Recommendations For Antibiotic Treatment Research Articles

Routine Infectious Disease Consultation Prior to an Allogeneic Hematopoietic Cell Transplant.

A transplant infectious disease (TID) assessment is essential to select recipients for an allogeneic hematopoietic cell transplant (HCT) and tailor prophylactic and empirical treatment recommendations. We performed a retrospective single-center study to describe our model of care based on a routine TID consultation prior to an allogeneic HCT between 2018 and 2022 in 292 adult (≥18-year-old) consecutive patients. We describe the performance of a TID consultation, arbitrarily defined as major (HCT postponement, procedure, cytomegalovirus [CMV] recipient serology reinterpretation) and minor interventions. Overall, 765 interventions were observed in 257 of 292 (88%) patients: 88 of 765 (11.5%) major and 677 of 765 (88.5%) minor interventions. Among major interventions, HCT was postponed in 8 of 292 (2.7%) patients and a procedure was requested in 18 of 292 (6.2%) patients. The CMV recipient serostatus was changed from indeterminate/low-titer positive to negative in 60 of 292 (20.5%) patients. Among 677 minor interventions, there were 68 (8.8%) additional consultations with other services requested, 260 (33.7%) additional diagnostic tests requested, 102 (13.2%) additional treatments recommended, 60 (7.8%) non-CMV serology reinterpretations performed, 115 (14.9%) deviations from routine anti-infective prophylaxis, and 72 (9.3%) deviations from routine empirical antibiotic treatment recommendations in case of neutropenic fever. We are proposing a structured, clearly defined, and comprehensive pretransplant checklist for an effective assessment of infectious disease risks and complications prior to an allogeneic HCT. Further studies or experiences like ours could help to define a global strategy or new models of care to be implemented in HCT centers in the future.

P18 Treatment patterns and extent of inappropriate antimicrobial treatment among female patients with uncomplicated urinary tract infection in England

P18 Treatment patterns and extent of inappropriate antimicrobial treatment among female patients with uncomplicated urinary tract infection in England

Neonatal sepsis: Challenges in data access, harmonisation and analysis to inform empirical antibiotic recommendations in South African neonatal units


 
 
 Severe bacterial and fungal infections (sepsis) are a leading cause of mortality among neonates in sub-Saharan Africa. In African neonatal units, most sepsis episodes are hospital acquired, and caused by Gram-negative, antimicrobial-resistant pathogens. With rising rates of antimicrobial resistance (AMR) in neonatal sepsis pathogens, there is an increasing probability of inappropriate empirical antibiotic therapy (so called ‘bug-drug’ mismatch or discordant therapy), as confirmation of pathogen identity and antibiotic susceptibility pattern is either not available or delayed. The impact of AMR and discordant empirical treatment on neonatal sepsis outcomes in Africa is largely unknown owing to the lack of the infection surveillance data needed to derive empirical antibiotic treatment recommendations. The Antibiotics for Neonatal Sepsis in Africa (ANSA) study will address this data gap by pooling and harmonising available single-centre research datasets and/or routine laboratory blood culture data to determine which antibiotics should be used for empirical treatment of neonatal sepsis. However, many challenges hamper these datasets, including: variable laboratory methods for pathogen identification and susceptibility testing; difficulty in collating and harmonising data from multiple sites; problems of record linkage in the absence of a single patient identifier; lack of centralised health data capturing systems; and difficulty accessing data due to complex data sharing agreements and custodian permissions. To overcome some of these challenges, minimum guidelines for the collection of neonatal sepsis data need to be defined, to ensure consistency between datasets. Greater collection of, access to and sharing of neonatal sepsis data from institutional, provincial and national laboratories, as well as individual neonatal units, would enable the establishment of a neonatal surveillance network. Development of a sustainably-funded neonatal sepsis surveillance network is a national priority, to ensure effective, evidence-based antimicrobial treatment of hospitalised neonates in South Africa.
 
