National and regional assessment of antimicrobial resistance among community-acquired respiratory tract pathogens identified in a 2005-2006 U.S. Faropenem surveillance study

Surveillance studies conducted in the United States over the last decade have revealed increasing resistance among community-acquired respiratory pathogens, especially Streptococcus pneumoniae, that may limit future options for empirical therapy. The objective of this study was to assess the scope and magnitude of the problem at the national and regional levels during the 2005-2006 respiratory season (the season when community-acquired respiratory pathogens are prevalent) in the United States. Also, since faropenem is an oral penem being developed for the treatment of community-acquired respiratory tract infections, another study objective was to provide baseline data to benchmark changes in the susceptibility of U.S. respiratory pathogens to the drug in the future. The in vitro activities of faropenem and other agents were determined against 1,543 S. pneumoniae isolates, 978 Haemophilus influenzae isolates, and 489 Moraxella catarrhalis isolates collected from 104 U.S. laboratories across six geographic regions during the 2005-2006 respiratory season. Among S. pneumoniae isolates, the rates of resistance to penicillin, amoxicillin-clavulanate, and cefdinir were 16, 6.4, and 19.2%, respectively. The least effective agents were trimethoprim-sulfamethoxazole (SXT) and azithromycin, with resistance rates of 23.5 and 34%, respectively. Penicillin resistance rates for S. pneumoniae varied by region (from 8.7 to 22.5%), as did multidrug resistance rates for S. pneumoniae (from 8.8 to 24.9%). Resistance to beta-lactams, azithromycin, and SXT was higher among S. pneumoniae isolates from children than those from adults. beta-Lactamase production rates among H. influenzae and M. catarrhalis isolates were 27.4 and 91.6%, respectively. Faropenem MICs at which 90% of isolates are inhibited were 0.5 mug/ml for S. pneumoniae, 1 mug/ml for H. influenzae, and 0.5 mug/ml for M. catarrhalis, suggesting that faropenem shows promise as a treatment option for respiratory infections caused by contemporary resistant phenotypes.     

Surface parasitism by Mycoplasma pneumoniae of respiratory epithelium

Identification of the attachment factor on virulent Mycoplasma pneumoniae organisms which permits surface parasitism of respiratory epithelium was attempted. Brief pretreatment of M. pneumoniae monolayers with protease prevented mycoplasma attachment ot sensitive host cells without reducing viability of the microorganisms. Gel electrophoretic analysis of mycoplasma proteins before and after exposure of intact mycoplasmas to protease revealed the absence of a major protein species (P1) in enzyme-treated preparations while other protein bands with the exception of P2 were virtually unaffected. The absence of P1 correlated with the failure of enzyme-treated mycoplasmas to attach to tracheal explants. P1 regeneration after protease treatment of mycoplasma monolayers was directly associated with reattachment capabilities in M. pneumoniae. Erythromycin inhibited P1 resynthesis, thus preventing resumed attachment activity by mycoplasmas. Lactoperoxidase-catalyzed iodination of intact M. pneumoniae organisms further confirmed that P1 was an external membrane protein and suggested that his surface component was required for the successful membrane-membrane interaction between host and parasite.     

In vitro adherence of Streptococcus pneumoniae to oropharyngeal cells: enhanced activity and colonization of the upper respiratory tract in patients with recurrent respiratory infections

In vitro adherence of Streptococcus pneumoniae (S. pneumoniae) to oropharyngeal cells was assessed in 3 age matched groups of 29 subjects. The first group included patients with chronic pulmonary disease and recurrent respiratory infections due to S. pneumoniae or a recent respiratory infection caused by this organism. Patients of the second group has similar underlying pulmonary disease to the first group, but they had no S. pneumoniae respiratory infection for at least the past 3 years. Healthy subjects or patients without underlying pulmonary disease constituted the third group. The mean adherence of S. pneumoniae to oropharyngeal cells was 10.6 +/- 4.7 bacteria (bact.)/cell in the first group, 3.6 +/- 2.8 bact./cell in the second group and 1.9 +/- 2.1 bact./cell in the third group. A significant difference was found (p less than 0.01) when the mean of the first group was compared to those of the second and third groups, whereas there was no significant difference between the means of the second and third groups. In addition, a survey of bacterial colonization of the upper respiratory tract was conducted in all the subjects included in this study. Over 6 months, 5 of the 8 patients in the first group had throat cultures (5 cases) and nasal cultures (3 cases) positive for S. pneumoniae, while no one in the second or third group was a carrier of this bacterium in the upper respiratory tract during the same period. Patients with recurrent or recent respiratory infections caused by S. pneumoniae are characterised by an in vitro enhanced ability of this organism to adhere to their oropharyngeal cells. In vivo, this phenomenon is reflected by an increased susceptibility of the upper respiratory tract to colonization by S. pneumoniae.     

