Prophylactic Antimicrobial Treatment Research Articles

Risk of Acute Kidney Injury and Fracture-Related Infection After Antibiotic Prophylaxis With Piperacillin-Tazobactam in Open Fractures.

To evaluate the effects of prophylactic piperacillin-tazobactam (PT) on inpatient acute kidney injury (AKI) and fracture-related infection (FRI) in patients with open fractures. The study was conducted at a Level 1 trauma center. We reviewed 358 Gustilo-Anderson type II and III open fractures at our institution from January 2013 to December 2017. Administration of PT (the PT group) or antibiotics other than PT (the historical control group) during the first 48 hours of arrival for open fracture antibiotic prophylaxis. The main outcome measurements were rates of inpatient AKI and FRI within six months after definitive fixation. There were 176 patients in the PT group and 182 patients in the historical control group. The PT group had worse American Society of Anesthesiologists class ( P = 0.004) and injury severity scores ( P < 0.001), a higher average number of debridements before closure/coverage ( P = 0.043), and higher rates of gross soil contamination ( P = 0.049) and staged procedures ( P = 0.008) compared with the historical control group.There was no difference in the rate of AKI between the PT and historical control groups (5.7% vs. 2.7%, P = 0.166) nor when stratified by Gustilo-Anderson fracture classification (type II: 5.8% vs. 3.6%, P = 0.702; type III: 5.6% vs. 2.0%, P = 0.283). There was no significant difference in the rate of FRI between the PT and historical control groups (23.6% vs. 19.6%, P = 0.469). The use of PT in prophylactic antimicrobial treatment in patients with Gustilo-Anderson type II and III open fractures does not increase the rate of AKI or FRI. We believe PT can be used as an effective monotherapy in these patients without an increased risk of renal injury, but future investigations are necessary. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

3D-printed reservoir-type implants containing poly(lactic acid)/poly(caprolactone) porous membranes for sustained drug delivery.

Implantable drug delivery systems are an interesting alternative to conventional drug delivery systems to achieve local or systemic drug delivery. In this work, we investigated the potential of fused-deposition modelling to prepare reservoir-type implantable devices for sustained drug delivery. An antibiotic was chosen as a model molecule to evaluate the potential of this type of technology to prepare implants on-demand to provide prophylactic antimicrobial treatment after surgery. The first step was to prepare and characterize biodegradable rate-controlling porous membranes based on poly(lactic acid) (PLA) and poly(caprolactone) (PCL). These membranes were prepared using a solvent casting method. The resulting materials contained different PLA/PCL ratios. Cylindrical implants were 3D-printed vertically on top of the membranes. Tetracycline (TC) was loaded inside the implants and drug release was evaluated. The results suggested that membranes containing a PLA/PCL ratio of 50/50 provided drug release over periods of up to 25days. On the other hand, membranes containing lower PCL content did not show a porous structure and accordingly the drug could not permeate to the same extent. The influence of different parameters on drug release was evaluated. It was established that film thickness, drug content and implant size are critical parameters as they have a direct influence on drug release kinetics. In all cases the implants were capable of providing drug release for at least 25days. The antimicrobial properties of the implants were evaluated against E. coli and S. aureus. The resulting implants showed antimicrobial properties at day 0 and even after 21days against both type of microorganisms. Finally, the biocompatibility of the implants was evaluated using endothelial cells. Cells exposed to implants were compared with a control group. There were no differences between both groups in terms of cell proliferation and morphology.

Impact of antimicrobial stewardship intervention in clean and clean-contaminated surgical procedures at a Vietnamese national hospital.

