Narrow-spectrum Therapy Research Articles

P-90. Culture negative vs Culture positive Acute Hematogenous Osteomyelitis in Pediatrics: A single study experience

Abstract Background Acute hematogenous osteomyelitis (AHO) is a rare but serious infection in children that can result in acute and chronic sequelae. Despite guidelines, optimal management continues to be a source of debate, particularly in children without positive cultures. We examined treatment approaches and outcomes in AHO patients stratified by culture positivity. Consort Flow Diagram of the Study on Culture Negative vs. Culture Positive Acute Hematogenous Osteomyelitis in Pediatrics. This diagram illustrates the participant flow through each stage of the retrospective study, including enrollment, allocation, follow-up, and analysis. The numbers of participants assessed for eligibility, included in the study, and analyzed for the primary outcome are detailed, alongside reasons for exclusions at each stage. Methods This retrospective cohort study included children (< 19y) admitted at CHOP from 2005-2020 with a primary diagnosis of AHO. Cases were identified by APR-DRG and ICD-9 codes followed by chart review to determine inclusion/exclusion criteria (Table 1). Patients were divided into culture-positive (CX+) and culture-negative (CX-) groups. Wilcoxon rank sum tests were used to compare continuous variables and Chi-square test was used to compare categorical variables between groups. Inclusion/Exclusion criteria for defining AHO cohort This table details the criteria used to identify pediatric patients for inclusion and exclusion in the Study on Culture Negative vs. Culture Positive Acute Hematogenous Osteomyelitis in Pediatrics. Inclusion criteria focus on patient characteristics and clinical presentation necessary for study entry, including age, hospitalization duration, diagnosis, symptomology, and relevant imaging findings. Exclusion criteria are subdivided into primary factors, which identify general patient disqualifications, and secondary factors, which specifically differentiate between culture-positive and culture-negative cases. These criteria ensure a focused and relevant patient cohort for analysis. Results Of 796 children with a primary diagnosis of AHO, 395 [236 (59.7%) culture-negative and 159 (40.2%) culture-positive] met no secondary exclusion criteria. Patient characteristics are shown in Table 2. Blood culture was performed more frequently in CX+ cases (94.3% vs 84.1%, p=0.004), as were bone cultures (54.8% vs. 11.1%, p< 0.001). The proportion of CX- cases decreased over time (2005-8: 66%, 2009-12: 60%, 2013-16: 59%, 2017-20: 57%; p=0.12). The most common organisms identified in CX+ group were MSSA (73.6%) and MRSA (21.4%). CX+ more often received narrow-spectrum beta-lactams empirically (27.5% vs. 10.1%, p< 0.001) and as definitive therapy (60.9% vs 18.0%, p< 0.001). CX+ less often received anti-MRSA antibiotics empirically (65.2% vs. 83.1%, p< 0.001) or as definitive treatment (30.4% vs 78.1%, p< 0.001). CX+ patients had a shorter median hospital stay (4 days) than CX- patients (5 days, p< 0.001). There was no difference in treatment duration, treatment failure or need for repeat surgical intervention. Features of culture-positive and culture-negative AHO cases This table summarizes the demographic and clinical characteristics, site of infection, presenting features, and laboratory values at admission for pediatric patients diagnosed with AHO, categorized by culture-positive and culture-negative cases. Data are presented as medians with interquartile ranges (IQR) or as numbers with percentages. Statistical significance between groups is evaluated and shown in the rightmost column as p-values, highlighting differences in infection sites, symptom presentation, and initial laboratory findings between the two groups. Conclusion Nearly two-thirds of AHO cases were culture-negative at our hospital. The benefits of obtaining cultures (narrower spectrum therapy, shorter hospital stay) should be weighed since outcomes were similar between these groups. Disclosures Kevin J. Downes, MD, Paratek, Inc.: Grant/Research Support|Veloxis Pharmaceuticals, Inc.: Grant/Research Support

Association Between Procalcitonin and Antibiotics in Children With Community-Acquired Pneumonia.

To determine whether empirical antibiotic initiation and selection for children with pneumonia was associated with procalcitonin (PCT) levels when results were blinded to clinicians. We enrolled children <18 years with radiographically confirmed pneumonia at 2 children's hospitals from 2014 to 2019. Blood for PCT was collected at enrollment (blinded to clinicians). We modeled associations between PCT and (1) antibiotic initiation and (2) antibiotic selection (narrow versus broad-spectrum) using multivariable logistic regression models. To quantify potential stewardship opportunities, we calculated proportions of noncritically ill children receiving antibiotics who also had a low likelihood of bacterial etiology (PCT <0.25 ng/mL) and those receiving broad-spectrum therapy, regardless of PCT level. We enrolled 488 children (median PCT, 0.37 ng/mL; interquartile range [IQR], 0.11-2.38); 85 (17%) received no antibiotics (median PCT, 0.32; IQR, 0.09-1.33). Among the 403 children receiving antibiotics, 95 (24%) received narrow-spectrum therapy (median PCT, 0.24; IQR, 0.08-2.52) and 308 (76%) received broad-spectrum (median PCT, 0.46; IQR, 0.12-2.83). In adjusted analyses, PCT values were not associated with antibiotic initiation (odds ratio [OR], 1.02, 95% confidence interval [CI], 0.97%-1.06%) or empirical antibiotic selection (OR 1.07; 95% CI, 0.97%-1.17%). Of those with noncritical illness, 246 (69%) were identified as potential targets for antibiotic stewardship interventions. Neither antibiotic initiation nor empirical antibiotic selection were associated with PCT values. Whereas other factors may inform antibiotic treatment decisions, the observed discordance between objective likelihood of bacterial etiology and antibiotic use suggests important opportunities for stewardship.

