Comparative kill and growth rates determined with cefdinir and cefaclor and with Streptococcus pneumoniae and beta-lactamase-producing Haemophilus influenzae.

The relationship between the growth rate and the kill rate was used to evaluate and to compare the in vitro bactericidal activities of cefdinir, a new oral cephalosporin, and cefaclor against Streptococcus pneumoniae and beta-lactamase-producing strains of Haemophilus influenzae. These frequently encountered pathogens of community-acquired respiratory tract infections are usually susceptible to both drugs. The MIC ranges for cefdinir and cefaclor were, respectively, 0.03 to 0.06 and 0.25 to 0.5 micrograms/ml for S. pneumoniae and 0.25 and 4 to 8 micrograms/ml for H. influenzae. The colony counts (CFU per milliliter) measured after 6 h of exposure to a range of antibiotic concentrations in broth were plotted against the colony count of the control culture over the same period of time. Higher kill rates versus bacterial growth rates were noted for S. pneumoniae for both drugs (positive balance). Conversely, lower kill rates versus growth rates were noted for H. influenzae for both drugs (negative balance). In conclusion, the bactericidal activities of both drugs against S. pneumoniae and H. influenzae were similar when expressed by the relationship between the growth rate and the kill rate at 6 h, but cefdinir was more active at lower concentrations.     

Treatment of experimental pneumonia due to penicillin-resistant Streptococcus pneumoniae in immunocompetent rats.

A model of pneumonia due to Streptococcus pneumoniae resistant to penicillin was developed in immunocompetent Wistar rats and was used to evaluate the efficacies of different doses of penicillin, cefotaxime, cefpirome, and vancomycin. Adult Wistar rats were challenged by intratracheal inoculation with 3 x 10(9) CFU of one strain of S. pneumoniae resistant to penicillin (MICs of penicillin, cefotaxime, cefpirome, and vancomycin, 2, 1, 0.5, and 0.5 microg/ml, respectively) suspended in brain heart broth supplemented with 0.7% agar. The rats experienced a fatal pneumonia, dying within 5 days and with peak mortality (70 to 80%) occurring 48 to 72 h after infection, and the bacterial counts in the lungs persisted from 8.87 +/- 0.3 log10 CFU/g of lung at 24 h of the infection to 9.1 +/- 0.3 log10 CFU/g at 72 h. Four hours after infection the animals were randomized into the following treatment groups: (i) control without treatment, (ii) penicillin G at 100,000 IU/kg of body weight every 2 h, (iii) penicillin G at 250,000 IU/kg every 2 h, (iv) cefotaxime at 100 mg/kg every 2 h, (v) cefpirome at 200 mg/kg every 2 h, and (vi) vancomycin at 50 mg/kg every 8 h. Two different protocols were used for the therapeutic efficacy studies: four doses of beta-lactams and one dose of vancomycin or eight doses of beta-lactams and two doses of vancomycin. Results of the therapy for experimental pneumonia caused by penicillin-resistant S. pneumoniae showed that initially, all the antimicrobial agents tested had similar efficacies, but when we prolonged the treatment, higher doses of penicillin, cefotaxime, and cefpirome were more effective than penicillin at lower doses in decreasing the residual bacterial titers in the lungs. Also, when we extended the treatment, vancomycin was more efficacious than penicillin at lower doses but was less efficacious than higher doses of penicillin or cefpirome. The model that we have developed is simple and amenable for inducing pneumonia in immunocompetent rats and could be used to explore the pathophysiology and to evaluate optimal therapy of this infection in the immunocompetent host.     

Treatment of experimental endocarditis due to penicillin-resistant Streptococcus pneumoniae.

