Prolonged Antibiotic Use Research Articles

Impact of pharmacist intervention in antibiotic stewardship programmes for critically ill neonates: A systematic review and meta-analysis.

Antibiotic stewardship programmes (ASPs) are introduced to ensure effective antibiotic use. Pharmacists can be involved in ASPs to facilitate the appropriate antibiotic use. Prolonged use of antibiotics causes adverse events in critically ill neonates. Hence, this systematic review and meta-analysis was aimed at investigating pharmacists' functions in ASPs in critically ill neonates and the effect of ASP implementation on antibiotic use. A comprehensive search of PubMed/Medline, Embase, and Cochrane Library databases until January 2021 was conducted and studies that reported the functions of pharmacists in ASPs for critically ill neonates and the results of ASP implementation were included in this review. All processes were performed by two reviewers independently, and any discordance between the two was resolved by discussion. In all, 19studies were included in this review. Pharmacists were found to have various functions in ASPs, such as participating in the development of antibiotic use guidelines, auditing antibiotic prescriptions, participating in multidisciplinary ward rounds, educating other ASP team members, checking blood culture or laboratory data, and monitoring antibiotic use. A meta-analysis revealed that ASP implementation in critically ill neonates was significantly associated with a 23% reduction in the overall antibiotic use rate (ratio of means: 0.77, 95% confidence interval: 0.69-0.87, p<0.001). Moreover, the overall duration of antibiotic therapy significantly reduced by 15% with ASP implementation (ratio of means: 0.85, 95% confidence interval: 0.78-0.91, p<0.001). The implementation of ASPs involving pharmacists, especially in critically ill neonates, was associated with the reduced use and duration of antibiotic treatment. Thus, pharmacists played a key role in ASPs in critically ill neonates.

84 Looking back to move forward; can fetal placental inflammatory response play a role in risk of sepsis and clinical decision making in preterm infant

Abstract Primary Subject area Neonatal-Perinatal Medicine Background Sepsis adversely impacts the survival of very low birth weight infants (VLBW), with a mortality risk up to 50%. Its diagnosis in premature infants is challenging. Conversely, prolonged antibiotic use is associated with perilous potential consequences, propelling the need to better identify those at risk of sepsis. The presence of a histological intra-amniotic inflammation (IAI) response may be associated with an increased risk of early onset sepsis (EOS). Currently, it is unknown how the diagnosis of histological IAI impacts the risk of sepsis. Objectives Our research goal is to explore histological fetal and maternal inflammation in the placenta in VLBW infants and to evaluate if specific recommendations about antibiotic management of VLBW infants with histological fetal response can be proposed. Design/Methods Retrospective cohort study of all infants &amp;lt; 1500 g born to a mother with histologically confirmed IAI. Demographic information about the pregnancy, delivery and postnatal course up to 28 days of life was extracted. Descriptive statistical analysis was conducted to compare the characteristics of infants with histological fetal response using χ2 test or Fisher’s exact test and Wilcoxon rank sum test or ANOVA. Results Seventy-three mother-baby pairs were reviewed. EOS prevalence (19%) in our IAI group of VLBW infants is much higher than EOS observed in all VLBW infants from the Canadian Neonatal Network database (below 3%). In our cohort, the majority had fetal inflammatory stage 1 (31.6%) and fetal inflammatory grade 0 (50%). There was no statistically significant distribution amongst the fetal stages or grades. Time to sepsis event analysis showed that the earlier fetal inflammatory grade was associated with positive cultures occurring earlier, while in the later grades there demonstrated longer latency to positive cultures. This trend was also true when looking at the maternal inflammatory stages. Nine infants who had antibiotics discontinued from day of life (DOL) 2-5 developed a positive blood culture ≤ DOL8. Conclusion Our results suggest that the presence of mild fetal inflammatory changes is associated with earlier positive cultures. We hypothesize that later grades may be associated with longer infection exposure leading to prolonged maternal antibiotics, resulting in less EOS. Majority of positive cultures were within the 3-8 day window, suggesting a role of knowing the fetal inflammatory response when deciding duration of antibiotic treatment.