Macrolide resistance in Streptococci and Haemophilus influenzae

Antimicrobial resistance is a growing problem among pathogens from respiratory tract infections. b-Lactam resistance rates are escalating among Streptococcus pneumoniae and Haemophilus influenzae. Macrolides are increasingly used for the treatment of respiratory tract infections, but their utility is compromised by intrinsic and acquired resistance. This article analyses macrolide-resistance mechanisms and their worldwide distributions in S pneumoniae, S pyogenes, and H influenzae.     

Subinhibitory concentrations of erythromycin reduce pneumococcal adherence to respiratory epithelial cells in vitro

We have investigated the influence of subinhibitory concentrations of erythromycin on the interaction between Streptococcus pneumoniae and human respiratory epithelial cells. Confluent in vitro cell cultures were inoculated with erythromycin-resistant S. pneumoniae and incubated for 24 h. Erythromycin significantly reduced adherence of the pneumococci after 4 h and 24 h: 4.0% +/- 0.7% (mean +/- S.E.M. ) of the pneumococci adhered to the epithelial cells in medium with erythromycin, compared with 7.7% +/- 0.8% in medium without erythromycin (P: = 0.002) after 4 h, and the corresponding values after 24 h were 24.2% +/- 5.3% and 38.4% +/- 5.0%, respectively (P: = 0.038). Disruption of epithelial integrity by S. pneumoniae, measured as the decrease in transepithelial electrical resistance, was delayed in the presence of erythromycin. Neither addition of erythromycin to the culture medium nor infection of the cell cultures with pneumococci significantly affected secretion of interleukin-8 by the epithelial cells. Addition of erythromycin to a pneumococcal suspension in cell culture medium without respiratory epithelial cells almost completely prevented the release of pneumolysin. We conclude that erythromycin at subinhibitory concentrations reduces the adherence to and disruption of respiratory epithelial cells by S. pneumoniae, possibly by interfering with pneumolysin release.     

Accuracy of broth microdilution and E test methods for detecting chloramphenicol acetyl transferase mediated resistance in Streptococcus pneumoniae: Geographic variations in the prevalence of resistance in The SENTRY Antimicrobial Surveillance Program (1999)

High antimicrobial resistance rates in Streptococcus pneumoniae has caused a need for alternative therapies. Chloramphenicol is currently being reconsidered as an empiric treatment for respiratory tract infections particularly in developing countries. In this study, we assessed the ability of the reference broth microdilution and Etest (AB BIODISK, Solna, Sweden) methods to detect chloramphenicol resistance among pneumococci as compared to the chloramphenicol acetyltransferase (CAT) assay. In the 1999 SENTRY Antimicrobial Surveillance Program, 1671 S. pneumoniae strains from respiratory tract infections were collected from 49 participants located in the Americas and Europe. The rates of penicillin and macrolide non-susceptibility were 15.6-41.3 and 12.4-26.8%, respectively. All chloramphenicol-resistant strains were CAT assay positive (n = 154; 9.2% of isolates) with highest resistance rates in Europe (12.7%; range among sites, 0.0-38.5%) and the United States (10.6%; range, 0.0-25.6%). Etest MICs correlated with reference results and the current breakpoint for chloramphenicol resistance (> or = 8 microg/mL) remains valid for S. pneumoniae and Haemophilus influenzae (eight strains tested). CAT-mediated resistances dominate among chloramphenicol-resistant S. pneumoniae, and marked geographic variations in susceptibility were discovered.     

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.     

