loaded calcium sulfate artificial bone, 3 cases by a flap with peroneal artery perforator and peroneal nerve trophic vessel combined with antibiotic-loaded calcium sulfate artificial bone, 3 cases by a posterior tibial artery perforator flap combined with antibiotic-loaded calcium sulfate artificial bone, and one by a peroneus longus muscle flap combined with antibiotic-loaded calcium sulfate artificial bone. Postoperatively, the flap survival, bone union time, ankle function and complications were observed; the therapeutic efficacy was evaluated by comparing infection control indexes at the final follow-up [clinical manifestations like local redness, swelling, pain, ulceration, and exudation, and white blood cell count (WBC), C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and calcitoninogen (PCT)].Results:All the flaps survived except for one which developed necrosis at the distal 1/3 of the flap but responded to dressing change. All the patients were followed up for (22.6±11.5) months. The 6-month follow-up revealed that all the flaps were fine in shape and texture. Re-examinations showed that WBC, CRP, ESR and PCT were normal or close to normal, the local skin was free of redness, swelling or ulceration, and protective sensation was restored to varying degrees. X-ray at (12.1±2.3) months showed that lesions disappeared, bony union was achieved, the ankle joint regained basic flexion and extension, and the affected limb also regained weight-bearing and walking functions in all the patients but one whose X-ray at 18 months showed poor bony union but no other symptoms or signs.Conclusion:In the treatment of foot and ankle osteomyelitis, a calf tissue flap combined with antibiotic-loaded calcium sulfate artificial bone can promote bone healing and restore the function of the foot and ankle because it not only fills the cavity and covers the wound but also effectively controls the infection.

Dermatosis ampollar por IgA lineal inducida por Vancomicina: reporte de un caso / Vancomycin-induced linear igabollous dermatosis: a case report

RESUMEN La dermatosis ampollar por IgA lineal del adulto (DLA) es una enfermedad autoinmune adquirida infrecuente, caracterizada por el depósito lineal de anticuerpos IgA en la membrana basal. La mayoría de los casos reportados son de causa idiopática, pero esta entidad también se ha visto asociada a ciertos fármacos, siendo la vancomicina el más frecuente. Se presenta un caso de DLA asociada a vancomicina, con extensa afectación cutánea y compromiso mucoso, tratado con dapsona y corticoides sistémicos con buena respuesta.

ABSTRACT Adult linear IgA bollous dermatosis (LABD) is a rare acquired autoimmune disease characterized by linear deposition of IgA antibodies on the basement membrane. Most of the reported cases are of idiopathic cause, but this entity has also been associated with certain drugs, vancomycin being the most frequent. We present a case of LABD associated with vancomycine, with extensive skin and mucosal involvement, treated with dapsone and systemic corticosteroids with a good response.

Risk of acute kidney injury and cost-effectiveness analysis comparing vancomycin and linezolid for the treatment of pediatric patients infected with Gram-positive bacteria / Risco de lesão renal aguda e custo-efetividade comparando vancomicina e linezolida para o tratamento de pacientes pediátricos infectados por bactérias Gram-positivas

Objective: This study aimed to compare the occurrence of acute kidney injury (AKI) in pediatric patients who used vancomycin (VAN) or linezolid (LNZ) to treat Gram-positive coccus (GPC) infections and to assess which treatment (VAN or LNZ) is the most cost-effective considering a pediatric hospital perspective. Methods: A retrospective cohort was performed to evaluate the occurrence of nephrotoxicity in pediatric patients without previous AKI, with GPC infections that used LNZ, or VAN monitored by serum VAN levels. Initially, descriptive analysis and Fisher and chisquare test were performed for this comparison. Then, a cost-effectiveness analysis was conducted through a decision tree model. The outcomes of interest were the rate of AKI related to the drug and the rate of admission to the intensive care unit (ICU) and cure. Results: In patients without previous acute kidney injury (AKI), 20% developed nephrotoxicity associated with VAN versus 9.6% in the LNZ group (p = 0.241). As there was no difference in nephrotoxicity between VAN andlinezolid (LNZ), vancomycin (VAN) monitored by serum VAN levels can optimize and rationalize the treatment. The nephrotoxicity risk criterion should not guide the prescription for LNZ. Furthermore, the average global cost of treatment with VAN was approximately R$ 43,000, while for LNZ, it was R$ 71,000. Conclusion: VAN was considered dominant (lower cost and greater effectiveness) over LNZ for treating patients with GPC infection.

