Activity of cefditoren against beta-lactamase-positive and -negative Haemophilus influenzae and Moraxella catarrhalis

Cefditoren is a novel broad-spectrum oral cephalosporin. To determine the influence of beta-lactamase production on cefditoren activity, 1,170 H. influenzae and 641 M. catarrhalis isolated during 2000 were tested by NCCLS broth microdilution methodology (M7-A5, 2000). Against H. influenzae the potency of cefditoren (MIC(90,) 0.015 microg/mL) was similar to that of ceftriaxone (MIC(90,) < or = 0.015 microg/mL) and levofloxacin (MIC(90,) 0.015 microg/mL), and its MIC distribution was unaffected by beta-lactamase production. In comparison, the beta-lactamase status of M. catarrhalis affected the potency of all beta-lactams tested, including cefditoren, as well as trimethoprim-sulfamethoxazole. However, regardless of the presence of beta-lactamase, cefditoren demonstrated potent activity, as concentrations of 0.5 and 1 microg/mL inhibited 93.1 and 100% of M. catarrhalis isolates, respectively. We conclude that cefditoren is highly active in vitro against beta-lactamase-positive H. influenzae and M. catarrhalis.     

Antimicrobial resistance in Haemophilus influenzae and Moraxella catarrhalis respiratory tract isolates: results of the Canadian Respiratory Organism Susceptibility Study, 1997 to 2002

A total of 7,566 unique patient isolates of Haemophilus influenzae and 2,314 unique patient isolates of Moraxella catarrhalis were collected between October 1997 and June 2002 from 25 medical centers in 9 of the 10 Canadian provinces. Among the 7,566 H. influenzae isolates, 22.5% produced beta-lactamase, while 92.4% of the 2,314 M. catarrhalis isolates produced beta-lactamase. The incidence of beta-lactamase-producing H. influenzae isolates decreased significantly over the 5-year study period, from 24.2% in 1997-1998 to 18.6% in 2001-2002 (P < 0.01). The incidence of beta-lactamase-producing M. catarrhalis isolates did not change over the study period. The overall rates of resistance to amoxicillin and amoxicillin-clavulanate for H. influenzae were 19.3 and 0.1%, respectively. The rank order of cephalosporin activity based on the MICs at which 90% of isolates were inhibited (MIC(90)s) was cefotaxime > cefixime > cefuroxime > cefprozil > cefaclor. On the basis of the MICs, azithromycin was more active than clarithromycin (14-OH clarithromycin was not tested); however, on the basis of the NCCLS breakpoints, resistance rates were 2.1 and 1.6%, respectively. Rates of resistance to other agents were as follows: doxycycline, 1.5%; trimethoprim-sulfamethoxazole, 14.2%; and chloramphenicol, 0.2%. All fluoroquinolones tested, including the investigational fluoroquinolones BMS284756 (garenoxacin) and ABT-492, displayed potent activities against H. influenzae, with MIC(90)s of < or = 0.03 microg/ml. The MIC(90)s of the investigational ketolides telithromycin and ABT-773 were 2 and 4 microg/ml, respectively, and the MIC(90) of the investigational glycylcycline GAR-936 (tigecycline) was 4 microg/ml. Among the M. catarrhalis isolates tested, the resistance rates derived by using the NCCLS breakpoint criteria for H. influenzae were <1% for all antibiotics tested except trimethoprim-sulfamethoxazole (1.5%). In summary, the incidence of beta-lactamase-positive H. influenzae strains in Canada is decreasing (18.6% in 2001-2002), while the incidence of beta-lactamase-positive M. catarrhalis strains has remained constant (90.0% in 2001-2002).     

Antibiotic resistance in respiratory tract isolates of Haemophilus influenzae and Moraxella catarrhalis collected from across Canada in 1997-1998

Between September 1997 and November 1998 respiratory tract isolates of Haemophilus influenzae (n = 1352) and Moraxella catarrhalis (n = 428) were collected by 18 Canadian medical centres. beta-Lactamase was produced by 24.0 and 94.2% of H. influenzae and M. catarrhalis isolates, respectively. Resistance rates for H. influenzae were highest for ampicillin (24.0%), trimethoprim/sulphamethoxazole (13. 7%), loracarbef (6.1%) and cefaclor (4.2%), and 相似文献   

Antimicrobial susceptibility of Haemophilus influenzae isolates collected from 4 centers in Brazil (1990-2003)

