Carbapenems versus alternative ß-lactams monotherapy or in combination for febrile neutropenia: Systematic review and meta-analysis of randomized controlled trial.

BACKGROUND: Febrile neutropenia (FN) in cancer patients can be life threatening and require the timely antimicrobial agents treatment. METHODS: To compare the effectiveness and safety of carbapenems versus ß-lactams for FN. PubMed, Medline (Ovid SP), Cochrane CENTRAL, and Embase were searched up to March 2019. FN in patients due to undergoing chemotherapy and treated with carbapenems and ß-lactams were included. Odds ratio (OR) and 95% confidence interval (CI) were estimated. RESULTS: Fifty randomized controlled trials (RCTs) studies involving 10,995 participants were included. Carbapenems were more likely to experience treatment success without modification (OR = 1.34, 95% CI = 1.24-1.46) compared with ß-lactams. Meropenem (OR = 1.36, 95% CI = 1.18-1.56; OR = 1.24, 95% CI = 1.01-1.53), imipenem/cilastatin (OR = 1.40, 95% CI = 1.19-1.65; OR = 1.31, 95% CI = 1.04-1.67) showed higher effectiveness from that by ß-lactams monotherapy or in combination with aminoglycoside, respectively. Carbapenems-aminoglycoside combination therapy does not provide an advantage over carbapenems alone. Meropenem showed similar risk of adverse events (AEs) versus ß-lactams. Imipenem/cilastatin was related to higher risk of AEs compared with ß-lactams. There was no significant difference between carbapenems and ß-lactams monotherapy or in combination. CONCLUSION: Meropenem and imipenem/cilastatin monotherapy appears to be available treatment for FN compared with ß-lactams. Imipenem/cilastatin was related to higher risk of AEs. Balancing the evidence for drug efficacy and side effects, meropenem monotherapy appears to be available treatment for FN. Individual centers should select the best matching therapy regimens according to local epidemiology and susceptibility patterns.

Surgery combined with antibiotics for the treatment of endogenous endophthalmitis caused by liver abscess.

BACKGROUNDS: Endogenous endophthalmitis is a serious disease caused by intraocular infection that can rapidly progress to cause blindness. This study evaluated the clinical features, surgical and antibiotics treatment strategies, and treatment outcomes in patients with endophthalmitis caused by liver abscess. METHODS: Between April 2014 and April 2019, the clinical data of 16 patients (19 eyes) with endophthalmitis associated with liver abscess who underwent surgery at Shengjing Hospital were retrospectively analyzed. Furthermore, we evaluated the final visual outcomes in the patients to determine the efficacy of surgery. RESULTS: Fifteen patients (18 eyes) underwent intravitreal injection followed by vitrectomy after admission. One patient (1 eye) only underwent intravitreal injection. Of the 16 patients, 3 patients (3 eyes) had recurrent intraocular inflammation and eventually underwent evisceration. Systemic antibiotics were administered for all patients based on the results of vitreous humor culture, blood culture, and antibiotic susceptibility tests. Outpatient follow-ups were performed until the patients were stable (6 months). Of the 19 eyes, 1 eye (5%) had visual acuity restored to 20/200, 6 eyes (31%) had visual acuity restored to counting fingers (CF), 2 eyes (11%) had visual acuity restored to hand motion (HM), 4 eyes (22%) showed only light perception (LP), and the remaining 6 eyes (31%) showed no light perception (NLP). Drug susceptibility tests suggested that the carbapenems exhibited significant effects in the inflammatory reaction. CONCLUSION: Endogenous endophthalmitis caused by liver abscess is a very serious condition, and the final visual outcome is poor. Timely surgical intervention combined with antibiotic treatment is essential, and the primary disease must be treated to control disease progression at the earliest.

Use of carbapenems and glycopeptides increases risk for Clostridioides difficile infections in acute myeloid leukemia patients undergoing intensive induction chemotherapy.

Patients with acute myeloid leukemia (AML) are often exposed to broad-spectrum antibiotics and thus at high risk of Clostridioides difficile infections (CDI). As bacterial infections are a common cause for treatment-related mortality in these patients, we conducted a retrospective study to analyze the incidence of CDI and to evaluate risk factors for CDI in a large uniformly treated AML cohort. A total of 415 AML patients undergoing intensive induction chemotherapy between 2007 and 2019 were included in this retrospective analysis. Patients presenting with diarrhea and positive stool testing for toxin-producing Clostridioides difficile were defined to have CDI. CDI was diagnosed in 37 (8.9%) of 415 AML patients with decreasing CDI rates between 2013 and 2019 versus 2007 to 2012. Days with fever, exposition to carbapenems, and glycopeptides were significantly associated with CDI in AML patients. Clinical endpoints such as length of hospital stay, admission to ICU, response rates, and survival were not adversely affected. We identified febrile episodes and exposition to carbapenems and glycopeptides as risk factors for CDI in AML patients undergoing induction chemotherapy, thereby highlighting the importance of interdisciplinary antibiotic stewardship programs guiding treatment strategies in AML patients with infectious complications to carefully balance risks and benefits of anti-infective agents.