Broad spectrum antimicrobial PDMS-based biomaterial for catheter fabrication

BackgroundIn addition to the widespread use of antibiotics in healthcare settings, the current COVID-19 pandemic has escalated the emergence of antibiotic resistance. Nosocomial infections among hospitalized patients is a leading site for such resistant microbial colonization due to prolonged use of invasive devices and antibiotics in therapies. Invasive medical devices, especially catheters, are prone to infections that could accelerate the development of resistant microbes. Often, catheters - particularly urinary catheters - are prone to high infection rates. Antibiotic-coated catheters can reduce infection rates and although commercially available, are limited in efficacy and choices.MethodsHerein, a novel and facile method to fabricate PMDS-based biomaterial for the development of antimicrobial eluting catheters is presented. Silicone based organic polymer polydimethylsiloxane (PDMS) was used to prepare a biomaterial containing novel polymeric imidazolium antimicrobial compound.ResultsIt was found that the PDMS-based biomaterials could eradicate microbial colonization even after 60 days in culture with continuous microbial challenge, be recycled over multiple uses, stored at room temperature for long-term usage and importantly is biocompatible.ConclusionThe PDMS-based biomaterial displayed biocidal functionality on microbes of clinical origin, which form major threats in hospital acquired infections.Graphical

How do terminal modifications of short designed IIKK peptide amphiphiles affect their antifungal activity and biocompatibility?

HypothesisThe widespread and prolonged use of antifungal antibiotics has led to the rapid emergence of multidrug resistant Candida species that compromise current treatments. Natural and synthetic antimicrobial peptides (AMPs) offer potential alternatives but require further development to overcome some of their current drawbacks. AMPs kill pathogenic fungi by permeabilising their membranes but it remains unclear how AMPs can be designed to maximise their antifungal potency whilst minimising their toxicity to host cells. ExperimentsWe have designed a group of short (IIKK)3 AMPs via selective terminal modifications ending up with different amphiphilicities. Their antifungal performance was assessed by minimum inhibition concentration (MICs) and dynamic killing to 4 Candida strains and Cryptococcus neoformans, and the minimum biofilm-eradicating concentrations to kill 95% of the C. albicans biofilms (BEC95). Different antifungal actions were interpreted on the basis of structural disruptions of the AMPs to small unilamellar vesicles from fluorescence leakage, Zeta potential, small angle neutron scattering (SANS) and molecular dynamics simulations (MD). FindingAMPs possess high antifungal activities against the Candida species and Cryptococcus neoformans; some of them displayed faster dynamic killing than antibiotics like amphotericin B. G(IIKK)3I-NH2 and (IIKK)3II-NH2 were particularly potent against not only planktonic microbes but also fungal biofilms with low cytotoxicity to host cells. It was found that their high selectivity and fast action were well correlated to their fast membrane lysis, evident from data measured from Zeta potential measurements, SANS and MD, and also consistent with the previously observed antibacterial and anticancer performance. These studies demonstrate the important role of colloid and interface science in further developing short, potent and biocompatible AMPs towards clinical treatments via structure design and optimization.

Biofilm regulation in Clostridioides difficile: Novel systems linked to hypervirulence.

Clostridiodes difficile (C. difficile) was ranked an “urgent threat” by the Centers for Disease Control and Prevention (CDC) in 2019. C. difficile infection (CDI) is the most common healthcare-associated infection (HAI) in the United States of America as well as the leading cause of antibiotic-associated gastrointestinal disease. C. difficile is a gram-positive, rod-shaped, spore-forming, anaerobic bacterium that causes infection of the epithelial lining of the gut. CDI occurs most commonly after disruption of the human gut microflora following the prolonged use of broad-spectrum antibiotics. However, the recurrent nature of this disease has led to the hypothesis that biofilm formation may play a role in its pathogenesis. Biofilms are sessile communities of bacteria protected from extracellular stresses by a matrix of self-produced proteins, polysaccharides, and extracellular DNA. Biofilm regulation in C. difficile is still incompletely understood, and its role in disease recurrence has yet to be fully elucidated. However, many factors have been found to influence biofilm formation in C. difficile, including motility, adhesion, and hydrophobicity of the bacterial cells. Small changes in one of these systems can greatly influence biofilm formation. Therefore, the biofilm regulatory system would need to coordinate all these systems to create optimal biofilm-forming physiology under appropriate environmental conditions. The coordination of these systems is complex and multifactorial, and any analysis must take into consideration the influences of the stress response, quorum sensing (QS), and gene regulation by second messenger molecule cyclic diguanosine monophosphate (c-di-GMP). However, the differences in biofilm-forming ability between C. difficile strains such as 630 and the “hypervirulent” strain, R20291, make it difficult to assign a “one size fits all” mechanism to biofilm regulation in C. difficile. This review seeks to consolidate published data regarding the regulation of C. difficile biofilms in order to identify gaps in knowledge and propose directions for future study.