 

Neonatal sepsis: Challenges in data access, harmonisation and analysis to inform empirical antibiotic recommendations in South African neonatal units


 
 
 Severe bacterial and fungal infections (sepsis) are a leading cause of mortality among neonates in sub-Saharan Africa. In African neonatal units, most sepsis episodes are hospital acquired, and caused by Gram-negative, antimicrobial-resistant pathogens. With rising rates of antimicrobial resistance (AMR) in neonatal sepsis pathogens, there is an increasing probability of inappropriate empirical antibiotic therapy (so called ‘bug-drug’ mismatch or discordant therapy), as confirmation of pathogen identity and antibiotic susceptibility pattern is either not available or delayed. The impact of AMR and discordant empirical treatment on neonatal sepsis outcomes in Africa is largely unknown owing to the lack of the infection surveillance data needed to derive empirical antibiotic treatment recommendations. The Antibiotics for Neonatal Sepsis in Africa (ANSA) study will address this data gap by pooling and harmonising available single-centre research datasets and/or routine laboratory blood culture data to determine which antibiotics should be used for empirical treatment of neonatal sepsis. However, many challenges hamper these datasets, including: variable laboratory methods for pathogen identification and susceptibility testing; difficulty in collating and harmonising data from multiple sites; problems of record linkage in the absence of a single patient identifier; lack of centralised health data capturing systems; and difficulty accessing data due to complex data sharing agreements and custodian permissions. To overcome some of these challenges, minimum guidelines for the collection of neonatal sepsis data need to be defined, to ensure consistency between datasets. Greater collection of, access to and sharing of neonatal sepsis data from institutional, provincial and national laboratories, as well as individual neonatal units, would enable the establishment of a neonatal surveillance network. Development of a sustainably-funded neonatal sepsis surveillance network is a national priority, to ensure effective, evidence-based antimicrobial treatment of hospitalised neonates in South Africa.
 
 

Lyme disease and the pursuit of a clinical cure.

Lyme disease, caused by the spirochete Borrelia burgdorferi, is the most common vector-borne illness in the United States. Many aspects of the disease are still topics of controversy within the scientific and medical communities. One particular point of debate is the etiology behind antibiotic treatment failure of a significant portion (10-30%) of Lyme disease patients. The condition in which patients with Lyme disease continue to experience a variety of symptoms months to years after the recommended antibiotic treatment is most recently referred to in the literature as post treatment Lyme disease syndrome (PTLDS) or just simply post treatment Lyme disease (PTLD). The most commonly proposed mechanisms behind treatment failure include host autoimmune responses, long-term sequelae from the initial Borrelia infection, and persistence of the spirochete. The aims of this review will focus on the in vitro, in vivo, and clinical evidence that either validates or challenges these mechanisms, particularly with regard to the role of the immune response in disease and resolution of the infection. Next generation treatments and research into identifying biomarkers to predict treatment responses and outcomes for Lyme disease patients are also discussed. It is essential that definitions and guidelines for Lyme disease evolve with the research to translate diagnostic and therapeutic advances to patient care.

The role of clinical models in understanding the etiology of pneumonia

The etiology of pneumonia has changed since the beginning of the antibiotic era. Clinical and etiological classifications and protocols recommend immediate empiric antibiotic treatment after diagnosing. However, recommendations for antibiotic treatment, on the one hand, and clinical misunderstanding of the etiology, on the other, gave rise to this review, reflecting the significance of clinical radiological and laboratory epidemiological models in detecting the etiology of pneumonia. We conducted a systematic review of domestic and English-language literature on the etiology of pneumonia. We reviewed articles on the etiology of various forms of pneumonia. We have studied many cases as well as the works that are cited and found as a result of the search.

Persistent Borrelia burgdorferi Sensu Lato Infection after Antibiotic Treatment: Systematic Overview and Appraisal of the Current Evidence from Experimental Animal Models.