成人耐大环内酯类抗生素肺炎链球菌的实验研究

目的了解近年我国成人患者中分离的肺炎链球菌的耐药现状,为社区获得性呼吸道感染的抗菌药物选用提供依据。方法对临床明确诊断为社区获得性肺炎（CAP）及慢性气管炎急性加重（AECB）患者中分离获得肺炎链球菌;采用微量稀释法测定15种常用抗菌药物对肺炎链球菌的体外药敏结果;进行克林霉素诱导耐药性D试验;PCR扩增方法检测耐药基因。结果71株肺炎链球菌中,青霉素敏感肺炎链球菌（PSSP）70株（70／71）,占98．6％,青霉素中介肺炎链球菌（PISP）1株（1／70）,占1．4％。大环内酯类抗生素耐药肺炎链球菌（MRSP）60株（60／71）,占84．5％,MRSP中以cMLSn型耐药的菌株为主,有54株,占90％,其次为iMLS B型,占8．3％（5／60）,1株为M型,占1．7％（1／60）。60株MRSP中ermB基因阳性检出率最高,占98．3％（59／60）。结论我国成人引起社区获得性呼吸道感染的肺炎链球菌对大环内酯类抗生素的耐药率高,大环内酯类抗生素在CAP治疗中可依据体外药敏试验结果选用,并需与β内酰胺类抗生素联合应用。     

Patterns of macrolide resistance determinants among S. pyogenes and S. pneumoniae isolates in Saudi Arabia

In the study we characterized the macrolide sensitivity of recent clinical isolates of Streptococcus pyogenes and S. pneumoniae collected from major Saudi Arabian hospitals. Susceptibility testing was performed using standard National Committee for Clinical Laboratory Standards methodology on 335 S. pyogenes and 350 S. pneumoniae isolates. Macrolide resistance mechanism phenotypes were identified using double-disk diffusion. All S. pyogenes were penicillin sensitive, while 6.3% were macrolide resistant, the main mechanism of which was of M phenotype (96%). Approximately 51% of S. pneumoniae were penicillin non-susceptible. Macrolide resistance in S. pneumoniae accounted for 18.8%, the majority of which were M phenotype (91%). Low-level resistance mediated by mef-bearing strains pre-dominated. Newer macrolides, including azithromycin, are still considered drugs of choice for empirical treatment of respiratory infection in such circumstances.     

In vitro pharmacodynamic modelling simulating free serum concentrations of fluoroquinolones against multidrug-resistant Streptococcus pneumoniae

An in vitro pharmacodynamic model was used to compare bacterial killing and the development of resistant mutants in the presence of respiratory fluoroquinolones and ciprofloxacin. Free (protein unbound) serum concentrations were simulated using peak serum concentrations and AUC(24), achieved after standard oral doses for treatment of community-acquired respiratory infections. Respiratory fluoroquinolones reduced the inoculum of isolates of multidrug-resistant Streptococcus pneumoniae below the level of detection in the model at 12 h and did not allow regrowth to occur over 48 h. In contrast, ciprofloxacin had a bacteriostatic (<3 log(10) reduction of the initial inoculum) effect, with rapid regrowth occurring over 48 h. Bacterial regrowth and the development of resistant mutants did not occur with any of the respiratory fluoroquinolones. Rapid regrowth and the development of resistant mutants, with MICs two- to eight-fold higher than the MIC before treatment, occurred with ciprofloxacin. These data suggest that the new respiratory fluoroquinolones with a free AUC(24)/MIC of 35-63 reduce the inoculum of multidrug-resistant S. pneumoniae below the level of detection without regrowth or development of resistance over 48 h. This study also demonstrated the poor activity of ciprofloxacin against S. pneumoniae.     

Microbiology of newer fluoroquinolones: focus on respiratory pathogens

Community-acquired pneumonia, acute exacerbations of chronic bronchitis, and acute sinusitis are among the most common bacterial infections encountered in clinical practice. Pathogens frequently associated with these infections include Streptococcus pneumoniae, Hemophilus influenzae, Moraxella catarrhalis, Chlamydia pneumoniae, Legionella pneumophila, and Mycoplasma pneumoniae. Unfortunately, resistance to antimicrobials commonly used for the treatment of these infections is increasing, limiting the clinical efficacy of these agents. Fluoroquinolones offer several advantages over other classes of antimicrobials used for the treatment of community-acquired respiratory tract infections. In general, fluoroquinolones have excellent in vitro activity against common respiratory pathogens, including some drug-resistant strains of S. pneumoniae. Microbial resistance to the newer fluoroquinolones is relatively uncommon, currently occurring in approximately 1% of clinical isolates in North America. Fluoroquinolones currently in clinical development may offer additional benefits over the marketed agents because they maintain good potency against isolates of S. pneumoniae displaying resistance to older quinolones (i.e., ofloxacin or ciprofloxacin) and may have a lower potential to engender resistance. This article reviews the in vitro activity of several newer fluoroquinolones, including agents currently in clinical development, against common respiratory pathogens, including antimicrobial-resistant strains. The mechanisms and prevalence of resistance of beta-lactam antimicrobials, macrolides, and fluoroquinolones also are reviewed.     

