Optimal management of community-acquired acute bacterial rhinosinusitis: the allergist's perspective.

OBJECTIVES: To characterize the antibiotic resistance seen in community-acquired respiratory tract infections (RTIs) and determine which characteristics to look for in an antibiotic to improve clinical outcomes and decrease the potential for development of resistance. DATA SOURCES: Using MEDLINE, we performed a search of articles published from 1966 to 2004 to evaluate the current literature on the subject of antibiotic resistance and strategies to overcome it. Additional cited references, such as abstracts, were also identified. STUDY SELECTION: Relevant original research articles, reviews, and published abstracts were selected for inclusion in this review. RESULTS: Several factors were identified that should be considered when choosing empiric antibiotic therapy for community-acquired RTIs with the goal of improving clinical outcomes while minimizing the risk of resistance. These factors include spectrum of activity, bactericidal vs bacteriostatic activity, chemical structure, elimination half-life, and potency. CONCLUSIONS: The results of these studies support the use of targeted antibiotic agents that, based on structural and chemical properties, are optimized to have a low potential to induce resistance. This approach to antimicrobial therapy appears to be the most suitable for patients with acute bacterial rhinosinusitis and other community-acquired RTIs.     

Safeguarding future antimicrobial options: strategies to minimize resistance

Current antimicrobial therapy for community-acquired respiratory tract infections (RTIs) is empirical and is influenced by local differences in etiology and bacterial susceptibility. As the rates of resistance and cross-resistance to currently available classes of antimicrobial agents increase, their effectiveness becomes compromised. These issues demand improved strategies for antimicrobial usage, and the development of new agents that do not select resistance are essential to safeguard future antimicrobial efficacy. Strategies to minimize antimicrobial resistance among common RTIs include reducing antimicrobial consumption and controlling the development and spread of resistance through appropriate prescribing and the use of short-duration, once-daily treatments to improve patient compliance. Importantly, the ketolides, which are a new family of antimicrobials, have been recently developed specifically for the treatment of community-acquired RTIs. The first member of this new family, telithromycin, has been shown to have potent activity against common and atypical respiratory pathogens, including β-lactam- and macrolide-resistant strains, and has a low potential to select for or induce cross-resistance. These properties, combined with its good tolerability across patient groups, make telithromycin an attractive option for the first-line empiric treatment of RTIs with the potential to limit the future development of resistance.     

Primary care clinician antibiotic prescribing decisions in consultations for children with RTIs: a qualitative interview study

BackgroundRespiratory tract infections (RTIs) are a major primary care challenge in children because they are common and costly, there is uncertainty regarding their diagnosis, prognosis, and management, and the overuse of antibiotics leads to illness medicalisation and bacterial resistance.AimTo investigate healthcare professional (HCP) diagnostic and antibiotic prescribing decisions for children with RTIs.MethodInterviews were audiorecorded, transcribed, imported into NVivo 9, and analysed thematically.ResultsHCPs varied in the symptom and clinical examination findings used to identify children they thought might benefit from antibiotics. Their diagnostic reasoning and assessment of perceived clinical need for antibiotics used a dual process, combining an initial rapid assessment with subsequent detailed deductive reasoning. HCPs reported confidence diagnosing and managing most minor and severe RTIs. However, residual prognostic uncertainty, particularly for the intermediate illness severity group, frequently led to antibiotic prescribing to mitigate the perceived risk of subsequent illness deterioration. Some HCPs perceived a need for more paediatrics training to aid treatment decisions. The study also identified a number of non-clinical factors influencing prescribing.ConclusionPrognostic uncertainty remains an important driver of HCPs’ antibiotic prescribing. Experience and training in recognising severe RTIs, together with more evidence to help HCPs identify the children at risk of future illness deterioration, may support HCPs’ identification of the children most and least likely to benefit from antibiotics.     

