Inappropriate Antimicrobials Research Articles

Anti-Alzheimer’s and Anti-Fungal Activities of Pyrrolo[1,2-a] Quinoline Derivatives

Psychiatrists have described the protein deposits in the brain that causes various diseases such as cerebral, functional,physiological dysfunction, and neurodegenerative diseases. Although Alzheimer's disease is detectable, its treatment remainsunattainable. More than 4.6 million new patients are recorded yearly, who are affected by Alzheimer's disease and only a fewdrugs are currently in use for treatment with side effects. Hence, there is a clinical need for new drugs, design, and development.On the other hand, despite the development of antifungal therapeutics over the last three decades, antifungal resistance is still amajor cause. Regularly using inappropriate antimicrobials has become a major healthcare problem globally in the 21st century andhas been titled a "silent tsunami facing modern medicine." It has been estimated that over 8,000,000 die yearly, which providesscope for developing novel antifungal drugs. In this research paper, we describe the synthesized dimethyl-1-(4-substitutedbenzoyl)-5-methylpyrrolo[1,2-a] quinoline-2,3-dicarboxylate 1a-c and ethyl-1-(4-substituted benzoyl) 5-methylpyrrolo[1,2-a]quinoline-3-carboxylate 1d-f were evaluated for in vitro antifungal and anti-Alzheimer’s activities. The derivatives1a-f wereobtained by 1,3-dipolar cycloaddition reaction by treating quaternary salt with dimethyl acetylene dicarboxylate and ethylpropiolate respectively, in the presence of K2CO3 and DMF as a solvent. Among all compounds, 1a, 1d, and 1e showed thehighest inhibitory capacity with IC50 values of 0.28, 0.32, and 0.30 μM, respectively. On the other hand, derivatives were alsoscreened for antifungal activity that displayed moderate activity, whereas 1a and 1f derivatives showed good activity.

A Needs Assessment for Infectious Diseases Consultation in Community Hospitals.

Infectious diseases (ID) consultations have been demonstrated to improve patient outcomes in the treatment of severe infections. However, ID consultation is often unavailable to patients that live in rural communities. Little is known regarding the treatment of infections in rural hospitals with no coverage from an ID specialist. We characterized the outcomes of patients cared for in hospitals without coverage from an ID physician. Patients aged 18years or older admitted to eight community hospitals without access to ID consultation during a 6.5-month period were assessed. All patients had received at least three days of continuous antimicrobial therapy. The primary outcome was the need for transfer to a tertiary facility for ID services. The secondary outcome was the characterization of antimicrobials received. Antimicrobial courses were evaluated independently by two board-certified ID physicians. 3706 encounters were evaluated. Transfers for ID consultation occurred in 0.01% of patients. The ID physician would have made modifications in 68.5% of patients. Areas for improvement included treatment of chronic obstructive pulmonary disease exacerbations, broad-spectrum treatment of skin and soft tissue infection, long courses of azithromycin, and management of Staphylococcus aureus bacteremia, including choice and length of therapy, as well as obtaining echocardiography. Patients evaluated received 22,807days of antimicrobial therapy. Patients hospitalized in community hospitals are rarely transferred for ID consultation. Our work demonstrates a need for ID consultation in community hospitals, identifying opportunities to enhance patient care by modifying antimicrobial regimens to improve antimicrobial stewardship and avoid inappropriate antimicrobials. Efforts to expand the ID workforce to include coverage at rural hospitals will likely improve antibiotic utilization.

A study on acute undifferentiated febrile illness in children (Age 2 Months to 18 Years)

: Acute Undifferentiated Febrile Illness (AUFI) is a common cause of patients seeking healthcare in India. Appropriate diagnosis is essential for proper management of children, since failure to identify the nature of the causative pathogen results in increased morbidity and mortality due to diseases either being untreated or treated with inappropriate antimicrobials, Also there is waste of medicines and increased resistance to antimicrobials, which has a major public health threat worldwide.: To study clinical profile of children admitted with AUFI and to find out common causes of AUFI in Children (2 months to 18 years of age) and their seasonal trends. : A prospective study was carried out over 200 children of age 2 months to 18 months admitted in Balchikitsalaya MBGH Hospital with Acute Undifferentiated Febrile Illness of less than 7 days duration over a period of 12 months from November 2021 to October 2022. : Majority of the patients were in the age group of 10-15 years (32.5%). Out of 200 AUFI patients, majority had undifferentiated illness (53%) followed by Malaria (16.5%), UTI (12.5%), Dengue(11%), Scrub Typhus(5%) and Enteric Fever(2.5%). Higher incidence of AUFI was seen from August to November. : More than 50% cases of Acute Febrile Illness were due to Undifferentiated Illnesses, hence it can be concluded that provided the cause of undifferentiated illness is found, the irrational use of antibiotics and antimalarial should be prevented.