Subtractive Proteomics Supported with Rational Drug Design Approach Revealed ZINC23121280 as a Potent Lead Inhibitory Molecule for Multi-drug Resistant Francisella tularensis

Francisella tularensis is a Gram-negative bacterium and is the etiological agent of taluremia. The prolonged use of antibiotics is the reason for pathogen resistance to antibiotics such as beta-lactams and macrolides. This leads to the search to explore novel drug targets for F. tularensis to inhibit its growth. Subtractive proteomics revealed Glucose-1-phosphate thymidylyltransferase (G1PTT) as the most promising protein as a drug target. A pharmacophore model was generated for virtual screening of a druglike library comprised of 1,000,000 drug molecules. Based on a pharmacophore-based search, a set of 152 compounds was predicted as the most potent inhibitors against this enzyme. The screened hits were docked with the target enzyme; which unveiled ZINC23121280 as the best-docked inhibitor having Autdock Vina binding energy of -7.2 kcal/mol and the GOLD score of 64.06. Moreover, the timedependent dynamic behavior of the complex was analyzed using Molecular Dynamics (MD) simulation studies that revealed a stable system with a Root Mean Square Deviation (RMSD) average value of 2.25 Å and Root Mean SquareFluctuations (RMSF) of 1.16 Å. Radial Distribution Function (RDF) predicted strong hydrogen interactions between the ligand and Trp221 from the enzyme active pocket. The higher affinity of the antagonist for the enzyme was further supported by Molecular Mechanics Energies combined with the Poisson–Boltzmann and Surface Area (MMPBSA) and or Generalized Born and Surface Area (MMGBSA) with the estimated binding free energy of −1.07 kcal/mol and −29.59 kcal/mol, respectively. Findings from this present computational framework may provide the foundation for future drug discovery against F. tularensis.

Guest Editorial: The Job to Be Done with Biofilm and Titanium Implants

Guest Editorial: The Job to Be Done with Biofilm and Titanium Implants

Potential therapeutic targets of Klebsiella pneumoniae: a multi-omics review perspective.

The multidrug resistance developed in many organisms due to the prolonged use of antibiotics has been an increasing global health crisis. Klebsiella pneumoniae is a causal organism for various infections, including respiratory, urinary tract and biliary diseases. Initially, immunocompromised individuals are primarily affected by K. pneumoniae. Due to the emergence of hypervirulent strains recently, both healthy and immunocompetent individuals are equally susceptible to K. pneumoniae infections. The infections caused by multidrug-resistant and hypervirulent K. pneumoniae strains are complicated to treat, illustrating an urgent need to develop novel and more practical approaches to combat the pathogen. We focused on the previously performed high-throughput analyses by other groups to discover several novel enzymes that may be considered attractive drug targets of K. pneumoniae. These targets qualify most of the selection criteria for drug targeting, including an absence of its homolog's gene in the host. The capsule, lipopolysaccharide, fimbriae, siderophores and essential virulence factors facilitate the pathogen entry, infection and survival inside the host. This review discusses K. pneumoniae pathophysiology, including its virulence determinants and further the potential drug targets that might facilitate the discovery of novel drugs and effective treatment regimens shortly.

Perceptions of surgeons on surgical antibiotic prophylaxis use at an urban tertiary hospital in Tanzania.