It's time to step up the management of community-acquired pneumonia

Optimal therapy for serious Streptococcal pneumoniae infections with intermediate or high-grade resistance to penicillin is controversial. It should be noted that data regarding the efficacy of penicillins or cephalosporins for penicillin-resistant strains are limited. Despite the paucity of clinical trials, most clinicians still agree that penicillins remain the mainstay of therapy for community-acquired pneumonia caused by Streptococcal pneumoniae-susceptible strains. Macrolide antibiotics are effective for treatment of community-acquired pneumonia caused by susceptible strains of Streptococcus pneumoniae. But resistance to all macrolides, based on current National Committee for Clinical Laboratory Standards breakpoints, should be assumed among isolates with erythromycin resistance. The late-generation fluoroquinolones have a role for treatment of community-acquired pneumonia, however, there is also the potential for evolution of antimicrobial resistance. Performance indicators for community-acquired pneumonia are being established with implementation of protocols for inpatients with pneumonia. These indicators are being monitored by the Center for Medicare and Medicaid Services (CMS) for medicare patients as part of a national project. The indicators also address documentation of influenza and pneumococcal vaccine status in patients. Several other indicators, such as obtaining blood cultures before antibiotic administration, using antibiotics according to current guidelines, and timely administration of antibiotics, will play critical roles in the management of community-acquired pneumonia. Because of increased incremental costs associated with community-acquired pneumonia, early diagnosis and timely intravenous to oral switch therapy will continue to be emphasized and monitored in those admitted into hospitals, together with the appropriate decision tree-based pneumonia specific severity of illness scoring system.     

Reducing uncertainty in managing respiratory tract infections in primary care

Respiratory tract infections (RTIs) remain the commonest reason for acute consultations in primary care in resource-rich countries. Their spectrum and severity has changed from the time that antibiotics were discovered, largely from improvements in the socioeconomic determinants of health as well as vaccination. The benefits from antibiotic treatment for common RTIs have been shown to be largely overstated. Nevertheless, serious infections do occur. Currently, no clinical features or diagnostic test, alone or in combination, adequately determine diagnosis, aetiology, prognosis, or response to treatment. This narrative review focuses on emerging evidence aimed at helping clinicians reduce and manage uncertainty in treating RTIs. Consultation rate and prescribing rate trends are described, evidence of increasing rates of complications are discussed, and studies and the association with antibiotic prescribing are examined. Methods of improving diagnosis and identifying those patients who are at increased risk of complications from RTIs, using clinical scoring systems, biomarkers, and point of care tests are also discussed. The evidence for alternative management options for RTIs are summarised and the methods for changing public and clinicians'' beliefs about antibiotics, including ways in which we can improve clinician–patient communication skills for management of RTIs, are described.     

Cost of Care for Inpatients with Community-Acquired Intra-Abdominal Infections

Few studies have assessed the actual costs associated with failure of initial empiric antibiotic therapy administered to patients with community-acquired intra-abdominal infections. The goals of this study were (i) to determine the frequency of unsuccessful initial empiric therapy in a real-world setting and (ii) to determine the associated impact on medical costs. Thus, a retrospective chart review was performed at four acute-care university hospitals in France. A total of 292 patients hospitalized for community-acquired intra-abdominal infection were included. The mean age of the cohort was 51 years, and 42% of the patients were female. The most commonly administered empiric regimens were intravenous amoxicillin/clavulanate alone (69 patients) or in combination with other antibiotics (n=87) and piperacillin/tazobactam alone (n=24) or in combination (n=48). Other regimens included broad-spectrum penicillin, cephalosporins, and fluoroquinolones administered alone or in combination (n=64). Empiric therapy was successful in 189 (65%) patients and unsuccessful in 103 (35%). Among the 292 patients with community-acquired infection, 15 died of the infection, 8 required reoperation and 80 required second-line antibiotic therapy. Patients with unsuccessful initial empiric therapy had significantly more parenteral antibiotic days (10.3 vs. 7.6 days) and a longer length of stay (16.2 vs. 12.8 days) compared to those with successful initial empiric therapy. A better selection of initial empiric antibiotic therapy may significantly influence the medical costs associated with patients who are hospitalized with community-acquired intra-abdominal infections. Electronic Publication     

Surveillance of resistance in bacteria causing community-acquired respiratory tract infections

Bacterial resistance to antibiotics in community-acquired respiratory tract infections is a serious problem and is increasing in prevalence world-wide at an alarming rate. Streptococcus pneumoniae , one of the main organisms implicated in respiratory tract infections, has developed multiple resistance mechanisms to combat the effects of most commonly used classes of antibiotics, particularly the β -lactams (penicillin, aminopenicillins and cephalosporins) and macrolides. Furthermore, multidrug-resistant strains of S. pneumoniae have spread to all regions of the world, often via resistant genetic clones. A similar spread of resistance has been reported for other major respiratory tract pathogens, including Haemophilus influenzae , Moraxella catarrhalis and Streptococcus pyogenes . To develop and support resistance control strategies it is imperative to obtain accurate data on the prevalence, geographic distribution and antibiotic susceptibility of respiratory tract pathogens and how this relates to antibiotic prescribing patterns. In recent years, significant progress has been made in developing longitudinal national and international surveillance programs to monitor antibiotic resistance, such that the prevalence of resistance and underlying trends over time are now well documented for most parts of Europe, and many parts of Asia and the Americas. However, resistance surveillance data from parts of the developing world (regions of Central America, Africa, Asia and Central/Eastern Europe) remain poor. The quantity and quality of surveillance data is very heterogeneous; thus there is a clear need to standardize or validate the data collection, analysis and interpretative criteria used across studies. If disseminated effectively these data can be used to guide empiric antibiotic therapy, and to support—and monitor the impact of—interventions on antibiotic resistance.     

