Single Prophylactic Dose Research Articles

Editorial Comment

Prostate biopsy is one of the most common procedures performed by urologists with an estimated >2 million performed in the United States and Europe every year, 1 Borghesi M. Ahmed H. Nam R. et al. Complications after systematic, random, and image-guided prostate biopsy. Eur Urol. 2017; 71: 353-365 Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar , 2 Loeb S. Carter H.B. Berndt S.I. et al. Complications after prostate biopsy: data from SEER-Medicare. J Urol. 2011; 186: 1830-1834 Abstract Full Text Full Text PDF PubMed Scopus (451) Google Scholar and is the gold standard for the diagnosis of prostate cancer. The majority of prostate biopsies in the United States are done in the office setting using the ultrasound probe through a transrectal approach. The proximity of the posterior prostate to the anterior rectal wall provides easy access the peripheral zone which is known to harbor >70% of malignancies. 3 McNeal J.E. Normal histology of the prostate. Am J Surg Pathol. 1988; 12: 619-633 Crossref PubMed Scopus (421) Google Scholar However, this approach is associated with a significant risk of infectious complications, with rates ranging from 1 to 17.5% in the literature. Furthermore, the risk of serious infectious complications requiring hospitalization has been shown to be increasing over time, 4 Anastasiadis E. van der Meulen J. Emberton M. Hospital admissions after transrectal ultrasound-guided biopsy of the prostate in men diagnosed with prostate cancer: a database analysis in England. Int J Urol. 2015; 22: 181-186 Crossref PubMed Scopus (35) Google Scholar likely as a result of the increased prevalence of fluoroquinolone-resistant Escherichia coli. 5 Tukenmez Tigen E. Tandogdu Z. Ergonul O. et al. Outcomes of fecal carriage of extended-spectrum beta-lactamase after transrectal ultrasound-guided biopsy of the prostate. Urology. 2014; 84: 1008-1015 Abstract Full Text Full Text PDF PubMed Scopus (23) Google Scholar Partly in response to this, several centers are increasingly using the transperineal (TP) approach to prostate biopsy. Rather than using broad-spectrum prophylaxis, which contributes to antibiotic resistance, TP biopsies are often performed after a single prophylactic dose of first generation cephalosporin. Large series using this approach have reported sepsis rates approaching zero. 1 Borghesi M. Ahmed H. Nam R. et al. Complications after systematic, random, and image-guided prostate biopsy. Eur Urol. 2017; 71: 353-365 Abstract Full Text Full Text PDF PubMed Scopus (180) Google Scholar To date, TP biopsy has been mostly performed under general anesthesia, having important implications on health care resources, cost and time. Although the TP approach has been more widely adopted in other countries, in the United States it has been mostly reserved for special situations where the transrectal approach is either not possible or is unsafe. In recent years, several devices have been developed allowing TP prostate biopsies to be performed in the office, under local anesthesia, without the need for bulky, cumbersome, expensive equipment. The authors of this manuscript present their initial experience using 1 such device, and demonstrate the safety and feasibility of office TP prostate biopsy in a small number of men. What is now needed are studies in larger cohorts of patients demonstrating safety on a large scale using standardized reporting, patient tolerability using validated pain questionnaires and confirmation of the diagnostic accuracy for prostate cancer. Advances in prostate imaging (eg magnetic resonance imaging) aim to decrease the overuse of prostate biopsy, similarly modifications of the approach and instrumentation for prostate biopsy aim to decrease the morbidity of the procedure. These efforts will continue to shift the balance in favor of screening and diagnosis of prostate cancer, and will thus benefit the population on a large scale.

The Role of a Single Dose of Vancomycin in Reducing Clinical Sepsis in Premature Infants Prior to Removal of Peripherally Inserted Central Catheter: A Retrospective Study.

Peripherally inserted central catheter (PICC) line removal is associated with bloodstream infections and clinical sepsis. We aim to investigate the role of a single prophylactic dose of vancomycin in decreasing the incidence of central line associated bloodstream infection associated with PICC removal. A retrospective chart review of patients in the neonatal intensive care unit was conducted. Patients were divided into two study groups based on whether a single dose of vancomycin was administered (exposed) or not (nonexposed). The primary outcome measured was clinical sepsis with or without positive blood culture. The incidence of clinical sepsis in the exposed group was 7.3% compared with 6.3% in the nonexposed group (p-value: 0.7860). The incidence of culture-positive sepsis in the exposed group was 2.2% compared with 1.6% in the nonexposed group (p-value: 0.7673). The overall incidence of clinical and culture-positive sepsis in the subgroup with infants weighing <1,500 g and <32 weeks' gestational age was similar to the main study group. Our data do not support routine vancomycin prophylaxis prior to PICC line removal in premature infants to prevent sepsis associated with PICC removal. However, a large randomized controlled trial is further needed to delineate these results.