Using two strains of pneumococci for which MICs of penicillin were 1 and 4 micrograms/ml, those of cefotaxime were 0.01 and 0.5 micrograms/ml, and those of teicoplanin were 0.01 and 0.1 micrograms/ml, we studied the efficacy of different dosages of penicillin, cefotaxime, and teicoplanin in the treatment of experimental pneumococcal endocarditis in rabbits. Animals treated with dosages of penicillin G procaine needed to achieve levels in serum near the MIC for pneumococci showed a significant reduction in log10 CFU per gram of vegetation, as compared with the control (P < 0.001), although only 20% of the animals showed sterile vegetations. When levels of penicillin in serum were in the range of three- to fourfold the MIC, a greater reduction in log10 CFU per gram of vegetation was seen, and 88% of the animals showed sterile vegetations. Only the regimen of penicillin that provided concentrations in serum above the MIC throughout the interval between two doses provided constant sterilization of the cardiac vegetations. Dosages of cefotaxime and teicoplanin selected to achieve concentrations in serum equivalent to that obtained in humans during treatment resulted in levels of antimicrobial agents in serum hundreds or thousands of times higher than the MICs for the infecting strains. In terms of antimicrobial efficacy, cefotaxime and teicoplanin were equivalent to regimens with high dosages of penicillin.     

Activity of gemifloxacin against Streptococcus pneumoniae and Haemophilus influenzae

This review focuses on the activity of gemifloxacin, a new respiratory fluoroquinolone, against the two most important bacterial pathogens associated with lower respiratory tract infections, namely Streptococcus pneumoniae and Haemophilus influenzae.     

Trovafloxacin in treatment of rabbits with experimental meningitis caused by high-level penicillin-resistant Streptococcus pneumoniae.

The fluoroquinolone trovafloxacin was bactericidal (0.47 +/- 0.23 delta log10 CFU/ml x h after 10 mg/kg of body weight and 0.78 +/- 0.15 delta log10 CFU/ml x h after 30 mg/kg) in the treatment of experimental meningitis caused by a highly penicillin-resistant (MIC and minimum bactericidal concentration = 4 and 4 microg/ml) strain of Streptococcus pneumoniae. Combinations with ampicillin and rifampin were indifferent compared to single drugs.     

儿童社区获得性呼吸道感染的肺炎链球菌和流感嗜血杆菌耐药性监测

目的监测2000-2004年连续5年5岁以下呼吸道感染患儿鼻咽拭子分离的肺炎链球菌和流感嗜血杆菌对抗菌药物的耐药性.方法采用E试验和K-B纸片法对临床分离541株肺炎链球菌、521株流感嗜血杆菌进行抗菌药物耐药性测定.结果肺炎链球菌对青霉素不敏感率由2000年的22%增加到2004年的32.9%,P＜0.05;对头孢呋辛和头孢克洛不敏感率由7%增加到25%左右,P＜0.01;对红霉素不敏感率由88%增加到94.3%,P＞0.05;对四环素和复方磺胺甲噁唑不敏感率分别为90%以上和80%以上.流感嗜血杆菌对氨苄西林耐药率和产β内酰胺酶率由2000年的5.0%增加到2004年的14.3%,P＜0.05;对阿莫西林-克拉维酸、头孢曲松和头孢呋辛非常敏感;对头孢克洛不敏感率由2%增加到14.3%,P＜0.01.结论肺炎链球菌对青霉素不敏感率和流感嗜血杆菌对氨苄西林耐药率和产β内酰胺酶率呈明显上升趋势.     

Antimicrobial resistance among respiratory isolates of Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae in the United States.

A national surveillance study was conducted to determine trends in antimicrobial resistance patterns among three common causes of community-acquired respiratory tract infections. Fifteen participating U.S. medical centers submitted clinically significant isolates of Haemophilus influenzae, Moraxella (Branhamella) catarrhalis, and Streptococcus pneumoniae to two central laboratories for testing with a group of 12 antimicrobial agents. The majority of isolates were recovered from adult males greater than 50 years old. Overall, 84.1% of 378 M. catarrhalis and 16.5% of 564 H. influenzae (29.5% of type b strains; 15.0% of non-type b strains) produced beta-lactamase and were thus resistant to penicillin, ampicillin, and amoxicillin. Resistance in H. influenzae to other agents was 2.1% to tetracycline, 0.7% to trimethoprim-sulfamethoxazole, 1.1% to cefaclor, and 0.2% to cefuroxime and amoxicillin-clavulanate, while the M. catarrhalis isolates yielded very low MICs of these latter drugs. As demonstrated in prior studies, erythromycin showed little activity against H. influenzae. Of 487 S. pneumoniae isolates, 1 (0.2%) was penicillin resistant, while 3.8% were relatively resistant to penicillin, 4.5% were resistant to trimethoprim-sulfamethoxazole, 2.3% were resistant to tetracycline, 1.2% were resistant to chloramphenicol, and 0.2% were resistant to erythromycin. Overall, the lowest resistance rates for these common bacterial respiratory pathogens were noted with amoxicillin-clavulanate, cefuroxime, and cefaclor.     