Can one use probabilistic protocols for antibiotic therapy in intensive care units?]

Due to a large spectrum, empiric antibiotics treatments participate to the increase in bacterial resistance. In order to improve its indications, the implementation of therapeutic guidelines in an ICU was studied. Empiric therapy was administered in 30% of the 178 patients receiving antimicrobial agents. Large spectrum drugs were prescribed in 26% of empiric treatments. The mean duration of empiric antibiotics administration was 3.2 days. It was concluded that it was possible to use guidelines of empiric antibiotic in an intensive care unit.     

Antibiotic prescribing and admissions with major suppurative complications of respiratory tract infections: a data linkage study.

BACKGROUND: Systematic reviews of antibiotic treatment of common acute respiratory tract infections (RTIs) suggest modest symptomatic benefit, but provide limited evidence that prescribing prevents complications. AIM: To assess the relationship between penicillin prescribing (the most commonly used group of antibiotics for RTIs) and hospital admission with complications. DESIGN OF STUDY: Data linkage study. SETTING: Ninety-six health authorities of England for the year 1997-1998. METHOD: Hospital admissions related to RTIs were linked with prescribing analysis and cost (PACT) data. RESULTS: There was close correlation between items of penicillin use and total antibiotic use (r = 0.96). After controlling for SMR, age, sex, and Townsend score, a one-unit increase in penicillin use (items dispensed per capita) was associated with a reduction in annual incidence per 10,000 of admissions for quinsy (-3.55 admissions, 95% confidence interval [CI] = -6.85 to -0.26), and mastoiditis (square root of incidence of admissions = -1.05, 95% CI = -1.82 to -0.27). This does not represent lower referral thresholds among higher prescribers as higher prescribing was associated with more admissions for tonsillectomy and overall admissions. Increasing prescribing by 2000 items of penicillin for a practice of 10,000 patients could possibly prevent one admission for either mastoiditis or quinsy. CONCLUSION: Higher antibiotic prescribing is associated with significantly fewer admissions with major complications. However, the overall size of the effect is modest and it is difficult to advocate an overall increase in prescribing to prevent complications. Future research should concentrate on finding better methods of targeting antibiotics to individuals at risk of poor outcome.     

The WHO essential medicines list AWaRe book: from a list to a quality improvement system

Antibiotics are often prescribed inappropriately, either when they are not necessary or with an unnecessarily broad spectrum of activity. AWaRe (AccessWatchReserve) is a system developed by WHO to classify antibiotics based on their spectrum of activity and potential for favouring the development of antibiotic resistance (Access: narrow spectrum/low potential for resistance; Watch: broader spectrum/higher potential for resistance; Reserve: last resort antibiotics to use very selectively). The WHO target is that by 2023, at least 60% of prescribed antibiotics globally should be from the Access category. The WHO AWaRe Book aims to improve empiric antibiotic prescribing by providing simple guidance for common infections based on the principles of AWaRe in alignment with the Model Lists of Essential Medicines for adults and children.     

Association between point-of-care CRP testing and antibiotic prescribing in respiratory tract infections: a systematic review and meta-analysis of primary care studies

Background

Most patients with respiratory tract infections (RTIs) are prescribed antibiotics in general practice. However, there is little evidence that antibiotics bring any value to the treatment of most RTIs. Point-of-care C-reactive protein testing may reduce antibiotic prescribing.

Aim

To systematically review studies that have examined the association between point-of-care (POC) C-reactive protein testing and antibiotic prescribing for RTIs in general practice.

Design and setting

Systematic review and meta-analysis of randomised controlled trials and observational studies.

Method

MEDLINE^® and Embase were systematically searched to identify relevant publications. All studies that examined the association between POC C-reactive protein testing and antibiotic prescribing for patients with RTIs were included. Two authors independently screened the search results and extracted data from eligible studies. Dichotomous measures of outcomes were combined using risk ratios (RRs) with 95% confidence intervals (CIs) either by fixed or random-effect models.