[The impact of carbapenem-resistance Pseudomonas aeruginosa infections on mortality of patients with hematological disorders].

Objective: To assess the risk factors for mortality and clinical outcome of carbapenem-resistant Pseudomonas aeruginosa (CRPA) infections in patients with hematological disorders. Methods: The data of in-patients with hematological disorders infected by CRPA or carbapenem-susceptible Pseudomonas aeruginosa (CSPA) were recorded in a seven-year retrospective cohort study. Risk factors for CRPA infections and impact of on mortality were identified. The primary end point was 30-day all-cause mortality. Results: A total of 81 patients with PA infections were included in the study, including 58 CSPA and 23 CRPA. Most of the primary diseases were acute leukemia or lymphoma (79.0%, 64/81). The median absolute neutrophil count at infection onset was 0.24×10(9)/L. Independent risk factors associated with carbapenem-resistance included longer duration of hospital stay (P=0.013, OR=1.045) and carbapenem exposure one month prior to infections (P=0.005, OR=8.132). The 30-day all-cause mortality of the whole cohort was 29.6%(24/81), and 30-day attributable mortality was 13.6%(11/81). Pulmonary infection was the leading cause of death, accounting for 41.7%(10/24). The adjusted 30-day mortality rate was significantly higher in patients with CRPA compared with CSPA [60.9%(14/23) vs. 17.2%(10/58), P<0.001, respectively]. CRPA infection was an independent prognostic factor for 30-day mortality(P=0.011, OR=5.427). Other factors included old age, longer duration of neutropenia and poor functional performance. Conclusions: Patients with hematological disorders have high mortality rate and poor prognosis caused by CRPA infections, which mainly develop in lungs.

Antimicrobial utilization and antimicrobial resistance in patients with haematological malignancies in Japan: a multi-centre cross-sectional study.

BACKGROUND: Infection is a major complication for patients with haematological malignancies. It is important to better understand the use of antimicrobial agents and antibiotic resistance for appropriate treatment and prevention of drug resistance. However, very few multi-centre analyses have focused on the use of antimicrobial agents and antibiotic resistance have been carried out in Japan. This study aimed to describe the characteristics of the use of antimicrobial agents and antibiotic resistance in patients with haematological malignancies. METHODS: We conducted a cross-sectional study using administrative claims data and antimicrobial susceptibility data in Japan. We included patients diagnosed with haematological malignancies, who were hospitalized in a haematology ward between 1 April 2015 and 30 September 2017 in 37 hospitals. Descriptive statistics were used to summarize patient characteristics, antimicrobial utilization, bacterial infections, and antibiotic resistance. RESULTS: In total, 8064 patients were included. Non-Hodgkin lymphoma (50.0%) was the most common malignancy. The broad-spectrum antibiotics displayed a following antimicrobial use density (AUD): cefepime (156.7), carbapenems (104.8), and piperacillin/tazobactam (28.4). In particular, patients with lymphoid leukaemia, myeloid leukaemia, or myelodysplastic syndromes presented a higher AUD than those with Hodgkin lymphoma, non-Hodgkin lymphoma, or multiple myeloma. The most frequent bacterial species in our study cohort was Escherichia coli (9.4%), and this trend was also observed in blood specimens. Fluoroquinolone-resistant E. coli (3.6%) was the most frequently observed antibiotic-resistant strain, while other antibiotic-resistant strains were rare. CONCLUSIONS: Broad-spectrum antibiotics were common in patients with haematological malignancies in Japan; however, antibiotic-resistant bacteria including carbapenem-resistant or multidrug-resistant bacteria were infrequent. Our results provide nationwide, cross-sectional insight into the use of antimicrobial agents, prevalence of bacteria, and antibiotic resistance, demonstrating differences in antimicrobial utilization among different haematological diseases.

Proposed Guidelines for the Management of ESBL in Prosthetic Joint Infections.

