The new fluoroquinolones (clinafloxacin, gatifloxacin, gemifloxacin, grepafloxacin, levofloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin) offer excellent activity against Gram-negative bacilli and improved Gram-positive activity (e.g. against Streptococcus pneumoniae and Staphylococcus aureus) over ciprofloxacin. Ciprofloxacin still maintains the best in vitro activity against Pseudomonas aeruginosa. Clinafloxacin, gatifloxacin, moxifloxacin, sitafloxacin, sparfloxacin and trovafloxacin display improved activity against anaerobes (e.g. Bacteroides fragilis) versus ciprofloxacin. All of the new fluoroquinolones display excellent bioavailability and have longer serum half-lives than ciprofloxacin allowing for once daily dose administration. Clinical trials comparing the new fluoroquinolones to each other or to standard therapy have demonstrated good efficacy in a variety of community-acquired respiratory infections (e.g. pneumonia, acute exacerbations of chronic bronchitis and acute sinusitis). Limited data suggest that the new fluoroquinolones as a class may lead to better outcomes in community-acquired pneumonia and acute exacerbations of chronic bronchitis versus comparators. Several of these agents have either been withdrawn from the market, had their use severely restricted because of adverse effects (clinafloxacin because of phototoxicity and hypoglycaemia; grepafloxacin because of prolongation of the QTc and resultant torsades de pointes; sparfloxacin because of phototoxicity; and trovafloxacin because of hepatotoxicity), or were discontinued during developmental phases. The remaining fluoroquinolones such as gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin have adverse effect profiles similar to ciprofloxacin. Extensive post-marketing safety surveillance data (as are available with ciprofloxacin and levofloxacin) are required for all new fluoroquinolones before safety can be definitively established. Drug interactions are limited; however, all fluoroquinolones interact with metal ion containing drugs (eg. antacids). The new fluoroquinolones (gatifloxacin, gemifloxacin, levofloxacin and moxifloxacin) offer several advantages over ciprofloxacin and are emerging as important therapeutic agents in the treatment of community-acquired respiratory infections. Their broad spectrum of activity which includes respiratory pathogens such as penicillin and macrolide resistant S. pneumoniae, favourable pharmacokinetic parameters, good bacteriological and clinical efficacy will lead to growing use of these agents in the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis and acute sinusitis. These agents may result in cost savings especially in situations where, because of their potent broad-spectrum activity and excellent bioavailability, they may be used orally in place of intravenous antibacterials. Prudent use of the new fluoroquinolones will be required to minimise the development of resistance to these agents.

A Critical Review of the Fluoroquinolones

Background Resistance to erythromycin has been very uncommon among group A streptococci in the United States. Methods As part of a longitudinal study, we obtained surveillance throat cultures twice monthly and with each new respiratory tract illness from children in kindergarten through grade 8 at one school in Pittsburgh. Screening for resistance to erythromycin and clindamycin was initially accomplished with use of the Kirby–Bauer disk-diffusion test. The minimal inhibitory concentration of resistant isolates was determined by the E test. A double disk-diffusion test was used to characterize the resistance phenotype, and the polymerase-chain-reaction assay was used to identify the resistance gene. The molecular relatedness of strains was determined by field-inversion gel electrophoresis. Results A total of 1794 throat cultures were obtained from 100 children between October 2000 and May 2001, of which 318 cultures (18 percent) from 60 of the children were positive for group A streptococci. Forty-eight p...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa013169

Erythromycin-resistant group A streptococci in schoolchildren in Pittsburgh.

In vitro surveys of antimicrobial resistance among clinically important anaerobes are an important source of information that can be used for clinical decisions in the choice of empiric antimicrobial therapy. This study surveyed the susceptibilities of 556 clinical anaerobic isolates from four large medical centers using a broth microdilution method. Piperacillin-tazobactam was the only antimicrobial agent to which all the isolates were susceptible. Similarly, imipenem, meropenem, and metronidazole were highly active (resistance, <0.5%), whereas the lowest susceptibility rates were noted for penicillin G, ciprofloxacin, and clindamycin. For most antibiotics, blood isolates were less susceptible than isolates from intra-abdominal, obstetric-gynecologic, and other sources. All isolates of the Bacteroides fragilis group were susceptible to piperacillin-tazobactam and metronidazole, while resistance to imipenem and meropenem was low (<2%). For these same isolates, resistance rates (intermediate and resistant MICs) to ampicillin-sulbactam, cefoxitin, trovafloxacin, and clindamycin were 11, 8, 7, and 29%, respectively. Among the individual species of the B. fragilis group, the highest resistance rates were noted among the following organism-drug combinations: for clindamycin, Bacteroides distasonis and Bacteroides ovatus; for cefoxitin, Bacteroides thetaiotaomicron, B. distasonis, and Bacteroides uniformis; for ampicillin-sulbactam, B. distasonis, B. ovatus, and B. uniformis; and for trovafloxacin, Bacteroides vulgatus. For the carbapenens, imipenem resistance was noted among B. fragilis and meropenem resistance was seen among B. fragilis, B. vulgatus, and B. uniformis. With few exceptions all antimicrobial agents were highly active against isolates of Prevotella, Fusobacterium, Porphyromonas, and Peptostreptococcus. These data further establish and confirm that clinically important anaerobes can vary widely in their antimicrobial susceptibilities. Fortunately most antimicrobial agents were active against the test isolates. However, concern is warranted for what appears to be a significant increases in resistance to ampicillin-sulbactam and clindamycin.