Lyme borreliosis is caused by spirochetes belonging to the Borrelia burgdorferi sensu lato group, which are transmitted by Ixodes tick species living in the temperate climate zones of the Northern Hemisphere. The clinical manifestations of Lyme borreliosis are diverse and treated with oral or intravenous antibiotics. In some patients, long-lasting and debilitating symptoms can persist after the recommended antibiotic treatment. The etiology of such persisting symptoms is under debate, and one hypothesis entails persistent infection by a subset of spirochetes after antibiotic therapy. Here, we review and appraise the experimental evidence from in vivo animal studies on the persistence of B. burgdorferi sensu lato infection after antibiotic treatment, focusing on the antimicrobial agents doxycycline and ceftriaxone. Our review indicates that some in vivo animal studies found sporadic positive cultures after antibiotic treatment. However, this culture positivity often seemed to be related to inadequate antibiotic treatment, and the few positive cultures in some studies could not be reproduced in other studies. Overall, current results from animal studies provide insufficient evidence for the persistence of viable and infectious spirochetes after adequate antibiotic treatment. Borrelial nucleic acids, on the contrary, were frequently detected in these animal studies and may thus persist after antibiotic treatment. We put forward that research into the pathogenesis of persisting complaints after antibiotic treatment for Lyme borreliosis in humans should be a top priority, but future studies should most definitely also focus on explanations other than persistent B. burgdorferi sensu lato infection after antibiotic treatment.

Ulceroglandular form of tularemia after squirrel bite: a case report

BackgroundThe diagnosis of tularemia is not often considered in Germany as the disease is still rare in this country. Nonetheless, Francisella tularensis, the causative agent of tularemia, can infect numerous animal species and should, therefore, not be neglected as a dangerous pathogen. Tularemia can lead to massively swollen lymph nodes and might even be fatal without antibiotic treatment. To our knowledge, the case described here is the first report of the disease caused by a squirrel bite in Germany.Case presentationA 59-year-old German woman with a past medical history of hypothyroidism and cutaneous lupus erythematosus presented at the emergency room at St. Katharinen Hospital with ongoing symptoms and a swollen right elbow persisting despite antibiotic therapy with cefuroxime for 7 days after she had been bitten (right hand) by a wild squirrel (Eurasian red squirrel). After another 7 days of therapy with piperacillin/tazobactam, laboratory analysis using real-time polymerase chain reaction (PCR) confirmed the suspected diagnosis of tularemia on day 14. After starting the recommended antibiotic treatment with ciprofloxacin, the patient recovered rapidly.ConclusionThis is the first report of a case of tularemia caused by a squirrel bite in Germany. A naturally infected squirrel has recently been reported in Switzerland for the first time. The number of human cases of tularemia has been increasing over the last years and, therefore, tularemia should be taken into consideration as a diagnosis, especially in a patient bitten by an animal who also presents with headache, increasing pain, lymphadenitis, and fever, as well as impaired wound healing. The pathogen can easily be identified by a specific real-time PCR assay of wound swabs and/or by antibody detection, for example by enzyme-linked immunosorbent assay (ELISA), if the incident dates back longer than 2 weeks.

Comparison of Physical and Digital Treatment and Documentation of Uncomplicated Cystitis.

IntroductionSymptomatic criteria have a diagnostic specificity of approximately 90% for uncomplicated cystitis. Today there are triage bots that can collect patient history and document simultaneously. Acute uncomplicated cystitis could potentially be managed digitally, due to the symptom-based approach to diagnosis, but no studies have yet validated this approach.AimWe determined the extent of criteria documentation and evaluated adherence to antibiotic recommendations in order to compare physical and digital patient consultations for uncomplicated cystitis.Materials and methodsThis cross-sectional study recruited sixteen 50-year-old women who presented with urinary symptoms to digital healthcare or to three primary physical healthcare facilities. The primary endpoint was the proportion of patients who had two or more documented criteria and received correct antibiotic treatment.ResultsIn total, 307 patient visits were included in the study (278 in the digital arm and 40 in the physical arm). The proportion of patients who had two or more documented diagnostic criteria and correct treatment was significantly higher in the digital arm (96 vs 81.6 %, p < 0.001). The total proportion of patients who had fully documented diagnostic criteria did not differ significantly between the arms, however, the proportion with two or more documented criteria was significantly higher in the digital arm (95 vs 77.5%, p < 0.001). The proportion of treated patients who had documented exclusion of diagnostic complicating factors was higher in the digital arm (85.5 vs 0%, p < 0.001).ConclusionsMore patients with urinary tract infection (UTI) now seek digital healthcare providers who have similar or better adherence to antibiotic treatment recommendations and documentation.