526. Antimicrobial Selection Based on Precision Metagenomics Compared with Standard Urine Culture/Susceptibility: A Reliability and Inter-rater Agreement Analysis for Application in Patients with Urinary Tract Infections

Abstract Background Management of urinary tract infections (UTIs) is highly variable and ∼50% of affected women may receive inappropriate antimicrobials. Precision Metagenomics-based detection of pathogens and antimicrobial resistance (AMR) markers can inform antimicrobial selection in support of stewardship practices. We investigated inter-physician agreement of culture and metagenomic results in a retrospective analysis. Methods We used de-identified urine samples with results of urine culture & antimicrobial susceptibility testing (AST, n=25, 76% culture-positive) and the Explify® Urinary Pathogen ID/AMR Panel (UPIP, IDbyDNA Inc). UPIP is a Precision Metagenomics method to detect >170 uropathogens and >2,000 AMR markers. Four physicians reviewed culture/AST and UPIP results independently to assess if and how they would treat based on each set of results in a middle-aged, female patient with uncomplicated UTI (no comorbidities or medication allergies). Consensus was defined by simple majority; treatment decisions and antimicrobial choice were adjudicated by an infectious disease trained pharmacist. Inter-rater agreement (Fleiss’ kappa) and reliability for accurate case management (reference: adjudicator) were estimated for each method. Results Analytical agreement for uropathogen identification between the two methods was 72% with 95% positive agreement for common uropathogens. Consensus on whether or not to treat was reached for 96% (24/25) of cases for both culture/AST and UPIP; decisions were concordant between methods for 88% of cases (22/25). Inter-rater agreement was high (culture: k=0.73, UPIP: k=0.68; p< 0.05). Physicians were more likely to decide to treat based on culture results (17/25, 68%) than UPIP (15/25, 60%). UPIP detected additional organism(s) and/or AMR marker(s) compared with culture/AST alone that were informative for stewardship-guided treatment decisions in 28% (7/25) of samples. Figure 1: Physician Consensus Treatment Decisions Based on Results of Urine Sample Analysis by Precision Metagenomics or Urine Culture/AST Four infectious disease physicians independently reviewed paired results from analysis of a set of 25 clinical remnant urine samples by an investigational Precision Metagenomics method (UPIP) and by standard urine culture/AST and determined whether or not treatment would be warranted. Figure 2:Summary of Changes in Antimicrobial Selection based on Interpretation of Precision Metagenomics vs Culture/AST Results An infectious disease pharmacist reviewed and adjudicated hypothetical antimicrobial selections. All antimicrobial selections based on the results of the Precision Metagenomics method (UPIP) were found to be appropriate; in 7/15 cases, hypothetical treatment based on UPIP results would have resulted in a change in management that was evaluated to be consistent with stewardship practices. Conclusion Physician agreement on hypothetical treatment recommendations was comparable between the investigational method (UPIP) and the reference method (urine culture/AST). In no case was there inappropriate consensus to treat based on UPIP results alone. The findings from this pilot analysis support the feasibility of metagenomics-guided management of UTIs. Disclosures Benjamin Briggs, MD, PhD, CloudCath: Advisor/Consultant|CosmosID: Employee Benjamin Briggs, MD, PhD, CloudCath: Advisor/Consultant|CosmosID: Employee Robert Schlaberg, MD, MPH, IDBYDNA INC: Board Member|IDBYDNA INC: Explify-related IP|IDBYDNA INC: Employee|IDBYDNA INC: Stocks/Bonds.