Surgical Site Infections are a major cause of morbidity and mortality among operated patients. In spite of the accessibility of universal and national guidelines for surgical prophylaxis, recent studies surveying the present routine of prophylaxis have demonstrated overutilization of a wide range antibacterial medication for a single patient. Few studies have shown qualitatively factors influencing this and perceptions of surgeons on surgical antibiotic prophylaxis use. Unfortunately, none of these studies have been done in Tanzania. To describe the perceptions of surgeons on surgical antibiotic prophylaxis use at an urban tertiary hospital. A qualitative study involving in-depth interviews with surgeons was conducted in English by the primary investigator. The interviews were audio-recorded and transcribed verbatim. Systematic text condensation by Malterud was used for data analysis. Fourteen surgeons and obstetrics and gynaecologists participated. Their perceptions were summarized into three main categories: Inadequate data to support practice; one who sees the patient decides the antibiotic prophylaxis; prolonged antibiotic use for fear of unknown. The participants perceived that choice of antibiotic should be based on local hospital data for bacterial resistance pattern, however the hospital guidelines and data for surgical site infection rates are unknown. Fear of getting infection and anticipating complications led to prolonged antibiotics use. The study provides an understanding of surgical antibiotic prophylaxis use and its implementation challenges. This was partly expressed by unavailability of local data and guidelines to enhance practice. To improve this, there is a need of guidelines that incorporates local resistance surveillance data and enhanced antibiotic stewardship programmes. A strong consideration should be placed into ways to combat the fears of surgeons for complications, as these significantly affect the current practise with use of surgical antibiotic prophylaxis.

Effects of Perioperative Probiotics and Synbiotics on Pancreaticoduodenectomy Patients: A Meta-Analysis of Randomized Controlled Trials.

Post-pancreaticoduodenectomy infections cause mortality, morbidity, and prolonged antibiotic use. Probiotics or synbiotics may be advantageous for preventing postoperative infections, but their benefits on pancreaticoduodenectomy outcomes are controversial. This study evaluated the efficacy of probiotics and synbiotics in pancreaticoduodenectomy. The Embase, Web of Science, PubMed, and Cochrane Library databases were comprehensively searched for randomized controlled trials (RCTs) that evaluated the effects of probiotics or synbiotics on pancreaticoduodenectomy as of April 16, 2021. Outcomes included perioperative mortality, postoperative infectious complications, delayed gastric emptying, hospital stay length, and antibiotic-use duration. The results were reported as mean differences (MDs) and relative risks (RRs) with 95% confidence intervals (CI). Six RCTs involving 294 subjects were included. Probiotic or synbiotic supplementation did not reduce the perioperative mortality (RR, 0.34; 95% CI, 0.11, 1.03), but reduced the incidences of postoperative infection (RR, 0.49; 95% CI, 0.34, 0.70) and delayed gastric emptying (RR, 0.27; 95% CI, 0.09, 0.76) and also reduced the hospital stay length (MD, −7.87; 95% CI, −13.74, −1.99) and antibiotic-use duration (MD, −6.75; 95% CI, −9.58, −3.92) as compared to the controls. Probiotics or synbiotics can prevent infections, reduce delayed gastric emptying, and shorten the hospital stay and antibiotic-use durations in patients undergoing pancreaticoduodenectomy. These findings are clinically important for promoting recovery from pancreaticoduodenectomy, reducing the incidences of antibiotic resistance and iatrogenic infections, and reducing the medical burden.

Complex Foot Infection Treated With Surgical Debridement and Antibiotic Loaded Calcium Sulfate—A Retrospective Cohort Study of 137 Cases

Complex foot infections involving bone and soft tissue in patients with co-morbidities such as diabetes and peripheral arterial disease (PAD) are a cause of significant hospital admission. They are associated with substantial economic costs to health services worldwide. Historically, severe foot infection has been treated with surgical debridement and prolonged courses of systemic antibiotics. Prolonged systemic antibiotic use increases the risk of drug side effects, antimicrobial resistance and Clostridium difficile infection. The purpose of this study was to investigate whether surgical debridement and implantation of antibiotic loaded calcium sulfate is effective in the resolution of foot infection and wound healing. A retrospective cohort study of 137 consecutive cases of osteomyelitis (127) or significant soft tissue infection (10) over 62 months from 02/2013 to 04/2018 was conducted following local ethical approval. All cases of infection were treated with surgical debridement and local antibiotic-loaded calcium sulfate. The primary outcomes of infection resolution, time to healing and duration of postoperative antibiotics were measured. In 137 cases, 88.3% of infections resolved. Infection was eradicated in 22 patients without postoperative systemic antibiotics. About 82.5% of wounds healed, with an average healing time of 11.3 weeks. Healing time was significantly increased for the co-morbidities of diabetes and PAD (p =< .05) and for those requiring prolonged systemic postoperative antibiotics. Conservative surgical debridement and implantation of local antibiotic impregnated calcium sulfate is safe and effective in managing complex foot infections. We advocate early surgical intervention before deeper tissue involvement to help preserve lower limb structure and function.