We investigated the characteristics of prophylactic antimicrobial use in clean and clean-contaminated surgical procedures and assessed the efficacy of a prophylactic antimicrobial stewardship intervention at Thong Nhat Hospital, Ho Chi Minh City, Vietnam. A cross-sectional study was conducted on 354 patients who underwent either clean or clean-contaminated surgical procedures at Thong Nhat Hospital. Eligible patients were classified with respect to three periods of intervention from 2017 to 2020. Data collection included surgical procedures, patient characteristics, and prophylactic antimicrobial usage. We determined the efficacy of antimicrobial stewardship intervention based on comparisons among the primary outcome (the appropriateness of prophylactic antimicrobials) and secondary outcomes (postoperative antimicrobial prophylaxis (AP) prolongation, length of postoperative hospital stay, and cost of antimicrobials). The mean age of patients in periods 1, 2, and 3 was 54.5 ± 16.6, 50.2 ± 16.5, and 52.8 ± 17.3years, respectively, with an overall male/female ratio of 1.1/1. No significant differences were detected in basic patient characteristics during the three periods. Majority of the surgical procedures were clean (56%-59%) and scheduled (85%-86%). Prophylactic antimicrobial stewardship intervention enhanced AP appropriateness (by 12.7%, 12.7%, and 39.0% in periods 1, 2, and 3, respectively, p < 0.001), decreased postoperative prophylactic antimicrobial duration [3.0 (0-6), 1.5 (0-5), and 0.0 (0-1) days, respectively, p < 0.001], and reduced average antimicrobial expenses (p < 0.001). The prophylactic antimicrobial stewardship interventions introduced at Thong Nhat Hospital had several positive impacts on the appropriateness of prophylactic antimicrobial use and treatment costs.

Impact of the practical guideline on appropriate usage of antimicrobial treatments for surgical site infections in reconstructive surgery of head and neck cancer

ObjectivesIn 2016, Japanese Society of Chemotherapy and Japan Society for Surgical Infection presented the practical guideline for appropriate usage of antimicrobial agents to prevent postoperative infections. This study aims to exhibit the validity of the guideline as a series of effective strategies for prevention of surgical site infections (SSIs) during reconstructive surgery of the head and neck cancer. MethodsWe retrospectively evaluated patients who underwent head and neck reconstructive surgery with free or pedicle flaps in a single institute in Japan between July 2010 and July 2020. We evaluated the incidence of SSIs, patient backgrounds, and microbiological characteristics on the basis of antimicrobial prophylaxis recommended by the guideline. ResultsEnrolled in this study were 102 patients in our institution who underwent head and neck reconstructive surgery with free or pedicle flaps between July 2010 and July 2020. In the period between January 2018 to July 2020 after the SSI guideline was advocated (SSI guideline period), the ratio of administration of sulbactam/ampicillin (SBT/ABPC) was significantly higher (P < 0.001) and the duration of prophylactic antimicrobial treatment was significantly shorter than in the period between July 2010 to December 2017 before the SSI guideline was advocated (Pre-SSI guideline period) (P < 0.001). Incidence of SSIs were similar, even when antibiotic use was changed to be short-term single-agent administration in accordance with the practical guideline. ConclusionsAdherence to the current Japanese practical guideline on appropriate antimicrobial prophylaxis for SSIs can shorten the duration of usage of antimicrobial treatment without increasing the risk for occurrence of SSIs.

Antimicrobial prophylaxis and post-chemotherapy neutropenic fever in patients with leukemia: comparisons of C-reactive protein, procalcitonin and immediate fever outcome measures between those with and without prophylaxis, and the implications for practice

PurposeThe efficacy of prophylactic antimicrobial treatment renders challenges in patients with leukemias receiving chemotherapy. The study aimed to compare differences in C-reactive protein (CRP) and procalcitonin (PCT) at presentation and the immediate outcome measures of post-chemotherapy NF between patients with and without antimicrobial prophylaxis.MethodsA 5-year observational study included 282 NF episodes in 133 leukemia patients requiring hospital care from January 2014 to May 2019. We collected demographic characteristics, laboratory data of blood cell counts and inflammatory biomarkers, and immediate outcome measures of NF, including microbiologically diagnosed infections, presence of predominant pathogens, required modification of antibiotics during NF, adverse medical complications, total fever duration, and deaths. We evaluated data between patients with and without prophylaxis.ResultsOf patients, 77.3%, 68.4%, and 20.6% had antibiotic prophylaxis, antifungal prophylaxis, and no prophylaxis, respectively. There were totally 15 deaths—13 with antibiotic prophylaxis and 10 with antifungal prophylaxis. CRP, PCT, and immediate outcome measures of NF did not show significant differences between those with and without antimicrobial prophylaxis. Although between-group differences showed no statistical significance, higher median fever duration, CRP and PTC values, and higher proportions of NF requiring modification of antibiotics were found more frequently in those with antimicrobial prophylaxis than in those without.ConclusionThe benefits of using antimicrobial prophylaxis were less supported. Enhancing diagnostic laboratory and medical complication surveillance and periodic evaluation of institutional data during post-chemotherapy neutropenia and NF in relation to antimicrobial prophylaxis is promising in providing insights to redefine the risk–benefit accounts of using prophylaxis.