Multicenter survey of the changing in vitro antimicrobial susceptibilities of clinical isolates of Bacteroides fragilis group, Prevotella, Fusobacterium, Porphyromonas, and Peptostreptococcus species.

ContextMost sore throats are due to viral upper respiratory tract infections.
Group A β-hemolytic streptococci (GABHS), the only common cause of sore
throat warranting antibiotics, is cultured in 5% to 17% of adults with sore
throat. The frequency of antibiotic use for pharyngitis has greatly exceeded
the prevalence of GABHS, but less is known about specific classes of antibiotics
used. Only penicillin and erythromycin are recommended as first-line antibiotics
against GABHS.ObjectivesTo measure trends in antibiotic use for adults with sore throat and
to determine predictors of antibiotic use and nonrecommended antibiotic use.Design, Setting, and SubjectsRetrospective analysis of 2244 visits to primary care physicians in
office-based practices in the National Ambulatory Medical Care Survey, 1989-1999,
by adults with a chief complaint of sore throat.Main Outcome MeasuresTreatment with antibiotics and treatment with nonrecommended antibiotics,
extrapolated to US annual national rates.ResultsThere were an estimated 6.7 million annual visits in the United States
by adults with sore throat between 1989 and 1999. Antibiotics were used in
73% (95% confidence interval [CI], 70%-76%) of visits. Patients treated with
antibiotics were given nonrecommended antibiotics in 68% (95% CI, 64%-72%)
of visits. From 1989 to 1999, there was a significant decrease in use of penicillin
and erythromycin and an increase in use of nonrecommended antibiotics, especially
extended-spectrum macrolides and extended-spectrum fluoroquinolones (P<.001 for all trends). In multivariable modeling, increasing
patient age (odds ratio [OR], 0.86 per decade; 95% CI, 0.79-0.94) and general
practice specialty (OR, 1.54 compared with family practice specialty; 95%
CI, 1.10-2.14) were independent predictors of antibiotic use. Among patients
receiving antibiotics, nonrecommended antibiotic use became more frequent
over time (OR, 1.17 per year; 95% CI, 1.11-1.24).ConclusionsMore than half of adults are treated with antibiotics for sore throat
by community primary care physicians. Use of nonrecommended, more expensive,
broader-spectrum antibiotics is frequent.

https://jamanetwork.com/journals/jama/articlepdf/194178/joc10465.pdf

Antibiotic treatment of adults with sore throat by community primary care physicians: a national survey, 1989-1999

Results There were an estimated 6.7 million annual visits in the United States by adults with sore throat between 1989 and 1999. Antibiotics were used in 73% (95% confidence interval [CI], 70%-76%) of visits. Patients treated with antibiotics were given nonrecommended antibiotics in 68% (95% CI, 64%-72%) of visits. From 1989 to 1999, there was a significant decrease in use of penicillin and erythromycin and an increase in use of nonrecommended antibiotics, especially extended-spectrum macrolides and extended-spectrum fluoroquinolones (P,.001 for all trends). In multivariable modeling, increasing patient age (odds ratio [OR], 0.86 per decade; 95% CI, 0.790.94) and general practice specialty (OR, 1.54 compared with family practice specialty; 95% CI, 1.10-2.14) were independent predictors of antibiotic use. Among patients receiving antibiotics, nonrecommended antibiotic use became more frequent over time (OR, 1.17 per year; 95% CI, 1.11-1.24). Conclusions More than half of adults are treated with antibiotics for sore throat by community primary care physicians. Use of nonrecommended, more expensive, broaderspectrum antibiotics is frequent.

Antibiotic Treatment of Adults With Sore Throat by Community Primary Care Physicians

The antimicrobial activities of trovafloxacin, moxifloxacin, sanfetrinem, quinupristin-dalfopristin, and 14 other antimicrobial agents against 218 Bacteroides fragilis group strains were determined. A group of 10 imipenem-resistant strains were also tested. Imipenem, meropenem, and sanfetrinem had the lowest MICs of all of the β-lactams. Quinupristin-dalfopristin inhibited all of the strains at 2 μg/ml. Overall, the MICs of trovafloxacin and moxifloxacin for 90% of the strains tested were 1 and 2 μg/ml, respectively.

Activities of new antimicrobial agents (trovafloxacin, moxifloxacin, sanfetrinem, and quinupristin-dalfopristin) against Bacteroides fragilis group: comparison with the activities of 14 other agents.

M. Luisa Palau

Papers

Activities of new antimicrobial agents (trovafloxacin, moxifloxacin, sanfetrinem, and quinupristin-dalfopristin) against Bacteroides fragilis group: comparison with the activities of 14 other agents.

Incidence of erythromycin resistance in Streptococcus pyogenes: a 10-year study.