Antibiotic stewardship for reptiles.

This review discusses the general principles underlying responsible antibiotic usage in reptiles. Verylittle evidence underlies antibiotic usage in reptiles, and there are no published guidelines for responsible antibiotic usage. A literature search was performed to review the evidence for bacterial involvement in the pathology of selected common diseases of reptiles, allowing the development of recommendations for responsible antibiotic treatment of those diseases.

The Impact of Syndromic Management of Vaginal Discharge Syndrome on Adverse Birth Outcomes in Botswana.

BackgroundVaginal discharge syndrome (VDS) is a common clinical diagnosis during pregnancy in Botswana; it is treated with broad-spectrum antibiotics using a syndromic approach. We evaluated associations between the syndromic management of VDS and adverse birth outcomes.MethodsThe Tsepamo Study performs birth outcomes surveillance at government hospitals throughout Botswana. Obstetric record data collected from August 2014 to March 2019 were analyzed. Chi-square tests were conducted to compare proportions of maternal characteristics and infant outcomes. To avoid immortal time bias, all analyses were conducted among women who presented to care before 24 weeks gestation, with VDS categorized as present or absent by 24 weeks gestation. Log-binomial regression models were generated to determine associations between treated VDS and infant outcomes.ResultsVDS was diagnosed in 36 731 (30.7%) pregnant women, of whom 33 328 (90.7%) received antibiotics. Adjusted analyses yielded a harmful association between treated VDS and very preterm delivery (adjusted risk ratio, 1.11; 95% CI, 1.02–1.21). This association remained when restricting to women with VDS who received the recommended antibiotic treatment regimen. Sensitivity analyses produced nonsignificant associations when women with treated VDS were compared with women without VDS who received antibiotics for other indications.ConclusionsA clinical diagnosis of VDS is common among pregnant women in Botswana, and the majority receive antibiotics in pregnancy. Although analyses of VDS occurring later in pregnancy are precluded by immortal time bias, a modest association between treated VDS and very preterm delivery was observed among women diagnosed with VDS by 24 weeks gestation.

103. Empiric Antibiotic Susceptibility Using a Traditional vs. Syndromic Antibiogram-Implications for Antimicrobial Stewardship Programs