A randomized control trial to determine the need for postoperative antibiotics after laparoscopic appendicectomy in nonperforated appendicitis

Background: Acute Appendicitis is the most common cause of acute pain in the abdomen. Appropriate use of prophylactic antibiotics prevents the risk of postoperative surgical site infections (SSIs). However, there is no conclusive guideline concerning the duration of antibiotic usage. A single preoperative prophylactic dose has been recommended by many randomized control trials. Hence, the study aimed to determine the need for postoperative antibiotics after laparoscopic appendicectomy for nonperforated appendicitis.Methods: A total of 100 patients with nonperforated appendicitis undergoing laparoscopic appendicectomy divided into two groups. Group A (n=50) patients received single dose of preoperative antibiotic and group B (n=50) patients received preoperative dose, as well as three postoperative doses of antibiotics. Routine investigations including complete blood count, blood urea, serum creatinine; other investigations such as ultrasound of abdomen were also performed. Following laparoscopic appendicectomy, surgical wound was inspected after 48 h, 72 h, and on day 7 to look for any signs of postoperative SSI.Results: The mean age in group A was 30.74±10.69 years compared to 30.72±9.56 years (p=0.757) in group B. All the patients in study presented with right iliac fossa pain. Three patients in group A (6%) and two patients in group B (4%) had grade III SSIs, which were managed conservatively. The difference between both the groups for incidence of SSIs was statistically insignificant (p=1.000).Conclusions: Prophylactic postoperative doses of antibiotics confer no additional benefit over a single preoperative dose in preventing the postoperative SSIs after laparoscopic appendicectomy.

STUDY OF NEW ORAL QUINOLONES (LEVOFLOXACIN AND SITAFLOXACIN) AS PROPHYLACTIC ANTIMICROBIAL AGENTS IN TRANSRECTAL PROSTATE NEEDLE BIOPSY

(Objective) A single prophylactic dose of new quinolones is recommended to prevent infection associated with transrectal prostate needle biopsy (TRPB), except in high-risk patients, and a single dose of levofloxacin (LVFX) 500 mg is often administered. We examined single administrations of LVFX and sitafloxacin (STFX), in relation to the frequency of febrile infection. (Patients and methods) The subjects were 411 patients deemed to be suitable candidates for TRPB and ranging in age from 52 to 84 years (median, 75 years). Their PSA values ranged from 3.89 to 2,450 ng/mL (median, 6.92 ng/mL). They were randomly assigned to receive LVFX (group A, 204 patients) or STFX (group B, 207 patients), and the two groups were compared for the incidence of infection with a temperature of 38°C or more within 48 hours after TRPB. (Results) Febrile infection was observed in 8 (3.92%) of the 204 patients in group A and 1 (0.48%) of the 207 patients in group B. Of the 9 patients with febrile infection, 8 had acute prostatitis. There was a significant difference in the incidences of febrile infection between the two groups (p = 0.041; odds ratio, 8.41; 95% confidence interval, 1.04-67.85). The pathogenic bacteria in the 9 patients were Escherichia coli in 7 (Extended-spectrum beta-lactamase [ESBL]-producing bacteria in 3, LVFX-resistant bacteria in 2), Klebsiella pneumoniae in one, and Enterococcus faecalis in one. (Discussion) Measures against quinolone-resistant bacteria, ESBL-producing bacteria, and gram-positive bacteria should be considered for the prevention of infections associated with TRPB. Based on our present observations, STFX is considered to have more favorable effects than LVFX.

Effectiveness of Single-dose Rasburicase in Patients With Lymphoid Malignancies at a High Risk for Tumor Lysis Syndrome.