Beta-lactamase-producing nontypeable Haemophilus influenzae fails to protect Streptococcus pneumoniae from amoxicillin during experimental acute otitis media

Acute otitis media (AOM) is the most common reason for outpatient antimicrobial therapy. Mixed infections pose a potential problem, since the first-line drug used for the treatment of AOM, amoxicillin, can be neutralized by beta-lactamase-producing pathogens of the upper respiratory tract. To study the effects of a 5-day course of amoxicillin on a mixed middle ear infection, rats were challenged with Streptococcus pneumoniae alone or in combination with beta-lactamase-producing nontypeable Haemophilus influenzae. Amoxicillin was introduced at the clinical peak of the infection. Local and systemic changes were monitored by otomicroscopy, bacterial culture, and analysis of histological changes and the expression of the transforming growth factor beta (TGF-beta) gene. beta-Lactamase-producing H. influenzae did not demonstrate an ability to protect S. pneumoniae. Amoxicillin eradicated the pneumococci in all treated animals but increased to some degree the ability of H. influenzae to persist at the site of infection. Thus, only an insignificant acceleration of the resolution of the AOM caused by a mixture of pathogens was observed during treatment. Moderate to major morphological changes could not be avoided by treatment of the mixed infections, but a slight downregulation of TGF-beta expression was observed. In contrast to infections caused by a single pathogen, the mixed infections induced white plaques in the tympanic membrane at a remarkably high frequency independent of treatment. These experimental findings constitute support for further studies of antimicrobial drugs and AOM caused by bacteria with and without mechanisms of antibiotic resistance.     

Pharmacokinetics and bacteriological efficacy of cefoperazone, ceftriaxone, and moxalactam in experimental Streptococcus pneumoniae and Haemophilus influenzae meningitis.

The pharmacokinetics and bacteriological efficacy of cefoperazone, cefuroxime, ceftriaxone, and moxalactam were evaluated in the experimental rabbit meningitis model of Haemophilus influenzae type b or Streptococcus pneumoniae infection. The cerebrospinal fluid penetration of these beta-lactam antibiotics was from 3 to 14% and was greater in Haemophilus-infected that in pneumococcus-infected animals. With the exception of moxalactam, the antibacterial activity in cerebrospinal fluid and change in concentration of bacteria during therapy with the test drugs were comparable to those of penicillin G in pneumococcal infection. In animals infected with H. influenzae, cefoperazone, moxalactam, and ceftriaxone were as effective as chloramphenicol in reducing the bacterial counts in cerebrospinal fluid. Moxalactam and ceftriaxone produced the largest cerebrospinal fluid bactericidal titers against this beta-lactamase-producing strain of Haemophilus. On the basis of these data, it was concluded that ceftriaxone and cefoperazone were effective against both pathogens in this meningitis model, whereas moxalactam was effective against only Haemophilus, and cefuroxime was effective against only S. pneumoniae.     

CP-45,899 in combination with penicillin or ampicillin against penicillin-resistant Staphylococcus, Haemophilus influenzae, and Bacteroides.