Oral D mannose in the prevention and treatment of recurrent urinary tract infections: A review

The results of several studies reveal that antibiotics may promote treatment resistance by causing alterations in the intestinal flora. The development of a gut reservoir of resistant bacteria promotes the development of UTIs through autoinfection. This review aims to address clinical reliability, efficacy and safety of long-term treatment with oral D mannose for the prevention of Recurrent Urinary Tract Infections (RUTI) in females. A comprehensive MEDLINE, Embase, Scopus and Cochrane search was performed for English language reports published before December 2018 using the term “recurrent urinary tract infections and D mannose” was carried out. We searched Medline, Embase, Scopus and the Cochrane Register of Controlled Trials from January 2010 to December 2018. Eligible studies did not include non-oral therapy, local (vaginal) treatment in women with recurrent UTIs. We identified eligible original articles. A few limitations of the review are the heterogeneity of the available studies, their different rational and aim, the assumption of D mannose for prophylaxis or treatment of recurrent UTIs. Oral D mannose performs well in the prevention of UTIs recurrences, significant improvement of urinary symptoms was observed, the disease- free time was longer in the groups of patients under prophylaxis with D mannose in comparison with control groups (no treatment, antibiotic prophylaxis, prophylaxis with Proanthocyanidin (PAC) etc. The review has limitations, as the studies are heterogeneous, the meta-analysis requires classifications that can also be arbitrary. Furthermore, single-arm studies are not included. Some of the authors found this evidence inconclusive, which results as a limitation of the study. D mannose prolonged the recurrence-free interval of recurrent UTIs, thus reducing the prolonged or cyclical use of antibiotics, improving clinical symptoms, with a significant difference between treatment and control groups (no treatment, antibiotic prophylaxis, prophylaxis with Proanthocyanidin). However, most clinical trials used an association of different substances commingled with D mannose, dosages and regimens of D mannose were different. For this reason, the evidence of the efficacy of D mannose remains low.

Adherence to Antibiotic Stewardship Program Associated with Shorter Course of Treatment and Fewer Adverse Events

Group Name: NorthShore University HealthSystemBackground: Prolonged antibiotic use has been attributed to an increased incidence of adverse drug events (ADEs). Cessation of unnecessary antibiotics would decrease length of treatment and may help prevent these adverse events. We evaluated whether an antibiotic stewardship intervention aimed at stopping unnecessary antibiotic usage would both shorten the duration of treatment and reduce ADEs. Methods: At NorthShore University HealthSystem, a 4-hospital, 832-bed system, we identified patients who were started on empiric antibiotics during a hospital admission between May 2, 2016, and June 30, 2018. Within 24 hours of antibiotic initiation, an infectious disease (ID) physician reviewed each patient chart. If the patient was unlikely to have a symptomatic bacterial infection, the ID physician left a note in the electronic medical record (EMR) recommending antibiotic cessation. Two physician reviewers retrospectively reviewed whether the treatment team accepted these recommendations and assessed potential ADEs for 30 days after the recommendation through inpatient and outpatient notes in the EMR. These ADEs were defined using previously published criteria. If the 2 reviewers disagreed on the presence of an ADE, an ID physician acted as the tie breaker. We compared the number of antibiotic days and the number of ADEs between cases in which the recommendations were followed and cases in which they were not. Results: We reviewed 168 cases: 78 (46.43%) followed recommendations and 90 (53.57%) did not. There were no significant differences in baseline patient characteristics between the 2 groups. There was a significant difference in total ADEs between the 2 groups: in 6 cases (7.69%) the recommendations were followed, and 21 (23.33%) they were not followed (P = .011). There was also a significant difference in antibiotic days between cases in which recommendations were followed (1.40 days) versus those in which they were not followed (1.99 days) (p &lt; 0.001). Conclusions: Antibiotic-associated adverse events can cause harm to patients and increase healthcare costs, particularly when used for patients who are unlikely to have a bacterial infection. An antibiotic stewardship program to identify patients in an EMR who are unlikely to benefit from antibiotic use can decrease the length of total antibiotic usage and help prevent adverse events.Funding: NoDisclosures: None

Prolonged antibiotic prophylaxis in tissue reconstruction using autologous fat grafting: Is there a benefit for wound healing?

