Geographically-based evaluation of multidrug resistance trends among Streptococcus pneumoniae in the USA: findings of the FAST surveillance initiative (2003-2004).

Surveillance initiatives to track Streptococcus pneumoniae resistance trends are important for understanding the current in vitro effectiveness of available antimicrobial agents. The antimicrobial susceptibility profiles of S. pneumoniae (n=1479 isolates) collected from 17 geographical areas across the USA (2003-2004) were analysed; 36.8% of isolates were resistant to one or more agents (24.4% were multidrug-resistant, i.e. resistant to two or more antimicrobial classes). Multidrug resistance involved resistance to beta-lactams, macrolides, tetracycline and trimethoprim/sulphamethoxazole, but rarely fluoroquinolones (>96% of multidrug-resistant isolates were fluoroquinolone-susceptible). Multidrug resistance rates were prominent regardless of the geographical region surveyed. As this trend continues, the empirical therapeutic options for S. pneumoniae infections will diminish and there will be an ongoing need to evaluate the effectiveness of potent fluoroquinolones such as gemifloxacin.

Adverse cutaneous reactions and drugs: a focus on antimicrobials.

Rashes are a common adverse event observed during antimicrobial therapy. Many rashes are mild to moderate in intensity, however some reactions can be the prelude to much more severe outcomes such as Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necolysis. Several risk or influencing factors are known such as female gender, age and concomitant viral infections, and these may apply to more than one drug class. The incidence of rashes and other cutaneous reactions vary, however rates of >3% are reported with the beta-lactams while serious reactions such as SJS are observed with trimethoprim-sulphamethoxazole. Newer fluoroquinolone agents are devoid of the moiety which caused phototoxic reactions, while rates of rash vary from < 1%-3% or higher if longer courses of therapy are given. Serious systemic events have not been reported with these agents unlike other older, well-accepted antimicrobials. Rashes, while occasionally itchy and sometimes transiently unsightly, have less of an impact on a patient's daily activities than diarrhea, nausea or other more profound adverse events. However, it is essential that any rash be carefully monitored for possible, but rare, serious systemic events ensuing.

Future trends in antimicrobial chemotherapy: expert opinion on the 43rd ICAAC.

The current document bestows an expert synopsis of key new information presented at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in 2003. Data is presented on the socio-political aspects of and policies on antimicrobial prescribing, novel mechanisms of resistance in Streptococcus pneumoniae, and current epidemiological trends in global resistance. Novel information on new (and existing) antimicrobial agents--new penicillins, cephalosporins, monobactams and oxipenem inhibitors, ketolides, glycopeptides, fluoroquinolones (and hybrids), peptides, daptomycin, aminomethylcyclines, glycylcyclines, and newer formulations of agents such as amoxycillin-clavulanate--provides renewed hope that resistant pathogens can be controlled through use of more potent agents. Improved strategies for the use of existing antimicrobial agents, such as the use of high-dose regimens, short-course therapy, also may delay or reduce the development of resistance and preserve the value of our antibiotic armamentarium.

Antimicrobial selection for community-acquired lower respiratory tract infections in the 21st century: a review of gemifloxacin.

Community-acquired lower respiratory tract infections (LRTIs) are more prevalent in the elderly than in children and younger adults and form a significant proportion of all consultations and hospital admissions in this older age group. Furthermore, in a world of increasing life expectancy the trend seems unlikely to be reversed. Antimicrobial treatment of community-acquired pneumonia (CAP) must cover Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis, and in many circumstances should also cover the intracellular (atypical) pathogens. In contrast, acute exacerbations of chronic bronchitis (AECB) are mainly associated with H. influenzae and S. pneumoniae and not with atypical bacteria: in severe cases, other Gram-negative bacteria may be involved. Frequently in LRTIs, the aetiology of the infection cannot be identified from the laboratory specimens and treatment has to be empirical. In such situations it is important to not only to use an antibiotic that covers all likely organisms, but also one that has good activity against these organisms given the local resistance patterns. Gemifloxacin is a new quinolone antibiotic that targets pneumococcal DNA gyrase and topoisomerase IV and is highly active against S. pneumoniae including penicillin-, macrolide- and many ciprofloxacin-resistant strains, as well as H. influenzae and the atypical pathogens. In clinical trials in CAP and AECB, gemifloxacin has been shown to be as effective a range of comparators and demonstrated an adverse event profile that was in line with the comparator agents. In one long-term study in AECB significantly more patients receiving gemifloxacin than clarithromycin remained free of recurrence after 26 weeks. The improved potency, broad spectrum of activity and proven clinical and bacteriological efficacy and safety profile should make it a useful agent in the 21st century battle against community-acquired LRTIs.