CP-45,899 is a new, semisynthetic beta-lactamase inhibitor. When tested alone, CP-45,899 displayed only weak antibacterial activity, with the notable exception of its potent action against penicillin-susceptible and -resistant Neisseria gonorrhoeae. A combination of 3.12 microgram of CP-45,899 per ml with 3.12 microgram of ampicillin per ml, tested in broth cultures, inhibited ca. 90% of resistant Staphylococcus and Haemophilus influenzae strains; similar data were obtained in a variety of media. The same combination of CP-45,899 with ampicillin or penicillin G inhibited 90% of Bacteroides fragilis as interpreted from agar dilution minimal inhibitory concentrations. Inhibitory concentrations of CP-45,899-ampicillin were bactericidal against H. influenzae strains and were as bactericidal as nafcillin or cephalothin against S. aureus. Ampicillin-resistant S. aureus, H. influenzae, and B. fragilis strains did not develop resistance to CP-45,899-ampicillin when transferred as many as six passages in the presence of a sublethal concentration of the combination.     

肺炎链球菌、流感嗜血杆菌、卡他莫拉菌的耐药性分析

目的　检测肺炎链球菌、流感嗜血杆菌和卡他莫拉菌的耐药性。方法　标本分别接种羊血平板和巧克力平板 ,用标准方法进行菌种鉴定 ;用微量肉汤稀释法分别测定其最低抑菌浓度。结果　青霉素不敏感肺炎链球菌占 2 5 .6 % ,左氧氟沙星、万古霉素和β 内酰胺类抗生素对肺炎链球菌有很高的抗菌活性 ,大环内酯类和复方磺胺甲唑耐药率较高 ;流感嗜血杆菌和卡他莫拉菌的产 β 内酰胺酶率分别为 32 .7%、91.3% ;头孢菌素对这3种细菌都有较高的抗菌活性。结论　头孢菌素是治疗 3种细菌感染的首选药物。     

Pharmacokinetics and bacteriological effect of ceftazidime in experimental Streptococcus pneumoniae, Haemophilus influenzae, and Escherichia coli meningitis

The pharmacokinetics and bacteriological effect of ceftazidime were evaluated in rabbits experimentally infected with Streptococcus pneumoniae, Haemophilus influenzae type b, and Escherichia coli K1. The mean penetration of ceftazidime into cerebrospinal fluid after single-dose or constant-infusion administration ranged from 7.8 to 14.9%. The median cerebrospinal fluid bactericidal titers were 1:64 against S. pneumoniae and H. influenzae and 1:128 against E. coli. The bacterial colony counts in cerebrospinal fluid were reduced by 58% to 100% (-2.3 to -3.9 log10 CFU/ml) in 3 h and by 100% (-3.2 to -5.1 log10 CFU/ml) in 9 h of constant infusion, whereas in untreated infected animals, bacterial counts increased from +1.4 to +2.1 log10 CFU/ml in 9 h. These data on ceftazidime compare favorably with those on penicillin, chloramphenicol, netilmicin, and moxalactam in this experimental meningitis model.     

In vitro activity of cefditoren and other comparators against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis causing community-acquired respiratory tract infections in China

The aim of this study was to evaluate the in vitro activity of cefditoren and comparators against Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis causing community-acquired respiratory tract infections (CARTIs). A total of 391 Streptococcus pneumoniae, 266 H. influenzae, and 76 M. catarrhalis were isolated from 10 centers located at 6 cities in China from January 2009 to May 2010. The microdilution method was used to determine minimum inhibitory concentrations (MICs). The pneumococci comprised 189 (48.3%) penicillin susceptible, 129 (33.0%) penicillin intermediate, and 73 (18.7%) penicillin resistant. Moxifloxacin and levofloxacin showed the highest activity (99.2% and 97.7%, respectively) against Streptococcus pneumoniae, followed by parenteral penicillin G (95.7%), cefditoren (83.1%) and amoxicillin-clavulanic acid (79.3%). Among the 266 H. influenzae isolates, 26 (9.8%) were ampicillin-resistant β-lactamase-producing strains and 24 (9.0%) were ampicillin-resistant β-lactamase-nonproducing strains (BLNAR). Most of antimicrobial agents demonstrated good activity (>97% susceptibility) against H. influenzae except ampicillin, cefuroxime, and cefaclor, which showed relatively lower activity (81.2%, 88.7%, and 88%, respectively). Cefditoren showed excellent activity with the lowest MIC(50) and MIC(90) (≤0.016/0.064 μg/mL) among all tested drugs, which is independent of β-lactamase production or ampicillin resistance. Cefditoren at a concentration of 0.5 μg/mL inhibited all BLNAR strains. Seventy of 76 isolates of M. catarrhalis produced β-lactamase. Cefditoren also showed excellent activity with MIC(90) of 0.064 μg/mL against β-lactamase-nonproducing strains and 0.5 μg/mL against β-lactamase-producing strains. In conclusion, the excellent intrinsic activity of cefditoren suggests that it may be a good choice for the treatment of CARTIs caused by Streptococcus pneumoniae, H. influenzae, and M. catarrhalis in China, while the activity should be closely monitored.     