Defining Antibiotic Inertia: Application of a Focused Clinical Scenario Survey to Illuminate A New Target for Antimicrobial Stewardship During Transitions of Care

In clinical scenario surveys, inpatient providers were more likely to report continuing inappropriate (odds ratio, 2.02 [95% confidence interval, 1.35-3.03]; P<.001) or broad-spectrum (1.8 [1.27-2.56]; P=.001) antibiotic therapy when initiated by emergency department providers, than to change to appropriate or narrow-spectrum therapy, respectively. Antibiotic inertia could represent a significant antibiotic stewardship target.

Antibiotic Prescribing Patterns for Hospitalized children with Community-Acquired Pneumonia in a Secondary Care Center

BackgroundNarrow-spectrum antibiotics are recommended as the first-line therapy for management of children hospitalized with community-acquired pneumonia (CAP). There are limited data evaluating the antibiotic prescription patterns for CAP in Saudi Arabia. The goal of this study to report on the antibiotic patterns in children hospitalized with CAP. MethodsA prospective cross-sectional study was conducted in children aged 1 month to 13 years who were hospitalized with a diagnosis of CAP at King Khalid Hospital in Majmaah, Saudi Arabia, between January 2019 and January 2020. ResultsData from 233 patients were collected. The majority of patients received amoxicillin clavulanate (57.9%), followed by ceftriaxone (30%), azithromycin (20.6%), cefuroxime (6%), ampicillin (2.1%), and piperacillin-tazobactam (2.1%). None of our patients were started on narrow-spectrum therapy. The younger age group (1-3 months) and patients with severe pneumonia were more likely to receive broad-spectrum cephalosporin and have a longer hospital stay (P = .000 and P = .002, respectively). However, the 4 months to 5 years age group was more likely to receive amoxicillin clavulanate (P = .001). Male gender was a significate risk factor for patients with severe pneumonia (P=.013) ConclusionsWe demonstrated the inappropriate use of broad-spectrum therapy in children hospitalized with CAP. Further large multicenter studies are necessary to evaluate the patterns of antibiotic use and implement antimicrobial stewardship programs or quality-improvement projects to improve adherence to guidelines.

Comparative analysis of the effectiveness of narrow-spectrum versus broad-spectrum antibiotics for the treatment of childhood pneumonia.

Objectives:The main objective of this study was to compare the effectiveness of empiric treatment with narrow-spectrum therapy versus broad-spectrum therapy for children hospitalized with community-acquired pneumonia (CAP) at the University of Gondar Referral Hospital, Gondar, Ethiopia.Methods:Institutional-based retrospective chart review was conducted at the University of Gondar Referral Hospital (GURH) pediatrics ward from 1 February 2016 to 30 April 2016. The collected data were entered and analyzed using Statistical Package for Social Sciences (SPSS) version 20. Descriptive statistics were done to present the basic features and summary of the data set. In addition, binary logistics and multivariable logistic regression analysis were conducted to test for an association between the dependent and independent variables. A P value of <0.05 was taken to declare statistical significance at a 95% confidence interval.Result:A total of 147 patients with CAP were included in the study. Seven different treatment regimens were employed for the 147 children hospitalized. About 63 (42.9%) of the study participants received a narrow-spectrum antibiotic and 84 (57.1%) received a broad-spectrum antibiotic. There was no significant difference between the broad and narrow spectrum treatment groups in main treatment outcomes. The median length of stay (LOS) for the study population was 3 days. The median LOS was shorter among those receiving narrow-spectrum therapy compared with those receiving broad-spectrum therapy. Treatment dose and duration of therapy were significantly associated with treatment outcome (P < 0.0001 and P = 0.003), respectively.Conclusion:The effectiveness of narrow-spectrum therapy is similar to that of broad-spectrum therapy for children hospitalized with CAP. Treatment regimens for children with community-acquired pneumonia should be selected based on their safety profile and their tendency for antibiotic resistance.