Tumor lysis syndrome (TLS) is a life-threatening disorder that occurs mainly in patients with high-tumor burden hemato-oncologic malignancies. It results in metabolic derangements, including hyperuricemia and acute renal failure. The powerful management for TLS is a daily dose of rasburicase for up to 5 days before chemotherapy; however, the optimal dose and duration of rasburicase for TLS prophylaxis have not been standardized for patients at high risk for TLS. Therefore, we evaluated the efficacy of single-dose rasburicase for prophylactic purposes in patients with malignant lymphoma at high risk for TLS. We retrospectively evaluated patients with malignant lymphoma at high risk for TLS treated with a prophylactic single-dose of rasburicase (0.1-0.2 mg/kg) from March 2012 to March2016. A total of 67 patients treated with a single-dose of rasburicase for prophylaxis were analyzed. A relatively large number of patients (n= 23; 34.3%) had the highly proliferative lymphoblastic lymphoma subtype (n= 14) or Burkitt lymphoma (n= 9) and were at the highest risks of tumor lysis. Two patients were newly diagnosed with TLS; the incidence of TLS after single-dose prophylaxis was 3.0%. Multivariate analysis revealed no predictable risk factors for response to prophylactic rasburicase, though increased level of serum creatinine approached statistical significance in reducing the efficacy of single-dose rasburicase to prevent TLS (odds ratio, 3.61; P= .054). Our data indicated that single-dose rasburicase effectively prevented progression of TLS, and, regardless of any risk factors, including increased creatinine, single-dose rasburicase for TLS prophylaxis was useful in patients with lymphoma at a high risk for TLS.

Single dose Intraoperative Antibiotics versus Postoperative Antibiotics for Patient Undergoing Laparoscopic Cholecystectomy for Symptomatic Cholelithiasis

Introduction: Surgical site infection is a common complication shown in literature following cholecystectomies. Smaller incision and use of trocars in laparoscopic cholecystectomy lessen the contamination resulting in less chances of surgical site infection. However, in fear of postoperative infection, many opt for the prolonged postoperative use of antibiotic and there is growing consensus against it. Antibiotics not only increases the cost and hospital stay duration but it aids in emergence of multidrug resistance. Because of the controversies, we conducted this clinical trial to see whether a single prophylactic dose of antibiotic at the time of induction of anesthesia for laparoscopic cholecystectomy was equally effective in controlling post-operative infection as multi-dose antibiotics during and post-operative period.&#x0D; Methods: The study was conducted at the department of general surgery, Lumbini Medical College Teaching Hospital, from November 2015 to October 2016. All cases with symptomatic cholelithiasis subjected for laparoscopic cholecystectomy were enrolled. Patients were randomized into two groups; Group SD received single dose of an intravenous dose of amikacin 500 mg, at induction of anesthesia and Group MD received multiple intravenous dose of amikacin, during and postoperatively for two days. Complications, hospital stay, and treatment cost in two groups were compared and analyzed.&#x0D; Results: There were a total of 240 patients in the study, 118 in Group SD and 122 in Group MD. Post-operative infection rate was 4.2% (n= 5, N=118) in Group SD and 3.3% (n=4, N=122) in Group MD; the difference was not significant (p=0.75). Hospital stay was prolonged and cost was higher significantly in Group MD.&#x0D; Conclusion: Single dose of prophylactic antibiotic, administered at induction of anesthesia, is equally effective as multiple doses of post surgical antibiotics to prevent post-operative infection in patients undergoing elective laparoscopic cholecystectomy for uncomplicated cholelithiasis.

Single dose Intraoperative Antibiotics versus Postoperative Antibiotics for Patient Undergoing Laparoscopic Cholecystectomy for Symptomatic Cholelithiasis

&#x0D; Introduction: Surgical site infection is a common complication shown in literature following cholecystectomies. Smaller incision and use of trocars in laparoscopic cholecystectomy lessen the contamination resulting in less chances of surgical site infection. However, in fear of postoperative infection, many opt for the prolonged postoperative use of antibiotic and there is growing consensus against it. Antibiotics not only increases the cost and hospital stay duration but it aids in emergence of multidrug resistance. Because of the controversies, we conducted this clinical trial to see whether a single prophylactic dose of antibiotic at the time of induction of anesthesia for laparoscopic cholecystectomy was equally effective in controlling post-operative infection as multi-dose antibiotics during and post-operative period.&#x0D; &#x0D; Methods: The study was conducted at the department of general surgery, Lumbini Medical College Teaching Hospital, from November 2015 to October 2016. All cases with symptomatic cholelithiasis subjected for laparoscopic cholecystectomy were enrolled. Patients were randomized into two groups; Group SD received single dose of an intravenous dose of amikacin 500 mg, at induction of anesthesia and Group MD received multiple intravenous dose of amikacin, during and postoperatively for two days. Complications, hospital stay, and treatment cost in two groups were compared and analyzed.&#x0D; &#x0D; Results: There were a total of 240 patients in the study, 118 in Group SD and 122 in Group MD. Post-operative infection rate was 4.2% (n= 5, N=118) in Group SD and 3.3% (n=4, N=122) in Group MD; the difference was not significant (p=0.75). Hospital stay was prolonged and cost was higher significantly in Group MD.&#x0D; &#x0D; Conclusion: Single dose of prophylactic antibiotic, administered at induction of anesthesia, is equally effective as multiple doses of post surgical antibiotics to prevent post-operative infection in patients undergoing elective laparoscopic cholecystectomy for uncomplicated cholelithiasis.

Epidemiologic analysis: Prophylaxis and multidrug-resistance in surgery.

Surgical site infection is defined as an infection related to the surgical procedure in the area of manipulation occurring within the first 30 postoperative days. The diagnostic criteria include: purulent drainage, isolation of microorganisms, and signs of infection. To describe the epidemiologic characteristics and differences among the types of prophylactic regimens associated with hospital-acquired infections at the general surgery service of a tertiary care hospital. The electronic case records of patients that underwent general surgery at a tertiary care hospital within the time frame of January 1, 2013 and December 31, 2014 were reviewed. A convenience sample of 728 patients was established and divided into the following groups: Group 1: n=728 for the epidemiologic study; Group 2: n=638 for the evaluation of antimicrobial prophylaxis; and Group 3: n=50 for the evaluation of multidrug-resistant bacterial strains in the intensive care unit. The statistical analysis was carried out with the SPSS 19 program, using the Mann-Whitney U test and the chi-square test. A total of 728 procedures were performed (65.9% were elective surgeries). Three hundred twelve of the patients were males and 416 were females. Only 3.98% of the patients complied with the recommended antimicrobial prophylaxis, and multidrug-resistant bacterial strains were found in the intensive care unit. A single prophylactic dose is effective, but adherence to this recommendation was not adequate. The prophylactic guidelines are not strictly adhered to in our environment. There was a significant association between the development of nosocomial infections from multidrug-resistant germs and admission to the intensive care unit.

Enhanced Probiotic Potential of Lactobacillus reuteri When Delivered as a Biofilm on Dextranomer Microspheres That Contain Beneficial Cargo.

As with all orally consumed probiotics, the Gram-positive bacterium Lactobacillus reuteri encounters numerous challenges as it transits through the gastrointestinal tract of the host, including low pH, effectors of the host immune system, as well as competition with commensal and pathogenic bacteria, all of which can greatly reduce the availability of live bacteria for therapeutic purposes. Recently we showed that L. reuteri, when adhered in the form of a biofilm to a semi-permeable biocompatible dextranomer microsphere, reduces the incidence of necrotizing enterocolitis by 50% in a well-defined animal model following delivery of a single prophylactic dose. Herein, using the same semi-permeable microspheres, we showed that providing compounds beneficial to L. reuteri as diffusible cargo within the microsphere lumen resulted in further advantageous effects including glucosyltransferase-dependent bacterial adherence to the microsphere surface, resistance of bound bacteria against acidic conditions, enhanced adherence of L. reuteri to human intestinal epithelial cells in vitro, and facilitated production of the antimicrobial compound reuterin and the anti-inflammatory molecule histamine. These data support continued development of this novel probiotic formulation as an adaptable and effective means for targeted delivery of cargo beneficial to the probiotic bacterium.

Low molecular weight heparins prevent the induction of autophagy of activated neutrophils and the formation of neutrophil extracellular traps

The protection exerted by neutrophils against invading microbes is partially mediated via the generation of neutrophil extracellular traps (NETs). In sterile conditions NETs are damaging species, enriched in autoantigens and endowed with the ability to damage the vessel wall and bystander tissues, to promote thrombogenesis, and to impair wound healing. To identify and reposition agents that can be used to modulate the formation of NETs is a priority in the research agenda. Low molecular weight heparins (LMWH) are currently used, mostly on an empirical basis, in conditions in which NETs play a critical role, such as pregnancy complications associated to autoimmune disease. Here we report that LMWHs induce a profound change in the ability of human neutrophils to generate NETs and to mobilize the content of the primary granules in response to unrelated inflammatory stimuli, such as IL-8, PMA and HMGB1. Autophagy consistently accompanies NET generation in our system and autophagy inhibitors, 3-MA and wortmannin, prevent NET generation. Pretreatment with LMWH in vitro critically jeopardizes neutrophil ability to activate autophagy, a mechanism that might contribute to neutrophil unresponsiveness. Finally, we verified that treatment of healthy volunteers with a single prophylactic dose of parnaparin abrogated the ability of neutrophils to activate autophagy and to generate NETs. Together, these results support the contention that neutrophils, and NET generation in particular, might represent a preferential target of the anti-inflammatory action of LMWH.

A Review of Antibiotic Prophylaxis for Interventional Radiology Procedures and Identification of Antimicrobial Stewardship Opportunities

BackgroundAntibiotics used for peri-procedural prophylaxis are dispensed by providers or nurses from automated dispensing machines in the interventional radiology (IR) suites. These antibiotics are administered without pharmacist review which skips a critical point in time for antimicrobial stewardship intervention. The purpose of this study was to evaluate antibiotic prophylaxis for IR procedures and identify opportunities for antimicrobial stewardship.MethodsAll patients who underwent an IR procedure and received antibiotic prophylaxis from April 2016 to April 2017 were identified. We performed a manual chart review to determine procedure type, antibiotic prophylaxis, concomitant systemic antibiotics, and antibiotic concordance with the Society of Interventional Radiology (SIR) guidelines.ResultsThere were 410 IR procedures where the patient received a single prophylactic antibiotic dose; 261 were inpatient procedures. See Table 1 for procedure and antibiotic data. There were 74 patients (18%) who concomitantly received systemic antibiotics. There were 126 cases (31%) discordant with the SIR guidelines. Reasons for discordance include prophylaxis not recommended, inappropriate antibiotic selection, or patient already receiving an antibiotic with similar spectrum of coverage.ConclusionAntibiotics are frequently administered as prophylaxis for IR procedures. For many IR procedures, data to support prophylaxis is limited; however, there are opportunities for antimicrobial stewardship intervention which include optimizing antibiotic selection and withholding prophylaxis when not indicated or when patients are receiving systemic antibiotics.Table 1ProcedureNo. of procedures, n = 410Routine prophylaxis recommended (y/n), antibioticAntibiotic dosesTunneled line or port placement181No consensusCFZ 162 VAN 8 LVX 6 CRO 5Genitourinary59Yes, no consensusCRO 43 LVX 14 CFZ 2Gastrointestinal or abscess drainage55Yes, no consensusCRO 36 LVX 10 CFZ 9Embolization or chemoembolization44Yes, no consensusCRO 22 CFZ 18 LVX 2 VAN 2Gastrostomy tube placement40Yes, CFZCFZ 30 CRO 7 LVX 2 VAN 1Vascular28No, noneCFZ 23 CRO 4 LVX 1Biopsy3No, noneCFZ 2 CRO 1CFZ, cefazolin; CRO, ceftriaxone; LVX, levofloxacin; VAN, vancomycin.Disclosures All authors: No reported disclosures.

Epidemiologic analysis: Prophylaxis and multidrug-resistance in surgery

BackgroundSurgical site infection is defined as an infection related to the surgical procedure in the area of manipulation occurring within the first 30 postoperative days. The diagnostic criteria include: purulent drainage, isolation of microorganisms, and signs of infection. AimsTo describe the epidemiologic characteristics and differences among the types of prophylactic regimens associated with hospital-acquired infections at the general surgery service of a tertiary care hospital. Material and methodsThe electronic case records of patients that underwent general surgery at a tertiary care hospital within the time frame of January 1, 2013 and December 31, 2014 were reviewed. A convenience sample of 728 patients was established and divided into the following groups: Group 1: n=728 for the epidemiologic study; Group 2: n=638 for the evaluation of antimicrobial prophylaxis; and Group 3: n=50 for the evaluation of multidrug-resistant bacterial strains in the intensive care unit. The statistical analysis was carried out with the SPSS 19 program, using the Mann-Whitney U test and the chi-square test. ResultsA total of 728 procedures were performed (65.9% were elective surgeries). Three hundred twelve of the patients were males and 416 were females. Only 3.98% of the patients complied with the recommended antimicrobial prophylaxis, and multidrug-resistant bacterial strains were found in the intensive care unit. DiscussionA single prophylactic dose is effective, but adherence to this recommendation was not adequate. ConclusionsThe prophylactic guidelines are not strictly adhered to in our environment. There was a significant association between the development of nosocomial infections from multidrug-resistant germs and admission to the intensive care unit.

Vitamin K Prophylaxis in Newborn: Current Hospital Practices in a Metropolitan City

Vitamin K deficiency may cause unexpected bleeding sometimes severe one into the brain in previously apparently healthy neonates, known as Vitamin K Deficiency Bleeding (VKDB) of newborn. Vitamin K prophylaxis in the newborn continues to be a worldwide health concern. A single intramuscular prophylactic dose (0.5 to 1 mg) of vitamin K within first 6 hrs of delivery is preferable till date in preventing VKDB. This observational study was carried out to see the current practices of vitamin K prophylaxis in newborn in different health care centers of a metropolitan area of Chittagong in Bangladesh from July 2013 to December 2013. Total 103 cases were enrolled in this study among them in 82 (79.61%) cases vitamin K prophylaxis was administered after initiation of breast feeding and in 21 (20.39%) cases it was offered before initiation of breast feeding. In 89 (86.40%) cases route of administration was oral whereas in 2 (1.94%) and 12 (11.65%) cases routes were intramuscular and intravenous respectively. In this study it is observed that most of the neonates received vitamin K prophylaxis orally, which is not the currently recommended route to prevent VKDB. So awareness should be promoted in this regard.&#x0D; JCMCTA 2016 ; 27 (1) : 46 - 50

Preoperative Antibiotics Do Not Reduce Postoperative Infections Following Needle-Localized Lumpectomy.

Many surgeons routinely use a single preoperative prophylactic dose of an antibiotic prior to needle-localized lumpectomy, despite the lack of evidence that this practice reduces the rate of infection. The aim of this study is to determine if antibiotic administration reduces wound infection for needle-localized lumpectomy. A retrospective chart review of patients that underwent needle-localized lumpectomy from 2010 to 2012 was conducted. Data regarding patient demographics, comorbid conditions, medical history, operative details, and pathology were collected. Surgical infections requiring opening of the wound or treatment with antibiotics were documented if occurred during the first 3 months following surgery. Fisher's exact tests were used for statistical analyses. Two hundred and twenty patients were identified. Thirty-six percent (80/220) of patients received preoperative prophylactic antibiotics. The antibiotic and the nonantibiotic group were similar in age, body mass index, tobacco use, history of radiation, history of neo-adjuvant chemotherapy, duration of surgery, duration needle in place, and pathology. Two percent (4/220) of patients had wound infections. Two percent (3/140) of patients in the nonantibiotic group had infections, versus 1% (1/80) in the antibiotic group. In an analysis of patients that developed infections (n = 4) and patients that did not (n = 216), there was no statistically significant difference in patient demographic, duration of surgery, duration of time needle in place, or pathology. It is safe to omit the use of antibiotics prior to needle-localized lumpectomy and avoid the cost of the medication, patient adverse reactions, and increase in resistant organisms.

Adequacy of a hospital-wide standard dose of 7 mg/kg bodyweight gentamicin sufficient to achieve an adequate prophylactic maximum serum concentration (Cmax) in burn patients undergoing surgical burn wound treatment

IntroductionPharmacokinetics of drugs can be significantly altered in burn patients. The aim of our study was to validate if the current hospital-wide standard dosage of 7mg/kg total bodyweight gentamicin is sufficient to achieve an adequate prophylactic Cmax (Cmax≥20mg/L). Materials and methodsA prospective observational cohort pharmacokinetic study was conducted in burn patients undergoing surgical burn wound treatment. Results36/40 (90%) burn patients undergoing surgical burn wound treatment at Rotterdam Burn Centre (Maasstad Hospital), the Netherlands, achieved adequate prophylactic serum concentrations (Cmax≥20mg/L) after a single prophylactic intravenous dose of 7mg/kg total bodyweight gentamicin. Total Body Surface Area (TBSA) burned and total bodyweight were statistically significantly correlated with the Cmax, with correlation coefficients of −0.316, 0.443 and p values of 0.047, 0.004, respectively. Other covariates (age, time after injury, serum creatinine, dose, gender, intensive care admittance) were not statistically significantly correlated. Occurrence of postoperative infection was limited (n=1), no statistically significant difference was observed between patients with a therapeutic and patients with a subtherapeutic serum concentration. ConclusionThe current hospital-wide standard dosage of 7mg/kg total bodyweight is sufficient to achieve an adequate prophylactic Cmax in burn patients undergoing surgical burn wound treatment.

Prophylactic versus postoperative antibiotics in septoplasty

Background and objective: Septoplasty is one of the most common procedures worldwide in otolaryngology clinics. The use of antibiotics in Septoplasty is a common practice among most otolaryngologists. However, there are few studies proving the efficacy, which is considered unnecessary by some others. This study aimed to compare the efficacy of prophylactic versus postoperative antibiotic in septoplasty and strengthen the evidence base for antibiotic use. Methods: This prospective study was conducted on 90 patients that underwent septoplasty over six months period from August 1st, 2012 to January 31st, 2013 in Rizgary Teaching Hospital, Erbil city. They were equally divided into two groups; 45 patients in Group A and 45 patients in Group B. Their age ranged between 17-49 years old. Results: No significant difference was observed in reduction of infection rate between Group A and Group B. No any statistically significant difference was found concerning pain, fever, purulent discharge and bleeding. Two of the patients (one from each group) developed septal hematoma. Conclusions: Infection after septoplasty is rare and if occur is usually minor in nature. The outcome of postoperative antibiotic use does not outweigh that of a single prophylactic dose of antibiotic.

Enhancement of innate immunity with granulocyte colony-stimulating factor did not mitigate disease in pigs infected with a highly pathogenic Chinese PRRSV strain

Porcine reproductive and respiratory syndrome virus (PRRSV) is responsible for one of the most economically important diseases in swine worldwide. It causes reproductive failure in sows and pneumonia in pigs that predisposes them to secondary bacterial infections. Methods to control PRRSV and/or limit secondary bacterial infections are desired to reduce the impact of this virus on animal health. Neutrophils play a major role in combatting infection; they can act as phagocytes as well as produce and release lytic enzymes that have potent antimicrobial effects leading to the destruction and clearance of bacterial pathogens. Granulocyte-colony stimulating factor (G-CSF) is a cytokine that controls the production, differentiation and function of granulocytes (including neutrophils) from the bone marrow. Recent work from our laboratory has shown that encoding porcine G-CSF in a replication-defective adenovirus (Ad5-G-CSF) and delivering a single dose to pigs induced a neutrophilia lasting more than two weeks. As secondary bacterial infection is a common occurrence following PRRSV infection, particularly following challenge with highly pathogenic (HP)-PRRSV, the aim of the current study was to evaluate the effectiveness of a single prophylactic dose of adenovirus-encoded G-CSF to mitigate secondary bacterial disease associated with HP-PRRSV infection. Administration of Ad5-G-CSF induced a significant neutrophilia as expected. However, between 1 and 2days following HP-PRRSV challenge the number of circulating neutrophils decreased dramatically in the HP-PRRSV infected group, but not the non-infected Ad5-G-CSF group. Ad5-G-CSF administration induced monocytosis as well, which was also reduced by HP-PRRSV challenge. There was no difference in the progression of disease between the Ad5-G-CSF and Ad5-empty groups following HP-PRRSV challenge, with pneumonia and systemic bacterial infection occurring in both treatment groups. Given the impact of HP-PRRSV infection on the neutrophilia induced by the Ad5-G-CSF administration, additional studies are warranted to evaluate the timing of Ad5-G-CSF induced neutrophilia and multiple G-CSF inoculations on protection against secondary bacterial infection following PRRSV infection. Nevertheless, this study may provide insight into the pathogenesis of HP-PRRSV.

The detection and upgrade rates of prostate adenocarcinoma following transperineal template-guided prostate biopsy - a tertiary referral centre experience.

IntroductionWe aim to present transperineal template-guided prostate biopsy (template biopsy) outcomes at a tertiary referral centre. Furthermore, to identify the detection rate of prostate cancer in those with a previous negative transrectal ultrasound guided prostate biopsy and the upgrade rate of those on active surveillance for Gleason 3 + 3 = 6 prostate adenocarcinoma.Material and methodsWe conducted a prospective study of 200 consecutive men who underwent template biopsy over a 22-month period in a tertiary referral centre, using a standard 24 region template prostate biopsy technique. Indications and histology results, as well as complications, were recorded.ResultsMedian age was 67 years and median PSA was 10 ng/mL. Overall detection rate was 47%. 39.5% of cases with previous negative transrectal biopsies were found to have prostate adenocarcinoma. 47.5% of cases on active surveillance for Gleason 3 + 3 = 6 prostate adenocarcinoma were upgraded. The most frequent complication was acute urinary retention at a rate of 12.5%, however, the use of a single prophylactic dose of tamsulosin was found to be beneficial, with 13 cases needed to treat to prevent one episode.ConclusionsTemplate biopsies are safe and efficacious with an overall detection rate of 47% in the present series. Due to the high detection rate, one must consider template biopsy following one negative transrectal biopsy where there is persistent clinical suspicion. Furthermore, those considering active surveillance for Gleason 3 + 3 = 6 disease should be offered template biopsy to confirm the grade of their disease.

TLR5 Agonist Recombinant Flagellin, CBLB502 Increases Anti-CMV Immunity By Increasing T-Bet and Eomes Expressing T Cells after MCMV Infection

We have previously shown that highly purified cGMP grade recombinant flagellin, CBLB502, a TLR5 agonist, protected allo-HSCT recipients from GvHD without compromising anti-CMV immunity of donor T cells in vivo. A single prophylactic dose (25mg/mouse i.p) of CBLB502 in wild type C57BL/6 (B6) mice also enhanced anti-CMV immunity of NK cells against CMV. CMV is a potential opportunistic infectious agent and most often causes severe life-threatening clinical complications in immunocompromized patients, particularly in cancer patients treated with allogenic bone marrow transplantation (allo-BMT). A mechanism by which CBLB502 protected host against CMV infection has not been well investigated. Transcription factors ROR gammaT, T-bet and EOMES are known to control immune responses of innate and adaptive immunity in vivo. In this study, we have explored the transcription factors ROR gammaT, T-bet and EOMES expressing NK and T cells in CBLB502-treated and MCMV-infected B6 mice. Total numbers of spleen cells increased by 1.7-fold within 48 hours of CBLB502 treatment (day 0 MCMV infection) and by 2.3-fold on day 3 after MCMV infection compared with PBS-treated MCMV-infected mice. T-bet expressing CD8+ T cells (not CD4+ T cells) increased significantly on day 0 of mCMV infection, 48hrs after CBLB502 treatment (CD4, p=0.1; CD8, p<0.001) and both CD4+ and CD8+ T cells increased significantly on day 3 (CD4, p<0.001; CD8, p<0.01) after MCMV infection. CBLB502 treatment had no effect on the ROR gammaT expression on T cells. Interestingly, although EOMES expressing CD4+ and CD8+ T cells increased significantly on day 0 (48 hrs after CBLB502 treatment) (CD4, p<0.01; CD8, p<0.01) and day 3 (CD4, p<0.001; CD8, p<0.001) in the spleens of CBLB502-treated mice compared with the PBS-treated mice, EOMES expression on CMV-specific tetramer+ CD8+ T cells rapidly decreased by day 10 after infection in both CBLB502 and PBS treated mice. However, >90% of CMV-specific CD8+ T cells had persistent expression of T-bet even after 30 days post CMV infection. In contrast, CBLB502 treatment did not have a significant effect on the numbers of ROR gammaT, T-bet and EOMES expressing NK cells compared with PBS-treated mice. These data suggest that 1) CBLB502-induced anti-CMV immunity of T cells is persistently maintained through increased T-bet expression but not by EOMES expression; and 2) CBLB502-induced anti-viral immune regulation is not maintained through transcription factor ROR gammaT. 3) CBLB502-induced increased anti-CMV immunity of NK cells is independent of transcription factors ROR gammaT, T-bet and EOMES. Taken together, these data support the early peri-transplant use of TLR5 agonists as a novel method to enhance antigen-specific anti-viral immunity in recipients of allo-BMT. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Comparison of Azithromycin and Amoxicillin Before Dental Implant Placement: An Exploratory Study of Bioavailability and Resolution of Postoperative Inflammation.

Studies suggest that a single prophylactic dose of amoxicillin reduces early implant complications, but it is unclear whether other antibiotics are also effective. This study compared the local antimicrobial and anti-inflammatory effects resulting from a single dose of azithromycin or amoxicillin before surgical placement of one-stage dental implants. Healthy adult patients requiring one-stage dental implant placement were allocated randomly to receive either 2 g amoxicillin (n = 7) or 500 mg azithromycin (n = 6) before surgery. Peri-implant crevicular fluid (PICF) samples from the new implant and gingival crevicular fluid (GCF) from adjacent teeth were sampled on postoperative days 6, 13, and 20. Inflammatory mediators in the samples were analyzed by immunoassay, and antibiotic levels were measured by bioassay. On day 6, azithromycin concentrations in GCF and PICF were 3.39 ± 0.73 and 2.77 ± 0.90 μg/mL, respectively, whereas amoxicillin was below the limit of detection. During early healing, patents in the azithromycin group exhibited a significantly greater decrease in GCF volume (P = 0.03, analysis of variance). At specific times during healing, the azithromycin group exhibited significantly lower levels of interleukin (IL)-6 and IL-8 in GCF than the amoxicillin group and exhibited significantly lower levels of granulocyte colony stimulating factor, IL-8, macrophage inflammatory protein-1β, and interferon-gamma-inducible protein-10 in PICF. Azithromycin was available at the surgical site for a longer period of time than amoxicillin, and patients taking azithromycin exhibited lower levels of specific proinflammatory cytokines and chemokines in GCF and PICF. Thus, preoperative azithromycin may enhance resolution of postoperative inflammation to a greater extent than amoxicillin.