Antimicrobial susceptibility was determined for 174 Haemophilus influenzae strains collected from patients with infection before and after vaccination against Hib (1990-1999 and 2000-2003, respectively) from 4 public health -laboratories in 3 Brazilian states. All strains were characterized for serotype and beta-lactamase production and in vitro activity of the following antimicrobial agents: -ampicillin, amoxicillin/clavulanate, ceftriaxone, rifampin, chloramphenicol, and trimethoprim/sulfamethoxazole (TMP-SMX). Minimum inhibitory concentrations were determined according to the guidelines of the National Committee for Clinical Laboratory Standards. Overall, ampicillin resistance was observed in 29 strains (17%), all beta-lactamase producers. All isolates were susceptible to amoxicillin/clavulanate and ceftriaxone. The prevalence of TMP-SMX-resistant isolates increased from 32.6% in the period 1990-1999 to 65.8% during the period 2000-2003. Among these isolates, 10.0% and 12.5% were resistant to ampicillin and chloramphenicol, respectively. Resistance to rifampin was detected in 8.2% and 9.7% of the strains, in 2 periods, respectively. Continued surveillance is necessary to monitor trends with the H. influenzae disease in Brazil.     

Antimicrobial susceptibilities of 1,730 Haemophilus influenzae respiratory tract isolates in Spain in 1998-1999

A beta-lactamase prevalence of 23% was found among 1,730 Haemophilus influenzae isolates. Ampicillin susceptibility was 70%, and 12% of beta-lactamase-negative strains presented diminished susceptibility to ampicillin (BLNAR phenotype). Susceptibility of 90% was found for cefaclor and clarithromycin, whereas it was nearly 100% for cefotaxime, cefixime, azithromycin, and cefuroxime. Ciprofloxacin-resistant (0.1%) and beta-lactamase-positive amoxicillin/clavulanate-resistant (BLPACR) phenotypes (0.1%) are anecdotal so far.     

Susceptibility of Pneumococci and Haemophilus influenzae to Antibacterial Agents

Strains of Diplococcus pneumoniae and Haemophilus influenzae were tested for susceptibility to numerous antibiotics by a twofold agar dilution method using an inocula replicator. Undiluted, fully grown broth cultures were used as inocula for both species, and cultures of pneumococci diluted 1:1,000 were also tested. The antibiotics included most of those in common use in the United States as well as some chemical modifications recently approved and others that are under investigation. The most striking aspect of the results was the marked susceptibility of the pneumococci to all the antibiotics tested except the polymyxins and most of the aminoglycoside antibiotics, although some new aminoglycosides were active in quite low concentrations. Some of the strains of pneumococci were of decreased susceptibility to penicillin G (minimal inhibitory concentrations, 0.2 to 0.4 mug/ml), but none were tetracycline resistant, although such strains had been reported previously from this laboratory. The strains of H. influenzae, which were all serologically nontypable, exhibited different patterns of susceptibility to the groups of antibiotics and to the individual chemically related ones. None of these strains (isolated early in 1972) were ampicillin resistant. The most active agents against H. influenzae were: carbenicillin and ampicillin, analogues related to each of them, rifampin, chloramphenicol, and the polymyxins. However, the tetracycline analogues other than tetracycline, some aminoglycosides, notably tobramycin, kanamycin, gentamicin, and verdamicin, erythromycin, and some new lincomycin analogues were also active in low concentrations. Trimethoprim alone was highly active, and in combination with sulfamethoxazole it was even more active and synergistic against strains of both D. pneumoniae and H. influenzae.     

儿童感染流感嗜血杆菌的耐药性分析

目的：了解苏州地区儿童感染流感嗜血杆菌(Hi)的耐药情况及β内酰胺酶的检出率，以指导临床合理用药。方法：对160株分离自儿童患者的Hi用K—B法进行药敏试验，头孢硝噻吩显色法进行β内酰胺酶测定。结果：本地区儿童感染的Hi对氨苄西林、复方磺胺甲噁唑、四环素、氯霉素、红霉素、头孢克洛和环丙沙星的耐药率分别为15．6％、53．8％、34．4％、14．4％、2．5％、1．3％和0．6％；β内酰胺酶的检出率为16．3％，无明确β内酰胺酶阴性耐氨苄西林Hi(BLNAR)发现。结论：本地区儿童感染Hi的耐药情况不容乐观，且多重耐药的菌株较多，并有对头孢克洛的耐药趋势，临床医师对此应予重视。头孢曲松、环丙沙星和阿奇霉素对该菌的抗菌活性较高，可供临床选用。     