Microbial aetiology of brain abscess in a UK cohort: Prominent role of Streptococcus intermedius

Brain abscess is an uncommon condition, but carries high mortality. Current treatment guidelines are based on limited data. Surveillance of clinical, radiological and microbiology data is important to inform patient stratification, interventions, and antimicrobial stewardship. We undertook a retrospective, observational study of patients with brain abscess, based on hospital coding, in a UK tertiary referral teaching hospital. We reviewed imaging data, laboratory microbiology, and antibiotic prescriptions. Over a 47 month period, we identified 47 adults with bacterial brain abscess (77% male, median age 47 years). Most of the abscesses were solitary frontal or parietal lesions. A microbiological diagnosis was secured in 39/47 (83%) of cases, among which the majority were of the Streptococcus milleri group (27/39; 69%), with a predominance of Streptococcus intermedius (19/27; 70%). Patients received a median of 6 weeks of intravenous antibiotics (most commonly ceftriaxone), with variable oral follow-on regimens. Ten patients (21%) died, up to 146 days after diagnosis. Mortality was significantly associated with increasing age, multiple abscesses, immunosuppression and the presence of an underlying cardiac anomaly. Our data suggest that there has been a shift away from staphylococcal brain abscesses, towards S. intermedius as a dominant pathogen. In our setting, empiric current first line therapy with ceftriaxone remains appropriate on microbiological grounds and narrower spectrum therapy may sometimes be justified. Mortality of this condition remains high among patients with comorbidity. Prospective studies are required to inform optimum dose, route and duration of antimicrobial therapy.

Antibiotics in General Surgical Practice

Introduction: Worldwide antibiotic prescription in surgical practices are inappropriate quite often, reasons being inappropriate indication, inappropriate antibiotic prophylaxis, continuation of empiric therapy despite negative cultures in a stable patient, and a lack of awareness of susceptibility patterns of common pathogens. Extended-spectrum b-lactamase, Carbapenemase resistant and multidrug-resistant strains of organisms causing intrabdominal infections, have developed. The occurrence of MRSA surgical site infection (SSI) has a significant impact on clinical and economic outcomes, notably an increase in postoperative mortality.&#x0D; Opportunities: There is an array of web of factors which affect the occurrence of SSI and antibiotics should not be answer or replacement to any of those factors. Narrow spectrum antibiotic active against the most probable pathogen to be encountered during operation, for a short period of time in adequate doses should be utilized. Broad-spectrum antimicrobial agents don’t result in lower rates of postoperative SSI compared to narrower spectrum. Elective laparoscopic cholecystectomy, parotidectomy, chest tube insertion and other clean procedures don’t warrant use of prophylaxis. For most patients who have had their wounds opened and adequately drained, antibiotic therapy is unnecessary. Antibiotics should be discontinued at time of incision closure (exceptions include implant-based breast reconstruction, joint arthroplasty, and cardiac procedures and liver transplantation. Hospital-specific antibiograms are important to guide the usage of diverse antibiotic agents to decrease resistance among pathogens. In intrabdominal infections source control is still integral and most important to the treatment of most patients. Routine use of antimicrobial therapy is not appropriate for all patients with intra-abdominal infections e.g. Patients with uncomplicated diverticulitis. In uncomplicated IAIs, when the focus of infection is treated effectively, the administration of antibiotics is unnecessary beyond prophylaxis e.g. Acute unperforated appendicitis removed surgically. In case of intraabdominal infections selection of empirical antimicrobial therapy depends on various factors which include probable contaminating pathogen/s, individual risk assessment and possibility of resistant pathogens. Higher risk patients are those, with severe sepsis/septic shock, elevated APACHE II score (&gt;10), multiple medical comorbidities, problematic or delayed source control. The possibility of resistant pathogens is low in community acquired infections (CAI) in contrast to healthcare or hospital-associated infection (HAI). In Lower risk patients with community-acquired IAI, narrower-spectrum therapy ( coli, Bacteroides) is recommended and there is no need for anti-enterococcal or antifungal therapy. In Higher risk patients with community-acquired IAI, broader-spectrum therapy is recommended with selective use of anti-enterococcal and antifungal therapy. In Patients with healthcare/hospital-associated IAI, broader-spectrum therapy is recommended with additional agents for resistant pathogens. Do not use clindamycin as an anti-anaerobic agent in combination regimens for the empiric treatment in adults and children unless metronidazole cannot be used. Duration of antimicrobial therapy can be significantly shortened to 4-7 days under most of the circumstances. Routine addition of an aminoglycoside to other agents having broad spectrum gram negative coverage provides no additional benefit in intrabdominal infections.&#x0D; Conclusion: Antibiotics are a treasure but not unlimited. Appropriate use is the need of the hour to save our present and future generations from the menace of antimicrobial resistance. JMS 2018;21(1):54-60&#x0D;

Narrow-spectrum, compared with broad-spectrum, antibiotics equally effective with less adverse events