BackgroundA primary tenet of antimicrobial stewardship programs (ASPs) is to establish empiric antibiotic treatment recommendations. While traditional antibiograms are useful, intrinsic variability in susceptibility exists when stratifying by source and/or location. In contrast, a syndromic antibiogram displays the likelihood of adequate coverage for a specific infection syndrome, considering the weighted incidence of pathogens causing that syndrome. The aim of the study was to compare antibiotic susceptibilities using a traditional versus syndromic antibiogram.MethodsBetween 2016–2019, 20 US institutions per year submitted up to 250 consecutive targeted gram-negative pathogens from hospitalized patients as part of the Study for Monitoring Antimicrobial Resistance Trends (SMART). MICs were determined by broth microdilution and interpreted using 2020 CLSI breakpoints, except for imipenem/relebactam (I/R) for which FDA breakpoints were used. The traditional antibiogram included the 3 most common Gram-negative pathogens from all sources and represented critical organisms considered for empiric antibiotic coverage; the syndromic antibiogram included the 3 most commonly isolated Gram-negative pathogens from a respiratory source based on patient location.Results17,561 Gram-negative isolates, including 6,654 lower respiratory isolates were evaluated. The top 3 most common Gram-negative organisms included: E. coli (n=6095, 44%), Klebsiella spp. (n=4097, 30%), P. aeruginosa (n=3649, 26%). Cumulative susceptibilities were comparable using a traditional vs. syndromic antibiogram (Figure 1); however, cefepime (FEP), piperacillin/tazobactam (TZP), and meropenem (MEM) susceptibilities were 5 – 8% lower when stratified by patient location (Figure 2) and ≥10% for P. aeruginosa (Figure 3). Ceftolozane/tazobactam (C/T) and I/R demonstrated ≥90% susceptibility regardless of respiratory source or patient location.Figure 1. Cumulative susceptibility of E. coli, Klebsiella spp, and P. aeruginosa for traditional vs. syndromic antibiogram Figure 2. Syndromic antibiogram evaluating cumulative susceptibility of E. coli (n = 637), Klebsiella spp. (n = 1190) and P. aeruginosa (n = 1997) respiratory isolates stratified by patient location Figure 3. Syndromic antibiogram evaluating susceptibility of P. aeruginosa (n = 1997) respiratory isolates stratified by patient location ConclusionOur analysis demonstrated that susceptibilities were lower for first-line agents when stratified by ICU and P. aeruginosa. ASPs should consider syndromic antibiograms based on source and patient location to optimize empiric antibiotic therapy recommendations.DisclosuresKenneth Klinker, PharmD, Merck & Co, Inc (Employee) Karri A. Bauer, PharmD, Merck Research Laboratories (Employee) C. Andrew DeRyke, PharmD, Merck & Co., Inc. (Employee, Shareholder) Levita K. Hidayat, PharmD BCIDP, Merck & Co (Employee)

Are conventional microbiological diagnostics sufficiently expedient in the era of rapid diagnostics? Evaluation of conventional microbiological diagnostics of orthopedic implant-associated infections (OIAI)

Background and purpose — In a time when rapid diagnostics are increasingly sought, conventional procedures for detection of microbes causing orthopedic implant-associated infections (OIAI) seem extensive and time-consuming, but how extensive are they? We assessed time to (a) pathogen identification, (b) antibiotic susceptibility patterns, and (c) targeted antibiotic treatment using conventional microbiological diagnostics of OIAI in a consecutive series of patients. Patients and methods — Consecutive patients aged ≥18 years undergoing first revision surgery for acute OIAI, including prosthetic joints, fracture, and osteotomy implants, in 2017–2018 at Akershus University Hospital (Ahus), Norway were included. Information regarding microbiological diagnostics and clinical data was collected retrospectively from the hospital’s diagnostic and clinical databases. Results — 123 patients fulfilled the inclusion criteria. Median time to pathogen identification was 2.5 days and to antibiotic treatment recommendations was 3.5 days. The most common pathogens were S. aureus (52%) and S. epidermidis (15%). Cultures were inconclusive in 11% of the patients. Of the 109 patients with culture-positive results, antibiotic treatment was changed in 66 (61%) patients within a median of 4 days (0–24) after the recommendation was given. Interpretation — Conventional microbiological diagnostics of OIAI is time-consuming, taking days of culturing. Same-day diagnostics would vastly improve treatment efficacy, but is dependent on rapid implementation by clinicians of the treatment recommendations given by the microbiologist.

Intraperitoneal ampicillin treatment for peritoneal dialysis- related peritonitis with Listeria monocytogenes \u2013 a case report