Objetivo: Este estudo objetivou comparar a ocorrência de lesão renal aguda (LRA) em pacientes pediátricos que usaram vancomicina (VAN) ou linezolida (LNZ) para tratar infecções por cocos Gram-positivos (CGP) e avaliar qual tratamento (VAN ou LNZ) é o mais custo-efetivo considerando a perspectiva de um hospital pediátrico. Métodos: Foi realizada uma coorte retrospectiva para avaliar a ocorrência de nefrotoxicidade em pacientes pediátricos sem LRA prévia, com infecções por CGP que utilizaram LNZ ou VAN, combinada com vancocinemia. Para essa comparação, inicialmente foram realizados análise descritiva e testes de Fisher e qui-quadrado. Em seguida, foi realizada uma análise de custo-efetividade por meio de um modelo de árvore de decisão. Os desfechos de interesse foram a taxa de LRA relacionada ao medicamento e a taxa de internação em unidade de terapia intensiva e cura. Resultados: Nos pacientes sem LRA prévia, 20% deles desenvolveram nefrotoxicidade associada à VAN versus 9,6% no grupo LNZ (p = 0,241). Como não houve diferença na nefrotoxicidade entre VAN e LNZ, a VAN combinada com a vancocinemia pode otimizar e racionalizar o tratamento, e a prescrição de LNZ não deve ser guiada pelo critério de risco de nefrotoxicidade. Além disso, o custo médio global do tratamento com VAN foi de aproximadamente R$ 43.000, enquanto para LNZ foi de R$ 71.000. Conclusão: Assim, a VAN foi considerada dominante (menor custo e maior eficácia) sobre a LNZ para o tratamento de pacientes com infecção por CGP.

Isolation of Enterococcus spp. in various clinical sample and their antimicrobial resistant pattern with MIC of vancomycin in patient attending tertiary care centre, RIMS, Ranchi, Jharkhand

Introduction- Enterococci are part of normal intestinal flora of humans and animals but have also emerged as important pathogens responsible for serious infections in hospital and community acquired infections.it is second most common cause of nosocomial infections in gastrointestinal tract, wound and genitourinary tract. To process all the clinicalAim- samples from various department in our hospital, for isolation of Enterococci spp. To speciate the isolates & to have resistance pattern of the isolates of vancomycin total 926 sample were collected from both outMaterial & Methods- patients and in patient in all clinical departments and transported to microbiology laboratory. specimens were processed by inoculating on to blood agar, MacConkey Agar, nutrient agar, potassium tellurite agar and incubated at 37°C for24-48 hr. Enterococci were identified by their typical arrangement in and salt tolerance test Gram stain, bile esculin test and biochemical tests. Antimicrobial susceptibility patterns were determined by performing Kirby-Bauer disc diffusion method and Minimum inhibitory concentration (MIC) values were identified by tube dilution methods. Result- a total of 926 sample, 645 (69.72%) were culture positive and 281 (30.28%) were culture negative. Among 645 culture positive cases, 81(12.55%) were Enterococcus faecalis. Antimicrobial susceptibility & MIC done as per standard protocols. The E. Faecalis showed 99% sensitive to Vancomycin. the resistance to vancomycin was 1% & further confirmed by MIC via tube dilution methods. In which MIC was ?32 ?g/ml in one isolate. About 8 of Enterococcal strains showed MIC of 0.0125?g/ml. species level identification of Enterococcus is important forConclusions- epidemiological study and also for analysis of drug resistant pattern. Effective detection of vancomycin resistance helps in reducing the morbidity and mortality of VRE in hospitalized patients

Real-life comparison of three intravitreal antibiotic drug regimens in endophthalmitis