Gerber JS, Ross RK, Bryan M, Localio AR, Szymczak JE, Wasserman R, et al. Association of Broad- vs Narrow-Spectrum Antibiotics With Treatment Failure, Adverse Events, and Quality of Life in Children With Acute Respiratory Tract Infections. JAMA 2017;318:2325-36. Question Among children with acute respiratory infections (acute otitis media, group A streptococcal pharyngitis, and acute sinusitis), what is the efficacy and safety profile of broad-spectrum, compared with narrow-spectrum, antibiotics? Design Retrospective and prospective cohorts. Stratified and propensity score-matched analyses. Setting Thirty-one pediatric practices in Pennsylvania and New Jersey. Participants Children 6 months to 12 years, with acute otitis media, group A streptococcal pharyngitis, and acute sinusitis. Intervention Broad- versus narrow-spectrum antibiotics. Outcomes Effectiveness and adverse events. Main Results Broad-spectrum antibiotics were not associated with less treatment failure, risk difference 0.3% (95% CI, −0.4% to 0.9%), and were associated with more clinician-reported and patient-reported adverse events, risk difference 1.1% (95% CI, 0.4% to 1.8%) and 12.2% (95% CI, 7.3% to 17.2%), respectively. Conclusions Narrow-, compared with broad-spectrum antibiotics were equally effective and demonstrated a lower rate of adverse events. Commentary This cohort study supports guidelines recommending narrow-spectrum amoxicillin or penicillin for treatment of acute otitis media, acute sinusitis, and group A streptococcal pharyngitis in children. Although broad-spectrum antibiotics, such as amoxicillin-clavulanate, are commonly prescribed based on conflicting guidelines for these conditions, they were not associated with improved outcomes compared to narrow-spectrum therapy. This large retrospective cohort demonstrated convincingly that broad-spectrum antibiotics do not lower overall rates of treatment failure, even when adjusting for differences in provider prescribing practices or illness severity using clinician-stratified and propensity-score matched analyses. The unique inclusion of patient-reported outcomes in a prospective cohort detected a 10-fold higher rate of adverse events compared with the retrospective cohort, which suggests most antibiotic adverse events are unreported and/or unrecognized by clinicians. Also, in this group, broad-spectrum antibiotics were associated with an increased risk of adverse events with no improvement in quality of life. While observational cohorts undoubtedly include children with viral infections that may obfuscate differences in antibiotic efficacy, this study reflects real clinical practice where the empiric choice of broad rather than narrow-spectrum antibiotics for acute respiratory infections in children may lead to more harm than benefit.

Antibiotic Prescribing Patterns Across the Continuum of Care for Children Hospitalized With Community-Acquired Pneumonia.

The aim of this study was to describe the variation in antibiotic prescribing practices for uncomplicated community-acquired pneumonia across the continuum of care for hospitalized pediatric patients to better inform future efforts at standardizing antibiotic therapy throughout a single hospitalization. This is a retrospective cohort study involving 4 hospitals caring for children aged 3 months to 18 years, hospitalized between January 1, 2011, and December 31, 2012, with diagnosis of uncomplicated pneumonia and without complex chronic medical conditions.Data collected include antibiotics prescribed before hospitalization, at the emergency department (ED) encounter, during hospitalization, and at hospital discharge. Six hundred nine children met inclusion criteria, with a mean age of 5.3 years and median length of stay of 2 days. Emergency department providers prescribed narrow-spectrum therapy 27% of the time, whereas discharging providers prescribed narrow-spectrum therapy 56% of the time. Third- and fourth-generation cephalosporins were less often prescribed in the preadmission setting and at discharge but were more often prescribed in the ED and inpatient setting. There was an association between inpatient prescription of broad-spectrum antibiotics when a blood culture was obtained, when broad-spectrum antibiotics were prescribed in the ED, and with increasing length of stay. Broad-spectrum antibiotic therapy for community-acquired pneumonia, especially third- and fourth-generation cephalosporins, often originates in the ED. When initiated in this setting, it is likely to be continued in the inpatient setting.

Microbiology of Vertebral Osteomyelitis and Implications on Empiric Therapy

BackgroundThe management of vertebral osteomyelitis (VO) includes empiric antibiotic therapy while clinical cultures are being processed. Optimal antimicrobial therapy for VO, particularly when Gram-negative (GN) organisms are involved, is an area of ongoing debate. Narrow spectrum and oral antimicrobial therapy are preferred. The objective of this study was to identify characteristics of local pathogens and to formulate an institution-specific antibiotic protocol for empiric treatment of VO.MethodsWe conducted a retrospective case series study of adults diagnosed with VO from August 1, 2010 to August 31, 2015 at Palmetto Health Hospitals in Columbia, South Carolina. Cases identified by ICD-9 codes were included in the analysis if they met clinical, imaging and microbiology, criteria.ResultsAnalysis is based on 150 cases of VO with a mean age of 61 years, a male predominance (91; 61%), and an average body mass index of 29kg/m2. Comorbidities included diabetes mellitus (69; 46%), tobacco use (33; 22%), and hemodialysis (20; 13%). Thirty-seven (25%) cases had recent related injury or vertebral surgery, and 14 (9%) had prior hardware. Bone, disc, or adjacent tissue cultures were obtained in 129 (86%) of cases; 60 (40%) of these had >1 sample taken. The remaining 14% had blood cultures alone. Thirty-six cases (24%) had culture negative VO. In the remaining 114 cases, 132 organisms were isolated. A total of 111 (84%) organisms were Gram-positive cocci (GPC). Of those, the majority was Staphylococcus aureus. (66; 59%) (26/66 were methicillin-resistant), coagulase-negative staphylococci (20; 18%) and Streptococcus spp. (17; 15%). Enterobacteriaceae accounted for 13/17 Gram-negative bacilli (GNB), with only one isolate of Pseudomonas aeruginosa. Of the GNB, 11/17 were susceptible to either ceftriaxone or ciprofloxacin.ConclusionThere was a predominance of VO due to GPC suggesting that intravenous vancomycin monotherapy may be reasonable for empiric therapy in noncritically ill patients while awaiting Gram stain and clinical culture results. Addition of either ceftriaxone or ciprofloxacin to vancomycin would increase cumulative antimicrobial coverage from 84 to 92%.Disclosures All authors: No reported disclosures.