Temporal Resistome and Microbial Community Dynamics in an Intensive Aquaculture Facility with Prophylactic Antimicrobial Treatment.

Excessive use of antimicrobials in aquaculture is concerning, given possible environmental ramifications and the potential contribution to the spread of antimicrobial resistance (AR). In this study, we explored seasonal abundance of antimicrobial resistance genes and bacterial community composition in the water column of an intensive aquaculture pond stocked with Silver Carp (Hypophthalmichthys molitrix) prophylactically treated with sulfamethoprim (25% sulfadiazine; 5% trimethoprim), relative to an adjacent unstocked reservoir. Bacterial community composition was monitored using high-throughput sequencing of 16S rRNA gene amplicons in eight sampling profiles to determine seasonal dynamics, representing principal stages in the fish fattening cycle. In tandem, qPCR was applied to assess relative abundance of selected antimicrobial resistance genes (sul1, sul2, dfrA1, tetA and blaTEM) and class-1 integrons (int1). Concomitantly, resistomes were extrapolated from shotgun metagenomes in representative profiles. Analyses revealed increased relative abundance of sulfonamide and tetracycline resistance genes in fishpond-03, relative to pre-stocking and reservoir levels, whereas no significant differences were observed for genes encoding resistance to antimicrobials that were not used in the fishpond-03. Seasons strongly dictated bacterial community composition, with high abundance of cyanobacteria in summer and increased relative abundance of Flavobacterium in the winter. Our results indicate that prophylactic use of sulfonamides in intensive aquaculture ponds facilitates resistance suggesting that prophylactic use of these antimicrobials in aquaculture should be restricted.

Duration of antibiotics for penetrating spine trauma: a systematic review.

Penetrating trauma to the spine with resultant spinal and paraspinal infection represents a potentially devastating injury for which there is little consensus regarding management. The duration, route and type of antibiotics required to prevent infections such as epidural abscess, vertebral osteomyelitis, and discitis is remain controversial. Several studies support standard prophylactic antimicrobial treatment for 48 hours following penetrating spinal trauma while others demonstrate that extended therapy for one week or greater is necessary to reduce risk of infection. However, there is no established protocol or consensus for management. Our systematic review aims to determine the ideal duration of antibiotics following penetrating spine trauma. Three databases (PubMed, SCOPUS, and Ovid) were queried using the following keywords: penetrating spine trauma, spine infection, spine trauma antibiotics. Nine articles were found to meet the inclusion criteria for this systematic review. The majority of studies included in final analysis discussed penetrating spinal trauma in the form of gunshot wounds. 459 patients were included in total across all studies and 21 patients developed spinal or paraspinal infection (4.58%). Five studies demonstrated an infection rate below 5% with antibiotic therapy for 5 days or longer while 2 more recent studies demonstrated a similar infection rate in their cohort with only 48 hours of antimicrobial prophylaxis. Our systematic review finds a low rate of paraspinal and spinal infections following penetrating spine trauma. As all studies included are retrospective in nature, no definitive recommendations can be made regarding duration of therapy. Forty-eight hours of antimicrobial prophylaxis may be sufficient for most patients except for those with trans-colonic injuries as these are associated with a greater contamination and risk for spinal infection.

A case series of non-valvular cardiac aspergillosis in critically ill solid organ transplant and non-transplant patients and systematic review.

Non-valvular cardiac aspergillosis is a rare infection of the pericardium, myocardium or endocardium and is associated with a high mortality. There is a paucity of reports of non-valvular cardiac aspergillosis in critically ill and solid organ transplant (SOT) patients. The majority of cases have been reported in haemato-oncology patients, some of whom have undergone a bone marrow transplant. We describe four cases affected by non-valvular cardiac aspergillosis in the intensive care setting including a systematic review of this extremely rare infection which is associated with high mortality. All four-patients died but presented with varying clinical, radiological and microbiological evidence of the disease. Three patients presented following complications after solid organ transplantation, two in the context of acute liver failure and emergency liver transplant and one several years after a double lung transplant. The last patient presented with necrotising gall stone pancreatitis, multi-organ failure and subsequently a prolonged intensive care unit (ICU) stay. On review of the literature, January 1955 to July 2019, 45 cases were identified, with different risk factors, clinical and radiological manifestations, treatment regimen and outcome. Antemortem diagnosis of cardiac aspergillosis is difficult and rare, with no cases reporting positive blood culture results. Galactomannan serology has poor sensitivity in solid organ transplant patients, further reduced by prophylactic antimicrobial treatment, which is common in the ICU setting especially post-transplant patients. Due to the scarcity of cases, treatment is extrapolated from invasive aspergillosis management, with emphasis on early treatment with combination therapy.