Antimicrobial resistance mechanisms: what's hot and what's not in respiratory pathogens.

Community respiratory tract pathogens comprise Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and a few other select, but less frequent, species such as atypical bacteria, staphylococci, and some gram-negative organisms. In addition to an array of virulence factors, these bacteria have also developed a propensity to withstand a range of antimicrobial agents. These resistance mechanisms occur as either target site or antibiotic modifications or antibiotic transportation changes (prevention of cell entry or agent efflux). The genetic coding for these changes can be transmitted to progeny every 20 minutes or can be acquired from the normal flora via transformation. Presently, it is this acquisition of naked DNA by pneumococci that is a "hot" topic and the realization that unless antimicrobials are used more thoughtfully, then new agents can be rapidly rendered redundant. Other potential, but as yet unfounded, resistance scenarios include the acquisition of extended spectrum beta-lactamases by H. influenzae and the development of ribosomal changes to obviate the ketolides and oxazolidinones. To prevent the continued escalation of antimicrobial resistance, new approaches to antimicrobials must be implemented soon.

Clinical experience in Germany of treating community-acquired respiratory infections with the new 8-methoxyfluoroquinolone, moxifloxacin.

Moxifloxacin, a new 8-methoxyfluoroquinolone, was evaluated in a large community-based study involving 16,007 patients over a 9-month period. This study was designed as a large post-marketing observational study of the speed, efficacy and tolerability of moxifloxacin when used in clinical practice for the treatment of community-acquired bacterial pneumonia, or acute exacerbations of chronic bronchitis. Physicians and patients were specifically questioned about overall efficacy and safety as well as symptom relief. According to physicians' assessments 96.3% of patients were cured or improved after moxifloxacin treatment. Symptom relief ('feeling better') occurred in almost 70% of patients by day 3 and only 2.3% reported an adverse drug reaction. No individual adverse drug reaction was reported at a frequency above 1%. Among the 209 events considered as serious, only 34 were regarded as possibly or probably related to therapy. There were no moxifloxacin-related clinically relevant cases of phototoxicity, hepatotoxicity or cardiotoxicity. Overall, 92.1% of patients considered moxifloxacin to have been beneficial.

Treatment outcomes in acute exacerbations of chronic bronchitis: comparison of macrolides and moxifloxacin from the patient perspective.

Moxifloxacin, a new respiratory quinolone, was compared with the macrolides azithromycin, clarithromycin and roxithromycin in a cohort study to assess clinical, safety and health-related outcomes of these antimicrobials in general practice settings. In total 332 patients with acute exacerbations of chronic bronchitis (AECB) each received one of the antimicrobial agents for a standard short course of therapy. Random allocation of therapeutic agents occurred by centre, not individuals, and the drugs were prescribed in an open manner. In addition to clinical evaluation by their physicians, all patients kept daily diaries to assess AECB symptoms over the study period, therapy received and quality of life. The overall clinical response rate was 96% and all four regimens were well tolerated. After 14 days there were no significant differences between the study groups, but analyses of patients' daily evaluations of certain AECB specific symptoms showed a faster response rate in the moxifloxacin group.

Antimicrobial susceptibility of Gram-positive bacteria: what's current, what's anticipated?

Changing patterns of pathogens and antibiotic susceptibility present clinicians with difficult choices for antimicrobial prescribing. In particular, multiresistant staphylococci, enterococci and pneumococci present problems in many settings. The number of predictably active antimicrobials is decreasing in many centres, with significant consequences for both patients and society as a whole. New antimicrobial options have been few in recent years and several promising quinolones have been compromised by formulation and/or toxicity issues. Nevertheless, the recent introduction of linezolid and quinupristin/dalfopristin provides clinicians with valuable new options against Gram-positive cocci. These options should further increase with the likely introduction of daptomycin, oritavancin and tigilcycline. A range of surveillance programmes helps monitor the ever-changing patterns of resistance and thus guides clinicians in their empirical prescribing. Empirical use of powerful newer agents may be justifiable in seriously ill patients in those settings, units and countries where there is a substantial background rate of resistance.