Analysis of the management of ventriculitis cases at a UK neurosurgery centre

SummaryBackgroundVentriculitis is an infection of the ventricular system of the central nervous system associated with neurosurgery and/or indwelling medical devices mainly caused by coagulase-negative staphylococci and increasingly by Gram-negative bacilli and other Gram-positive bacteria. The Infectious Diseases Society of America (IDSA) and the neurosurgery department University Hospital Coventry and Warwickshire (UHCW) have treatment guidelines for ventriculitis which recommend antimicrobials and device removal.MethodsData on ventriculitis cases, their management and outcomes were collected from electronic laboratory and hospital records as well as patients' paper records from 2009 to 2019. Cases included patients with CSF shunts or external ventricular drainage. The management of the cases was then compared to both Infectious Diseases Society of America (IDSA) and UHCW guidelines. The data collected included the causative organisms and the use of inappropriate antimicrobials. The cost of inappropriate antimicrobials was calculated.Results99 patients with microbiologically confirmed ventriculitis were identified. Some cases had multiple devices and the total number of devices was 105.98% of cases had medical device removal as part of their care. Only 50% and 56% of cases had antimicrobial treatment which was compliant with local (UHCW) and IDSA guidelines, respectively. The most frequently inappropriate antimicrobials used were meropenem and linezolid, at an estimated cost of £201,172 over 10 years. The most frequently isolated organisms were coagulase negative staphylococci. Mortality rate was estimated at 14% of cases.ConclusionsWe report the first analysis of the management of ventriculitis cases at UHCW over a 10-year period and demonstrate the importance of antimicrobial stewardship. We also report the local epidemiology of causes of ventriculitis at UHCW which will guide the empirical treatment of ventriculitis at UHCW.

P25 An opportunity for antimicrobial stewardship? Assessing the diagnosis and treatment of lower urinary tract infections among inpatients aged 65 and older in a large English teaching hospital

BackgroundBetween 2015 and 2019 the rate of bacteraemias reported in the UK increased by 16.9% along with an increase of 32.5% of resistant organisms associated with bloodstream infections. This increase appears to be driven by a high number of Gram-negative bloodstream infections (GNBSI). There were 312 GNBSI within Leeds Teaching Hospital NHS Trust (LTHT) for the financial year (FY) of 2019–20 and 275 in FY 2020–21. Escherichia coli has been identified as the most common Gram-negative organism associated with bacteraemias. Urinary tract infections (UTIs) have been consistently highlighted as a primary source of E. coli infections, alongside other Gram-negative infections, therefore justifying a review of practice within LTHT regarding diagnosis and treatment of UTI in patients over the age of 65. This quality improvement work aimed to build on the foundations laid by NHS England's Commissioning for Quality and Innovations (CQUIN) scheme 2019–20, which had a focus on the treatment of UTIs in patients over the age of 65. This interventional prospective project was carried out to assess the impact of an antimicrobial stewardship (AMS) pharmacist-led review of patients prescribed antimicrobial treatment for UTIS.ObjectivesTo assess the impact of a pharmacist led clinical review of the diagnosis and treatment of UTIs in patients over the age of 65.StandardsEighty percent compliance was expected in the following standards: (i) patients having symptoms of a UTI documented in their clinical notes; (ii) a urine dipstick is not used as part pf the diagnosis pathway; (iii) have a had a midstream urine sample sent; and (iv) if appropriate, an antibiotic prescribed that complies with NICE/Trust guidelines.MethodsA prospective study of 87 inpatients prescribed antimicrobials for lower UTI (LUTI) was conducted from September 2020 to November 2020. The study aimed to evaluate if LUTI was diagnosed in accordance with PHE guidance, treated as per Trust guidelines and the impact an AMS pharmacist interventions had on treatment. Patients were identified using a daily antimicrobial list; searching and filtering based on indication for antimicrobial prescribed. Online medical notes were reviewed for information relating to the standards, where no information could be found wards were contacted with recommendations or further questions. If a patient was identified as requiring an intervention, for example a change of treatment, this was communicated with the ward team by an appropriate route as well as documenting in the medical notes. Inclusion criteria: >65 years old, prescribed an antibiotic for the treatment of LUTI or catheter associated UTI. Exclusion criteria: <65 years old, complicated UTI, upper UTI, urosepsis.ResultsEighty-seven patients were audited against the criteria: documentation of UTI symptoms = 74%; urine dipstick was not used to diagnose UTI = 69%; urine sample requested = 82%; appropriate antimicrobial was prescribed = 76% (Figures 1 and 2). As a treatment pathway 32% (28 patients) met all four criteria required to accomplish compliance to the diagnosis and treatment of LUTI. Of the 24% of antimicrobial prescriptions deemed inappropriate common themes included: not prescribing appropriate first line antibiotic; no clear indication for antibiotics; resistant to antibiotic prescribed; and inappropriate IV antibiotic prescribing (Figure 3). After an AMS pharmacist contacted the clinical teams to discuss the 24% of inappropriate antimicrobials it resulted in 92% of the antimicrobials being amended to appropriate antimicrobial choices. Increasing appropriate antimicrobials prescribed from 76% to 99%.Figure 1.Graph showing the percentage of datasets meeting the standard.Figure 2.Pie chart showing the percentage of inappropriate versus appropriate antimicrobial prescriptions.Figure 3.Bar chart showing the number of inappropriate antimicrobials and the reasons associated with them being inappropriate.ConclusionsThe results show that whilst most patients met some of the criteria expected to diagnose a LUTI, most did not meet all four. This warrants further quality improvement work to improve the recognition and adherence of the diagnosis and treatment of LUTIs with the aim to embed the processes across all age groups. The interventions of an AMS pharmacist positively impacted the prescribing of antimicrobials in LUTI and appears to be significant, particularly with regards to stopping inappropriate antimicrobials and recommending better treatment choices. These decisions included: promoting oral antibiotics instead of IV; recommending effective treatment based on renal impairment; acting on urine culture sensitivities; and choosing more narrow spectrum antibiotics. This provides a new potential tool for targeted AMS in relation to the treatment of LUTI within a large scale teaching hospital.

