Safety and efficacy of a novel drug elores (ceftriaxone + sulbactam + disodium edetate) in the management of multi-drug resistant bacterial infections in tertiary care centers: a post-marketing surveillance study

Abstract Objective: In India, Elores (CSE-1034: ceftriaxone + sulbactam + disodium edetate) was approved as a broad spectrum antibiotic in year 2011 and is used for management of Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections in tertiary care centers. The objective of this study was to investigate the efficacy of this drug in patients with Extended Spectrum Beta Lactamases/Metallo Beta lactamases infections and identify the incidence of adverse events in real clinical settings. Methods: This Post Marketing Surveillance study was conducted at 17 centers across India and included 2500 patients of all age groups suffering from various bacterial infections and treated with Elores (CSE1034). Information regarding demographic, clinical and microbiological parameters, dosage and treatment duration, efficacy and adverse events (AEs) associated with the treatment were recorded. Results: A total of 2500 patients were included in the study and efficacy was evaluated in 2487 patients. In total, 409 AEs were reported in 211 (8.4%) patients. The major AEs reported were vomiting (3.0%), pain at injection site (2.5%), nausea (2.3%), redness at site (1.96%), thrombophlebitis (1.4%). Of total reported AEs, 40 (5.3%) AEs were reported in pediatric, 310 (20.6%) in adult, and 59 (23.6%) in geriatric group. No AE belonging to grade IV or V was reported in any patient. In terms of efficacy, 1977 (79.4%) patients were cured, 501 (20.1%) patients showed clinical improvement and 5 (0.2%) patients were complete failure. The treatment duration varied from 5 to 7 days in different patients depending on the infection type. Conclusion: In this post-marketing surveillance study, CSE-1034 was found to be an effective and safe option against Pip tazo and meropenem in management of patients with multi-drug resistant (MDR) bacterial infections under routine ward settings.

ANTIBIOTIC PROPHYLAXIS IN BARIATRIC SURGERY: a continuous infusion of cefazolin versus ampicillin/sulbactam and ertapenem / Antibioticoprofilaxia em cirurgia bariátrica: infusão contínua de cefazolina versus ampicilina/sulbactam e ertapenem

Background The incidence of surgical site infection in bariatric patients is significant and the current recommendations for antibiotic prophylaxis are sometimes inadequate. Objective The aim of this study was to analyze the effect of three prophylactic antibiotic regimens on the incidence of surgical site infection. Methods A prospective, cross-sectional study was conducted between January 2009 and January 2013 in which 896 Roux-en-Y gastric bypasses were performed to treat obesity. The study compared three groups of patients according to the perioperative antibiotic prophylaxis administered intravenously and beginning at anesthesia induction: Group I consisting of 194 patients treated with two 3-g doses of ampicillin/sulbactam; Group II with 303 patients treated with a single 1-g dose of ertapenem; and Group III with 399 patients treated with a 2-g dose of cefazolin at anesthesia induction followed by a continuous infusion of cefazolin 1g throughout the surgical procedure. The rate of surgical site infection was analyzed, as well as its association with age, sex, preoperative weight, body mass index and comorbidities. Results The rates of surgical site infection were 4.16% in the group treated prophylactically with ampicillin/sulbactam, 1.98% in the ertapenem group and 1.55% in the continuous cefazolin group. Conclusion The prophylactic use of continuous cefazolin in surgeries for morbid obesity shows very promising results. These findings suggest that some prophylactic regimens need to be reconsidered and even substituted by more effective therapies for the prevention of surgical site infections in bariatric patients. .

Contexto A incidência de infecção de sítio cirúrgico em pacientes bariátricos é significativa e as recomendações atuais para a profilaxia antibiótica são por vezes inadequadas. Objetivo O objetivo deste estudo foi analisar o efeito de três esquemas de antibióticos profiláticos sobre a incidência de infecção de sítio cirúrgico. Método Estudo prospectivo, transversal, foi realizado entre janeiro de 2009 e janeiro de 2013, em que 896 derivações gástricas em Y de Roux foram realizadas para tratar a obesidade. O estudo comparou três grupos de pacientes de acordo com a profilaxia antibiótica administrada no perioperatória por via intravenosa, iniciada na indução anestésica: Grupo I constituído de 194 pacientes tratados com duas doses de 3 g de ampicilina/sulbactam; Grupo II com 303 pacientes tratados com uma única dose de 1 g de ertapenem; e Grupo III com 399 pacientes tratados com uma dose de 2 g de cefazolina no momento da indução da anestésica seguida de uma infusão contínua de cefazolina 1 g durante o procedimento cirúrgico. A taxa de infecção de sítio cirúrgico foi analisada, bem como a sua associação com a idade, sexo, peso pré-operatório, o índice de massa corporal e comorbidades. Resultados As taxas de infecção do sítio cirúrgico foram de 4,16% no grupo tratado profilaticamente com ampicilina/sulbactam, 1,98% no grupo de ertapenem e 1,55% no grupo de cefazolina contínua. Conclusão O uso profilático de cefazolina contínua em cirurgias para obesidade mórbida apresenta resultados muito promissores. Estes resultados sugerem que alguns regimes profiláticos precisam ser reconsiderados e até mesmo substituídos por terapias mais eficazes para a prevenção de infecções de sítio cirúrgico em pacientes bariátricos. .