Fat grafting is a well‐established method in plastic surgery. Despite many technical advances, standardised recommendations for the use of prophylactic antibiotics in fat grafting are not available. This retrospective multicentre study aims to analyse the use of prophylactic antibiotics in fat grafting and to compare complication rates for different protocols. A retrospective medical chart review of 340 patients treated with fat grafting of the breast from January 2007 to March 2019 was performed in three plastic surgery centres. Complications, outcomes, and antibiotic regimes were analysed. The Clavien‐Dindo classification was applied. All patients received perioperative antibiotic prophylaxis: 33.8% (n = 115) were treated with a single shot (group 1), 66.2% (n = 225) received a prolonged antibiotic scheme (group 2). There was no significant difference in the number of sessions (P = .475). The overall complication rate was 21.6% (n = 75), including graft resorption, fat necrosis, infection, and wound healing problems. Complication rates were not significantly different between groups. Risk factors for elevated complication rates in this specific patient group are smoking, chemotherapy, and irradiation therapy. The complication rate for lipografting of the breast is low, and it is not correlated to the antibiotic protocol. The use of prolonged prophylactic antibiotics does not lower the complication rate.

Strategies to Improve Antimicrobial Utilization with a Special Focus on Developing Countries.

Antimicrobial resistance (AMR) is a high priority across countries as it increases morbidity, mortality and costs. Concerns with AMR have resulted in multiple initiatives internationally, nationally and regionally to enhance appropriate antibiotic utilization across sectors to reduce AMR, with the overuse of antibiotics exacerbated by the COVID-19 pandemic. Effectively tackling AMR is crucial for all countries. Principally a narrative review of ongoing activities across sectors was undertaken to improve antimicrobial use and address issues with vaccines including COVID-19. Point prevalence surveys have been successful in hospitals to identify areas for quality improvement programs, principally centering on antimicrobial stewardship programs. These include reducing prolonged antibiotic use to prevent surgical site infections. Multiple activities centering on education have been successful in reducing inappropriate prescribing and dispensing of antimicrobials in ambulatory care for essentially viral infections such as acute respiratory infections. It is imperative to develop new quality indicators for ambulatory care given current concerns, and instigate programs with clear public health messaging to reduce misinformation, essential for pandemics. Regular access to effective treatments is needed to reduce resistance to treatments for HIV, malaria and tuberculosis. Key stakeholder groups can instigate multiple initiatives to reduce AMR. These need to be followed up.

Comparision of Infection Frequency in 1-Day Vs 5-Days Post Operative Antibiotic Regimen in Open Treated Facial Fractures

Objective: To compare the frequency of surgical site infection by using postoperative prophylactic antibiotics (1day vs. &gt; 5 days) in patients following open surgical reduction of facial fractures. Design: Randomized Controlled Trial Setting: Department of Dental &amp;Maxillofacial Surgery, Liaquat National Hospital, Institute of Postgraduate Medical Studies &amp; Health Sciences, Karachi. Duration: 06months from 23 December 2016 to 22 June 2017. Subject and Methods: A total of 368 cases according to inclusion and exclusion criteria were included in this study. Patients were randomly divided into two groups. Antibiotic (Inj. Augmentin 1.2g) was given to group A from admission to 24 hours postoperatively and in Group B antibiotic was continue up to 05 days postoperatively. A surgeon evaluated participants of both groups at 1, 2, 3 and 4 weeks postoperatively for infection according to criteria of surgical site infection published by CDC. All information was noted in the proforma. Results: - The average age of the patients was 31.10±7.39 years. Rate of surgical site infection was not significant between groups (4.9% vs. 7.1%; p=0.379). Conclusion: In this study 1-day course of antibiotics postoperatively in facial fractures is as effective in preventing infective complications as a 5-day regimen. The use of prolonged postoperative antibiotics in uncomplicated facial fractures had no significant benefit in reducing the incidence of infections. Key Words: Maxillofacial Surgeons, Surgical site infection, Prophylactic antibiotics

Superinfection associated with prolonged antibiotic use in non-ventilator associated hospital-acquired pneumonia.

Background Non-ventilator associated hospital-acquired pneumonia accounts for significant antibiotic use and is associated with a high rate of resistance emergence. However, the optimal duration of antibiotic treatment is uncertain, especially in cases of non-fermenting gram-negative bacilli. Objective To compare a short course (5-7days) to a prolonged course (10-14days) of antibiotics for non-ventilator associated hospital-acquired pneumonia. Methods Data collected retrospectively on patients completed treatment in a Malaysian tertiary hospital from January 2017 till December 2018. Regression analysis determined variables independently associated with clinical outcome. Main outcome measures Clinical resolution, superinfection, 30-day and 90-day all-cause mortality between short and prolonged courses. Results Of the 167 patients included, 112 patients were treated with a short course antibiotic, whereas 55 patients received a prolonged course of therapy. Neither short nor prolonged course group has a significantly higher rate of clinical resolution. Short course group had significantly higher mean ± SD antibiotic-free days (21.9 ± 3.5 versus 15.1 ± 6.2days, p < 0.001). Higher rate of superinfection was observed in prolonged course group compared to short course group (6.3% versus 18.2%, p = 0.027). For non-ventilator associated hospital-acquired pneumonia caused by non-fermenting gram-negative bacilli, the superinfection rate was higher in prolonged course group (35.7% versus 15.4%, p = 0.385) while 30-day mortality rate was higher in the short course group (38.5% versus 14.3%, p = 0.209). Non-fermenting gram-negative bacilli cause higher rate of superinfection (p = 0.010). Conclusion We found no clinical benefit as defined by clinical resolution and reduction in all-cause mortality in prolonging antimicrobial therapy. Superinfections emerge more frequently in prolonged course of antibiotic therapy and more likely to develop in non-fermenting gram-negative bacilli.

FC 0104-WEEK ANTIBIOTIC THERAPY PREVENTS RECURRENT RENAL CYST INFECTIONS IN AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE

Abstract Background and Aims Renal cyst infection (CI) is a major complication of autosomal dominant polycystic kidney disease (ADPKD), associated with frequent hospitalization, worsening of kidney function and significant mortality. Data regarding treatment are scarce and recommendations only expert-based, with low level of evidence. Prolonged treatment duration and use of lipid-soluble antibiotics may increase antibiotic concentration in infected kidney cysts. However, benefits of this strategy have never been investigated in clinical practice. Method We undertook a monocentric retrospective study of CI in ADPKD patients from 2000 to 2018. CI were classified as “definite” (microbiologically proven), “probable” (clinical/biological and radiological signs) or possible (clinical/biological signs). Determinants of treatment failure and recurrences were studied. Results 139 CI (11 “definite”, 74 “probable”, 54 “possible”) were compiled among 90 patients. Median age was 53 years. 28/90 (31%) were kidney transplant recipients. Escherichia coli was identified in 89/106 (84%) episodes. Treatment failure was reported in 22/139 (16%), and found associated with cyst diameter &amp;gt;5cm (80% vs 36%, P&amp;lt;0.01), cyst wall thickening (53% vs 12%, P&amp;lt;0.001), cyst septations (18% vs 1%, P&amp;lt;0.01), intracystic gas (18% vs 1%, P&amp;lt;0.01), kidney abscess (35% vs 1%, P&amp;lt;0.001), higher C-reactive protein level (210 [140-358] vs 145 [99-213] mg/L, P&amp;lt;0.01) or documentation of Staphylococcus aureus and lugdunensis (P&amp;lt;0.001). Recurrence was reported in 20/139 (14%) cases within 1-year follow-up. Recurrence rate was lower in patients treated with lipid soluble antibiotics than with non-lipid soluble antibiotics (HR=0.34 [0.12-0.97], p=0.045). Most importantly, cases with definite and probable CI experienced significantly fewer recurrences when treated with longer treatment duration: 81% for treatment &amp;lt;21 days, 47% for 21-27 days, but only 2% for ≥28 days (p&amp;lt;0.0001). Conclusion Treatment of kidney CI should last ≥28 days and include when possible lipid soluble antibiotics.