Purpose: Real?life comparison of three intravitreal drug regimens used in cases of endophthalmitis at a tertiary care center in India. Methods: In this prospective, comparative study, patients of bacterial endophthalmitis were grouped according to intravitreal antibiotic drug regimens into Group 1 (ceftazidime and vancomycin), Group 2 (piperacillin + tazobactam and vancomycin), and Group 3 (imipenem and vancomycin). Forty?eight hours after injection nonresponding/worsening patients underwent vitrectomy. Vitreous samples were subjected to microbiological and pharmacokinetic tests. Results: A total of 64 patients were included and divided into Group 1: 29, Group 2: 20, and Group 3: 15 cases. Also, 75% of patients were post?surgical endophthalmitis, whereas 25% were post?traumatic. Improvement in vision (V90?0) and vision at 3 months (V90) were comparable between the three groups. Visual recovery was poorer in post?traumatic cases. In post?surgical cases, visual recovery was poorer in those presenting beyond 72 h of onset of symptoms (P = 0.0002). Polymerase chain reaction (PCR) positivity (66%) was higher than BACTECTM (33%) and culture (14%). Antibiotic resistance was comparable amongst the three groups. Most patients (62/64) further underwent vitrectomy. Ceftazidime and vancomycin achieved vitreous concentrations more than the minimum inhibitory concentration (MIC) at 48 h after the first injection. Conclusion: The choice of antibiotics did not affect the rate of vitrectomy and final vision in a real?life scenario. Ceftazidime and vancomycin can still be used as first?line intravitreal antibiotics owing to their comparable microbial sensitivity profile and adequate ocular bioavailability

Susceptibility to Vancomycin of Biofilm Producing Staphylococci Isolated from Tertiary Care Hospital of Nepal / Susceptibilidad a la vancomicina de estafilococos productores de biopelículas aislados del hospital de atención terciaria de Nepal

Background: Methicillin resistance and biofilm-producing Staphylococci are emerging as multidrug-resistant strains narrowing the efficacy of antimicrobial therapy. Although vancomycin is used as the drug of choice to treat such isolates, different studies worldwide have documented the emergence of strains that are intermediately susceptible or resistant to this antibiotic. Objective: The study aimed to determine the minimum inhibitory concentration of vancomycin to methicillin-resistant and biofilm-producing staphylococci isolated from different clinical specimens. Methods: 375 staphylococci isolated from different clinical specimens over one year were included in the study. Biofilm formation was determined by the Tissue culture plate method (TCP), and ica genes were identified by Polymerase Chain Reaction (PCR). Antibiotic susceptibility and methicillin resistance were done following Clinical and Laboratory Standards Institute (CLSI) guidelines. The minimum inhibitory concentration (MIC) of vancomycin in all isolates was determined by the agar dilution method. Results:Among 375 Staphylococci studied, 43% and 57% represented S. aureus and Coagulase-Negative Staphylococci (CNS), respectively. The rate of Methicillin-Resistant S. aureus (MRSA) and Methicillin-Resistant Coagulase Negative Staphylococci (MRCNS) were 81.4% and 66.8% respectively and determined by the disc diffusion method. The most potential antibiotics were tetracycline and chloramphenicol showing sensitivity to more than 90% isolates. The Minimum Inhibitory Concentration (MIC) value of oxacillin for staphylococci ranged from 0.125-32 µg/ml. Oxacillin agar diffusion method showed 51.6% and 79.9% isolates as MRSA and MRCNS, respectively, revealing a very high percentage of S. aureus and CNS isolates as methicillin-resistant. All isolates had susceptible vancomycin MICs that ranged from 0.125-2 µg/ml. Two S. aureus isolated from Central Venous Catheter (CVC) and catheter specimens were detected with intermediate susceptibility to vancomycin. Similarly, three CNS isolated from blood, CVC, and wound/pus (w/p) were intermediately susceptible to vancomycin. Strong biofilm formation was observed in 22.1% of clinical isolates, and the ica gene was detected among 22.9% of isolates. Only one S. aureus detected as a biofilm producer by the TCP method was found to have intermediate susceptibility to vancomycin. Conclusions: The increment in vancomycin MIC among methicillin-resistant and biofilm-producing staphylococci is alarming. Strict control measures to prevent methicillin-resistant isolates spread and routine surveillance for vancomycin-resistant isolates must be incorporated in hospitals to prevent antimicrobial treatment failure