Sulbactam-based therapy for Acinetobacter baumannii infection: a systematic review and meta-analysis

BACKGROUND: A number of studies have reported on the effectiveness of sulbactam-based therapies for Acinetobacter baumannii infection; however, there is little evidence that sulbactam-based therapies are more or less effective than alternative therapies. Unfortunately, there is a distinct lack of high quality data (i.e., from randomized controlled trials) available on this issue. Therefore, we conducted a systematic review and meta-analysis comparing the efficacy of sulbactam-based and non-sulbactam-based regimens in the treatment of A. baumannii infection. METHODS: We searched PubMed, MEDLINE, Biomedical Central, Google Scholar, the China National Knowledge Infrastructure, the Cochrane library, and the Directory of Open Access using the terms "sulbactam and baumannii" or "maxtam and baumannii". Randomized controlled trials, controlled clinical studies, and cohort studies were considered for inclusion. The primary outcome was the clinical response rate for sulbactam-based therapy vs comparator therapies. RESULTS: Four studies (1 prospective, 3 retrospective) were included in the metaanalysis. Sulbactam was given in combination with ampicillin, carbapenem, or cefoperazone (n = 112 participants). Comparator drugs included colistin, cephalosporins, anti-pseudomonas penicillins, fluoroquinolones, minocycline/doxycycline, aminoglycosides, tigecycline, polymyxin, imipenem/cilastatin, and combination therapy (n = 107 participants). The combined clinical response rate odds ratio did not significantly favor sulbactam-based therapy over comparator therapy (odds ratio = 1.054, 95% confidence interval = 0.550-2.019, p = 0.874), nor did any of the individual study odds ratios. CONCLUSIONS: The available evidence suggests that sulbactam-based therapy may be similarly efficacious to alternative antimicrobial therapies for the treatment of A. baumannii infection. Further research on this issue is warranted given the limited availability of data from high quality/randomized controlled trials.

The minimal inhibitory concentration for sulbactam was not associated with the outcome of infections caused by carbapenem-resistant Acinetobacter sp. treated with ampicillin/sulbactam

OBJECTIVE: The objective of this study was to evaluate whether the outcomes of carbapenem-resistant Acinetobacter infections treated with ampicillin/sulbactam were associated with the in vitro susceptibility profiles. METHODS: Twenty-two infections were treated with ampicillin/sulbactam. The median treatment duration was 14 days (range: 3-19 days), and the median daily dose was 9 g (range: 1.5-12 g). The median time between Acinetobacter isolation and treatment was 4 days (range: 0-11 days). RESULTS: The sulbactam minimal inhibitory concentration (MIC) ranged from 2.0 to 32.0 mg/L, and the MIC was not associated with patient outcome, as 4 of 5 (80%) patients with a resistant infection (MIC≥16), 5 of 10 (50%) patients with intermediate isolates (MIC of 8) and only 1 of 7 (14%) patients with susceptible isolates (MIC ≤4) survived hospitalization. CONCLUSION: These findings highlight the need to improve the correlation between in vitro susceptibility tests and clinical outcome. .