P684 Multiplex Gastrointestinal Pathogen Panel Testing is Associated with Higher Rates of Inflammatory Bowel Disease Therapy Escalation in Patients Hospitalised with Flare

Abstract Background Although the role of Clostridioides difficile infection (CDI) testing in inflammatory bowel disease (IBD) flare is well established, the function of additionally testing for non-CDI enteric infections (EI) via multiplex gastrointestinal pathogen polymerase chain reaction (GI panel) stool tests remains unclear. Patients with PCR-confirmed EI are less likely to have IBD therapy escalated; however, it is unknown whether performing testing itself affects IBD-related decision-making and outcomes. This is vital given the similar clinical presentations of flare and EI. We examined differences in IBD outcomes among patients who – in addition to testing for CDI – were and were not co-tested for EI during hospitalisation for flare. Methods We conducted a retrospective cohort study of IBD patients hospitalised with flare and tested for CDI at an urban academic medical centre. We collected data on demographics, IBD disease severity, IBD therapy, and antibiotic therapy. Patients were cohorted by co-testing for EI using a GI panel. The primary outcome was escalation of IBD therapy within 24 hours of emergency department presentation. Each IBD therapy was also studied separately. Secondary outcomes were antibiotic therapy, length of stay, and colectomy. Results Of 134 patients, 66 (49.3%) were co-tested and 7 (10.6%) had an EI detected. Disease severity and CDI rates were comparable between groups (Table 1). Co-tested patients were more likely to receive a new IBD therapy (92.4% vs. 75.0%, p=0.006), specifically intravenous (IV) steroids (89.4% vs. 36.8%, p=&amp;lt;0.001; Table 2). Patients who were not co-tested were more likely to have their existing IBD therapy continued on admission. Co-tested patients were less likely to undergo colonoscopy during admission and had lower rates of prolonged antibiotic therapy (&amp;gt;10 days; 4.5% vs. 14.7%, p=0.047), although prolonged antibiotic use was comparable between groups after excluding patients treated for CDI (5.1% co-tested vs. 1.8% not co-tested, p=0.276). Colectomy rates and length of stay were comparable between groups. Conclusion Co-testing for non-CDI enteric pathogens by GI panel was associated with a greater degree of inpatient IBD flare management – especially IV steroids. Patients not co-tested were more likely to stay on their existing IBD therapy regimen despite similar flare severities at presentation. Given the low pathogen detection rates, early negative testing for EI may promote provider confidence in intensifying IBD therapy. Early clinical improvement after therapy escalation may obviate the need for colonoscopy in these patients. Use of the GI panel may affect IBD decision-making during relapse, and should be considered in all IBD patients hospitalised with flare.

The Association between Prolonged Antibiotic Use in Culture Negative Infants and Length of Hospital Stay and Total Hospital Costs.

This study aimed to determine if prolonged antibiotic use at birth in neonates with a negative blood culture increases the total cost of hospital stay. This was a retrospective study performed at a 60-bed level IV neonatal intensive care unit. Neonates born <30 weeks of gestation or <1,500 g between 2016 and 2018 who received antibiotics were included. A multivariate linear regression analysis was conducted to determine if clinical factors contributed to increased hospital cost or length of stay. In total, 190 patients met inclusion criteria with 94 infants in the prolonged antibiotic group and 96 in the control group. Prolonged antibiotic use was associated with an increase length of hospital stay of approximately 31.87 days, resulting in a $69,946 increase in total cost of hospitalization. Prolonged antibiotics in neonates with negative blood culture were associated with significantly longer hospital length of stay and increased total cost of hospitalization. · Prolonged antibiotic use at birth is associated with prolonged hospital stay.. · Prolonged antibiotic use at birth is associated with increased cost of hospitalization.. · Prolonged antibiotic use at birth is associated with increased days on total parenteral nutrition.. · Prolonged antibiotic use at birth is associated with increased subsequent courses of antibiotics..