Comparative in vitro activity of older and newer fluoroquinolones against respiratory tract pathogens

The aim of this study was to evaluate the antibacterial activity of older (ciprofloxacin and ofloxacin) and newer (moxifloxacin, grepafloxacin, sparfloxacin and levofloxacin) fluoroquinolones. Minimal inhibitory concentrations (MICs) were determined, according to the NCCLS guidelines, against the following respiratory tract pathogens: penicillin-susceptible and -resistant Streptococcus pneumoniae, beta-lactamase-positive and beta-lactamase-negative Haemophilus influenzae and beta-lactamase-positive Moraxella catarrhalis. In addition, we evaluated the minimal bactericidal concentrations of the same antibiotics against all the pneumococci and the haemophili. Finally, the activity of ciprofloxacin, ofloxacin, sparfloxacin and moxifloxacin against 15 pneumococci were investigated by time-kill analysis. All fluoroquinolones tested exhibited a similar, good activity against H. influenzae and M. catarrhalis. Against S. pneumoniae, irrespective of penicillin susceptibility, moxifloxacin, grepafloxacin, sparfloxacin and levofloxacin exhibited excellent activity, better than ciprofloxacin and ofloxacin. Time-kill analysis showed that 99.9% killing of all strains was obtained after 24 h with moxifloxacin at 2 x MIC, whereas other antimicrobials obtained similar results at 4 x MIC. Moxifloxacin is characterized by an improved activity against respiratory pathogens, including penicillin-resistant and -susceptible S. pneumoniae. Its activity is not influenced by beta-lactamase production. These results suggest that moxifloxacin represents a promising alternative for treatment of respiratory tract infections.     

Community-acquired respiratory tract infections caused by resistant pneumococci: clinical and bacteriological efficacy of the ketolide telithromycin

The incidence of community-acquired respiratory tract infections caused by Streptococcus pneumoniae exhibiting antibacterial resistance has increased dramatically in recent years. Telithromycin is the first of a new class of antibacterials, the ketolides, which have been developed specifically to provide effective treatment for these infections. Data were analysed from 3935 patients who had participated in one Japanese Phase II study and 11 US/global Phase III studies in three indications: community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute sinusitis. Patients received either telithromycin 800 mg once daily or a comparator antibacterial. S. pneumoniae isolates considered to be causative for infection were tested for susceptibility to penicillin G and erythromycin A. In per-protocol analyses, telithromycin showed a high level of clinical efficacy against S. pneumoniae, with clinical cure rates of 92.8% for all isolates, 91.7% for those with reduced susceptibility to penicillin G and 86.0% for those with reduced susceptibility to erythromycin A. Bacterial eradication rates were consistent with the clinical outcomes. High rates of clinical cure and bacterial eradication were also observed for infections caused by isolates demonstrating high-level resistance to erythro-mycin A [MICs >/= 512 mg/L: 100% (13/13) clinical cure, 100% (13/13) bacterial eradication]. These results support the use of telithromycin as a first-line oral therapy for the treatment of community-acquired respiratory tract infections caused by S. pneumoniae with reduced susceptibility to penicillin G and erythromycin A.     

Augmentin (amoxicillin/clavulanate) in the treatment of community-acquired respiratory tract infection: a review of the continuing development of an innovative antimicrobial agent