Antimicrobial Resistance Situation in Indonesia: A Challenge of Multisector and Global Coordination.

High levels of antimicrobial resistance (AMR) in Indonesia are caused by the use of inappropriate antimicrobials (AM) in healthcare services and the livestock and fisheries sector. The available data and information about overused antibiotics and the AMR threat in Indonesia are limited. The aim of the study is to describe the AMR situation in Indonesia based on perceptions of government officials, health professionals, and the community to determine actions needed to develop AMR-related strategy and policy. The study was done in eight provinces in Indonesia and included reviewing AMR-related policy, collecting antibiotic use reports in primary health care from health offices and hospitals, and conducting in-depth interviews and focus group discussions with informants from health and nonhealth sectors. The results of the study show that AM misuse happens not only in healthcare facilities but also in communities. Medical officers are unfamiliar with AMR-related policy, as are officers in the livestock and fisheries sectors. There is limited coordination between sectors regarding the AMR situation in Indonesia. The government has to take stronger measures to oversee better implementation of AMR policies.

Implementation of a Urinary Tract Infection Treatment Protocol to Improve Prescribing Practices in the Long-Term Care Facility of a Veteran's Healthcare System.

Urinary tract infections (UTIs) are a commonly diagnosed problem in long-term care facilities (LTCFs), but antimicrobial treatment is often incorrectly prescribed. Although bacterial resistance to antimicrobials commonly used for UTIs, such as trimethoprim/sulfamethoxazole and fluoroquinolones, has been dramatically increasing, they are still commonly prescribed. The purpose of this project was to determine if implementation of a standard treatment protocol for UTIs, which emphasized correct UTI diagnosis and use of nitrofurantoin and cefpodoxime/ceftriaxone as empiric therapy per the institutional antibiogram, changed clinician prescribing practices. This quasi-experimental model utilized two years of pre-intervention and two years of post-intervention data. Three hundred patient encounters were included. Antibiotics prescribed in the pre-intervention period included: trimethoprim/sulfamethoxazole (32%), ciprofloxacin (14%), amoxicillin (13%), levofloxacin (9%), cefpodoxime (9%), ceftriaxone (8%), amoxicillin/clavulanate (5%), nitrofurantoin (4%), and other (6%). By contrast, antibiotics prescribed in the post-intervention period included: cefpodoxime (46%), nitrofurantoin (30%), ceftriaxone (10%), trimethoprim/sulfamethoxazole (8%), amoxicillin/clavulanate (1%), and other (5%). These differences in prescribed drug between the pre-intervention and post-intervention encounters were statistically significant (p < 0.001). Overall, appropriate empiric treatment was prescribed in only 48/217 encounters (22%) during the pre-intervention period, but this increased to 73/83 encounters (88%) in the post-intervention period (p < 0.001). The results indicate that the treatment protocol was successful in changing prescribing practices and decreasing the use of inappropriate antimicrobials at the LTCF.