Pharmacodynamic assessment of Amoxicillin-Sulbactam against Acinetobacter baumannii: searching the optimal dose and infusion time through a human ex-vivo model

Amoxicillin-sulbactam (AMX-SUL) is an aminopenicillin/ß-lactamase inhibitor combination currently available in 29 countries and may be a suitable option for treating infections caused by Acinetobacter spp. Thus, we sought to search the optimal dosing strategy for this formulation through an ex vivo pharmacodynamic human model against Acinetobacter baumanniii. Four volunteers were randomized to receive alternatively a single dose AMX-SUL infused both either over 30 min or 3h at the following ratios (g/g): 1/0.5; 1/1, and 0/2. Time-kill studies were performed with the 0-, 0.5-, 2-, 4-, 6- and 8-h sera after dose against a clinical isolate of A. baumannii (sulbactam MIC, 4µg/mL). Bactericidal activity (i.e. a mean decrease >3 log10 CFU/mL in the viable cell counts from the initial inoculum) was displayed by the 0.5- and the 2-h sera after dose for all formulations. The 4-h sera proved inhibitory with the AMX-SUL 1g/1g formulation, albeit a trend to regrowth was observed after 24-h incubation. With the AMX-SUL 0g/2g dose, the 4-h sera proved almost bactericidal activity (i.e. a mean decrease of 2.4 log10 CFU/mL in the viable cell counts from the initial inoculum), whereas the 6-h sera was inhibitory, with a trend to regrowth after 24-h incubation. When infused over 3h, AMX-SUL 1g/0.5g and 1g/1g, bactericidal activity was displayed by the 0.5-, 2- and the 4-h sera after dose and the 6-h sera proved inhibitory with the AMX-SUL 1g/1g formulation. The present study, albeit preliminary, might give a rationale for the dosing strategy to treat infections caused by A. baumannii with sulbactam, either alone or combined with amoxicillin. A 2-g sulbactam dose seems to be optimal to be infused over 30 min with a 6-h dosing interval. When infused over 3h, AMX-SUL 1g/1g given every 6h or 8h seems a suitable dosing schedule.

Intrathecal use of amikacin: a case report

Meningitis caused by Acinetobacter baumannii is rare and are mostly hospital acquired after neurosurgical procedure. We report a case of a 40-year old man was admitted to the intensive care unit due to subarachnoid haemorrhage. Our patient developed a ventriculitis due to A.baumannii treated successfully with sulbactam IV and intrathecal amikacin.

Bioequivalence study of the two 1.5 g cefoperazone and sulbactam IM injections in Thai healthy male volunteers.

OBJECTIVE: To perform a bioequivalence study of the two 1.5 g cefoperazone (1.0 g) and sulbactam (0.5 g) between Cefper and Sulperazon injections. MATERIAL AND METHOD: The present study was performed in 24 Thai healthy male volunteers who were intramuscularly injected a single dose of 1.5 g cefoperazone and sulbactam. A single dose, two periods, two sequences, double blind randomized crossover with a one-week washout period was used. Blood samples were collected before and at 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 4, 6, 8, and 12 hours after intramuscular injection and determined for cefoperazone and sulbactam plasma concentration by validated HPLC-UV methods. The pharmacokinetic parameters were analyzed by noncompartmental analysis and the ANOVA was carried out. RESULTS: Tax of both cefoperazone and sulbactam for volunteers who were injected with either Cefper or Sulperazon injection were not significantly different (p > 0.05). The 90% confidence intervals of the log of ratio of either C(max) or AUC(last) or AUC(inf) of both cefoperazone and sulbactam between 1.5 g Cefper and Sulperazon injections were within the bioequivalence range of 0.80-1.25. CONCLUSION: The 1.5 g cefoperazone and sulbactam injection of Cefper and Sulperazone used in the present study are bioequivalent.

Synergy of Arbekacin-based Combinations Against Vancomycin Hetero-intermediate Staphylococcus aureus

This study was undertaken to evaluate the in vitro activities of arbekacin-based combination regimens against vancomycin hetero-intermediate Staphylococcus aureus (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin-sulbactam, teicoplanin, or quinipristin-dalfopristin against seven hetero-VISA strains and two methicillin-resistant S. aureus strains were evaluated by the time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or ampicillinsulbactam showed the synergistic interaction against hetero-VISA strains. Data suggest that these arbekacin-based combination regimens may be useful candidates for treatment options of hetero-VISA infections.

Microbiological assay of ampicillin in serum and aqueous humor of patients given ampicillin-sulbactam injection.