Amoxicillin/clavulanate (Augmentin) is a broad-spectrum antibacterial that has been available for clinical use in a wide range of indications for over 20 years and is now used primarily in the treatment of community-acquired respiratory tract infections. Amoxicillin/clavulanate was developed to provide a potent broad spectrum of antibacterial activity, coverage of beta-lactamase-producing pathogens and a favourable pharmacokinetic/pharmacodynamic (PK/PD) profile. These factors have contributed to the high bacteriological and clinical efficacy of amoxicillin/clavulanate in respiratory tract infection over more than 20 years. This is against a background of increasing prevalence of antimicrobial resistance, notably the continued spread of beta-lactamase-mediated resistance in Haemophilus influenzae and Moraxella catarrhalis, and penicillin, macrolide and quinolone resistance in Streptococcus pneumoniae. The low propensity of amoxicillin/clavulanate to select resistance mutations as well as a favourable PK/PD profile predictive of high bacteriological efficacy may account for the longevity of this combination in clinical use. However, in certain defined geographical areas, the emergence of S. pneumoniae strains with elevated penicillin MICs has been observed. In order to meet the need to treat drug-resistant S. pneumoniae, two new high-dose amoxicillin/clavulanate formulations have been developed. A pharmacokinetically enhanced tablet dosage form of amoxicillin/clavulanate 2000/125 mg twice daily (available as Augmentin XR in the USA), has been developed for use in adult respiratory tract infection due to drug-resistant pathogens, such as S. pneumoniae with reduced susceptibility to penicillin, as well as beta-lactamase-producing H. influenzae and M. catarrhalis. Amoxicillin/clavulanate 90/6.4 mg/kg/day in two divided doses (Augmentin ES-600) is for paediatric use in persistent or recurrent acute otitis media where there are risk factors for the involvement of beta-lactamase-producing strains or S. pneumoniae with reduced penicillin susceptibility. In addition to high efficacy, amoxicillin/clavulanate has a well known safety and tolerance profile of the two new high-dose formulations are not significantly different from those of conventional formulations. Amoxicillin/clavulanate is included in guidelines and recommendations for the treatment of bacterial sinusitis, acute otitis media, community-acquired pneumonia and acute exacerbations of chronic bronchitis. Amoxicillin/clavulanate continues to be an important agent in the treatment of community-acquired respiratory tract infections, both now and in the future.     

中国14家教学医院2005-2008年临床分离肺炎链球菌耐药性分析

目的 监测2005-2008年我国不同地区14家教学医院临床分离肺炎链球菌的耐药性,为临床经验用药提供科学建议.方法 2005-2008年从14家教学医院收集非重复的1 317株临床分离肺炎链球菌,其中2005年271株、2006年391株、2007年363株、2008年292株.菌株主要为社区呼吸道感染病原菌,即以呼吸道感染收治的门诊和急诊患者或入院48 h内发生呼吸道感染的患者中分离的肺炎链球菌.菌株分离地区包括华北地区、东北地区、华南地区、华中及西北地区以及华东地区.患者按年龄分为成人组(≥18岁)、青少年组(6～17岁)和儿童组(≤5岁).菌株经中心实验室复核后,采用Etest法、琼脂稀释法或纸片扩散法测定8类17种抗菌药物的MIC或抑菌圈直径,数据输入WHONET5.5软件分析敏感率、中介率、耐药率、MIC50、MIC90.结果 肺炎链球菌对利奈唑胺(100%)和氟喹诺酮类药物(95.2%～99.7%)保持了高的敏感率.对于β内酰胺类药物,菌株对阿莫西林-克拉维酸敏感率为73.8%～92.1%,对青霉素、头孢曲松和头孢吡肟也有较高的敏感率,但逐年降低.3种二代头孢菌素的敏感率较低(2008年为36.3%～38.4%).对于红霉素、阿奇霉素、克林霉素、甲氧苄啶-磺胺甲 唑和四环素,菌株的敏感率均较低且逐年下降.PISP的比例在逐年增大,从2005年的4.4%上升至2008年的20.2%.华北地区的PNSP发生率较低(6.0%),而华中及西北地区和华东地区的PNSP发生率较高(30.1%和38.7%).成人组的PNSP发生率(15.7%)明显低于儿童组(33.0%),也低于青少年组(38.2%).结论 肺炎链球菌对利奈唑胺和氟喹诺酮类药物在2005-2008年间保持了较高的敏感性,而对青霉素类和头孢菌素类的敏感性逐年降低,临床需慎用对肺炎链球菌活性较低的药物,包括大环内酯类、克林霉素、甲氧苄啶-磺胺甲 唑和四环素.