PREVALENCE AND PREDICTORS OF SELF-MEDICATION PRACTICE WITH ANTIMICROBIALS IN PATIENTS VISITING PUBLIC SECTOR AT HOSPITAL KHAIRABAD DISTRICT NOWSHERA

Objective: To determine the prevalence and patterns of self-medication with antimicrobial drugs among patients visiting public hospital in District Nowshera Northwestern Pakistan. Materials and Methods: This cross-sectional study was conducted on patients attending Rural Health Center Khairabad District Nowshera from July to December 2019. The including criteria were: Males and females (non-doctors) attending the clinics aged between 18 and 60 years old, literate enough to read and write. Information regarding demographic characteristics, antimicrobial drugs use in past six months prior to the study were collected through self-administered questionnaires. The questionnaires written in Urdu and English language, were pretested and validated on a sample of 100 participants to determine the application time and to clarify possible questions from the study population. If antimicrobial drugs use was confirmed in the previous six months, supplementary information was asked: the name antimicrobial drug, the person who recommended the treatment and the disease treated with antimicrobial drugs. The collected data were registered in a database and analyzed using Spss. Results: Response rate of 99.4 %( 750/746) was observed, out of 746 participants 43.70% were females and 56.30% were males. 39.81% participants had used antimicrobials prior to the survey in which 33.33% were from rural and 66.67% urban areas. Most common users were of middle education level. Oral and dental problems were leading cause of inappropriate antimicrobials use. Self- medication was most common in age group of 38 years to 47 years old. The most abused drug was Amoxicillin clavulanate. Maximal use was by personal judgment. Conclusion: The results of this study confirm that self-medication with antimicrobial drugs is a relatively common practice among populace of north western District Nowshera Pakistan.

Correlation of antimicrobial prescription rate and county income in medicare part D.

The objective of this study was to examine whether patient income has an impact on likelihood of being prescribed an antimicrobial agent at the county level. A better understanding of factors that influence antimicrobial prescription is needed to efficiently mitigate rates of antimicrobial agents prescribed.This cross-sectional study used data from two publicly available datasets. The 2015 Medicare Part D PUF data quantifies the antimicrobial prescription rate at the county level and data from US Census Bureau provides information on socioeconomic status at the county level.At the county level, we explained 48% of the variation in antimicrobial prescriptions by socioeconomic status, age, gender, and race. More specifically, socioeconomic status accounted for 26% of the variation in antimicrobial rate and as income increased, correlation with antimicrobial prescription rate trended down.We determined patient income and other sociodemographics to influence the prescription of antimicrobial agents. Interventions should consider these factors to effectively evaluate antimicrobial prescription methods. Findings from this study can help guide intervention efforts which aim to minimize the number of inappropriate antimicrobials prescribed, such as antimicrobial stewardship programs. Effective interventions have the capability of decreasing levels of inappropriate antimicrobials prescribed and prevent future cases of resistance.

Antibiotic allergy labels in hospitalized and critically ill adults: A review of current impacts of inaccurate labelling.

Antibiotic allergy labels (AALs) are reported by approximately 20% of hospitalized patients, yet over 85% will be negative on formal allergy testing. Hospitalized patients with an AAL have inferior patient outcomes, increased colonization with multidrug-resistant organisms and frequently receive inappropriate antimicrobials. Hospitalized populations have been well studied but, to date, the impact of AALs on patients with critical illness remains less well defined. We review the prevalence and impact of AALs on hospitalized patients, including those in in critical care.

342. Time to Antimicrobial De-escalation/Discontinuation After Implementation of Cerebrospinal Fluid Polymerase Chain Reaction Tool