Antecedentes: Los estafilococos resistentes a la meticilina y productores de biopelículas están surgiendo como cepas multirresistentes que reducen la eficacia del tratamiento antimicrobiano. Aunque la vancomicina se utiliza como fármaco de elección para tratar dichos aislados, diferentes estudios realizados en todo el mundo han documentado la aparición de cepas intermedias susceptibles o resistentes a este antibiótico. Objetivo: El estudio tenía como objetivo determinar la concentración mínima inhibitoria de la vancomicina para los estafilococos resistentes a la meticilina y productores de biofilm aislados de diferentes muestras clínicas. Métodos: Se incluyeron en el estudio 375 estafilococos aislados de diferentes muestras clínicas durante un año. La formación de biopelículas se determinó mediante el método de la placa de cultivo de tejidos (TCP), y los genes ica se identificaron mediante la reacción en cadena de la polimerasa (PCR). La susceptibilidad a los antibióticos y la resistencia a la meticilina se realizaron siguiendo las directrices del Clinical and Laboratory Standards Institute (CLSI). La concentración inhibitoria mínima (MIC) de vancomicina en todos los aislados se determinó por el método de dilución en agar. Resultados:Entre los 375 estafilococos estudiados, el 43% y el 57% representaban S. aureus y estafilococos coagulasa-negativos (ECN), respectivamente. La tasa de S. aureus resistente a la meticilina (SARM) y de estafilococos coagulasa negativos resistentes a la meticilina (ECNM) fue del 81,4% y el 66,8%, respectivamente, y se determinó por el método de difusión de discos. Los antibióticos más potenciales fueron la tetraciclina y el cloranfenicol, que mostraron una sensibilidad superior al 90% de los aislados. El valor de la concentración inhibitoria mínima (CIM) de la oxacilina para los estafilococos osciló entre 0,125-32 µg/ml. El método de difusión en agar de la oxacilina mostró que el 51,6% y el 79,9% de los aislados eran SARM y MRCNS, respectivamente, lo que revela que un porcentaje muy elevado de los aislados de S. aureus y CNS son resistentes a la meticilina. Todos los aislados tenían MIC de vancomicina susceptibles que oscilaban entre 0,125-2 µg/ml. Se detectaron dos S. aureus aislados de muestras de catéteres venosos centrales (CVC) y catéteres con una susceptibilidad intermedia a la vancomicina. Del mismo modo, tres S. aureus aislados de sangre, CVC y herida/pus (w/p) fueron intermedianamente susceptibles a la vancomicina. Se observó una fuerte formación de biopelículas en el 22,1% de los aislados clínicos, y se detectó el gen ica en el 22,9% de los aislados. Sólo un S. aureus detectado como productor de biopelículas por el método TCP resultó tener una susceptibilidad intermedia a la vancomicina. Conclusiones: El incremento de la MIC de vancomicina entre los estafilococos resistentes a la meticilina y productores de biofilm es alarmante. Para evitar el fracaso del tratamiento antimicrobiano, deben incorporarse en los hospitales medidas de control estrictas para prevenir la propagación de los aislados resistentes a la meticilina y una vigilancia rutinaria de los aislados resistentes a la vancomicina

Genotypic characterization of vancomycin-resistant Enterococcus causing urinary tract infection in northern India