Effect of Antimicrobial Stewardship Program Guidance on the Management of Uncomplicated Skin and Soft Tissue Infections in Hospitalized Adults.

ObjectiveTo assess the effect of an antimicrobial stewardship program (ASP)–bundled initiative on the appropriate use of antibiotics for uncomplicated skin and soft tissue infections (uSSTIs) at 2 academic medical centers in Pittsburgh, Pennsylvania.Patients and MethodsA retrospective preintervention and postintervention study was conducted to compare management of patients admitted with uSSTIs before and after the implementation of the bundled initiative. The preintervention period was from August 1, 2014, through March 31, 2015, and the postintervention period was from August 1, 2015, through March 31, 2016.ResultsA total of 160 patients were included in the preintervention cohort, and 163 were included in the postintervention cohort. Compared with the preintervention group, the mean duration of therapy decreased (12.5 days vs 8.8 days; P<.001) and an appropriate duration of less than 10 days increased in more patients (20.6% [33 of 160] vs 68.7% [112 of 163]; P<.001) in the postintervention period. Fewer patients were exposed to antimicrobials with extended gram-negative (44.4% [71 of 160] vs 9.2% [15 of 163]; P<.001), anaerobic (39.4% [63 of 160] vs 9.8% [16 of 163]; P<.001), and antipseudomonal (16.3% [26 of 160] vs 1.8% [3 of 163]; P<.001) coverage. The mean length of stay decreased from 3.6 to 2.2 days (P<.001) without an increase in 30-day readmissions (6.3% [10 of 160] vs 4.9% [8 of 163]; P=.64). The ASP made recommendations for 125 patients, and 96% were accepted.ConclusionImplementation of an ASP-bundled approach aimed at optimizing antibiotic therapy in the management of uSSTIs led to shorter durations of narrow-spectrum therapy as well as shorter hospital length of stay without adversely affecting hospital readmissions.

Aspirations of the ilium and proximal femur increase the likelihood of culturing an organism in patients with presumed septic arthritis of the hip.

PurposeTo test the hypothesis that collecting material for culture from metaphyseal bone of the ilium and proximal femur at the time of a hip aspiration will increase the sensitivity to detect an infectious organism in patients with presumed septic arthritis of the hip.MethodsWe retrospectively reviewed a series of 36 patients with presumed septic arthritis of the hip, based on clinical exam and serum inflammatory markers, who underwent aspirations of hip synovial fluid as well as blood from the ilium and proximal femur. Culture results from aspirates of synovial fluid and bone and tissue from capsule were compared to determine the sensitivities and specificities of a synovial aspirate alone versus synovial aspirate plus aspirates of the ilium and proximal femur to detect infection.ResultsThe sensitivity of hip synovial fluid aspirates to detect infection via positive culture was only 63 %, though this increased significantly to 100 % when the results of cultures of aspirates of the ilium and proximal femur were included. The specificities were equivalent in both modalities (≥90 %). We conclude that obtaining aspirates of the ilium and proximal femur at the time of hip synovial fluid aspiration increases the likelihood that the procedure will return an infectious organism.ConclusionPositive cultures from a child with a septic hip or peri-articular hip infection help to efficiently and effectively guide antibiotic treatment. The child with a septic hip or peri-articular hip infection and positive cultures is likely to receive more narrow-spectrum therapy, potentially decreasing the overuse of broad-spectrum antibiotics.Level of evidence: diagnostic study level IIIDevelopment of diagnostic criteria on the basis of a series of non-consecutive patients (with universally applied reference “gold standard”).

Prospective surveillance of antibiotic use in the neonatal intensive care unit: results from the SCOUT study.