BackgroundCerebrospinal fluid (CSF) polymerase chain reaction (PCR) technology can be used as a rapid diagnostic tool that has the potential to more rapidly facilitate targeted antimicrobial therapy and reduce overall time to de-escalation and/or discontinuation of inappropriate antimicrobial usage in patients with suspected meningitis/encephalitis.MethodsThis was a single-center, retrospective cohort analysis with a primary objective focusing on time to de-escalation or discontinuation of inappropriate antimicrobials before and after implementation of a rapid diagnostic meningitis/encephalitis (ME) panel (BioFire FilmArray®). The pre-implementation group, containing 84 patients, examined individuals who had CSF cultures performed in the 6-months prior to implementation. The post-implementation group, containing 88 patients, examined individuals who had an ME panel done in the 6 months following a transitionary 1-month period following implementation. Categorical data analysis was performed using χ2 or Fisher’s exact test and continuous data was analyzed using the Mann–Whitney U test.ResultsTime to de-escalation/discontinuation of inappropriate ampicillin reported in median hours (IQR) was 47.5 (55) for pre-PCR group compared with 39.5 (23.5) in post-PCR group (P = 0.004). Time to de-escalation/discontinuation of Cefotaxime for pre-PCR group was 50.5 (42) compared with 45 (10) for post-PCR (P = 0.027). Using a subgroup analysis based on age, the results for ampicillin and cefotaxime were mirrored in the pediatric population; however, results were insignificant in the adult population. Subgroup analysis of the adult population showed significance in terms of de-escalation/discontinuation of acyclovir reported (in median hours) as 49 (68) in pre-PCR and 19 (18) in post-PCR group (P = 0.002).ConclusionTime to de-escalation and/or discontinuation of ampicillin and cefotaxime was significantly reduced after implementation of the ME panel suggesting clinical significance in high-risk populations such as neonates. Time to de-escalation and/or discontinuation of acyclovir was significantly reduced in the adult population.Disclosures All authors: No reported disclosures.

Otitis in a cat associated with Corynebacterium provencense

BackgroundThe role of corynebacteria in canine and feline otitis has not been investigated in detail; however, members of this genus are increasingly recognized as pathogens of otitis in both human and veterinary medicine.Case presentationHere we report the first case of feline otitis associated with the recently described species Corynebacterium provencense. A seven-month old cat presented with a head tilt and ataxia was diagnosed with peripheral vestibular syndrome associated with an otitis media/interna. This took place 6 weeks after resection of a polyp, having initially shown a full recovery with topical ofloxacin and glucocorticoid treatment. Bacteriology of an ear swab yielded a pure culture of corynebacteria, which could not be identified at the species level using routine methods. However, the 16S rRNA gene sequence was 100% identical to the recently published novel corynebacterium species, Corynebacterium provencense. Whole genome sequencing of the cat isolate and calculation of average nucleotide identity (99.1%) confirmed this finding. The cat isolate was found to contain additional presumptive iron acquisition genes that are likely to encode virulence factors. Furthermore, the strain tested resistant to clindamycin, penicillin and ciprofloxacin. The cat was subsequently treated with chloramphenicol, which lead to clinical improvement.ConclusionCorynebacteria from otitis cases are not routinely identified at the species level and not tested for antimicrobial susceptibility in veterinary laboratories, as they are not considered major pathogens. This may lead to underreporting of this genus or animals being treated with inappropriate antimicrobials since corynebacteria are often resistant to multiple drugs.

POLA KUMAN AEROB DAN KEPEKAAN ANTIMIKROBA PADA ULKUS KAKI DIABETIK

Diabetic foot ulcer is a common complication of diabetic disease which causes morbidity and foot amputation. One major pathogenesis is infection. Microbes which infect are varied. The use of inappropriate antimicrobials can or may cause drugs resistance. Data of microbes pattern and sensitivity test is important and may guide the clinician in giving the initial therapy. The aim of this retrospective study was to know the characteristics, microbial pattern, and the sensitivity to antimicrobial drugs of 31 diabetic foot ulcer patients who were hospitalized at Wahidin Sudirohusodo Hospital, Makassar in the period of January 2009 until June 2010. The study results showed the age mean was 54.06±12.4 years old, and the onset of diabetes mellitus was 7.62±5.77 years. The common microbes were gram negative bacteria (73.52%) including Enterobacter agglomerans, Proteus mirabilis and Klebsiella pneumonia, while the most common gram positive microbe was Streptococcus sp. Gram positive microbes were sensitive to meropenem, ceforoxim and amoxilin, while Gram negative microbes were sensitive to meropenem. Based on this study, the researchers concluded that the most common microbes which infect the feet were gram negative microbes. Gram positive microbes were still sensitive to meropenem, ceforoxim and amoxilin. Gram negative microbes were sensitive to meropenem.