Phase Ib of Copanlisib in Combination with Ibrutinib in Recurrent/Refractory Primary CNS Lymphoma (PCNSL)

BACKGROUND: PCNSL is an aggressive primary brain tumor with median progression free survival (PFS) after upfront methotrexate-based chemotherapy of 2-3 years. Outcome and treatment options are poor for recurrent/refractory (r/r) disease. This trial combines the pan-PI3K inhibitor copanlisib with Ibrutinib in patients with r/r PCNSL. METHODS: Eligible patients had r/r PCNSL, age≥18, ECOG≤2, normal end-organ function, and an unrestricted number of CNS directed prior therapies. Ibrutinib was given orally daily; copanlisib intravenously on days 1, 8, and 15 of each 28-day cycle. RESULTS: Six patients have been enrolled so far and received copanlisib at 60 mg and ibrutinib at 560 mg. Median age was 68 (range 50-77); 3 were women. Median ECOG was 1 (0: 2, 1: 3, 2: 1). All had recurrent parenchymal disease. Three had additional cerebrospinal fluid (CSF) involvement. Two had received prior single-agent ibrutinib. Initially, no prophylactic antimicrobial treatment was required. PCP prophylaxis was made mandatory after one patient developed PCP pneumonia leading to a grade 5 lung infection. Four patients are still on trial and one withdrew due to personal choice. Two grade 4 adverse events were observed in 2 patients (LFT elevation, lymphopenia); four grade 3 events in 3 patients (rash, lymphopenia, LFT elevation). The most common toxicities at any grade were transient, infusion-related hyperglycemia and hypertension. No Aspergillus infections have been observed. Enrollment into the next dose level (copanlisib 60 mg, ibrutinib 840 mg) is ongoing. After a median follow-up of 180 days (range 46-249), all patients were evaluated for response with an overall response rate of 67% with 1 CR, 3 PR, 1 SD and 1 PD as best response. CONCLUSION: Treatment with copanlisib and ibrutinib in patients with PCNSL has manageable adverse events after initiation of mandatory PCP prophylaxis. Clinical response was seen in 67% of patients. Disclosures Grommes: Squipps: Speakers Bureau; Kite: Consultancy; BTG: Consultancy. OffLabel Disclosure: The combination of the BTK inhibitor ibrutinib and the pan PI3K inhibitor copanlisib in recurrent PCNSL will be discussed

Methotrexate and Cytarabine for Adult Patients with Newly Diagnosed Langerhans Cell Histiocytosis: A Single Arm, Single Center, Prospective Phase 2 Study