Background & objectives: Infections caused by vancomycin-resistant Enterococci are difficult to treat given the limited therapeutic alternatives. Different gene clusters are known to confer vancomycin resistance. vanA and vanB genes are transferable and are clinically relevant. This cross-sectional study aimed to identify the vancomycin-resistant genotypes in the strains causing urinary tract infection and also to test the in vitro efficacy of linezolid and pristinamycin against the vancomycin-resistant isolates. Methods: Antimicrobial resistance profile of 118 enterococcal isolates was evaluated. Minimum inhibitory concentration of vancomycin, teicoplanin and high-level gentamicin (HLG) was determined by micro broth dilution. The vancomycin-resistant isolates were tested against linezolid and pristinamycin by micro-broth dilution and E strip method. The presence of vancomycin-resistant genes was detected by multiplex polymerase chain reaction and was sequenced and analyzed. Results: Most commonly isolated species were Enterococcus faecalis (76.9%) and Enterococcus faecium (16.9%). It was found that 43 per cent of the isolates were resistant to HLG and 16.9 per cent to vancomycin. Higher resistance was seen against fluoroquinolones, erythromycin, tetracycline and ?-lactam drugs. However, 5.08 per cent strains were resistant to tigecycline. All vancomycin-resistant strains were sensitive to pristinamycin and one was resistant to linezolid. vanA and vanB gene were found in 15 and five isolates, respectively. The gene sequences were submitted to NCBI gene bank and accession numbers were obtained. Interpretation & conclusions: The present study showed prevalence of vanA and vanB genes carrying Enterococcus in a tertiary care centre in north India. The emergence of resistance against drugs such as tigecycline and linezolid is a topic of concern as it will be a therapeutic challenge for physicians.

Monitoramento orientado pela área sob a curva da vancomicina em pacientes pediátricos / Vancomycin area under the curve-guided monitoring in pediatric patients

RESUMO Objetivo: Avaliar a probabilidade de atingir o alvo pela razão entre a área sob a curva e a concentração inibitória mínima de vancomicina em pacientes pediátricos após o esquema de dose empírica e demonstrar a aplicabilidade desse método para o monitoramento da vancomicina. Metódos: Foi realizado um estudo de coorte retrospectivo que incluiu pacientes pediátricos com função renal normal internados entre janeiro e dezembro de 2020. O modelo de um compartimento com cinética de primeira ordem foi utilizado para estimar os parâmetros farmacocinéticos, e a área sob a curva foi calculada pela regra do trapézio. O alvo terapêutico foi definido como a razão entre a área sob a curva e a concentração inibitória mínima ≥ 400 e < 600. O teste do qui-quadrado foi aplicado para comparar a probabilidade de atingir o alvo nos grupos etários, enquanto os parâmetros farmacocinéticos foram comparados pelo teste de Kruskal-Wallis com o teste de Dunn para análises post hoc. Consideraram-se significativos os valores de p < 0,05. Resultados: Foram analisados, no total, 42 pares de níveis de vancomicina de 17 pacientes inscritos neste estudo. Após a dose diária empírica de vancomicina, o alvo terapêutico foi atingido em cinco (29%) pacientes; quatro pacientes (24%) apresentavam razão entre a área sob a curva inicial supraterapêutica e o valor de concentração inibitória mínima (> 600mg.h/L) e oito (47%) tinham valores subterapêuticos (< 400mg.h/L). Os patógenos mais identificados foram Staphylococcus spp. (n = 7). Os níveis de vale e as áreas sob a curva mostraram valores moderados de correlação (R2 = 0,73). Um (6%) paciente apresentou lesão renal aguda. Conclusão: A maioria dos pacientes não atingiu o alvo terapêutico com esquema de dose empírica de vancomicina, e a implementação de dosagem baseada na área sob a curva usando duas medições de amostra permitiu ajustes de dose em tempo real com base nos parâmetros farmacocinéticos dos indivíduos.

ABSTRACT Objective: To assess the percentage of vancomycin area under the curve/minimum inhibitory concentration target attainment in pediatric patients after the empirical dose regimen and to demonstrate the applicability of this method for vancomycin monitoring. Methods: A retrospective cohort study was performed including pediatric patients with normal renal function admitted between January 2020 and December 2020. The one-compartment model with first-order kinetics was used to estimate the pharmacokinetic parameters, and the area under the curve was calculated by the trapezoidal rule. The therapeutic target was defined as area under the curve/minimum inhibitory concentration ≥ 400 and < 600. The Chi-squared test was applied to compare the percentage of target attainment over age groups, while the pharmacokinetic parameters were compared by the Kruskal-Wallis test with Dunn's test for post hoc analyses. We considered significant p-values < 0.05. Results: In total, 42 pairs of vancomycin levels were analyzed from 17 patients enrolled in this study. After empirical vancomycin daily dosing, the therapeutic target was achieved in five (29%) patients; four patients (24%) had a supratherapeutic initial area under the curve/minimum inhibitory concentration value (> 600mg.h/L), and eight (47%) patients had subtherapeutic values (< 400mg.h/L). The most identified pathogens were Staphylococcus spp. (n = 7). Trough levels and areas under the curve showed moderate correlation values (R2 = 0.73). Acute kidney injury occurred in one (6%) patient. Conclusion: Most patients did not reach the therapeutic target with a vancomycin empirical dose regimen, and the implementation of area under the curve-based dosing using two sample measurements allowed for real-time dose adjustments based on individuals' pharmacokinetic parameters.