The aim of this study was to determine the bacterial growth inhibitory activities of ampicillin in aqueous humor and serum of patients administered ampicillin-sulbactam combination intramuscularly prior to cataract surgery. 43 patients received a combination of both antibiotics intramuscularly at varying periods (60-140 minutes) prior to surgery. Aqueous humor and venous blood were collected at the beginning of the surgery. For microbiological assay, spores of Bacillus subtilis were incorporated in the agar. The test sample and the standard solutions (calibrators) of ampicillin and ampicillin-sulbactam combination were placed in 3 mm wells in the agar. The diameter zones of growth inhibitory activities of ampicillin of the calibrators and the test samples measured in mm were extrapolated to the standard curve and were recorded as ampicillin activity in micrograms/ml. The results of the assay were placed in 5 groups according to the time intervals between injection and collection of serum and aqueous humor (< or = 70, 75, 80, 90, > 90 minutes). Ampicillin activities in sera and aqueous humor of group 5 (> 90 minutes) were significantly higher than the others (p < 0.001). The ratio of ampicillin activities of sera and aqueous humor in group 5 patients was significantly lower indicating higher concentration of ampicillin activity in aqueous humor during this period. Bacterial growth inhibitory activities of ampicillin-sulbactam combination were adequate in aqueous humor of all patients with highest activity being 90 minutes after intramuscular administration indicating the potential usefulness of this antibiotic combination as chemoprophylaxis prior to cataract surgery.

Uso de cefoperazona/sulbactam en pacientes pediátricos con sepsis intraabdominal / Use of sulbactam/cefoperazone in paediatrics patients with intraabdominal sepsis

De enero a octubre de 1994, se trataron 20 niños con peritonitis, todos mayores de 3 años. En 18 casos, la peritonitis fue secundaria a apendicitis aguda (14 perforadas, 2 gangrenosas y 2 flegomonosas), en un caso a divertículo de Meckel perforado y en otro a perforación accidental de recto. En todos se encontró pus libre en cavidad peritoneal. El tiempo de evolución clínica previo a la hospitalización fue menor de 48 horas en casos, de 48 horas a 72 horas en 13 y mayor de 72 horas en 3. Se administró cefoperazona/sulbactam (SBT/CPZ) endovenosa a 100 mgs x peso x día, fraccionada cada 8 horas por un máximo de 8 días en 15 pacientes, el resto lo recibió entre 9 y 10 días. La estancia hospitalaria fue en 11 casos hasta 7 días. Se determinó al inicio y al final del tratamiento transaminasas, urea, creatinina y plaquetas; en todos los casos los resultados fueron normales. Solo un paciente presentó tiempo de protrombina prolongado. Cinco niños presentaron absceso de pared (resuelto sólo con drenaje), uno ameritó reintervención por absceso intraabdominal, en este caso se cambió la antibióticoterapia, otro se reintervino por síndrome adherencial. Se demostró la utilidad de SBT/CPZ en el tratamiento de la sepsis intraabdominal

Histerectomía laparoscópica minimamente invasiva: técnica de Pelosi de punción única / Laparoscopic hysterectomy minimally invasive: Pelosi's technique by single punction

El propósito de este trabajo es determinar las indicaciones, factibilidad, resultados, complicaciones y costos de histerectomía laparoscópica utilizando punción única, introducir esta técnica en América-Latina. Los resultados sugieren que esta nueva técnica es segura, efectiva y mas económica que otras técnicas de histerectomía por laparoscopía

Operación cesárea: técnica simplificada de Pelosi / Cesarean section: Pelosi's simple technique

Se introduce una nueva técnica de cesárea, mínimamente invasiva. Sus ventajas son: simplicidad, costo-beneficio, recuperación mas rápida y mínima morbilidad

Estudio clínico microbiológico de uretritis gonococcicas tratadas con amoxicilina-sulbactama / Microbiological clinic study of gonococci infection of genital tract treated with amoxycillin-sulbactam

Se trataron 49 pacientes ambulatorios, de sexo masculino, de edades comprendidas entre 13 y 60 años, con diagnóstico de uretritis gonocóccica, provenientes del Hospital "J. R. Vidal" del Centro Dermatológico de la Ciudad de Corrientes y de consultorios externos del Instituto de Patología Regional de la Universidad Nacional del Nordeste de Resistencia (Argentina). En todos los casos se aisló Neisseria gonorrhoeae en el cultivo, siendo el 35 por ciento de las cepas estudiadas productoras deÿß-lactamasas, cifra similar a la obtenida en otros estudios nacionales. Todos los pacientes fueron tratados con una dosis única de amoxicilina-sulbactama de 3 grs. cada componente. Se confirmó curación clínica en el 94 por ciento de los pacientes mientras que en 3 (6 por ciento) hubo mejoría clínica. Presentaron erradicación bacteriológica el 98 por ciento y solo un fracaso bacteriológico. La administración de la asociación fué muy bien tolerada, solo dos pacientes presentaron síntomas digestivos. En conclusión la asociación amoxicilina-sulbactama ha demostrado ser efectiva "in vitro" e "in vivo", y constituye una opción terapéutica válida y útil para el tratamiento de las uretritis gonocóccicas