Implementation of antimicrobial stewardship in a South African private healthcare setting

Background: Antimicrobial resistance is a global concern and antimicrobial stewardship is suggested as an intervention that could slow the development of resistance. According to local as well as international studies inappropriate antimicrobials are prescribed in 50% of hospitalised patients. Antimicrobial surgical prophylaxis, combination therapy and prolonged therapy have been identifiedasareaswhere theappropriateuseof antimicrobials could be improved. Methods & Materials: Antimicrobial stewardship was introduced to all 52 Southern African hospitals in the group. As part of the antimicrobial stewardship initiative a guideline on the use of antimicrobials for surgical prophylaxis was compiled out of international references and consultation with local experts. The guideline was distributed to the hospitals and comment from local specialists was encouraged. A quarterly report was developed to measure antimicrobial utilisation as well as the impact of interventions in a comparable, uniform manner. The report determines progress and trends in the hospital groupas well as in individual hospitals and compares hospitals with the same size and case mix. One section of this report is dedicated to antimicrobials used inappropriately as surgical prophylaxis. The provided guideline was used to identify antimicrobials used inappropriately. Results:Data had been collected from January 2010. The results of the last twofinancial yearswere compared. The average percentage surgical cases with inappropriate antimicrobial drug choice for prophylaxis decreased from 16.0% in the financial year April 2011 – March 2012 to 12.5% from April 2012 to March 2013. The first quarter of 2010 had 19% undesired antimicrobial drug choice for prophylaxis and it decreased to 10% in the third quarter of 2013. Conclusion: The data indicated that certain antibiotics were moreoftenprescribed inappropriately thanothers. Itwas also identified that ceftriaxone, a previously highly recommended drug in surgical prophylaxis, was still wildly utilised despite the recent changes in international as well as local guidelines. Pharmacists managed to change with the guideline as reference, a number of these old prescribing habits.

Outcome of nonadherence to antimicrobial treatment guidelines in ambulatory patients with acute cystitis: a nationwide population-based study.

The recurrence rate after acute cystitis treatment failure with inappropriate antimicrobials remains unclear. The goal of this study was to explore the relationship between cystitis recurrence and nonadherence of antimicrobial prescriptions to national guidelines using a nationwide population-based data set. This was a retrospective longitudinal observational cohort study that was conducted using the clinical records of the National Health Insurance Research Database in Taiwan from 2006-2007. After excluding patients younger than 18 years of age, with concurrent infections, urinary tract anomaly, and no antimicrobial treatment, the remaining study population included 36,395 patients with acute cystitis. We evaluated the hazard ratio (HR) of cystitis recurrence within 28 days between the adherence and nonadherence groups using Cox proportional hazard regression analysis. Adherence to antimicrobial prescription guidelines was the factor that most strongly influenced acute cystitis recurrence, with a HR of 0.91 (95% confidence interval 0.87-0.95) after adjusting for all variables. The incidence rate of acute cystitis in patients receiving antimicrobials adherent to national guidelines was 59.78 per 10,000 person-days. The results of the likelihood ratio test indicated that age, sex, and guideline nonadherence were significant risk factors for recurrent cystitis. The percentage of first-generation cephalosporin prescription was 31.61%, making it the most frequently prescribed guideline-recommended drug. Acute cystitis patients with or without multiple chronic comorbidities should be treated with antimicrobials that adhere to recommended guidelines to attain a better therapeutic outcome.

Antimicrobial therapeutic determinants of outcomes from septic shock among patients with cirrhosis

It is unclear whether practice-related aspects of antimicrobial therapy contribute to the high mortality from septic shock among patients with cirrhosis. We examined the relationship between aspects of initial empiric antimicrobial therapy and mortality in patients with cirrhosis and septic shock. This was a nested cohort study within a large retrospective database of septic shock from 28 medical centers in Canada, the United States, and Saudi Arabia by the Cooperative Antimicrobial Therapy of Septic Shock Database Research Group between 1996 and 2008. We examined the impact of initial empiric antimicrobial therapeutic variables on the hospital mortality of patients with cirrhosis and septic shock. Among 635 patients with cirrhosis and septic shock, the hospital mortality was 75.6%. Inappropriate initial empiric antimicrobial therapy was administered in 155 (24.4%) patients. The median time to appropriate antimicrobial administration was 7.3 hours (interquartile range, 3.2-18.3 hours). The use of inappropriate initial antimicrobials was associated with increased mortality (adjusted odds ratio [aOR], 9.5; 95% confidence interval [CI], 4.3-20.7], as was the delay in appropriate antimicrobials (aOR for each 1 hour increase, 1.1; 95% CI, 1.1-1.2). Among patients with eligible bacterial septic shock, a single rather than two or more appropriate antimicrobials was used in 226 (72.9%) patients and was also associated with higher mortality (aOR, 1.8; 95% CI, 1.0-3.3). These findings were consistent across various clinically relevant subgroups. Conclusion: In patients with cirrhosis and septic shock, inappropriate and delayed appropriate initial empiric antimicrobial therapy is associated with increased mortality. Monotherapy of bacterial septic shock is also associated with increased mortality. The process of selection and implementation of empiric antimicrobial therapy in this high-risk group should be restructured. (Hepatology 2012;56:2305–2315)