Results

Thirteen studies containing 10 005 patients met the inclusion criteria. POC C-reactive protein testing was associated with a significant reduction in antibiotic prescribing at the index consultation (RR 0.75, 95% CI = 0.67 to 0.83), but was not associated with antibiotic prescribing at any time during the 28-day follow-up period (RR 0.85, 95% CI = 0.70 to 1.01) or with patient satisfaction (RR 1.07, 95% CI = 0.98 to 1.17).

Conclusion

POC C-reactive protein testing significantly reduced antibiotic prescribing at the index consultation for patients with RTIs. Further studies are needed to analyse the confounders that lead to the heterogeneity.     

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.     

Epidemiology of community-acquired Staphylococcus aureus bacteremia.

Methicillin-resistant Staphylococcus aureus (MRSA) is an important nosocomial pathogen which has been isolated with increasing frequency in recent decades. Community-acquired MRSA (CA-MRSA) infections have also become increasingly important in recent years. This study retrospectively analyzed the risk factors, duration of hospitalization, yearly trend and seasonal variation in prevalence, and antibiotic susceptibility of isolates of community-acquired S. aureus (CASA) bacteremia and CA-MRSA bacteremia from patients treated in a teaching hospital in northern Taiwan. A total of 104 clinical isolates of CASA bacteremia were collected between January 1999 and December 2001. Among these, 35 (33.7%) were identified as MRSA. After multivariate analysis, the independent risk factors for developing CA-MRSA bacteremia were diabetes mellitus (p=0.028), chronic obstructive lung disease (p=0.037), and renal insufficiency (p=0.041). Only 6 (17.1%) patients in the MRSA group had no identified risk factors. Most of the isolates of CA-MRSA had a high degree of resistance to most antibiotics, including clindamycin (71.4%), trimethoprim-sulfamethoxazole (65.7%), and chloramphenicol (41.2%). No major trend or seasonal variation in the prevalence was found during the study period. No difference in mortality related to resistance pattern was found. Although CA-MRSA is not the major pathogen in community-acquired bacteremia, it should be included in the differential diagnosis of Gram-positive bacterial bloodstream infection, especially in those patients with risk factors. Early empiric therapy with glycopeptides in these patients may reduce morbidity and mortality.     

Genomic tools to profile antibiotic mode of action

Abstract

The increasing emergence of antimicrobial multiresistant bacteria is of great concern to public health. While these bacteria are becoming an ever more prominent cause of nosocomial and community-acquired infections worldwide, the antibiotic discovery pipeline has been stalled in the last few years with very few efforts in the research and development of novel antibacterial therapies. Some of the root causes that have hampered current antibiotic drug development are the lack of understanding of the mode of action (MOA) of novel antibiotic molecules and the poor characterization of the bacterial physiological response to antibiotics that ultimately causes resistance. Here, we review how bacterial genetic tools can be applied at the genomic level with the goal of profiling resistance to antibiotics and elucidating antibiotic MOAs. Specifically, we highlight how chemical genomic detection of the MOA of novel antibiotic molecules and antibiotic profiling by next-generation sequencing are leveraging basic antibiotic research to unprecedented levels with great opportunities for knowledge translation.     

Hospital antibiogram: a necessity

The hospital antibiogram is a periodic summary of antimicrobial susceptibilities of local bacterial isolates submitted to the hospital's clinical microbiology laboratory. Antibiograms are often used by clinicians to assess local susceptibility rates, as an aid in selecting empiric antibiotic therapy, and in monitoring resistance trends over time within an institution. Antibiograms can also used to compare susceptibility rates across institutions and track resistance trends. Some hospitals have adequate support from the computer department to be able to extract data from their reporting module. The WHONET software can be freely downloaded and used for analysis. Consensus guidelines have been developed by the Clinical and Laboratory Standards Institute (CLSI) to standardise methods used in constructing antibiograms. These guidelines can be incorporated into the WHONET software for analysis. Only the first isolate from the patient is to be included in the analysis. The analysis should be done on the basis of patient location and specimen type. The percentage susceptibility of the most frequently isolated bacteria should be presented in the antibiogram, preferably in a tabular form. The antibiogram must be printed or put up in the intranet for easy access to all clinicians. Antibiotic policy is one of the mandatory requirements for accreditation, and making an antibiogram is the first step before framing the antibiotic policy. The future of antibiograms would be the incorporation of patient related data to make information more reliable and for predicting outbreaks.