The aim of this paper is to establish guidelines for the management of extendedspectrum beta-lactamases (ESBL) associated prosthetic joint infections (PJI). This study reviewed 21 patients in the literature documented with ESBL associated PJI. Literature suggests that patients with ESBL PJI are stratified into either early infections (<3 weeks) or late infections (>3 weeks), for which, appropriate laboratory and imaging studies need to be completed. Favorable outcomes require a two-stage revision with an antibiotic-impregnated spacer and a prolonged course of intravenous carbapenem antibiotic.

Assessing the relevance of carbapenem prescriptions by an antibiotic stewardship team.

OBJECTIVES: To assess the level and factors of compliance of carbapenem prescriptions with guidelines and to determine the impact of an antibiotic stewardship team in a university hospital. PATIENTS AND METHODS: Five-month prospective study in the intensive care, surgery, and medicine units to measure the compliance of carbapenem prescriptions with guidelines from French scientific societies; compliance was assessed by an infectious disease specialist warned by the pharmacy, and the prescribers' compliance with the infectious disease specialist's advice was then assessed. RESULTS: One hundred and four treatment initiations for 94 patients were included. Prescriptions were mostly empirical (64%), for pulmonary (35%), urinary tract (23%), and intra-abdominal (17%) infections. Prescriptions were mostly made in an intensive care unit (50%), by a junior physician (66%), with the use of imipenem (74%), and were followed by an objective reassessment (80%). Compliance with guidelines (82%) was significantly higher for empirical than documented prescriptions (91% vs 65%, P<0.001). Compliance was higher in intensive care units than medicine units (87% vs 61%, P=0.037). No change in the compliance rate was observed during the study. Compliance with the infectious disease specialist's advice (68%) improved, although not significantly (P=0.066). CONCLUSIONS: Because of a higher than expected compliance of carbapenem prescriptions with guidelines and a lower than expected inclusions in the study, we did not show any impact. The diffusion of guidelines and long-term control of carbapenem prescriptions seem to be possible and necessary in hospitals to limit their ecological impact.

Erro de administração de medicamentos anti-infeciosos por omissão de doses / Error de administración de medicamentos antiinfecciosos por omisión de dosis / Anti-infective medication administration errors by dose omission

Resumo Objetivos: Mensurar a taxa de erro de administração de medicamentos anti-infeciosos por omissão de doses em Unidade de Terapia Intensiva Adulto. Métodos: Estudo descritivo, transversal e prospectivo, realizado nos meses de outubro e novembro de 2018, em Unidade de Terapia Intensiva adulto de um Hospital de Ensino do Distrito Federal. A amostra foi por conveniência e foram registrados o número de medicamentos prescritos e o número de omissões de doses das prescrições em dois formulários. Os medicamentos foram classificados conforme o Anatomical Therapeutic Chemical Code. Realizada análise estatística com regressão logística e testes para proporções. Resultados: Coletaram-se informações de 7.140 medicamentos prescritos e foram identificadas 310 omissões de doses, correspondendo a 4,34% de taxa de erro na administração de medicamentos em geral. A amostra continha 711 anti-infeciosos (9,95%), e nestes ocorreram 48 omissões de doses, correspondendo a 6,75% de taxa de erro por omissão de doses. Entre os anti-infeciosos, o maior número de omissões foi nos carbapenêmicos (n=13; 27,08%), prescritos para serem ministrados por via intravenosa (n=38; 79,16%) e no horário das 20h (n=10; 20,83%). Conclusão: A taxa de erro de administração por omissão de dose dos anti-infeciosos foi alta, maior que entre os demais medicamentos, mais frequente pela via intravenosa e nos horários próximos às trocas de turnos. Barreiras de segurança devem ser implementadas, como a tripla checagem das doses - na farmácia, no recebimento na UTI e na administração propriamente dita, além de aprazamento adequado, educação permanente e treinamento em uso seguro de medicamentos.