BackgroundPeritoneal dialysis (PD)-related peritonitis is a rare but serious complication and is associated with increased morbidity and mortality rates. It is most commonly caused by Staphylococcus aureus or Staphylococcus epidermidis, but infection with Listeria monocytogenes may also occur. Recommendations for antibiotic treatment of a Listeria infection are currently based on a small number of case reports and suggest the administration of ampicillin. But unlike vancomycin or gentamicin, for ampicillin the route of application, the dosage, and the duration of treatment have not yet been established. We report a case in which PD-associated peritonitis due to Listeria infection was treated with ampicillin administered intravenously and intraperitoneally, separately and in combination.Case presentationA 72-year-old man with chronic kidney disease stage 5 dialysis (CKDG5D) secondary to hypertension and diabetes was hospitalised in April 2020 because of PD-related peritonitis caused by a Listeria infection. In accordance with the results of resistance tests, the patient was treated with intravenous ampicillin at a dosage of 6 g twice daily. After initial treatment the leukocyte count in the PD effluent had decreased substantially, but it was permanently reduced only with the addition of intraperitoneal ampicillin (4 g daily). Efficient serum concentrations of ampicillin were determined for both routes of administration, intravenous and intraperitoneal.ConclusionThis is the first case report demonstrating that PD-related peritonitis due to Listeria monocytogenes infection can be treated with intraperitoneal ampicillin and monitored by the determination of peripheral serum concentrations of ampicillin.

Clinical Experience of Implementing Oral Versus Intravenous Antibiotics (OVIVA) in a Specialist Orthopedic Hospital.

The Oral Versus Intravenous Antibiotics (OVIVA) Trial demonstrated that oral therapy, when used during the initial 6 weeks in the treatment in bone and joint infection (BJI), is noninferior to intravenous therapy. To date there are no reports describing reproducibility of these findings in a real-world setting. We studied all patients diagnosed with BJI at our hospital 12 months pre- and postimplementation of the OVIVA trial findings into clinical practice. An infection consultant recommended antibiotic treatment and patients were followed up by an outpatient parenteral antibiotic therapy (OPAT) service. Prospective data from a local registry was used to analyze baseline clinical details, outcome, length of hospital stay (LOS), and costs. A cohort of 328 patients (145 pre- and 183 postimplementation) was analyzed. Postimplementation, 66.1% of patients were switched to a suitable oral antibiotic regimen. Definite failure at 1 year was 13.6% in the preimplementation group and 18.6% in the postimplementation group (P = .154). Postimplementation, definite failure was more common in patients requiring intravenous antibiotics due to lack of suitable oral options (intravenous, 26.7% and oral, 14.3%). Adverse drug reactions (ADRs) requiring closer monitoring or change to treatment were more common postimplementation (21.0% and 37.1%, respectively). ADR-related hospital readmissions were similar in both groups (2.1 and 2.2%). Comparing both groups, the postimplementation group showed a reduction of 4 days in the median LOS and a median cost reduction of £2764.28 per patient. The OVIVA trial findings can be safely implemented into clinical practice when patients on oral antibiotics are followed up by an established OPAT service. Two-thirds of patients were switched to a suitable oral antibiotic regimen. Implementation led to reductions in hospital LOS and antibiotic costs.

Conjunctival Scarring, Corneal Pannus, and Herbert's Pits in Adolescent Children in Trachoma-endemic Populations of the Solomon Islands and Vanuatu.

BackgroundIn the Solomon Islands and Vanuatu, the sign trachomatous inflammation—follicular (TF) is common, but ocular infection with Chlamydia trachomatis is not. It is therefore debatable whether azithromycin mass drug administration (MDA), the recommended antibiotic treatment strategy for trachoma’s elimination as a public health problem, is necessary in this setting. We set out to estimate what proportion of adolescents were at risk of progression of trachomatous scarring.MethodsA cross-sectional survey was undertaken of all children aged 10–14 years resident in communities identified as high-TF clusters during previous population-based mapping. Graders examined children for clinical evidence of trachomatous scarring, pannus, and Herbert’s pits (HPs) or limbal follicles in both eyes. A dried blood spot was collected from each child and tested for antibodies to C. trachomatis.ResultsA total of 492 children in 24 villages of the Solomon Islands and Vanuatu were examined. In total, 35/492 (7%) of children had limbal signs (pannus and/or HPs) plus any conjunctival scarring. And 9/492 (2%) had limbal signs and moderate or severe conjunctival scarring; 22% of children were anti-Pgp3 seropositive.ConclusionsFew adolescents here are at risk of future complications from trachoma, supporting the conclusion that further antibiotic MDA is not currently required for trachoma elimination purposes in these settings.

Supporting patients with long-term problems after Lyme disease.

There has been controversy about Lyme disease (LD), first about whether people really can have persistent problems after Lyme disease, and then about whether more antibiotic treatment is beneficial if they do still have symptoms. This overview compiles into one summary information about what the studies have found about the cause of the symptoms and the possible treatments, so that GPs are better able to advise patients who have the long-term problems. Some patients have persistent symptoms after LD, despite having had the recommended antibiotic treatment. A small proportion of LD patients have a relevant delay in treatment, which may increase their risk for the development of problems that can last a long time, perhaps a few years. These delays can sometimes result from the difficulty of diagnosis, particularly as many LD cases do not have the erythema migrans rash.1 Catching LD while holidaying abroad may make a delay more likely because it may be some time before the patient returns home and sees a doctor. The Royal College of General Practitioners has prepared an LD toolkit2 and mentions post-treatment Lyme disease syndrome (PTLDS) as one term used to describe these long-term problems. PTLDS can significantly impact quality of life3 and recovery may be extremely slow, with no apparent improvement from one month to the next, although very subtle improvement may be seen from one year to the next. PTLDS results in extreme fatigue, cognitive disorders, and musculoskeletal pain. The fatigue has been described as profound and debilitating. The musculoskeletal pain is often roving, asymmetrical pain in the limbs, and is unlike fibromyalgia.4 Memory problems, particularly verbal memory, are also observed, as well as poor concentration, including auditory attention. A study by Fallon et al has shown that patients with PTLDS demonstrated significant flow reductions …

Intra-abdominal infections: the role of different classifications on the selection of the best antibiotic treatment

BackgroundIntra-abdominal infections (IAIs) represent a most frequent gastrointestinal emergency and serious cause of morbimortality. A full classification, including all facets of IAIs, does not exist. Two classifications are used to subdivide IAIs: uncomplicated or complicated, considering infection extent; and community-acquired, healthcare-associated or hospital-acquired, regarding the place of acquisition. Adequacy of initial empirical antibiotic therapy prescribed is an essential need. Inadequate antibiotic therapy is associated with treatment failure and increased mortality. This study was designed to determine accuracy of different classifications of IAIs to identify infections by pathogens sensitive to current treatment guidelines helping the selection of the best antibiotic therapy.MethodsA retrospective cohort study including all adult patients discharged from hospital with a diagnosis of IAI between 1st of January and 31st of October, 2016. All variables potentially associated with pre-defined outcomes: infection by a pathogen sensitive to non-pseudomonal cephalosporin or ciprofloxacin plus metronidazole (ATB 1, primary outcome), sensitive to piperacillin-tazobactam (ATB 2) and hospital mortality (secondary outcomes) were studied through logistic regression. Accuracy of the models was assessed by area under receiver operating characteristics (AUROC) curve and calibration was tested using the Hosmer-Lemeshow goodness-of-fit test.ResultsOf 1804 patients screened 154 met inclusion criteria. Sensitivity to ATB 1 was independently associated with male gender (adjusted OR = 2.612) and previous invasive procedures in the last year (adjusted OR = 0.424) (AUROC curve = 0,65). Sensitivity to ATB 2 was independently associated with liver disease (adjusted OR = 3.580) and post-operative infections (adjusted OR = 2.944) (AUROC curve = 0.604). Hospital mortality was independently associated with age ≥ 70 (adjusted OR = 4.677), solid tumour (adjusted OR = 3.127) and sensitivity to non-pseudomonal cephalosporin or ciprofloxacin plus metronidazole (adjusted OR = 0.368).The accuracy of pre-existing classifications to identify infection by a pathogen sensitive to ATB 1 was 0.59 considering place of acquisition, 0.61 infection extent and 0.57 local of infection, for ATB 2 it was 0.66, 0.50 and 0.57, respectively.ConclusionNone of existing classifications had a good discriminating power to identify IAIs caused by pathogens sensitive to current antibiotic treatment recommendations. A new classification, including patients’ individual characteristics like those included in the current model, might have a higher potential to distinguish IAIs by resistant pathogens allowing a better choice of empiric antibiotic therapy.

Minimum quality threshold in preclinical sepsis studies (MQTiPSS): quality threshold for fluid resuscitation and antimicrobial therapy endpoints

As outlined in the International Guidelines for Management of Sepsis and Septic Shock: 2016, initial fluid resuscitation and administration of antibiotics are key steps in the early management of sepsis and septic shock. However, such clear guidelines do not exist for preclinical sepsis models. To address these shortcomings, the Wiggers-Bernard conference on preclinical sepsis models was held in Vienna in May 2017. The participants reviewed 260 of the most highly cited papers between 2003 and 2012 that used sepsis models. The review demonstrated that over 70% of experiments either did not use or failed to report resuscitation and/or antibiotic treatment. This information served as the basis to create a series of recommendations and considerations for preclinical sepsis models; this Part III report details the recommendations for fluid resuscitation and antibiotic treatment that should be addressed in sepsis models. Similar to human sepsis, fluid resuscitation is recommended in the experimental setting unless part of the study. Iso-osmolar crystalloid solutions are preferred. The administration route and its timing should be adjusted to the specific requirements of the model with preference given to dynamic rather than static hemodynamic monitoring. Predefined endpoints for fluid resuscitation and avoidance of fluid overload should be considered. Preclinical sepsis studies display serious inconsistencies in the use of antimicrobial protocols. To remedy this, antimicrobials are recommended for preclinical studies, with choice and dose adjusted to the specific sepsis model and pathogen(s). Ideally, the administration of antimicrobials should closely mimic clinical practice, taking into account the drug's pharmacokinetic profile, alterations in absorption, distribution and clearance, and host factors such as age, weight, and comorbidities. These recommendations and considerations are proposed as "best practices" for animal models of sepsis that should be implemented.

Part III: Minimum Quality Threshold in Preclinical Sepsis Studies (MQTiPSS) for Fluid Resuscitation and Antimicrobial Therapy Endpoints.

As outlined in the "International Guidelines for Management of Sepsis and Septic Shock: 2016," initial fluid resuscitation and administration of antibiotics are key steps in the early management of sepsis and septic shock. However, such clear guidelines do not exist for preclinical sepsis models. To address these shortcomings, the Wiggers-Bernard conference on preclinical sepsis models was held in Vienna in May 2017. The participants reviewed 260 of the most highly cited papers between 2003 and 2012 that used sepsis models. The review demonstrated that over 70% of experiments either did not use or failed to report resuscitation and/or antibiotic treatment. This information served as the basis to create a series of recommendations and considerations for preclinical sepsis models; this Part III report details the recommendations for fluid resuscitation and antibiotic treatment that should be addressed in sepsis models. Similar to human sepsis, fluid resuscitation is recommended in the experimental setting unless part of the study. Iso-osmolar crystalloid solutions are preferred. The administration route and its timing should be adjusted to the specific requirements of the model with preference given to dynamic rather than static hemodynamic monitoring. Predefined endpoints for fluid resuscitation and avoidance of fluid overload should be considered. Preclinical sepsis studies display serious inconsistencies in the use of antimicrobial protocols. To remedy this, antimicrobials are recommended for preclinical studies, with choice and dose adjusted to the specific sepsis model and pathogen (s). Ideally, the administration of antimicrobials should closely mimic clinical practice, taking into account the drug's pharmacokinetic profile, alterations in absorption, distribution and clearance, and host factors such as age, weight, and comorbidities. These recommendations and considerations are proposed as "best practices" for animal models of sepsis that should be implemented.