Antimicrobial susceptibility patterns of respiratory pathogens--a global perspective.

Antimicrobial resistance among respiratory tract pathogens poses a major challenge for the ongoing use of antimicrobial agents for treating infected patients. Global antimicrobial susceptibility data has documented the existence of widespread resistance issues. Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis constitute the principal community-acquired respiratory tract bacterial pathogens. For H. influenzae, resistance to ampicillin varies from less than 5% in some European countries to greater than 30% in North America and Southeast Asia. For H. influenzae, resistance to trimethoprim/sulfamethoxazole has been shown to range from less than 5% in North America and Europe to greater than 25% in Europe, the Middle East, and India. For M. catarrhalis, 85% to 100% of isolates worldwide are beta-lactamase positive and, therefore, ampicillin and amoxicillin resistant. Penicillin-resistant S. pneumoniae shows considerable variability worldwide ranging from 6% to 80% whereas macrolide resistance among the pneumococci range from 0% to 90%. Clearly, documenting and understanding the emergence, dissemination, and infection with pathogens resistant to antimicrobial agents is essential for developing strategies to deal with this global problem. This article highlights the frequency of antimicrobial resistance among the respiratory pathogens from a global perspective. Also, mechanisms of resistance and factors associated with the emergence, dissemination, and colonization of resistant organisms are discussed.

Implementation and physician behavior change : an industry perspective.

Clinical practice guidelines are omnipresent and increasing in number; however, their utility and applicability are questioned. A great deal of effort is expended in their creation, but how they reach their ultimate customers is very variable. The pharmaceutical industry has considerable resources that may assist in this process; however, they need to be more involved in the development of clinical practice guidelines. This can happen only if both guideline developers and industry set aside their fears, concerns, and prejudices and collectively try to improve health care through more appropriate management of patients.

Acute exacerbation of COPD: factors associated with poor treatment outcome.

OBJECTIVES: To determine the effect of age, severity of lung disease, severity and frequency of exacerbation, steroid use, choice of an antibiotic, and the presence of comorbidity on the outcome of treatment for an acute exacerbation of COPD. DESIGN: A retrospective chart analysis over 24 months. SETTING: A university Veterans Affairs medical center. PATIENTS: Outpatients with COPD who were treated with an antibiotic over a period of 24 months for an acute exacerbation of COPD. METHODS: Severity of an acute exacerbation of COPD was defined using the criteria of Anthonisen et al: increased dyspnea, increased sputum volume, and increased sputum purulence. Severity of lung disease was stratified based on FEV(1) percent predicted using American Thoracic Society guidelines (stage I, FEV(1) > or = 50%; stage II, FEV(1) 35 to 49%; stage III, FEV(1) < 35%). Treatment outcome was judged successful when the patient had no return visit in 4 weeks for a respiratory problem. Failure was defined as a return visit for persistent respiratory symptoms that required a change of an antibiotic in < 4 weeks. RESULTS: One-hundred seven patients with COPD (mean age +/- SD, 66.9 +/- 9.5 years) experienced 232 exacerbations over 24 months. First-line antibiotics (trimethoprim-sulfamethoxazole, ampicillin/amoxicillin, and erythromycin) were used to treat 78% of all exacerbations. Treatment failure was noted in 12.1% of first exacerbations and 14. 7% of all exacerbations, with more than half the failures requiring hospitalization. Host factors that were independently associated with treatment failure included the following: FEV(1) < 35% (46.4% vs 22.4%; p = 0.047), use of home oxygen (60.7% vs 15.6%; p < 0. 0001), frequency of exacerbation (3.8 +/- 2.0 vs 1.6 +/- 0.91; p < 0. 001), history of previous pneumonia (64.3% vs 35.1 p < 0.007), history of sinusitis (28.6% vs 8.8%; p < 0.009) and use of maintenance steroids (32.1% vs 15.2% p = 0.052). Using stepwise logistic regression analysis to identify the top independent variables, the use of home oxygen (p = 0.0002) and frequency of exacerbation (p < 0.0001) correctly classified failures in 83.3% of the patients. Surprisingly, age, the choice of an antibiotic, and the presence of any one or more comorbidity did not affect the treatment outcome. CONCLUSION: The results of our study suggest that patient host factors and not antibiotic choice may determine treatment outcome. Prospective studies in appropriately stratified patients are needed to validate these findings.