Prolonged or unnecessary antibiotic use is associated with adverse outcomes in neonates. Our objectives were to quantify all antibiotic use in a Level-III neonatal intensive care unit and to identify scenarios where their use could be reduced. Surveillance and evaluation of all antibiotic use provided to every infant admitted to a Level-III neonatal intensive care unit from 10/3/11 to 11/30/12 was performed. Types of antibiotics, reasons for their initiation, discontinuation and duration, as well as clinical, laboratory and outcome data were recorded. Antibiotic use was quantified by days of therapy (DOT) per 1000 patient-days (PD). A total of 1607 infants were included. The total antibiotic use was 9165 DOT (343.2 DOT/1000 PD; 5.7 DOT/infant). Seventy-two percent of infants received 1 (43%) or more (29%) courses of antibiotics. Gentamicin (46%), ampicillin (39%) and oxacillin (8%) were the most frequently used agents. Ninety-four percent of antibiotic use (323 DOT/1000 PD) was empiric therapy for suspected infection. Sixty-three percent (216.2 DOT/1000 PD) was discontinued at approximately 48 hours when cultures were sterile (68%>48 hours, 32%≤48 hours). Twenty-six percent of all antibiotic use (89.4 DOT/1000 PD) was therapy for ≥5 days despite sterile cultures; pneumonia (16%) and "culture-negative" sepsis (8%) were the major contributors. Five percent (17.4 DOT/1000 PD) of antibiotic use was for culture-proven sepsis, 5% (16.6 DOT/1000 PD) was penicillin prophylaxis for group B Streptococcus and 1% (3.5 DOT/1000 PD) was preprocedural prophylaxis. Narrow-spectrum therapy accounted for >92% of antibiotic use and would not be monitored by most stewardship programs. Only 5% of antibiotic usage was due to culture-proven infection. Pneumonia and "culture-negative" sepsis were frequent reasons for prolonged therapy; further study of these conditions may allow reduction in treatment duration.

Development of antibiotic treatment algorithms based on local ecology and respiratory surveillance cultures to restrict the use of broad-spectrum antimicrobial drugs in the treatment of hospital-acquired pneumonia in the intensive care unit: a retrospective analysis.

IntroductionTimely administration of appropriate antibiotic therapy has been shown to improve outcome in hospital-acquired pneumonia (HAP). Empirical treatment guidelines tailored to local ecology have been advocated in antibiotic stewardship programs. We compared a local ecology based algorithm (LEBA) to a surveillance culture based algorithm (SCBA) in terms of appropriate coverage and spectrum of antimicrobial activity.MethodsWe retrospectively assessed 2 hypothetical empirical antibiotic treatment algorithms for HAP on an existing high-quality prospectively collected database in a mixed 36-bed tertiary intensive care unit (ICU). Data on consecutive episodes of microbiologically confirmed HAP were collected over a period of 40 months and divided in a derivation (1 July 2009 to 31 October 2010) and validation (1 November 2010 until 31 October 2012) cohort. On the derivation cohort we constructed a LEBA, based on overall observed bacterial resistance patterns, and a SCBA, which targeted therapy to surveillance culture (SC) in the individual patient. Therapy was directed against pathogens found in respiratory SC collected two to five days before HAP, and in the absence of these, presence or absence of multi-drug resistant (MDR) pathogens in other SC dictated broad-spectrum, respectively narrow spectrum antibiotic therapy. Subsequently, LEBA and SCBA were retrospectively reviewed and compared with actually prescribed antibiotics in the validation cohort.ResultsThe first 100 HAP episodes made up the derivation cohort and the subsequent 113 HAP episodes the validation cohort. Appropriate antibiotic coverage rates by applying LEBA and SCBA were 88.5% and 87.6%, respectively, and did not differ significantly with respect to appropriateness of the actually prescribed initial therapy (84.1%). SCBA proposed more narrow spectrum therapy as compared to LEBA and the actually prescribed antimicrobials (P <0.001). SCBA recommended significantly less combination therapy and carbapenems compared to LEBA (P <0.001). SCBA targeted antibiotics to recent respiratory SC in 38.1% (43 out of 113 episodes) of HAP; in these cases adequacy was 93% (40 out of 43).ConclusionRates of appropriate antimicrobial coverage were identical in LEBA and SCBA. However, in this setting of moderate MDR prevalence, the use of SCBA would result in a significant reduction of the use of broad-spectrum drugs and may be a preferential strategy when implementing antibiotic stewardship programs.

Comparative Effectiveness of Empiric Antibiotics for Community-Acquired Pneumonia

Narrow-spectrum antibiotics are recommended as the first-line agent for children hospitalized with community-acquired pneumonia (CAP). There is little scientific evidence to support that this consensus-based recommendation is as effective as the more commonly used broad-spectrum antibiotics. The objective was to compare the effectiveness of empiric treatment with narrow-spectrum therapy versus broad-spectrum therapy for children hospitalized with uncomplicated CAP. This multicenter retrospective cohort study using medical records included children aged 2 months to 18 years at 4 children's hospitals in 2010 with a discharge diagnosis of CAP. Patients receiving either narrow-spectrum or broad-spectrum therapy in the first 2 days of hospitalization were eligible. Patients were matched by using propensity scores that determined each patient's likelihood of receiving empiric narrow or broad coverage. A multivariate logistic regression analysis evaluated the relationship between antibiotic and hospital length of stay (LOS), 7-day readmission, standardized daily costs, duration of fever, and duration of supplemental oxygen. Among 492 patients, 52% were empirically treated with a narrow-spectrum agent and 48% with a broad-spectrum agent. In the adjusted analysis, the narrow-spectrum group had a 10-hour shorter LOS (P = .04). There was no significant difference in duration of oxygen, duration of fever, or readmission. When modeled for LOS, there was no difference in average daily standardized cost (P = .62) or average daily standardized pharmacy cost (P = .26). Compared with broad-spectrum agents, narrow-spectrum antibiotic coverage is associated with similar outcomes. Our findings support national consensus recommendations for the use of narrow-spectrum antibiotics in children hospitalized with CAP.

The importance of previous CT scans in the diagnosis of invasive pulmonary aspergillosis

A recent paper has drawn attention to the fact that the halo sign is not specific for invasive aspergillosis [Maschmeyer et al. 2009]. The authors also state that antifungal therapy is usually started in high-risk patients with fever and suggestive computerized tomography (CT) abnormalities. In a recent study, preemptive antifungal therapy triggered by CT abnormalities in allogeneic stem cell transplant recipients was shown to be feasible, even when broad spectrum antifungal prophylaxis is used [Dignan et al. 2009]. This is particularly important in the era of posaconazole, a broad spectrum azole that has been proved to reduce mortality in patients with acute myeloid leukaemia or high-risk myelodysplasia undergoing induction chemotherapy [Cornely et al. 2007]. The CT-based preemptive strategy reduced the use of parenteral antifungal agents by 68% [Dignan et al. 2009]. Owing to concerns of reduced sensitivity of galactomannan testing in patients receiving broad-spectrum antifungal prophylaxis, antifungal therapy in this study was triggered by symptoms and CTabnormalities [Dignan et al. 2009]. The evolution of CT findings in patients with invasive pulmonary aspergillosis is well characterized [Caillot et al. 2010]. The halo sign, which is a mass-like infiltrate surrounded by ground-glass opacity, is an early sign. However, the halo sign is indeed not pathognomonic for aspergillosis [Greene et al. 2007], and this is the pitfall in this approach. We recently treated a 66-year-old patient with high-risk myelodysplasia with an induction course of daunorubicin and cytarabine. She received antifungal prophylaxis with posaconazole. Chest X-ray before therapy was normal. On day 5 she developed fever, refractory to broad-spectrum antibiotics. On day 9 CT of the chest showed several halo signs in the right and left lung, very suggestive of invasive aspergillosis (Figure 1). She remembered that a CT of the chest had been performed 2 years before in another hospital during the investigation of a breast lesion (which was benign). The CT scans were compared and found to be identical. We judged the lesions not to be active but merely the consequences of pulmonary damage in the past. Posaconazole was continued and no other antifungal was started. The infection focus turned out to be the intravascular catheter. She recovered from neutropenia without fungal infections. Figure 1. Nodular lesion surrounded by ground-glass opacity (halo sign) in the right lung. This case illustrates that with the CT-based strategy of preemptive therapy, some patients may be treated despite the absence of new pulmonary lesions. In many cases, this means that broad-spectrum antifungal prophylaxis will be replaced by possibly narrower spectrum therapy directed at Aspergillus. Most patients are screened with chest X-ray before starting chemotherapy, but the sensitivity of X-ray for detecting aspergillosis-like lesions is low. We strongly encourage physicians to at least ask for previous pulmonary images. Possibly, baseline CT obtained before treatment could reduce the unnecessary use of antifungals. It may optimize exposure to evidence-based prophylaxis with posaconazole. Checking the ‘criminal record’ of previous chest CT scans may make decisions regarding antifungal therapy easier.

Impact of Antibiotic Policy in a Tertiary Care Research Institute Hospital in Egypt: Three Years Experience

Introduction The main forces driving the increase in antimicrobial-resistant bacteria are poor infection control practices and inappropriate use of antibiotics. Once these factors are addressed, specific antibiotic utilization strategies may help decrease or prevent the emergence of resistance. These strategies include antibiotic restriction, combination therapy, and antibiotic cycling. Dependence on one class of antibiotic to treat a population, despite optimal dosing and duration of treatment, may allow for the selection of resistant organisms within that population. Cycling, or rotating antibiotics within or between classes, by altering the selective pressure for bacteria to develop resistance to any particular antibiotic, may be an important component, from a population perspective, of antimicrobial stewardship. An antibiograms is particularly helpful for choosing empiric and pathogen-directed treatment regimens. It also assists in antibiotic streamlining, the process by which excessively broad-spectrum empiric antibiotic therapy can be switched to narrower spectrum therapy aimed only at the implicated pathogen(s). It must be acknowledged that an antibiogram-based guideline does not have an unlimited duration of utility. It is likely that shifts in antibiotic usage engendered by the creation of the guideline will, over time, lead to a change in resistance patterns. Thus, it is prudent to update antibiograms and antibiogram-based antibiotic guidelines on a regular basis. Antibiotic cycling involves the deliberate removal of the antimicrobial of choice to treat a particular infectious syndrome in a specific unit with the intention of reintroducing that antimicrobial at a predetermined time in the future. Several antibiotics are commonly rotated in this fashion. Cycling takes advantage of the observation that resistance to a particular antimicrobial decreases when that antimicrobial is no longer used. In addition to restriction, antibiotics are rotated to maintain or promote antibiotic heterogeneity in order to alter the selective pressures present and thus prevent the emergence of resistance to any particular antibiotic. Community prescribing practices have been shown to influence rates of resistance in common bacterial pathogens, and long-term–care facilities are increasingly being recognized as reservoirs for antibiotic-resistant pathogens. Antimicrobial resistance in S. aureus emerged soon after penicillin came into common use in the 1940s. During the next 2 decades, resistance of this pathogen to penicillin became widespread, followed by increasing resistance to the new semisynthetic penicillinase-resistant antimicrobial drugs (e.g., methicillin, oxacillin, nafcillin). In the last 20 years, methicillin-resistant S. aureus (MRSA) has spread throughout the world in healthcare settings. In addition, serious MRSA infection has been increasingly reported in persons without identified predisposing risk, including recent healthcare exposure. Members of the family Enterobacteriaceae producing beta-latamases constitute a serious threat to current beta-lactam therapy. In addition, guidelines of the National Committee for Clinical Laboratory Standard (NCCLS)6 suggest that confirmed extended spectrum beta-lactamase (ESBL) producing strains should be reported as resistant to all penicillins, cephalosporins and aztreonam. MRSA and ESBL infections have been increasing at an alarming rate world-wide over the past two decades. They are responsible for nosocomial infections and adverse patient outcomes. Numerous reports describe nosocomial outbreaks in various countries. These infections may be life-threatening and cause considerable morbidity as they are of special concern for several reasons. They are associated with prolonged hospitalization and increased costs with few therapeutic options. These multidrug-resistant bacteria (MRB) increasingly have spread from hospital settings to noninstitutional environments. On the other hand, prolonged MRSA carriage was found to occur after hospital discharge increasing the infection by this organism in both community and hospital settings. Transmission of such infections occurs primarily from colonized or infected patients to other patients or staff and vice versa mainly through transiently-colonized hands of healthcare personnel. The environment also contributes to such transmission. In our institute hospital, a surveillance study in 2004 showed that MRSA and ESBL represented 11.9% and 29.9% of nosocomial infections respectively. This triggered us to implement an antibiotic policy with cycling and follow up.

Usefulness of aetiological tests for guiding antibiotic therapy in community-acquired pneumonia

The goal with antibiotic therapy in community-acquired pneumonia (CAP) is to cure the patient, ideally without causing side effects and without contributing to the further development of antibiotic resistance. Although patients with severe CAP should be treated with broad-spectrum antibiotics, patients with non-severe CAP should preferably receive pathogen-directed therapy. Rapid aetiological tests, such as sputum Gram stain and urinary antigen tests, are useful for targeting initial pathogen-directed therapy. Non-rapid tests, such as cultures, can subsequently support a switch from initial broad-spectrum therapy to narrow-spectrum therapy and direct therapy changes in case of treatment failure. As conventional diagnostic methods often fail to identify the aetiology of CAP, PCR (polymerase chain reaction) tests for respiratory pathogens have become useful and should be further developed. Based on the test specificities, aetiological tests may provide diagnoses with varying reliability, i.e. definite aetiologies (e.g., blood culture and Legionella urinary antigen test), probable aetiologies (e.g., sputum culture and PCR for Mycoplasma pneumoniae), or possible aetiologies (e.g., culture of nasopharyngeal secretions and PCR for Streptococcus pneumoniae). A definite or probable aetiology can often be used to target antibiotic therapy.

Clinical and economic implications of antimicrobial resistance for the management of community-acquired respiratory tract infections.

Lower respiratory tract infections (RTIs), particularly community-acquired pneumonia (CAP), account for over 50 million deaths annually worldwide. They place an extensive clinical and financial burden on healthcare authorities. Upper RTIs, usually mild and non-life threatening, also incur significant healthcare costs. The rising prevalence of resistance of the major causative agents of CAP (Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis) to beta-lactam antimicrobials and newer macrolides has necessitated new strategies for appropriate antimicrobial usage. A successful clinical outcome will depend on the patient, choice of drug, and the epidemiology and resistance of the pathogen. Treatment failure will result in increased costs, particularly if hospitalization is required. Pharmacokinetic and pharmacodynamic parameters are being used increasingly to predict maximally effective therapy and optimal bacterial eradication, thus limiting the development of resistance. Antimicrobial susceptibility criteria by MIC should be dictated by the type and location of the infection. Modifying the current MIC breakpoints for penicillin so that more pneumococcal pneumonia isolates are reported appropriately as being susceptible may lead to a decrease in the use of broad-spectrum antimicrobial therapy and its associated increased costs, in favour of more narrow-spectrum therapy. Targeting the pathogen with the most effective antimicrobial in an appropriately selected patient should optimize clinical and microbiological success and, consequently, maximize response rates and economic outcomes. In addition, research efforts need to concentrate on developing new agents with low propensity to select for or induce resistance.

ON THE QUESTION OF BROAD OR NARROW SPECTRUM THERAPY

ON THE QUESTION OF BROAD OR NARROW SPECTRUM THERAPY