Resumen Objetivos: Medir el índice de error de administración de medicamentos antiinfecciosos por omisión de dosis en Unidad de Cuidados Intensivos Adultos. Métodos: Estudio descriptivo, transversal y prospectivo, realizado en los meses de octubre y noviembre de 2018 en la Unidad de Cuidados Intensivos Adultos de un hospital universitario del Distrito Federal. La muestra fue por conveniencia y se registró la cantidad de medicamentos prescriptos y la cantidad de omisiones de dosis de las prescripciones en dos formularios. Los medicamentos se clasificaron según el Anatomical Therapeutic Chemical Code. Se realizó el análisis estadístico con regresión logística y pruebas para proporciones. Resultados: Se recolectó información de 7.140 medicamentos prescriptos y se identificaron 310 omisiones de dosis, que corresponden al 4,34% de índice de error en la administración de medicamentos en general. La muestra contenía 711 antiinfecciosos (9,95%) y ocurrieron 48 omisiones de dosis de estos medicamentos, que corresponde al 6,75% de índice de error por omisión de dosis. En los antiinfecciosos, la mayor cantidad de omisiones fue en los carbapenémicos (n=13; 27,08%), prescriptos para administrarse por vía intravenosa (n=38; 79,16%) y en el horario de las 20h (n=10; 20,83%). Conclusión: El índice de error de administración por omisión de dosis de los antiinfecciosos fue alta, mayor que entre los demás medicamentos, más frecuente por vía intravenosa y en los horarios cerca de los cambios de turno. Deben implementarse barreras de seguridad, como el triple chequeo de las dosis (en la farmacia, al recibirlo en la UCI y en la administración propiamente dicha), además de la correcta programación, educación permanente y capacitación en el uso seguro de medicamentos.

Abstract Objectives: To measure anti-infective medication administration errors by dose omission in an adult intensive care unit. Methods: A descriptive, cross-sectional, and prospective study, carried out in October and November 2018 in an adult intensive care unit of a teaching hospital in the Federal District, Brazil. The sample was one of convenience. The numbers of prescribed medications and dose omissions were registered on two forms. The medications were classified according to the Anatomical Therapeutic Chemical Code. Data were treated statistically by applying logistic regression and tests for proportions. Results: Information on about 7,140 prescribed medications was gathered, and 310 dose omissions were identified, which corresponded to a 4.34% error rate in the administration of medications in general. The sample used 711 anti-infective drugs (9.95%), which were associated with 48 dose omissions, yielding a 6.75% error rate. Among the anti-infective medications, the highest number of omissions was in the group of carbapenems (n=13; 27.08%), to be administered intravenously (n=38; 79.16%) and at 8 pm (n=10; 20.83%). Conclusion: The anti-infective medication administration error rate by dose omission was significant and higher than for the other groups of drugs, showing a higher incidence using the intravenous route and at times approaching changes of shifts. Safety barriers must be implemented, such as dose triple-checking (at the pharmacy, when the medication is received at the intensive care unit, and at the time of administration). Additionally, adequate drug scheduling, continuing education, and training programs for safe use of medications can be useful for preventing these errors.

Carbapenem sparing in the management of post-transrectal prostate biopsy bacteraemia.

BACKGROUND: Sepsis following transrectal ultrasound (TRUS)-guided prostate biopsy is a major complication. With the emergence of multidrug-resistant organisms, empirical use of carbapenem antibiotics has been increasing. This study, conducted in the Illawarra Shoalhaven Local Health District (ISLHD), Australia, quantifies how much we can spare carbapenem use. METHODS: A retrospective audit of patients who underwent TRUS prostate biopsy and were admitted post-operatively with proven bacteraemia between January 2007 and April 2016. RESULTS: Of 2719 TRUS procedures, 50 (1.84%) cases had bacteraemia. The most common isolate was Escherichia coli in 44 of 50 (88%) of which six of 50 (12%) were extended-spectrum beta-lactamase (ESBL)-producing. Sixteen different empirical antimicrobial regimens were used, to which 42 of 50 (84%) of isolates were susceptible. Eight (16%) isolates were resistant to the chosen empiric combination, with five switched over to appropriate treatment once antimicrobial sensitivity results became available. Empirical carbapenem was utilized in 12 of 50 (24%) patients with only two of the ESBL isolates covered. A further 10 of 50 patients received carbapenems during their admission. Carbapenems could have been avoided in 18 of 22 (82%). A total of 86% of organisms (n = 43) were susceptible to the combination of amoxicillin-clavulanate and gentamicin. CONCLUSION: Although the rates of bacteraemia with ESBL-producing organisms post-TRUS biopsy are increasing, use of carbapenem-free combination antimicrobials as empirical therapy appears to be safe and effective in our setting. Clinicians can utilize local resistance patterns to inform targeted and appropriate therapy for septic patients.

Using local clinical and microbiological data to develop an institution specific carbapenem-sparing strategy in sepsis: a nested case-control study.

Background: From a stewardship perspective it is recommended that antibiotic guidelines are adjusted to the local setting, accounting for the local epidemiology of pathogens. In many settings the prevalence of Gram-negative pathogens with resistance to empiric sepsis therapy is increasing. How and when to escalate standard sepsis therapy to a reserve antimicrobial agent, is a recurrent dilemma. The study objective was to develop decision strategies for empiric sepsis therapy based on local microbiological and clinical data, and estimate the number needed to treat with a carbapenem to avoid mismatch of empiric therapy in one patient (NNTC). Methods: We performed a nested case control study in patients (> 18 years) with Gram-negative bacteremia in 2013-2016. Cases were defined as patients with Gram-negative bacteremia with in vitro resistance to the combination 2nd generation cephalosporin AND aminoglycoside (C-2GC + AG). Control patients had Gram-negative bacteremia with in vitro susceptibility to cefuroxime AND/OR gentamicin, 1:2 ratio. Univariate and multivariable analysis was performed for demographic and clinical predictors of resistance. The adequacy rates of empiric therapy and the NNTC were estimated for different strategies. Results: The cohort consisted of 486 episodes of Gram-negative bacteremia in 450 patients. Median age was 66 years (IQR 56-74). In vitro resistance to C-2GC + AG was present in 44 patients (8.8%). Independent predictors for resistance to empiric sepsis therapy were hematologic malignancy (adjusted OR 4.09, 95%CI 1.43-11.62, p < 0.01), previously cultured drug resistant pathogen (adjusted OR 3.72. 95%CI 1.72-8.03, p < 0.01) and antibiotic therapy during the preceding 2 months (adjusted OR 12.5 4.08-38.48, p < 0.01). With risk-based strategies, an adequacy rate of empiric therapy of 95.2-99.3% could be achieved. Compared to treating all patients with a carbapenem, the NNTC could be reduced by 82.8% (95%CI 78.5-87.5%) using the targeted approaches. Conclusions: A risk-based approach in empiric sepsis therapy has the potential to better target the use of reserve antimicrobial agents aimed at multi-resistant Gram-negative pathogens. A structured evaluation of the expected antimicrobial consumption and antibiotic adequacy rates is essential to be able to weigh the costs and benefits of potential antibiotic strategies and select the most appropriate approach.

A national quality incentive scheme to reduce antibiotic overuse in hospitals: evaluation of perceptions and impact.

Background: In 2016/2017, a financially linked antibiotic prescribing quality improvement initiative Commissioning for Quality and Innovation (AMR-CQUIN) was introduced across acute hospitals in England. This aimed for >1% reductions in DDDs/1000 admissions of total antibiotics, piperacillin/tazobactam and carbapenems compared with 2013/2014 and improved review of empirical antibiotic prescriptions. Objectives: To assess perceptions of staff leading antimicrobial stewardship activity regarding the AMR-CQUIN, the investments made by hospitals to achieve it and how these related to achieving reductions in antibiotic use. Methods: We invited antimicrobial stewardship leads at acute hospitals across England to complete a web-based survey. Antibiotic prescribing data were downloaded from the PHE Antimicrobial Resistance Local Indicators resource. Results: Responses were received from 116/155 (75%) acute hospitals. Owing to yearly increases in antibiotic use, most trusts needed to make >5% reductions in antibiotic consumption to achieve the AMR-CQUIN goal of 1% reduction. Additional funding was made available at 23/113 (20%) trusts and, in 18 (78%), this was <10% of the AMR-CQUIN value. Nationally, the annual trend for increased antibiotic use reversed in 2016/2017. In 2014/2015, year-on-year changes were +3.7% (IQR -0.8%, +8.4%), +9.4% (+0.2%, +19.5%) and +5.8% (-6.2%, +18.2%) for total antibiotics, piperacillin/tazobactam and carbapenems, respectively, and +0.1% (-5.4%, +4.0%), -4.8% (-16.9%, +3.2%) and -8.0% (-20.2%, +4.0%) in 2016/2017. Hospitals where staff believed they could reduce antibiotic use were more likely to do so (P < 0.001). Conclusions: Introducing the AMR-CQUIN was associated with a reduction in antibiotic use. For individual hospitals, achieving the AMR-CQUIN was associated with favourable perceptions of staff and not availability of funding.

Higher third-generation cephalosporin prescription proportion is associated with lower probability of reducing carbapenem use: a nationwide retrospective study.

Background: The ongoing extended spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) pandemic has led to an increasing carbapenem use, requiring release of guidelines for carbapenem usage in France in late 2010. We sought to determine factors associated with changes in carbapenem use in intensive care units (ICUs), medical and surgical wards between 2009 and 2013. Methods: This ward-level multicentre retrospective study was based on data from French antibiotic and multidrug-resistant bacteria surveillance networks in healthcare facilities. Antibiotic use was expressed in defined daily doses per 1000 patient-days. Factors associated with the reduction in carbapenem use (yes/no) over the study period were determined from random-effects logistic regression model (493 wards nested within 259 healthcare facilities): ward characteristics (type, size…), ward antibiotic use (initial antibiotic use [i.e., consumption of a given antibiotic in 2009], initial antibiotic prescribing profile [i.e., proportion of a given antibiotic in the overall antibiotic consumption in 2009] and reduction in the use of a given antibiotic between 2009 and 2013) and regional ESBL-PE incidence rate in acute care settings in 2011. Results: Over the study period, carbapenem consumption in ICUs (n = 85), medical (n = 227) and surgical wards (n = 181) was equal to 73.4, 6.2 and 5.4 defined daily doses per 1000 patient-days, respectively. Release of guidelines was followed by a significant decrease in carbapenem use within ICUs and medical wards, and a slowdown in use within surgical wards. The following factors were independently associated with a higher probability of reducing carbapenem use: location in Eastern France, higher initial carbapenem prescribing profile and reductions in consumption of fluoroquinolones, glycopeptides and piperacillin/tazobactam. In parallel, factors independently associated with a lower probability of reducing carbapenem use were ICUs, ward size increase, wards of cancer centres, higher initial third-generation cephalosporin (3GC) prescribing profile and location in high-risk regions for ESBL-PE. Conclusions: Our study suggests that a decrease in 3GCs in the overall antibiotic use and the continuation of reduction in fluoroquinolone use, could allow reducing carbapenem use, given the well-demonstrated role of 3GCs and fluoroquinolones in the occurrence of ESBL-PE. Thus, antibiotic stewardship programs should target wards with higher 3GC prescription proportions to reduce them.

The North Wind and the Sun: Pediatric Antimicrobial Stewardship Program Combining Restrictive and Persuasive Approaches in Hematology-Oncology Ward and Hematopoietic Stem Cell Transplant Unit.

BACKGROUND: The Japanese government's goal for the reduction of antimicrobial consumption is two-thirds of the 2013 rate by 2020. While the antimicrobial stewardship programs (ASPs) are essential in health care facilities, ASP data on pediatric hematology-oncology and hematopoietic stem cell transplant (HSCT) patients are limited. Our aim was to evaluate the impact of restrictive and persuasive ASP on immunocompromised children. METHODS: The ASP for hematology-oncology and HSCT patients at Tokyo Metropolitan Children's Medical Center was assessed. Phase 1 was a postprescriptive review of carbapenem conducted between April 2010 and September 2011. Phase 2 consisted of the preauthorization of carbapenem, prospective audit with feedback, a weekly luncheon meeting among physicians, consensus on febrile neutropenia management, and implementation of viral molecular diagnostics between October 2011 and September 2015. Both phases were compared for day-of-therapy per 1,000 patient-days, cost of intravenous antimicrobial agents, average hospitalization duration, all-cause mortality, infection-related mortality at 30 days, and appropriateness of empirical treatment of bacteremia. RESULTS: The ASP did not differ from phase 1 to phase 2 in terms of average hospitalization length, mortality rate, or appropriateness of empirical treatment for bacteremia. Day-of-therapies of cefepime, piperacillin/tazobactam, meropenem, vancomycin, liposomal amphotericin B, and fosfluconazole decreased by 20%, 45%, 57%, 38%, 85% and 44%, respectively (P < 0.05). The total cost of antibiotic and antifungal agents decreased by 27%, for a savings of $59,905 USD annually. CONCLUSION: Restrictive and persuasive ASP in the hematology-oncology ward and the HSCT unit safely decreased the use of antibacterial and antifungal agents.

Multidepartmental Response to a Duodenoscope Used on a CRE Patient: A Case Study.

Transmission of carbapenem-resistant Enterobacteriaceae (CRE) via duodenoscopes, specialized endoscopes used during endoscopic retrograde cholangiopancreatography (ERCP) procedures, has attracted media attention since early 2015. This attention has placed increasing focus on the reprocessing of duodenoscopes. Current reprocessing recommendations for these endoscopes require either high-level disinfection or ethylene oxide sterilization. While reprocessing duodenoscopes, staff at endoscopy locations within the Mercy health system perform a single high-level disinfection cycle that is preceded by two cycles of manual cleaning. The Mercy system has 37 locations for gastrointestinal endoscopic procedures and nine that can accommodate patients requiring ERCP. In early 2016, the Mercy Oklahoma City location performed an ERCP on a patient known prior to the case to be a carrier of CRE. After the case, multiple departments located in both the Oklahoma City and St. Louis facilities partnered to culture and sterilize the duodenoscope used in that case to ensure its safety for use on subsequent patients. This case study presents the situation and discusses culturing of endoscopes. In light of the evidence presented, the importance of enhanced communication and cooperation to achieve patient safety should be paramount to all other factors.

Enterobacterias portadoras de KPC en un hospital universitario / KPC-producing Enterobacteriaceae in a university hospital

La resistencia a carbapenemes en enterobacterias representa una situación de alto impacto clínico debido a las limitadas opciones terapéuticas disponibles para el tratamiento de las infecciones causadas por estos microorganismos multirresistentes que cursan con altas tasas de morbilidad y mortalidad. En nuestro país, en los últimos 5 años, se observó la diseminación de aislamientos de Klebsiella pneumoniae portadores de carbapenemasa de tipo KPC pertenecientes al ST258, clon diseminado mundialmente. En nuestro hospital la incidencia de episodios fue aumentando, especialmente la infección del sitio quirúrgico y las bacteriemias. En el último bienio se observó la diseminación del mecanismo de resistencia a otras enterobacterias y probablemente a otros secuenciotipos de K pneumoniae con mayor sensibilidad a antibióticos no ß-lactámicos. Se hace necesario instaurar las correctas medidas de prevención y control para evitar la diseminación de estos patógenos.

The presence of carbapenem -resistant Enterobacteriaceae in clinical settings represents a concerning issue due to the limited therapeutic options available for the treatment of the infections caused by these multi-drug resistant bacteria which usually have high mortality rates. The spread of Klebsiella pneumoniae isolates belonging to ST258 was observed in the last 5 years in our country. In our hospital the number of episodes has grown with the years and the most prevalent infections were the surgical site and bacteremia. In the last 2 years KPC spread to other Enterobacteriaceae and probably to other STs in K pneumoniae which showed different susceptibility patterns to non ß-lactamic antimicrobials. We believe that it is vital to install the appropriate measures to prevent and control the dissemination of these microorganisms.

Pyogenic vertebral osteomyelitis caused by Yersinia pseudotuberculosis.

Septic vertebral osteomyelitis caused by Yersinia pseudotuberculosis is extremely rare. We report the first case of pyogenic vertebral osteomyelitis due to Y. pseudotuberculosis. A 65-year-old man presented with low back pain and fever. He had a history of psoriasis vulgaris treated with adalimumab. The patient reported drinking adequate amounts of well water daily. Clinical examination revealed no neurological deficit of the lower limbs. Laboratory findings included increased inflammatory reactions. Magnetic resonance imaging showed diffuse changes in intensity at the T10 and L3 vertebrae, and multiple nodular lesions in the thoracic, lumbar, sacral, and iliac regions. We performed an open biopsy. Y. pseudotuberculosis was cultured from both the T10 and L3 vertebrae lesions. Y. pseudotuberculosis is sensitive to almost all antibiotics. After initiating antibiotic treatment, the laboratory parameters normalized and the patient recovered completely, without any neurological deficits. To our knowledge, our report represents the first case of pyogenic vertebral osteomyelitis due to Y. pseudotuberculosis.

Transrectal ultrasound-guided biopsy sepsis and the rise in carbapenem antibiotic use.

BACKGROUND: This study sought to determine the number of hospital admissions for sepsis following transrectal ultrasound-guided (TRUS) biopsy, and the rate of both prophylactic and therapeutic use of carbapenem antibiotics for TRUS biopsy, at a single institution. METHODS: A retrospective review of prospectively collected data from the medical records electronic database of Cabrini Health, a private metropolitan hospital, was queried for coding of admissions under any admitting urologist for sepsis and prostate-related infections from 2009 to 2012. Records were examined for whether a TRUS biopsy had been performed within 14 days prior and if a therapeutic carbapenem was required. The database also queried the use of carbapenems as prophylaxis in patients undergoing TRUS biopsy. RESULTS: Of the 63 admissions for TRUS biopsy sepsis, multi-drug-resistant organisms were isolated from 26 (41%). Twenty-three admissions were from the 1937 patients who underwent a TRUS biopsy at Cabrini (a sepsis rate of 1.2%) and 40 were following TRUS biopsies at other centres. Thirty-seven (58.7%) patients received therapeutic carbapenems either empirically, or after culture results. Of the 1937 Cabrini TRUS biopsy patients, 154 (8%) were given a carbapenem as prophylaxis, with a rapid increase in prophylactic use over the 4 years studied from 0.25% to 13%. CONCLUSION: This study did not show evidence of an increasing rate of hospital admissions for TRUS biopsy sepsis at this institution. However, there was a dramatic uptake in prophylactic administration of carbapenems. Increasing carbapenem use may contribute to development of carbapenem-resistant bacteria. Alternative methods of prostate biopsy that avoid sepsis should be considered.

Eficacia y seguridad de ertapenem en infecciones urinarias en pediatría: revisión sistemática / Efficacy and safety of ertapenem for urinary tract infections in children: A systemic review

Introducción: Las infecciones urinarias complicadas son una causa común y potencialmente grave de morbilidad en la edad pediátrica. En los últimos años, se ha observado un incremento en la resistencia de los bacilos gram negativos a los antibióticos tanto en las infecciones urinarias intrahospitalarias como en las provenientes de la comunidad. El ertapenem es un antibiótico carbapenémico de amplio espectro, con una estructura diferente de la del resto de antibióticos ß-lactámicos que permite su administración una o dos veces por día y por vía intramuscular lo que permitiría el manejo ambulatorio de esta patología. Objetivo: evaluar la evidencia disponible sobre la eficacia y seguridad de ertapenem en infecciones urinarias en pediatría. Material y Métodos: revisión sistemática de la literatura. Se priorizó la incorporación de revisiones sistemáticas, ensayos clínicos controlados aleatorizados, y cohortes que compararan el uso de ertapenem con otros antibióticos para el tratamiento de infección urinaria complicada y cuyo punto final fuera la seguridad y/o eficacia del antibiótico. Resultados: Luego de la lectura de los resúmenes quedaron seleccionados 7 artículos de los que se dispuso del texto completo. No se encontraron revisiones sistemáticas sobre el tema. Conclusiones: La seguridad y eficacia del ertapenem fue documentada en pocos trabajos pediátricos. Se requieren más estudios de alta calidad de evidencia para recomendar el uso de ertapenem en el manejo de infecciones urinarias complicadas en pediatría. Sin embargo en casos en que sea la única opción de tratamiento ambulatorio podría considerarse su uso (AU)

Introduction: Complicated urinary infections are a common and potentially severe cause of morbidity in children. Over the past years, increased resistance of gram-negative bacilli to antibiotics has been found in both nosocomial- and communityacquired urinary infections. Ertapenem is a broad-spectrum carbapenem antibiotic with a structure different from other ß-lactam antibiotics and once- or twice-daily intramuscular administration allowing for out-patient management of the pathology. Objective: To evaluate the available evidence on efficacy and safety of ertapenem use in urinary infections in children. Material and methods: A systematic review of the literature was conducted. Systematic reviews, randomized controlled trials, and cohort studies comparing the use of ertapenem with other antibiotics for the treatment of complicated urinary infections with the endpoint of safety and/ or efficacy of the antibiotic were considered. Results: After reading the abstracts, seven studies of which the entire text was available were selected. No systemic reviews were found on the topic. Conclusions: Few studies have been published on the safety and efficacy of ertapenem in children. Further high-quality evidence studies are necessary to recommend the use of ertapenem in the management of complicated urinary infections in children. Nevertheless, in cases in which outpatient treatment is the only option the use of ertapenem may be considered (AU)

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. .

Disposition and metabolism of [¹4C]PTZ601 in healthy volunteers.

1. Six healthy male subjects were given a single dose of 500 mg of [14C]PTZ601 (mean radioactivity 79.2 µCi) by intravenous (IV) infusion over 1 h, and observed for 5 days post-dose during which pharmacokinetic (PK) samples were collected. Plasma PTZ601 concentrations and metabolite identification were determined using LC-MS/MS; PK parameters were estimated by non-compartmental analysis. Excretion and mass balance were determined with liquid scintillation analysis and metabolites profiling was characterized by HPLC online radiochemical detection. 2. The disposition of PTZ601 was best described by a fast absorption, followed by a biphasic elimination phase. Peak PTZ601 plasma concentrations were reached within 0.5-1 h. The mean elimination half-life was 1.6 h and clearance was 13 L/h. 3. Recovery of the radioactivity dose was complete (mean 92%). The main route of excretion (parent and metabolites) was the renal route, as urine accounted for 69-77%, while feces only 13-22%, of the total radioactivity. 4. The majority of the drug was excreted in urine as multiple open ring metabolites: M17.3 (oxidative ring-opened product) and M22.2 (di-cysteine conjugate of 17.3); unchanged PTZ601 in urine contributed to 15% of radioactivity. The major metabolites detected in plasma were M17.3, M12.8 (acetylated M17.3), M22.2, and M41.4 (methylated M17.3). 5. PTZ601 was well tolerated.