Reply to Tamma &amp; Cosgrove and Esposito

TO THE EDITOR—We are grateful for the comments of Drs Tamma and Cosgrove [1] on the issue of duration of therapy, particularly as it impacts antibiotic exposure in the child and the community. Greater antibiotic exposure is associated with greater antimicrobial resistance and also adds to costs and toxicities of therapy. This particular issue prompted considerable discussion within the writing group. However, with no scientific evidence in children from randomized controlled trials or even high-quality observational studies conducted in North American centers, the extrapolated data from community-acquired pneumonia (CAP) in adults, well-reviewed by Tamma and Cosgrove, was not felt to be of sufficient relevance to make these recommendations for children. Although children may have fewer comorbid conditions than adults, our guidelines do review the many other differences, including the relative immune incompetence in preschool-aged children compared with adults, as well as the role of viral coinfections. Differences in outcomes for children compared with adults with urinary tract infections highlight the challenges of extrapolating adult treatment protocols to children [2]. However, we certainly agree with the critical importance of this issue and included it as one of our research priorities, as provided in our Table 10: “Develop clinical trial designs that can provide information on the lowest effective antimicrobial dose for the shortest duration of therapy to decrease the development of antimicrobial resistance and the risk of antimicrobial toxicity.” Although the guidelines are unable to address the duration of antibiotic therapy based on adequate evidence, they do emphasize the importance of viral infection as a cause of pneumonia in the preschool-aged child and state that “antimicrobial therapy is not routinely required for preschool-aged children with CAP, because viral pathogens are responsible for the great majority of clinical disease.” We believe that if this recommendation is followed, it will significantly decrease the use of inappropriate antimicrobials in children and is well aligned with the goals expressed by Drs Tamma and Cosgrove. We also thank Dr Esposito for her letter citing 8 concerns regarding the Executive Summary of the Pediatric Infectious Diseases Society and the Infectious Diseases Society of America clinical practice guidelines on the management of CAP in children >3 months [3, 4]. In her review of the Executive Summary, she may have overlooked the reference (p 618) to the full-text electronic article for the guidelines that provides a detailed description of the methods, background, and, most important, the Evidence Summaries that support each recommendation. The comments and questions she raises are all addressed within the full text that is available online (doi: 10.1093/cid/cir531).

Impact of Inappropriate Empiric Antimicrobial Therapy on Mortality of Septic Patients with Bacteremia: A Retrospective Study

Background. Inappropriate empiric antimicrobials could be a major cause of unfavorable mortality rates in co-morbid patients. This study aimed to assess the prevalence and impact of first-dose and 24-hour inappropriate antimicrobials on mortality rates of bacteremic septic patients. Methods. A retrospective cohort study was employed. Case record forms of patients diagnosed as sepsis, severe sepsis, or septic shock with positive hemoculture during 2009 were retrieved from the medical wards, Siriraj Hospital. Demographic data, antimicrobial use, types of bacteria isolated from blood and susceptibilities, patients' comorbidities, 28-day and overall mortality rates were collected and analyzed. Results. There were 229 cases, mean age (SD) of 63.5 (17.2) years and mean (SD) APACHE II score of 24.7 (6.8). The prevalence of first-dose and 24-hour inappropriate antimicrobials was 29.7% and 25.3%, respectively. The 28-day and overall mortality rates between first-dose inappropriate and appropriate antimicrobial were 67.6% versus 60.2% (P = 0.301) and 75.0% versus 68.3% (P = 0.345), consequently. Patients with septic shock and inappropriate first-dose antimicrobials significantly had higher 28-day mortality rate (61.6% versus 41.9%; P = 0.017). Conclusion. Higher mortality rates in bacteremic septic patients were substantially associated with inappropriate first-dose antimicrobials and 3-hour delayed antimicrobial administration after sepsis diagnosis.

Early changes of procalcitonin may advise about prognosis and appropriateness of antimicrobial therapy in sepsis

PurposeThe objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis. MethodsA prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%. ResultsDeath occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003). ConclusionsChanges of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials.