Outpatient Treatment Of Community-acquired Pneumonia Research Articles

Comparative safety of different antibiotic regimens for the treatment of outpatient community-acquired pneumonia among otherwise healthy adults.

Evidence is limited about the comparative safety of antibiotic regimens for treatment of community-acquired pneumonia (CAP). We compared the risk of adverse drug events (ADEs) associated with antibiotic regimens for CAP treatment among otherwise healthy, non-elderly adults. We conducted an active comparator new-user cohort study (2007-2019) of commercially-insured adults 18-64 years diagnosed with outpatient CAP, evaluated via chest x-ray, and dispensed a same-day CAP-related oral antibiotic regimen. ADE follow-up duration ranged from 2-90 days (e.g., renal failure [14 days]). We estimated risk differences [RD] per 100 treatment episodes and risk ratios using propensity score weighted Kaplan-Meier functions. Ankle/knee sprain and influenza vaccination were considered as negative control outcomes. Of 145,137 otherwise healthy CAP patients without comorbidities, 52% received narrow-spectrum regimens (44% macrolide, 8% doxycycline) and 48% received broad-spectrum regimens (39% fluoroquinolone, 7% β-lactam, 3% β-lactam + macrolide). Compared to macrolide monotherapy, each broad-spectrum antibiotic regimen was associated with increased risk of several ADEs (e.g., β-lactam: nausea/vomiting/abdominal pain [RD per 100, 0.32; 95% CI, 0.10-0.57]; non-Clostridioides difficile diarrhea [RD per 100, 0.46; 95% CI, 0.25-0.68]; vulvovaginal candidiasis/vaginitis [RD per 100, 0.36; 95% CI, 0.09-0.69]). Narrow-spectrum antibiotic regimens largely conferred similar risk of ADEs. We generally observed similar risks of each negative control outcome, indicating minimal confounding. Broad-spectrum antibiotics were associated with increased risk of ADEs among otherwise healthy adults treated for CAP in the outpatient setting. Antimicrobial stewardship is needed to promote judicious use of broad-spectrum antibiotics and ultimately decrease antibiotic-related ADEs.

Utilization of broad- versus narrow-spectrum antibiotics for the treatment of outpatient community-acquired pneumonia among adults in the United States.

To characterize antibiotic utilization for outpatient community-acquired pneumonia (CAP) in the United States. We conducted a cohort study among adults 18-64 years diagnosed with outpatient CAP and a same-day guideline-recommended oral antibiotic fill in the MarketScan® Commercial Database (2008-2019). We excluded patients coded for chronic lung disease or immunosuppressive disease; recent hospitalization or frequent healthcare exposure (e.g., home wound care, patients with cancer); recent antibiotics; or recent infection. We characterized utilization of broad-spectrum antibiotics (respiratory fluoroquinolone, β-lactam + macrolide, β-lactam + doxycycline) versus narrow-spectrum antibiotics (macrolide, doxycycline) overall and by patient- and provider-level characteristics. Per 2007 IDSA/ATS guidelines, we stratified analyses by otherwise healthy patients and patients with comorbidities (coded for diabetes; chronic heart, liver, or renal disease; etc.). Among 263 914 otherwise healthy CAP patients, 35% received broad-spectrum antibiotics (not recommended); among 37 161 CAP patients with comorbidities, 44% received broad-spectrum antibiotics (recommended). Ten-day antibiotic treatment durations were the most common for all antibiotic classes except macrolides. From 2008 to 2019, broad-spectrum antibiotic use substantially decreased from 45% to 19% in otherwise healthy patients (average annual percentage change [AAPC], -7.5% [95% CI -9.2%, -5.9%]), and from 55% to 29% in patients with comorbidities (AAPC, -5.8% [95% CI -8.8%, -2.6%]). In subgroup analyses, broad-spectrum antibiotic use varied by age, geographic region, provider specialty, and provider location. Real-world use of broad-spectrum antibiotics for outpatient CAP declined over time but remained common, irrespective of comorbidity status. Prolonged duration of therapy was common. Antimicrobial stewardship is needed to aid selection according to comorbidity status and to promote shorter courses.

Comparative Efficacy of Levofloxacin Versus Amoxycillin/Clavulanic Acid Combined with Azithromycin in Treatment of Community-Acquired Pneumonia

Background: Community-acquired pneumonia (CAP) is an important cause of mortality and morbidity worldwide. Early initiation of antibiotics is highly recommended. In most CAP cases, multiple drug options are increasingly becoming available, but there is often a lack of evidence that allows for a direct comparison of the efficacy of one drug versus another. Aim: The main objective was to compare treatment outcomes using oral levofloxacin alone and combined azithromycin and amoxicillin/Clavulanic acid in outpatient treatment of Community-acquired pneumonia. Methods: This study was a prospective longitudinal design. Patients diagnosed with CAP were randomly assigned to first and second treatment groups. Community-acquired pneumonia was diagnosed according to America Thoracic Society criteria. The sample size of 78 was arrived at by Yamane Taro (1967) formula. Every patient diagnosed and treated in the outpatient department who gave written consent to participate was enrolled in the study and randomly assigned to one of the treatment groups. Minors below 18 years were excluded from the study. Data were analysed using SPSS for Windows version 26. An independent t-test compared the effectiveness of the two treatment groups. Changes in white blood cell count during the follow-up visits were done using a chi-square test. A p-value of <0.05 was considered statistically significant. Results. The majority, 33(50%) of the patients, were aged between 21 and 29 years, and over sixty percent, 42(63.6%) of participants were females. Of all the participants, 66(100%) had a cough and chest pain, 57(86.4%) had crackles, and about ten percent, 6(9.1%) had difficulty breathing at the time of admission into the study. About 29(43.9%) of patients had a fever at baseline, and 14(21.2%) had a respiratory rate between 16 and 29 breaths per minute at baseline. A combination of azithromycin and amoxycillin/clavulanic acid was associated with statistically significant faster resolution of chest pains and cough (mean 1.7 and 3.14 days, respectively) compared to levofloxacin group (mean 2.21 and 3.71 days, respectively) in patients who had community-acquired pneumonia (p=0.009. There was no difference in fever resolution, time to crackles subsidence, resolution of difficulty in breathing, and change in white blood cell count in participants in the two treatment groups. Conclusions: Azithromycin combined with amoxycillin/clavulanic acid reduced chest pain in 1.70 days (SD=0.618) compared to levofloxacin alone (2.21 days, SD=1.204) (p=0.009). Azithromycin combined with amoxycillin/clavulanic acid reduced cough in 3.14 days (SD=0.789) versus levofloxacin alone (3.70 days, SD=0.588) (p=0.014). Hence, the azithromycin plus amoxycillin/clavulanic acid combination was found to be superior for managing CAP.

Pharmacist-Driven Implementation of Outpatient Antibiotic Prescribing Algorithms Improves Guideline Adherence in the Emergency Department

Background: Inappropriate prescribing of antibiotics has been identified as the most important modifiable risk factor for antimicrobial resistance. Objective: The purpose of this project was to improve guideline adherence and promote optimal use of outpatient antibiotics in the emergency department (ED). Methods: Prescribing algorithms for community-acquired pneumonia (CAP), skin and soft tissue infections (SSTI), and urinary tract infections (UTI) were developed to integrate clinical practice guideline recommendations with local ED antibiogram data. Outcomes were evaluated through chart review of patients prescribed outpatient antibiotics by ED providers. The primary outcome was adherence to clinical practice guidelines, defined as the selection of an appropriate antibiotic agent, dose, and duration of therapy for each patient discharged. Results: When compared to patients discharged from the ED prior to algorithm implementation (N = 325), the post-implementation group (N = 353) received more antibiotic prescriptions that were completely guideline adherent (61.5% vs 11.7%, P < .00001). Post-implementation discharge orders demonstrated improvement in the selection of an appropriate agent (87.3% vs 45.5%, P < .00001), dose (91.5% vs 77.2%, P < .00001), and duration of therapy (71.1% vs 39.1%, P < .01). Additionally, fluoroquinolone prescribing rates were reduced (2.3% vs 12.3%, P < .00001). A reduction in all-cause 30-day returns to the ED or urgent care was observed (15.3% vs 21.5%, P = .036). Conclusion: Pharmacist-driven implementation of antibiotic prescribing algorithms improved guideline adherence in the outpatient treatment of CAP, SSTI, and UTI.

2066. Development and Implementation of Prescribing Algorithms for Antibiotics on Discharge from the Emergency Department

BackgroundIn the emergency department (ED), rapid decision-making and frequent distractions are often challenging to implementing effective antimicrobial stewardship. The purpose of this project is to improve guideline adherence and promote optimal use of outpatient antibiotic therapy for community-acquired infections.MethodsPrescribing algorithms were developed to integrate clinical practice guideline recommendations with emergency department-specific antibiogram data. Algorithms for treating community-acquired pneumonia (CAP), skin and soft-tissue infections (SSTI), and urinary tract infections (UTI) were made available throughout the ED. Outcomes were evaluated through a chart review of patients prescribed empiric outpatient antibiotics for CAP, SSTI, or UTI by ED providers. Patients were excluded if they were <18 years old, pregnant, or taking antibiotics prior to arrival. The primary outcome was rate of adherence to clinical practice guidelines, defined as the selection of an appropriate antibiotic agent, dose, and duration of therapy for each patient discharged. Secondary outcomes included the rate of fluoroquinolone use, as well as all-cause 30-day returns to the ED or urgent care.ResultsWhen compared with patients discharged from the ED prior to algorithm implementation (N = 325), the post-implementation group (N = 172) received more antibiotic prescriptions that were completely guideline adherent (57.0% vs. 11.7%, P < 0.01). Post-implementation discharge orders demonstrated improvement in the selection of an appropriate agent (86.6% vs. 45.5%, P < 0.01), dose (89.0% vs. 77.2%, P < 0.01), and duration of therapy (63.4% vs. 39.1%, P < 0.01). Additionally, fluoroquinolone prescribing rates in this population were reduced (2.9% vs. 12.3%, P < 0.01). In the post-implementation patients who presented at least 30 days prior to analysis (N = 124), a reduction in all-cause 30-day returns to the ED or urgent care was observed (12.9% vs. 21.5%, P < 0.05).ConclusionImplementation of antibiotic prescribing algorithms improved guideline adherence in the outpatient treatment of CAP, SSTI, and UTI. By developing prescribing algorithms, pharmacists may reduce the unnecessary use of broad-spectrum antibiotics and prevent patient returns to the ED.Disclosures All authors: No reported disclosures.

Risks Related to the Use of Non-Steroidal Anti-Inflammatory Drugs in Community-Acquired Pneumonia in Adult and Pediatric Patients.

Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used to alleviate symptoms during community-acquired pneumonia (CAP), while neither clinical data nor guidelines encourage this use. Experimental data suggest that NSAIDs impair neutrophil intrinsic functions, their recruitment to the inflammatory site, and the resolution of inflammatory processes after acute pulmonary bacterial challenge. During CAP, numerous observational data collected in hospitalized children, hospitalized adults, and adults admitted to intensive care units (ICUs) support a strong association between pre-hospital NSAID exposure and a delayed hospital referral, a delayed administration of antibiotic therapy, and the occurrence of pleuropulmonary complications, even in the only study that has accounted for a protopathic bias. Other endpoints have been described including a longer duration of antibiotic therapy and a greater hospital length of stay. In all adult series, patients exposed to NSAIDs were younger and had fewer comorbidities. The mechanisms by which NSAID use would entail a complicated course in pneumonia still remain uncertain. The temporal hypothesis and the immunological hypothesis are the two main emerging hypotheses. Current data strongly support an association between NSAID intake during the outpatient treatment of CAP and a complicated course. This should encourage experts and scientific societies to strongly advise against the use of NSAIDs in the management of lower respiratory tract infections.

Minocycline as A Substitute for Doxycycline in Targeted Scenarios: A Systematic Review

Doxycycline, a commonly prescribed tetracycline, remains on intermittent shortage. We systematically reviewed the literature to assess minocycline as an alternative to doxycycline in select conditions, given doxycycline's continued shortage. We identified 19 studies, 10 of which were published before 2000. Thirteen of the studies were prospective, but only 1 of these studies was randomized. Based on the available data, we found minocycline to be a reasonable substitute for doxycycline in the following scenarios: skin and soft-tissue infections and outpatient treatment of community-acquired pneumonia in young, otherwise healthy patients or in patients with macrolide-resistant Mycoplasma pneumoniae, as well as Lyme disease prophylaxis and select rickettsial disease should doxycycline be unavailable.

Effect of Clarithromycin Administration during Late Gestational Period on the Pregnant Albino Rats and Their Fetuses

Clarithromycin, a new macrolide antibiotic, is effective in the management of a wide range of clinical problems including outpatient treatment of community-acquired pneumonia, shortening the course of peptic ulcer disease associated with Helicobacter pylori infection and curing previously resistant respiratory infections in immune-compromised patients. The present study is planned to study the effect of clarithromycin on the pregnant female rats and their fetuses during the last gestational period stage. This study includes the effect of clarithromycin on therate of abortion, malformation of fetuses, skeletal, histological changes and DNA fragmentation of liver cells of pregnant rats and their fetuses. In the present study two groups of pregnant animals were used. The first group received distilled water from 15th to 19th days of gestation and used as control and sacrificed at 20th day of gestation. The other group is orally administered with 45mg/kgclarithromycin from 15th to 19th days and sacrifices at 20th day of gestation (the therapeutic dose). The obtained results showed a significant decrease in maternal body weight gain and increase in the rate of abortion, resorption and growth retardation of fetuses.Fetuses of the treated group showed severe lack of ossification on the skull bones, phalanges and sternum bone as well as shortness in the ulna and radius bones. Histological studies of pregnant rats revealed congestion and dilatation of the central vein of the liver lobules and fatty degeneration of the hepatocytes with severe DNA fragmentation.In 20 day-fetuses, there were a marked increase of necrotic hepatocytes associated with increased average of megakaryocytes and periportal leukocytic infiltration.

Risk Factors for Drug‐resistant Streptococcus pneumoniae and Antibiotic Prescribing Practices in Outpatient Community‐acquired Pneumonia

Due to antimicrobial resistance in Streptococcus pneumoniae, national guidelines recommend a respiratory fluoroquinolone or combination antimicrobial therapy for outpatient treatment of community-acquired pneumonia (CAP) associated with risk factors for drug-resistant S. pneumoniae (DRSP). The objectives of this study were to assess the prevalence of these risk factors and antibiotic prescribing practices in cases of outpatient CAP treated in the acute care setting. This was a retrospective cohort study of adult outpatients treated for CAP in the emergency department (ED) or urgent care center of an urban, academic medical center from May 1, 2009, through October 31, 2009, and comparison of antibiotic therapy in cases with and without DRSP risk factors. Of 175 patients, 90 (51%) had at least one DRSP risk factor, most commonly asthma (n = 28, 16%), alcohol abuse (n = 24, 14%), diabetes mellitus (n = 18, 10%), chronic obstructive pulmonary disease (n = 16, 9%), age > 65 years (n = 16, 9%), and use of antibiotics within 3 months (15, 9%). Antibiotic prescriptions were similar among cases with and without DRSP risk factors: a macrolide (62% vs. 59%, respectively, p = 0.65), doxycycline (27% vs. 28%, p = 0.82), or a respiratory fluoroquinolone (9% vs. 9%, p = 0.90). Concordance with national guideline treatment recommendations was significantly lower in cases with DRSP risk factors (9% vs. 87%, p < 0.0001). DRSP risk factors were present in approximately half of outpatient CAP cases treated in the acute care setting; however, guideline-concordant antibiotic therapy was infrequent. Strict adherence to current guidelines would substantially increase use of fluoroquinolones or combination therapy. Whether the potential risks associated with these broad-spectrum regimens are justified by improved clinical outcomes requires further study.

Fluoroquinolones in the management of community-acquired pneumonia in primary care

A literature search was conducted to evaluate the pharmacokinetic and pharmacodynamic profile of the respiratory fluoroquinolones (gemifloxacin, levofloxacin and moxifloxacin) and their efficacy and safety in the management of community-acquired pneumonia (CAP). Data show that CAP is a common presentation in primary care practice, and is associated with high rates of morbidity and mortality, particularly in the elderly. Although the causative pathogens differ depending on treatment setting and patient factors, Streptococcus pneumoniae is the primary pathogen in all treatment settings. As a class, the respiratory fluoroquinolones have a very favorable pharmacokinetic and pharmacodynamic profile. Pharmacodynamic criteria suggest that moxifloxacin and gemifloxacin are more potent against S. pneumoniae, which may have the added benefit of reducing resistance selection and enhancing bacterial eradication. The respiratory fluoroquinolones are also generally well tolerated, and are first-line options for outpatient treatment of CAP in patients with comorbidities or previous antibiotic use.

Hospital visits and costs following outpatient treatment of CAP with levofloxacin or moxifloxacin

Background:Hospital admissions (inpatient and emergency room) are a major source of medical costs for community-acquired pneumonia (CAP) initially treated in the outpatient setting. Current CAP treatment guidelines do not differentiate between outpatient treatment with levofloxacin and moxifloxacin.Objective:Compare health care resource use and medical costs to payers for CAP outpatients initiating treatment with levofloxacin or moxifloxacin.Research design and methods:CAP episodes were identified in the PharMetrics database between 2Q04 and 2Q07 based on: pneumonia diagnosis, chest X-ray and treatment with levofloxacin or moxifloxacin. Subsequent 30-day risk of pneumonia-related hospital visits and 30-day health care costs to payers for levofloxacin vs. moxifloxacin treatment were estimated after adjusting for pre-treatment demographics, health care resource use and pneumonia-specific risk factors using propensity score and exact factor matching.Results:A total of 15,472 levofloxacin- and 6474 moxifloxacin-initiated CAP patients were identified. Among 6352 matched pairs, levofloxacin treatment was associated with a 35% reduction in the odds of pneumonia-related hospital visits (odds ratio = 0.65, P = 0.004), lower per-patient costs for pneumonia-related hospital visits ($102 vs. $210, P = 0.001), lower pneumonia-related total costs (medical services and prescription drugs, $363 vs. $491, P < 0.001) and lower total costs ($1308 vs. $1446, P < 0.001) vs. moxifloxacin over the 30-day observation period.Limitations:Although observational analyses of claims data provide large sample sizes and reflect routine care, they do have several inherent limitations. Since randomization of subjects is not possible, adequate statistical techniques must be used to ensure that patient characteristics are well-balanced between treatment groups. In addition, data may be missing or miscoded.Conclusions:CAP outpatients initiated with levofloxacin generated substantially lower costs to payers compared to matched patients initiated with moxifloxacin. The cost savings for patients initiated with levofloxacin were largely attributable to reduced rates of pneumonia-related hospitalization or ER visits.

Amoxicillin is effective against penicillin-resistant Streptococcus pneumoniae strains in a mouse pneumonia model simulating human pharmacokinetics.

High-dose oral amoxicillin (3 g/day) is the recommended empirical outpatient treatment of community-acquired pneumonia (CAP) in many European guidelines. To investigate the clinical efficacy of this treatment in CAP caused by Streptococcus pneumoniae strains with MICs of amoxicillin > or =2 microg/ml, we used a lethal bacteremic pneumonia model in leukopenic female Swiss mice with induced renal failure to replicate amoxicillin kinetics in humans given 1 g/8 h orally. Amoxicillin (15 mg/kg of body weight/8 h subcutaneously) was given for 3 days. We used four S. pneumoniae strains with differing amoxicillin susceptibility and tolerance profiles. Rapid bacterial killing occurred with an amoxicillin-susceptible nontolerant strain: after 4 h, blood cultures were negative and lung homogenate counts under the 2 log(10) CFU/ml detection threshold (6.5 log(10) CFU/ml in controls, P < 0.01). With an amoxicillin-intermediate nontolerant strain, significant pulmonary bacterial clearance was observed after 24 h (4.3 versus 7.9 log(10) CFU/ml, P < 0.01), and counts were undetectable 12 h after treatment completion. With an amoxicillin-intermediate tolerant strain, 24-h bacterial clearance was similar (5.4 versus 8.3 log(10) CFU/ml, P < 0.05), but 12 h after treatment completion, lung homogenates contained 3.3 log(10) CFU/ml. Similar results were obtained with an amoxicillin-resistant and -tolerant strain. Day 10 survival rates were usually similar across strains. Amoxicillin with pharmacokinetics simulating 1 g/8 h orally in humans is bactericidal in mice with pneumonia due to S. pneumoniae for which MICs were 2 to 4 microg/ml. The killing rate depends not only on resistance but also on tolerance of the S. pneumoniae strains.

Bacteremic pneumococcal pneumonia associated with macrolide failure

Despite rising rates of macrolide resistance to Streptococcus pneumoniae, the current guidelines for outpatient treatment of community-acquired pneumonia include a macrolide as initial empiric therapy. There have only been a few previously documented cases of macrolide treatment failure in community-acquired pneumonia and there is controversy as to whether macrolide resistance in S. pneumoniae is clinically important. Reported here are two cases of community-acquired pneumonia caused by S. pneumoniae, one of which was fatal, that failed to respond to clarithromycin.

GP management of community-acquired pneumonia in Italy: the ISOCAP study

Community-Acquired Pneumonia (CAP) is still a significant problem in terms of incidence, mortality rate, particularly in infants and the elderly, and socioeconomic burden. General Practitioners (GPs) are the first reference for patients with this disease, but there are few published studies regarding the outpatient treatment of CAP. The ISOCAP study aimed to identify the type and outcome of the diagnostic-therapeutic management of CAP by GPs in Italy, within the framework of developing a closer interrelationship between GPs and pulmonary specialists. Thirty-six Pulmonary Divisions throughout Italy each contacted 5 local GPs who agreed to recruit the first 5 consecutive patients who consulted them for suspected CAP within the study's 1-year observation period. A total of 183 GPs took part in the study and enrolled, by the end of the observation period, 763 CAP patients; of these, complete data was available for 737 patients [males=373, females=364, mean age (+/- SD) 58.8 +/- 19.6 years]. 64.4% of patients had concomitant diseases, mainly systemic arterial hypertension and COPD. Diagnosis of CAP was based by GPs on physical examination only in 41.6% of cases; in the remaining chest X-ray was also performed. In only 4.6% of patients were samples sent for microbiological analysis. All patients were treated with antibiotics: 76.7% in mono-therapy, 23.3% with a combination of antibiotics. The antibiotic class most prevalently used in mono-therapy was cephalosporin, primarily ceftriaxone; the most frequently used combinations were cephalosporin + macrolide and cephalosporin + quinolone. Mono-therapy was effective in 70% of cases, the combination of two or more antibiotics in 91.2% of patients. Overall treatment efficacy was 94.7%; hospitalisation was required in 8.5% of cases. Outpatient management of CAP by GPs in Italy is effective, hospitalisation being necessary only in the most severe cases due to age, co-morbidities or extent of pneumonia. This signifies a very significant savings in national health costs.

Antimicrobial Drug Prescribing for Pneumonia in Ambulatory Care

To determine patterns and predictors of antimicrobial drug use for outpatients with community-acquired pneumonia, we examined office visit and pharmacy claims data of 4 large third-party payer organizations from 2000 to 2002. After patients with coexisting conditions were excluded, 4,538 patients were studied. Despite lack of coexisting conditions, fluoroquinolone use was commonly observed and increased significantly (p < 0.001) from 2000 to 2002 (24%-39%), while macrolide use decreased (55%-44%). Increased age correlated with increased fluoroquinolone use: 18-44 years (22%), 45-64 years (33%), and > or =65 years (40%) (p < 0.001). Increased use of fluoroquinolones occurred in healthy young and old patients alike, which suggests a lack of selectivity in reserving fluoroquinolones for higher risk patients. Clear and consistent guidelines are needed to address the role of fluoroquinolones in treatment of outpatient community-acquired pneumonia.

Increasing fluoroquinolone use for the emergency department treatment of community-acquired pneumonia

Study objectives: Multiple guidelines exist for recommending initial antibiotic choice in the treatment of outpatient community-acquired pneumonia (CAP). Broad-spectrum macrolides, as well as doxycycline, are most often cited as appropriate first-line drugs. The guidelines also list fluoroquinolones as a possible initial antibiotic agent, but all discourage their use in otherwise healthy patients because of concerns about fluoroquinolone resistance. We determined the trends in antibiotic choice for treatment of CAP in the emergency department (ED) setting at a large academic medical center. Methods: A retrospective 3-year medical record review of consecutive patients discharged to home from the ED with a diagnosis of CAP was performed. CAP patients were included during the peak pneumonia season for 3 consecutive periods. Period 1 was October 1, 2000, to March 31, 2001; period 2 was October 1, 2001, to March 31, 2002; and period 3 was October 1, 2002, to March 31, 2003. A standardized form was completed by trained medical students and antibiotic choice was documented. Using the mean proportions for the 3 periods, pairwise comparisons between 2 periods for the 2 antibiotics (macrolides and fluoroquinolones) were performed using the Bonferroni adjustment to adjust for multiplicity. An interaction effect, antibiotic versus time, was included in the linear regression model. In addition, data were obtained from the microbiology laboratory concerning percentage of drug-resistant Streptococcus pneumoniae . The proportions of susceptibility for 4 years (2000 to 2003) were compared. Pairwise comparisons were performed between 2 years for susceptibility using the Bonferroni adjustment to adjust for multiplicity. Results: The proportion of macrolide use significantly decreased (79% to 71% to 59%), and the proportion of fluoroquinolone use significantly increased (7% to 16% to 21%) during the 3 periods. The comparisons reached statistical significance when period 1 was compared with period 3. Macrolides and fluoroquinolones (in percentage use) are negatively correlated with Pearson's correlation coefficient (–.6981; P S pneumonaie. Conclusion: Within a 3-year period, fluoroquinolone use at this academic institution is increasing, whereas macrolide use is decreasing, a trend not in accordance with published guidelines. This trend is concerning considering the emergence of fluoroquinolone-resistant S pneumoniae.

Impact of antimicrobial resistance on health outcomes in the out-patient treatment of adult community-acquired pneumonia: a probability model.

Out-patient treatment of community-acquired pneumonia (CAP) is a major challenge in an era of increasing prevalence of antimicrobial resistance. However, data describing the clinical impact of such resistance are scarce. A probability model was developed to estimate the impact of antimicrobial resistance on clinical outcomes for adults with CAP, eligible for out-patient care. The model assumed patients would be evaluated at 48-72 h, with those failing to improve being either hospitalized or switched to a different antibiotic. Two strategies were considered: amoxicillin followed by erythromycin (amoxicillin/erythromycin) and erythromycin followed by levofloxacin (erythromycin/levofloxacin). Analyses were conducted based on susceptibility of the major pathogens in France and the UK. Primary model-generated outcome measures were the proportion of patients successfully treated with first-line therapy and the proportion of patients subsequently hospitalized. The model estimated that in France, the amoxicillin/erythromycin strategy would lead to 67.8% improving within 48-72 h and 12.7% subsequently being hospitalized, compared with 48.6% and 13.7% for erythromycin/levofloxacin. For the UK, first-line success and hospitalization rates were, respectively, 71.7% and 8.1% for amoxicillin/erythromycin, and 65.3% and 9.3% for erythromycin/levofloxacin. The model estimated that antimicrobial resistance was responsible for >40% of hospitalizations in France and 15% in the UK. These data suggest that in areas with substantially reduced levels of susceptibility, antimicrobial resistance may be a significant contributor to subsequent hospitalization in adults initially treated as out-patients for CAP. Choice of out-patient treatment strategy should consider local resistance rates in order to maximize the likelihood of early cure, thereby minimizing hospitalizations.

Fluoroquinolones for the treatment of outpatient community-acquired pneumonia

The increasing prevalence of β-lactam and macrolide resistance in bacteria that cause respiratory infections has underscored the need for effective antimicrobial agents. The broad spectrum, excellent oral bioavailability, and once-daily dosing of fluoroquinolones contributed to the introduction of several new agents in the past decade. This class is among the world’s most used antimicrobial therapies in community and hospital settings. Fluoroquinolones are generally well tolerated, but safety profiles differ widely among agents. Knowledge of in vitro activity, local microbiologic susceptibility and resistance patterns, adverse effects, and potential drug interactions should influence the selection of the best agent for individual patients. This overview of the fluoroquinolones directs particular attention to use in community-acquired pneumonia and safety.

Management of community-acquired pneumonia in the era of pneumococcal resistance: a report from the Drug-Resistant Streptococcus pneumoniae Therapeutic Working Group.

To provide recommendations for the management of community-acquired pneumonia and the surveillance of drug-resistant Streptococcus pneumoniae (DRSP). We addressed the following questions: (1) Should pneumococcal resistance to beta-lactam antimicrobial agents influence pneumonia treatment? (2) What are suitable empirical antimicrobial regimens for outpatient treatment of community-acquired pneumonia in the DRSP era? (3) What are suitable empirical antimicrobial regimens for treatment of hospitalized patients with community-acquired pneumonia in the DRSP era? and (4) How should clinical laboratories report antibiotic susceptibility patterns for S pneumoniae, and what drugs should be included in surveillance if community-acquired pneumonia is the syndrome of interest? Experts in the management of pneumonia and the DRSP Therapeutic Working Group, which includes clinicians, academicians, and public health practitioners, met at the Centers for Disease Control and Prevention in March 1998 to discuss the management of pneumonia in the era of DRSP. Published and unpublished data were summarized from the scientific literature and experience of participants. After group presentations and review of background materials, subgroup chairs prepared draft responses, which were discussed as a group. When implicated in cases of pneumonia, S pneumoniae should be considered susceptible if penicillin minimum inhibitory concentration (MIC) is no greater than 1 microg/mL, of intermediate susceptibility if MIC is 2 microg/ mL, and resistant if MIC is no less than 4 microg/mL. For outpatient treatment of community-acquired pneumonia, suitable empirical oral antimicrobial agents include a macrolide (eg, erythromycin, clarithromycin, azithromycin), doxycycline (or tetracycline) for children aged 8 years or older, or an oral beta-lactam with good activity against pneumococci (eg, cefuroxime axetil, amoxicillin, or a combination of amoxicillin and clavulanate potassium). Suitable empirical antimicrobial regimens for inpatient pneumonia include an intravenous beta-lactam, such as cefuroxime, ceftriaxone sodium, cefotaxime sodium, or a combination of ampicillin sodium and sulbactam sodium plus a macrolide. New fluoroquinolones with improved activity against S pneumoniae can also be used to treat adults with community-acquired pneumonia. To limit the emergence of fluoroquinolone-resistant strains, the new fluoroquinolones should be limited to adults (1) for whom one of the above regimens has already failed, (2) who are allergic to alternative agents, or (3) who have a documented infection with highly drug-resistant pneumococci (eg, penicillin MIC > or =4 microg/mL). Vancomycin hydrochloride is not routinely indicated for the treatment of community-acquired pneumonia or pneumonia caused by DRSP.

Randomized double-blind trial of the comparative efficacy and safety of cefpodoxime proxetil and cefaclor in the treatment of acute community-acquired pneumonia

A randomized, controlled, double-blind, double-dummy, multicenter study compared the efficacy and safety of cefpodoxime proxetil with that of cefaclor in the outpatient treatment of community-acquired pneumonia. A total of 325 patients received 7 to 14 days of either 200 mg of cefpodoxime as cefpodoxime proxetil twice daily (n = 216) or 500 mg of cefaclor three times daily (n = 109). All study criteria were met by 125 patients (cefpodoxime, 77; cefaclor, 48). Streptococcus pneumoniae and Haemophilus influenzae were the most commonly identified pathogens. Of 198 pathogenic bacteria isolated from sputum, cefpodoxime susceptibility was tested in 178 and cefaclor susceptibility in 181. Isolates were more susceptible to cefpodoxime than to cefaclor ( P = 0.001): 94% were susceptible to cefpodoxime and 82% to cefaclor; 3% were moderately susceptible to cefpodoxime and 5% to cefaclor; 3% were resistant to cefpodoxime and 13% were resistant to cefaclor. Clinical outcome in the two treatment groups was similar: 77% of cefpodoxime-treated patients and 71% of cefaclor-treated patients were cured; 19% of cefpodoxime-treated and 25% of cefaclor-treated patients improved; and 4% of patients in each group were considered treatment failures. Gastrointestinal complaints were the most frequently reported drug-related adverse event (10%) in the cefpodoxime group, and dermatologic problems (5%) were the most commonly encountered drug-related adverse event in the cefaclor group. Overall frequencies of drug-related adverse events were similar (16% for cefpodoxime vs 14% for cefaclor) in the two groups. Cefpodoxime proxetil was as effective and as well tolerated as cefaclor in the outpatient treatment of community-acquired pneumonia.