Backgroud: Langerhans cell histiocytosis (LCH) is a rare, heterogeneous histiocytic disorder occurring in patients of all ages from neonates to the elderly. The features of LCH are well described in children, however, they remain poorly defined in adults. There is no standard first-line treatment for adult LCH. The current standard treatment protocol for children is vinblastine plus prednisone, which has never been proven effective for adults in a prospective study. Considering the relatively high frequency of pituitary involvement and late onset of neurodegenerative symptoms, patients may benefit from the combination of cytarabine and methotrexate as both these drugs cross the blood-brain barrier. Methods: This phase 2, prospective, single-center study enrolled 83 newly diagnosed adults multisystem (MS)-LCH or LCH with multifocal single system (SS-m) involved between January 2014 and March 2019 (NCT 02389400). The methotrexate (1g/m2by 24-hour infusion on day 1) and cytarabine (100 mg /m2by 24-hour infusion for 5 days) was administered every 35 days for a cycle and 6 cycles totally. The primary endpoint was event-free survival (EFS). Events were defined as a poor response to chemotherapy, reactivation after chemotherapy or death from any cause. Results: The median age was 33 years (range 18-65 years). Forty-nine patients were male (59.0%). Six patients were SS-m LCH (7.2%), 77 patients were MS LCH (92.8%). The most common organ involved in the total cohort was bone (78.3%), followed by lung (67.5%), pituitary (62.7%) and lymph nodes (38.6%). Twenty-three patients had liver involvement (27.7%), 11 patients with spleen involvement (13.3%), no patients had hematologic involvement. All patients received at least one course of chemotherapy, with median 6 (1-6) courses. Overall 69 patients (83.1%) completed protocol treatment, 14 patients (16.9%) went off protocol (13 patients' decision, 1 poor response). The overall response rate was 87.9%. including 43 patients (51.8%) as having non-active disease and 30 patients (36.1%) as active disease (AD)/better. After a median of 23 months (range 7-79 months) follow-up, one patient died of disease progression and 25 patients had reactivation of the disease. The estimated 3-year OS and EFS were 97.7% and 68.0% separately (Figure 1). To evaluate the prognostic factors of EFS using univariate analysis, liver, spleen, lung and skin involvement at baseline had significantly shorter EFS. EFS were also evaluated using multivariate Cox regression model, liver involvement remained predictive of poorer EFS (P = 0.012; HR 0.339, 95% CI 0.146-0.784). The most common toxicity was hematologic adverse events. All patients experienced neutropenia and thrombocytopenia. Thirty-five patients (42.2%) had grade 4 neutropenia, 43 patients (51.8%) had grade 3 neutropenia. Fourteen patients (16.9%) had grade 4 thrombocytopenia, 13 patients (15.7%) had grade 3 thrombocytopenia. No patients received prophylactic antimicrobial treatment during any of the cycles. Forty patients (48.2%) experienced febrile neutropenia, including 38 (45.8%) grade 3 and 2 (2.4%) grade 4. The most common non-hematological toxicities were gastrointestinal complications. Two patients developed grade 3 nausea. Grade 3 alanine aminotransferase increased occurred in in two patients. No treatment related death. One patient had secondary primary malignancy (oral squamous cell carcinoma), 56 months after the last course of MA regimen. Fifty-two of 82 surviving patients experienced sequelae to the disease that were not influenced by therapy. Forty-eight patients had diabetes insipidus and 4 presented with hypothyroidism. Conclusion: Methotrexate and cytarabine is an efficient and safe regimen for newly diagnosed adult LCH. The involvement of liver at baseline indicates a worse prognosis in adult LCH. Disclosures No relevant conflicts of interest to declare.

Haemorrhagic bowel syndrome in fattening pigs

BackgroundHaemorrhagic bowel syndrome (HBS) is a sporadically occurring disorder in fattening pigs, characterized by sudden death in combination with severe abdominal distension and intense red colouration of the intestine. Deep understanding of aetiology and pathogenesis of HBS are still lacking, although several risk factors are known.Case presentationIn a continuously stocked fattening farm with 1500 pigs and liquid feeding based on whey, the mortality rate increased from 1.7% to 3.5% during summer time. Sporadic sudden death of growing pigs occurred along with severe abdominal distension as the main sign in these animals. All batches arriving at the farm received in-feed medication with Tiamulin hydrogen fumarate (2 mg/kg body weight/day; according to the license for use in Switzerland) due to detection of Brachyspira hyodysenteriae in the past, although a partial sanitation had been conducted thereafter. No changes of the origins, housing and the feeding procedure were reported. A herd examination was conducted revealing a hygiene problem in the feeding system. For further diagnostics a necropsy was performed, showing a pale carcass with a bloated abdomen due to a haemorrhagic infarction of part of the small intestine caused by a mesenteric torsion. Furthermore, a feed analysis was conducted, revealing a pH-value of 5 in the liquid feed, and a severe contamination with Enterobacteriaceae was detected. Based on these examinations, HBS was diagnosed. Subsequently, the farmer controlled the pH-value of the liquid feed with formic acid, improved the cleaning procedure of the liquid feeding system and stopped the in-feed medication. Following the implementation of these measures, key performance indicators improved significantly, but 4 months later the same clinical manifestation occurred again. This time huge variations in the pH-value of the liquid feed between different feeding times were recorded and were attributed to improper mixing of the formic acid in the whey tank. After implementation of a technical solution to control the pH-value, the health status improved again.ConclusionIn the present case, it is likely that the cause of the clinical manifestation of HBS was a contamination of Enterobacteriaceae in the liquid feed facilitated by a hygiene problem in the feeding system, and a chronic dysbacteriosis of the intestinal tract due to the non-justified routine use of antimicrobials. Speculatively, the prophylactic antimicrobial treatment was unnecessary and might even have exacerbated the clinical problem.

Implementing Precision Antimicrobial Therapy for the Treatment of Bovine Respiratory Disease: Current Limitations and Perspectives.

The therapeutic efficacy of an early treatment protocol with an infection-stage adjusted fluoroquinolone regimen was evaluated in a field study on young bulls (YBs) presenting signs of bovine respiratory disease (BRD). A total of 195 YB (Charolais, Limousin, and Rouge-des-Prés breeds) from 6 farms implementing or not prophylactic antimicrobial treatments (PROPHY or absence) were randomly assigned to 1 of 2 experiment groups based on time of detection of BRD and first-line marbofloxacin regimen, early adjusted dose [Early 2 (E2)] or late standard dose [Late 10 (L10)]. Each YB was administered orally a reticulo-rumen bolus, allowing continuous monitoring of ruminal temperature. In the E2 group, YB presenting early signs of BRD, i.e., an increase in ruminal temperature over 40.2°C and persisting more than 12 h, confirmed by a clinical examination showing no or mild signs of BRD, were given 2 mg/kg of marbofloxacin. In the L10 group, YBs presenting moderate or severe signs of BRD at visual inspection, confirmed at clinical examination, were given 10 mg/kg of marbofloxacin. If needed, YBs were given a relapse treatment. The YBs were followed for 30 days. The proportions of first and relapse treatments were calculated, as well as the therapeutic efficacy at day 10. In the E2 group, the first-line treatments’ proportion was significantly higher (P < 0.05), while the relapse treatments’ proportion tended to be higher (P = 0.08), than in the L10 group. Evolution of clinical scores (CSs) of diseased YB was followed for 10 days. In both groups, CS and rectal temperature decreased significantly 24 h after treatment (P < 0.05). Treatment incidences (TI) representing antimicrobial consumption assessed on used daily doses (UDD) were calculated. Antimicrobial consumption of marbofloxacin and relapse treatments were not significantly different between the groups. These values were strongly influenced by the recourse to a prophylactic antimicrobial treatment, accounting for more than 90% of the antimicrobial amount in the herds implementing prophylaxis. The higher number of treatments in the groups treated on the basis of ruminal temperature monitoring, the accuracy of the detection method, and the necessary conditions to implement precision antimicrobial therapy in the field are discussed in this article.

Clinical implications of Paracoccus yeeii bacteremia in a patient with decompensated cirrhosis

Infections in patients with cirrhosis are common among those who develop variceal hemorrhage. Prophylactic antimicrobial treatment with third generation cephalosporins is recommended in patients with advanced cirrhosis and gastrointestinal hemorrhage. However no infectious source is identified in up to 50% of patients with cirrhosis and clinical sepsis. We report the first case of Paracoccus yeeii bacteremia in a patient with decompensated cirrhosis who presented with variceal hemorrhage. This rare gram negative organism that occurs naturally in the soil has been difficult to isolate until recent technological advances and may not be susceptible to third generation cephalosporins. Our case reinforces the challenges in isolating rare infections in patients with cirrhosis, the need to consider uncommon organisms in infected but culture negative patients with cirrhosis, and the importance of optimizing antimicrobials to reduce the incidence of drug resistant organisms.

Clinical and genetic features of IL12Rb1 deficiency: Single center experience of 18 patients.

Mendelian susceptibility to mycobacterial disease (MSMD) is characterized by infections with weakly virulent mycobacteria (BCG and environmental mycobacteria), M. tuberculosis, Salmonella, candida and some other intracellular microorganisms. Nine different genetic defects have been defined to cause MSMD and IL-12Rβ1 deficiency is the most common form. We present here the clinical and genetic features of 18 patients with IL12Rβ1 deficiency diagnosed by surface expression of IL-12Rβ1 and Sanger's sequencing. Seventeen patients showed classical presentation (infections with BCG, salmonella and candida) while one patient experienced recurrent leishmaniasis. In all patients the percentage of activated lymphocytes with surface expression of IL12Rβ1 was < 1% indicating that it is an effective method for the screening of these patients. Three recurrent mutations were responsible for 85% of our families. Prognosis was good in patients, in whom specific antimicrobial therapy was given before dissemination occurs, as well as prophylactic antimicrobial treatment when needed and IFN-γ therapy for severe infectious episodes.

Bacteria Isolated from Conspecific Bite Wounds in Norway and Black Rats: Implications for Rat Bite–Associated Infections In People

Bites associated with wild and domestic Norway and black rats (Rattus norvegicus and Rattus rattus) may have a variety of health consequences in people. Bite-related infections are among the most significant of these consequences; however, there is little data on the infectious agents that can be transmitted from rats to people through biting. This is problematic because without an accurate understanding of bite-related infection risks, it is difficult for health professionals to evaluate the adequacy of existing guidelines for empirical therapy. The objectives of this study were to increase our knowledge of the bacterial species associated with rat bites by studying bite wounds that wild rats inflict upon one another and to review the literature regarding rat bites and bite wound management. Wild Norway and black rats (n=725) were trapped in Vancouver, Canada, and examined for bite wounds in the skin. All apparently infected wounds underwent aerobic and anaerobic culture, and isolated bacteria were identified. Thirty-six rats had bite wound-related infections, and approximately 22 different species of bacteria belonging to 18 genera were identified. Staphylococcus aureus was the most common isolate; however, the majority of infections (72.5%) were polymicrobial. Rat bites can result in infection with a number of aerobic and anaerobic Gram-positive and Gram-negative bacteria. In humans, these wounds are best managed through early recognition and cleansing. The benefit of prophylactic antimicrobial treatment is debatable, but given the deep puncturing nature of rodent bites, we suggest that they should be considered a high risk for infection. Antibiotics selected should include coverage for a broad range of bacterial species.

Reduction of the use of antimicrobial drugs following the rapid detection ofStreptococcus agalactiaein the vagina at delivery by real‐timePCRassay

ObjectiveTo assess whether the determination of the presence of group B streptococci (GBS) in the vagina using a rapid polymerase chain reaction (PCR) assay at delivery was able to spare useless antimicrobial treatments, as compared with conventional culture at 34–38 weeks of gestation.DesignPractical evaluation and prospective cost‐effectiveness analysis.SettingA university hospital in France.PopulationA cohort of 225 women in labour at the University‐Hospital of Saint‐Etienne.MethodsEach woman had a conventional culture performed at 34–38 weeks of gestation. At the beginning of labour, two vaginal swabs were sampled for rapidPCRtesting and culture. The decision to prescribe a prophylactic antimicrobial treatment or not was taken according to the result of thePCRtest. A comparative cost‐effectiveness analysis of the two diagnostic strategies was carried out.Main outcome measuresNumber of women receiving inadequate prophylactic antimicrobial drugs following each testing strategy, costs ofPCRtesting and culture, frequency of vaginalGBS, and diagnostic performance of thePCRtest at delivery.ResultsThe percentage of unnecessarily treated women was significantly reduced using the rapid test versus conventional culture (4.5 and 13.6%, respectively;P &lt; 0.001). The rate of vaginalGBSat delivery was 12.5%. The incremental cost‐effectiveness ratio (ICER) for each inadequate management avoided was €36 and €173 from the point of view of the healthcare system and hospital, respectively.ConclusionsThePCRassay reduced the number of inadequate antimicrobial treatments aimed to prevent the early onset ofGBSdisease. However, this strategy generates extra costs that must be put into balance with its clinical benefits.

Fever after shockwave lithotripsy: risk factors and indications for prophylactic antimicrobial treatment

J Endourol. 2010; 24: 277-81.Purpose: To identify risk factors for fever after shockwave lithotripsy (SWL) and suggest guidelines for pro-phylactic antimicrobial treatment. Patients and Methods: Between 1985 and 2007, a total of 15,324 SWL procedures were performed in our institution using the Dornier HM3 lithotripter. Because stone analyses were not available in the majority of patients, management of stones larger than 2 cm in diameter were excluded from this analysis to minimize the ratio of struvite stones as a possible cause for postprocedural fever. In this analysis, 11,500 SWL treatments were included. Clinical parameters before, during, and after treatments were prospectively registered using a computerized database. Potential risk factors for fever after SWL were evaluated. Results: Fever >38.0 degrees C developed in 161 (1.4%) patients. The risk factors for fever after SWL were: A positive urine culture (P 38.0 degrees C) develops in only 1.4% of the patients undergoing SWL. Therefore, pro-phylactic antibiotic treatment is not indicated in all patients. Selective prophylactic treatment is recommended in patients who present with UTI, kidney or upper ureteral stones, and those for whom a nephrostomy tube or stent is necessary.

Fever After Shockwave Lithotripsy—Risk Factors and Indications for Prophylactic Antimicrobial Treatment

To identify risk factors for fever after shockwave lithotripsy (SWL) and suggest guidelines for prophylactic antimicrobial treatment. Between 1985 and 2007, a total of 15,324 SWL procedures were performed in our institution using the Dornier HM3 lithotripter. Because stone analyses were not available in the majority of patients, management of stones larger than 2 cm in diameter were excluded from this analysis to minimize the ratio of struvite stones as a possible cause for postprocedural fever. In this analysis, 11,500 SWL treatments were included. Clinical parameters before, during, and after treatments were prospectively registered using a computerized database. Potential risk factors for fever after SWL were evaluated. Fever >38.0 degrees C developed in 161 (1.4%) patients. The risk factors for fever after SWL were: A positive urine culture (P < 0.05), an indwelling nephrostomy tube or stent during the procedure (P < 0.001), lithotripsy of kidney or upper ureteral stones (P < 0.05) and preoperative symptomatic urinary tract infection (UTI) (P < 0.05) or sepsis (P < 0.05). Lithotripsy of mid and lower ureteral stones, stone size, and the use of ureteral catheters during the procedures were not associated with increased risk of fever after SWL. Fever (>38.0 degrees C) develops in only 1.4% of the patients undergoing SWL. Therefore, prophylactic antibiotic treatment is not indicated in all patients. Selective prophylactic treatment is recommended in patients who present with UTI, kidney or upper ureteral stones, and those for whom a nephrostomy tube or stent is necessary.

Diseases in neonatal foals. Part 1: The 30 day incidence of disease and the effect of prophylactic antimicrobial drug treatment during the first three days post partum

Neonatal diseases have been grouped and analysed but up-to-date statistically significant information about the incidence and prevalence of diseases in foals is limited. Since the 1950s it has been a common management practice to administer a 3 day course of antimicrobial drugs to neonatal foals. This was shown to significantly reduce the incidence of infections (Platt 1977). Since then management practices have improved and it is widely believed that prophylactic antimicrobial drugs are no longer necessary in foal rearing. To determine the 30 day incidences or prevalences (depending on case definition) of various diseases and conditions in the neonatal foal and ascertain the influence of a prophylactic 3 day treatment on the frequency of infections. The population consisted of Thoroughbred foals born on stud farms in the Newmarket (UK) area in 2005 (n = 1031). Depending on the stud farm's practice in the use of prophylactic antimicrobial drugs, 2 groups of newborn foals (treated and untreated) were identified and followed for 30 days. The 30 day incidences of infectious diseases under study were between 0.2% (osteomyelitis) and 5.85% (systemic disease with diarrhoea). The overall incidence for 'total infectious diseases' was 8.27%. The most commonly observed noninfectious condition was limb deformities (12.11% of all foals). There was no significant difference in the incidence of infectious diseases between the 2 groups. Infectious diseases are still an important problem in neonatal foals requiring further investigation as to which factors other than antimicrobial prophylaxis are relevant for disease prevention. The results provide an up-to-date overview about the frequencies of various neonatal foal diseases. They do not support the traditional prophylactic use of antimicrobials to prevent infectious diseases in healthy newborn foals. However, it should be noted that this study was not a randomised controlled trial and therefore does not provide the strongest possible evidence for this conclusion.

Infections Relevant to Lung Transplantation

Allograft infection after lung transplantation has a significant impact on the outcome and can be a diagnostic challenge. The increased susceptibility of the pulmonary allograft to infection is due to its direct contact with environmental microbes by inhalation, concurrent immunosuppression, and the impaired clearance mechanisms after denervation of the transplanted lung. The possible spectrum of microorganisms infecting the allograft after lung transplantation is broad, but commonly includes Pseudomonas aeruginosa, cytomegalovirus, community-acquired respiratory viruses, and Aspergillus species. Prophylactic antimicrobial treatment regimens after surgery reduced the incidence of infections. However, preventive strategies for reducing infectious complications used by different transplant centers are still heterogeneous, and many questions regarding efficacy remain unanswered.