An anterolateral thigh perforator chimeric flap combined with calcium sulfate impregnated with vancomycin for treatment of chronic fracture-related infection complicated with extensive soft-tissue defects / 中华创伤骨科杂志

Objective:To investigate the efficacy of an anterolateral femoral chimeric perforator flap combined with vancomycin-loaded calcium sulfate in the treatment of chronic infection after internal fixation of calf fracture with soft tissue defects.Methods:Retrospectively analyzed were the data of 16 patients with chronic infection combined with extensive soft tissue defects after internal fixation of calf fracture who had been admitted to Department of Orthopedics, Shenzhen Hospital Affiliated to Peking University from September 2008 to November 2020. There were 11 males and 5 females, aged from 16 to 62 years (average, 37 years). Infection sites: the upper tibia in 4 cases, the middle and lower tibia in 10 cases, and the middle fibula in 2 cases. According to the Cierny-Mader classification, all patients were anatomical type III and by the host classification, there were 14 cases of type B and 2 cases of type C type. The areas of soft tissue defects ranged from 6 cm × 4 cm to 23 cm × 14 cm. All patients were treated by transplantation of an anterolateral thigh chimeric perforator flap combined with vancomycin-loaded calcium sulfate therapy. At the last follow-up, the curative efficacy was evaluated according to the Paley fracture union scoring.Results:All patients were followed up for 8 to 24 months (mean, 16 months). Complete flap survival was achieved in 15 flaps and partial survival in one. According to the Paley fracture union scoring at the last follow-up, the curative efficacy was evaluated as excellent in 15 cases and as good in one. Both the grafted artificial bone and the tibia and fibula achieved bone union after 6 to 12 months (mean, 8.9 months). Infection with chronic sinus tract pus recurred in one case at post-operative one year. After re-debridement, the infection was controlled and the wound healed. The plate internal fixation was replaced by the unilateral or annular external fixator in 14 patients and retained in 2 patients. The lengths of the bone defects averaged 2.4 cm and the time for the external fixation 10.5 months (from 8 to 14 months).Conclusion:In the treatment of chronic infection after internal fixation of calf fracture with extensive soft tissue defects, the efficacy of an anterolateral femoral chimeric perforator flap combined with vancomycin-loaded calcium sulfate is satisfactory, because the flap can fully cover the bone and soft tissue defects while the vancomycin-loaded calcium sulfate can effectively control the infection.

Effect of vancomycin-loaded microbubbles combined with ultrasound targeted microbubble destruction technology on methicillin-resistant Staphylococcus aureus biofilms / 中华创伤杂志