Abstract：

Objective To investigate antimicrobial resistance among Streptococcus pneumoniae clinically isolated from 14 teaching hospitals located at different areas in China in 2005-2008 and to give logical guidance for clinical empirical therapy.Methods A total of 1 317 non-repetitive S.pneumoniae isolates in 14 teaching hospitals from 2005-2008 were collected and sent to the central lab for reidentification and susceptibility testing, including 271 isolates collected in 2005, 391 isolates collected in 2006, 363 isolates collected in 2007 and 292 isolates collected in 2008. Most of the isolates were from community-acquired respiratory tract infections, which were isolated from outpatient or emergency department patients with respiratory tract infections or those patients with respiratory tract infections within ≤48 hours hospitalization.The districts where the organisms were isolated include North China, Northeast China, South China, Central and Northwest China and East China.The patients included adults, teenagers and children.The minimum inhibitory concentrations (MICs) or inhibitory zone diameter of 17 antimicrobial agents were determined by Etest method, agar dilution method or disk diffusion method.WHONET5.5 software was used to analyze susceptibility rate, intermediate rate, resistance rate, MIC50 and MIC90.Results Linezolid (100%) and fluoroquinolones (95.2%-99.7%) showed excellent activities against S.pneumoniae.Among β-lactams, amoxicillin-clavulanic acid remained high activities (73.8%-92.1%),followed by penicillin, ceftriaxone and cefepime with year-over-year decrease in activities.The activities of three second-generation cephalosporins were low (36.3%-38.4% in 2008).The activities of erythromycin, azithromycin, clindamycin, trimethoprim/sulfamethoxazole and tetracycline against S.pneumoniae were poor and decreased year over year.The incidence of penicillin non-susceptible S.pneumoniae (PNSP) was increasing especially for PISP (from 4.4% in 2005 to 20.2% in 2008).The incidence of PNSP in North China was low (6.0%), while this value were high in central China and East China (30.1% and 38.7%, separately).The incidence of PNSP in adults (15.7%) was obviously lower than that in children(≤5 years:33.0%) and teenagers (6-17 years:38.2%).Conclusions linezolid and fluoroquinolones showed excellent in vitro activity against S.pneumoniae, followed by penicillin and cephalosporins with year-over-year decrease of activity. Clinicians should pay more attention when using those antimicrobial agents with poor activity against S.pneumoniae, which include macrolides, clindamycin, trimethoprim/sulfamethoxazole and tetracycline.     

Comparative efficacies of ciprofloxacin, amoxicillin, amoxicillin-clavulanic acid, and cefaclor against experimental Streptococcus pneumoniae respiratory infections in mice.

Experimental respiratory infections were established in mice by intranasal inoculation of Streptococcus pneumoniae. Inoculation of 10(7) CFU of either S. pneumoniae 1629 or S. pneumoniae 7 produced a fatal pneumonia in nontreated mice 2 to 3 days after infection. Oral therapy was commenced 1 h after infection and was continued three times a day for 2 days. The doses used in mice produced peak concentrations in serum and lung tissue similar to those measured in humans. Ciprofloxacin failed to eliminate either strain of pneumococcus from mouse lungs at any of the doses tested (40, 80, or 160 mg/kg of body weight) by the end of therapy (33 h). Mice that received ciprofloxacin at 160 mg/kg were clear of S. pneumoniae 7 5 days later, whereas persistence and regrowth of S. pneumoniae 1629 resulted in the death of 20% of animals treated with ciprofloxacin. Therapy with cefaclor (20 mg/kg) produced an effect similar to that of ciprofloxacin. In contrast, amoxicillin (10 and 20 mg/kg) and amoxicillin-clavulanic acid (10/5 and 20/10 mg/kg) were significantly (P less than 0.05) more effective in eliminating both strains of S. pneumoniae from the lungs by the end of therapy and, by 168 h, had prevented mortality in 80 to 100% of treated animals. The efficacy of ciprofloxacin against these experimental pneumococcal respiratory infections was poor, despite good penetration into lung tissue, and is a reflection of the low in vitro activity of the quinolone against S. pneumoniae, one of the most common pathogens in community-acquired pneumonia.     