Comparison of Streptococcus pneumoniae and Haemophilus influenzae susceptibilities from community-acquired respiratory tract infections and hospitalized patients with pneumonia: five-year results for the SENTRY Antimicrobial Surveillance Program

The SENTRY Antimicrobial Surveillance Program has been monitoring the activity of commonly prescribed and novel antimicrobial agents on a global scale from 1997 to the present. Specific objectives have documented the key resistance rates among pathogens from both patients hospitalized with pneumonia and those diagnosed with community-acquired pneumonia. Hemophilus influenzae and Streptococcus pneumoniae are common pathogens in both of these patient populations and the susceptibility profiles for these two species were compared to distinguish potential differences that may be evident in North American surveillance (1997-2001). A total of 6,515 isolates of S. pneumoniae and 6,726 H. influenzae strains were tested using reference broth microdilution methods at a monitoring center. Ampicillin resistance was approximately 25% among H. influenzae isolates and did not significantly differ between strains from community-acquired infections or hospitalized patients. beta-lactamase-negative ampicillin resistant strains and fluoroquinolone refractory strains were rare (0.3 and 相似文献   

Genetic characteristics of Haemophilus influenzae and Streptococcus pneumoniae isolated from children with conjunctivitis-otitis media syndrome

Acute conjunctivitis is the most common ocular disorders among children and frequently concomitant with acute otitis media (AOM) as conjunctivitis-otitis syndrome. In this study, we evaluated prevalence of causative pathogens and PCR-based genotypes of Haemophilus influenzae and Streptococcus pneumoniae among children with conjunctivitis-otitis media syndrome. Nontypeable H. influenzae (NTHi) is identified most often at 61.8% in conjunctiva exudates followed by S. pneumoniae at 28.2% and Moraxella catarrhalis at 19.1%. Genetic β-lactamase nonproducing ampicillin resistant (gBLNAR) strains of NTHi and genetic penicillin resistant S. pneumoniae (gPRSP) were identified at 72.1% and at 74.2% among conjunctiva isolates by polymerase chain reaction (PCR), respectively. Pneumococcal strains having either ermB or mefE genes were identified at 93.5% among conjunctiva isolates. The restriction fragment of patterns of 89.7% pairs of H. influenzae isolates and 100% pairs of pneumococcal isolates from conjunctiva exudates, middle ear fluids (MEFs) and nasopharyngeal swabs were identical.In contrast to the previous reports, most prevalent strains from conjunctivitis-otitis media syndrome was BLNAR H. influenzae in this study. The causative pathogen responsible for acute conjunctivitis will be originated from the nasopharynx. In the absence of MEFs one can possibly rely on the nasopharyngeal culture to guide an appropriate treatment.     

Postantibiotic Effects of ABT-773 and Amoxicillin-Clavulanate against Streptococcus pneumoniae and Haemophilus influenzae

This study determined the postantibiotic effect (PAE) of ABT-773 versus that of amoxicillin-clavulanate against clinical isolates of Streptococcus pneumoniae and Haemophilus influenzae. The PAEs of ABT-773 and amoxicillin-clavulanate ranged from 2.3 to 6.0 h and 0 to 2.2 h against S. pneumoniae and from 2.7 to 9.1 h and 0 to 0.8 h against H. influenzae, respectively.