Objective:To investigate the effect of vancomycin (Vm)-loaded microbubbles (MBs) combined with ultrasound targeted microbubble destruction (UTMD) technique on the morphological structure, thickness and bacterial viability of methicillin-resistant Staphylococcus aureus (MRSA) biofilms.Methods:Vm-MBs were prepared by thin film hydration. Sterile coverslips in a diameter of 13 mm were placed in 24-well plates to construct in vitro biofilm models using MRSA as the test strain, and the biofilm morphology was observed by naked eye and light microscopy after crystal violet staining. LIVE/DEAD, SYTO59 and DIL were used to stain biofilms and MBs, respectively. After staining, the biofilm morphology and position of the biofilm in relation to MBs were observed using laser confocal scanning microscopy. The biofilms were divided into control group, Vm group, Vm-MBs group, UTMD group and Vm-MBs+UTMD group according to the random number table method, with 9 samples in each group. After biofilms of each group were treated accordingly for 24 hours, the morphological and structural changes of biofilms in each group were observed using laser confocal scanning microscopy and scanning electron microscopy following LIVE/DEAD staining; the difference in biofilm density in each group was measured with the aid of an enzyme marker following crystal violet staining; the difference in biofilm thickness and bacterial viability in each group were observed by laser confocal scanning microscopy. Results:The prepared Vm-MBs met the experimental requirements. The constructed biofilm model observed by naked eye, light microscopy and laser confocal scanning microscopy showed that the biofilm structure was dense with a relatively uniform thickness of (13.8±0.2)nm, a small amount of dead bacteria inside the membrane and the percentage of live bacteria of (94.9±0.3)%. Laser confocal scanning microscopy showed that MBs could penetrate into deeper layers of biofilms. After the respective treatment was given to each group for 24 hours, Laser confocal scanning microscopy and scanning electron microscopy following LIVE/DEAD staining showed that the biofilm morphological structure was most significantly disrupted in Vm-MBs+UTMD group compared to control, Vm, Vm-MBs and UTMD groups. In Vm-MBs+UTMD group, a large number of dead bacteria was observed, with only a few scattered planktonic bacteria and irregular changes in cell membrane morphology. Crystal violet staining showed that the biofilm density was significantly lower in Vm-MBs+UTMD group compared to control group ( P<0.05), while the differences between Vm, Vm-MBs and UTMD groups were not statistically significant (all P>0.05). Laser confocal microscopy showed that the biofilm thickness was thinner in Vm-MBs, UTMD and Vm-MBs+UTMD groups compared to control group (all P<0.05), with no significant difference between Vm group and control group ( P>0.05) and that the biofilm thickness was thinner in Vm-MBs+UTMD group compared to Vm, Vm-MBs and UTMD groups (all P<0.01), with no significant differences between the other groups (all P>0.05). Bacterial activity in Vm, Vm-MBs, UTMD and Vm-MBs+UTMD groups was significantly lower than that in control group (all P<0.01), with lower in Vm-MBs+UTMD group compared to Vm, Vm-MBs and UTMD groups (all P<0.01), but without significant difference between the other groups (all P>0.05). Conclusion:Vm-MBs combined with UTMD technology can effectively destroy the biofilm morphological structure to reduce biofilm thickness. Meanwhile, Vm-MBs combined with UTMD technology can release antibiotics and significantly decrease bacterial viability to improve antibiotic bactericidal efficacy.

Characteristics and management of children with Clostridioides difficile infection at a tertiary pediatric hospital in China

ABSTRACT Background: Clostridiodes difficile infection (CDI) is one of the most common causes of antibiotic-associated diarrhea in children. Conventional antibiotics and emerging fecal micro-biota transplantation (FMT) are used to treat CDI. Methods: Children with CDI admitted to the Shanghai Children's Hospital, from September 2014 to September 2020, were retrospectively included to this observational study. Pediatric patients were assigned as initial CDI and recurrent CDI (RCDI), and symptoms, comorbid-ities, imaging findings, laboratory tests, and treatments were systematically recorded and analyzed. Results: Of 109 pediatric patients with CDI, 58 were boys (53.2%), and the median age was 5 years (range, 2-9 years). The main clinical symptoms of CDI children were diarrhea (109/109, 100%), hematochezia (55/109, 50.46%), abdominal pain (40/109, 36.70%); fever, pseudomembrane, vomit, and bloating were observed in 39 (35.78%), 33 (30.28%), and 24 (22.02%) patients, respectively. For the primary therapy with conventional antibiotics, 68 patients received metronidazole, and 41 patients received vancomycin. RCDI occurred in 48.53% (33/68) of those initially treated with metronidazole compared with 46.33% (19/41) of those initially treated with vancomycin (p=0.825). The total resolution rate of FMT for RCDI children was significantly higher than with vancomycin treatment (28/29, 96.55% vs 11/23, 47.83%, p < 0.001). There were no serious adverse events (SAEs) reported after two months of FMT. Conclusions: The major manifestations of children with CDI were diarrhea, hematochezia, and abdominal pain. The cure rate of FMT for pediatric RCDI is superior to vancomycin treatment.