The changing pathogenicity of Mycoplasma pneumoniae with passage in vitro. Correlates of virulence

An avirulent strain of Mycoplasma pneumoniae isolated by broth passage failed to produce pneumonia in hamsters. The major biological property lost in this avirulent strain is its ability to attach to the respiratory epithelium. Although the surface protein responsible for the specific attachment of virulent M. pneumoniae has been identified, protein analysis by gel electrophoresis has failed to produce evidence that could account for the loss of virulence in the avirulent strain. It is possible that the binding sites of the avirulent strain have been altered by mutational event(s) without affecting the molecular weight or electrophoretic mobility of this protein. Antigenic determinant analysis of the membrane proteins by the use of monoclonal antibodies is suggested as a relevant approach, which may lead to a better understanding of the molecular basis of attachment.     

Current issues on resistance,treatment guidelines,and the appropriate use of fluoroquinolones for respiratory tract infections

BACKGROUND: Community-acquired respiratory tract infections comprise a large percentage of diseases treated by primary care physicians, and rates of antimicrobial use for respiratory tract infections are increasing. The fluoroquinolones comprise a drug class with broad-spectrum activity against many of the key pathogens associated with community-acquired respiratory tract infections, including Streptococcus pneumoniae, and other significant pathogens, such as Staphylococcus aureus and Pseudomonas aeruginosa. While fluoroquinolones have gained popularity, the settings for their appropriate use in treating respiratory tract infections remain unclear. OBJECTIVE: In this article, the mechanisms of fluoroquinolone resistance in S. pneumoniae, treatment guidelines, and the mode of spread of resistance are reviewed. METHODS: The authors conducted a MEDLINE search for articles published from 1990 to the present. Search terms included Streptococcus pneumoniae, fluoroquinolones, and resistance. Articles were selected for inclusion based on their relevance to the objective of this review. RESULTS: Although 3 sets of treatment guidelines for community-acquired pneumonia (CAP) currently exist in the United States, a consensus for the role of fluoroquinolones in the outpatient management of CAP has not been achieved. Factors mitigating for restraint in the outpatient use of fluoroquinolones include concern for the spread of resistance to "innocent-bystander" organisms, such as S. aureus and P. aeruginosa, as well as possible inappropriate "trickle-down" use for other, less severe respiratory syndromes, such as bronchitis. CONCLUSION: Although the fluoroquinolones are potent agents against respiratory pathogens and have a clearly defined role in the treatment of hospitalized patients with CAP, their optimal role in the outpatient management of respiratory tract infections remains controversial.     

Cefotiam therapy of lower respiratory tract infections.

Cefotiam, a new cephalosporin, was evaluated in the treatment of lower respiratory tract infections in 29 patients. The bacteria isolated from the sputum of these patients included Streptococcus pneumoniae (31%), Klebsiella pneumoniae (31%), and Haemophilus influenzae (28%). Satisfactory response was observed in 90% of the patients. There were three treatment failures, two superinfections, and four colonizations with gram-negative organisms resistant to the drug. Superficial phlebitis was noted in two patients. The results of this study suggest that cefotiam is an effective and well-tolerated antibiotic for the treatment of lower respiratory tract infections due to susceptible organisms.     

2004-2005年中国社区获得呼吸道感染常见病原菌耐药性研究

目的调查中国6所教学医院2004--2005年分离的社区获得呼吸道感染常见病原菌的耐药性。方法收集2004年7月-2005年3月全国6个地区6所医院社区获得呼吸道感染患者中分离的510株肺炎链球菌、流感嗜血杆菌、卡他莫拉菌、p溶血链球菌及MSSA、非产ESBLs的肺炎克雷伯菌和大肠埃希菌，以琼脂稀释法测定头孢泊肟等9种抗菌药物的MIC。结果肺炎链球菌中，青霉素敏感肺炎链球菌（PSSP）、青霉素中介肺炎链球菌（PISP）、青霉素耐药肺炎链球菌（PRSP）对头孢泊肟的敏感率分别为98．9％、42．2％、6．4％。肺炎链球菌对莫西沙星的敏感率为100％；对米诺环素的敏感率为94．6％；对阿奇霉素的敏感率仅为10．7％；流感嗜血杆菌、MSSA、非产ESBL的肺炎克雷伯菌和大肠埃希菌对头孢泊肟、头孢丙烯、头孢克洛、莫西沙星和米诺环素的敏感率在51．3％～100％。结论呼吸道病原菌特别是肺炎链球菌、流感嗜血杆菌的耐药率与往年监测结果相比较呈增加趋势；头孢泊肟对呼吸道病原菌的抗菌活性优于头孢丙烯和头孢克洛。