Contribution of beta-lactamase and PBP amino acid substitutions to amoxicillin/clavulanate resistance in beta-lactamase-positive, amoxicillin/clavulanate-resistant Haemophilus influenzae

The roles of beta-lactamase and alterations in penicillin-binding protein in the development of amoxicillin and amoxicillin/clavulanate resistance in two beta-lactamase-positive, amoxicillin/clavulanate-resistant (BLPACR) strains of Haemophilus influenzae were investigated. Seven beta-lactamase-negative, ampicillin-resistant (BLNAR) strains were also studied for comparison of their resistance mechanisms. All strains had been recovered from patients in Japan. The TEM type beta-lactamase of the two BLPACR strains had 100% homology with the amino acid sequences of published TEM-1 beta-lactamase, showing that amoxicillin/clavulanate resistance was not associated with mutations in this beta-lactamase. However, these strains, as well as the seven BLNAR strains, had multiple mutations in ftsI, which encodes penicillin binding protein 3 (PBP3). The transformation of H. influenzae Rd strain with amplified ftsI genes from two BLPACR and two BLNAR strains enabled the selection of amoxicillin/clavulanate-resistant transformants with the same mutations as their parent strains. We concluded that amoxicillin/clavulanate resistance in the two BLPACR strains was due to changes in PBP3. The possibility of the presence of an extended spectrum beta-lactamase was excluded in the BLPACR strains studied.     

Manner and Meaning of Susceptibility Testing of Ampicillin-Resistant Haemophilus influenzae

We examined ampicillin-resistant strains of Haemophilus influenzae to compare the percentage of resistant organisms in each strain with the susceptibility to ampicillin by an agar dilution method. Using an inoculum of 10(4) colony-forming units, the minimal inhibitory concentration (MIC) increased with the percentage of resistant organisms in the strain. Laboratory-manipulated strains composed of different proportions of a susceptible and a resistant strain behaved similarly. The survival of isolated colony-forming units (colony MIC) was then determined by spreading inocula over the surface of a set of MIC plates, resulting in separation of individual colonies. This modification of the susceptibility test to the colony level gave end points that were clear and reproducible and that did not vary with changes in incubation time or temperature. True differences in susceptibility among strains were demonstrated by this method, whereas results of the conventional MIC test may reflect only the number of resistant organisms present in the inoculum.     

Susceptibility studies of multiply resistant Haemophilus influenzae isolated from pediatric patients and contacts

From February 1981 to December 1983, 225 strains were isolated from pediatric patients infected with Haemophilus influenzae. Forty-one strains were found to be resistant to ampicillin, chloramphenicol, and other antibiotics. They were isolated from 20 patients with invasive diseases (meningitis, 16; bacteremia, 4) and 21 with noninvasive diseases (otitis media, 19; conjunctivitis, 2). During this period, 44 patients with invasive diseases were seen (meningitis, 28; bacteremia, 16). Strains resistant to both ampicillin and chloramphenicol occurred in 45.4% of cerebrospinal fluid and blood isolates and in 51% of cerebrospinal fluid isolates only. In this group, individual resistance to ampicillin was 50%; chloramphenicol, 52.2%; tetracycline, 54.5%; and sulfamethoxazole-trimethoprim, 63.6%. No epidemiological relationship could be found among the patients. The presence of asymptomatic carriers was investigated in two nurseries and in eight family groups. From a total of 125 individuals studied, 80 were found to be colonized by H. influenzae, and 36 carried multiply resistant strains. From patients and carriers, 77 strains were found to be resistant to ampicillin, chloramphenicol, and other drugs; 39 belonged to type b (cerebrospinal fluid, 16; blood, 4; ear, 7; and nasopharynx, 12), and 38 were non-type b. The most frequent pattern of resistance was ampicillin-chloramphenicol-tetracycline-sulfamethoxazole-trimethoprim (94.8%), followed by ampicillin-chloramphenicol-tetracycline (3.9%). The disk diffusion method correctly predicted multiple resistance. The mean inhibition zone diameters were: ampicillin, 12.8 mm; chloramphenicol, 15.2 mm; tetracycline, 9.9 mm; and sulfamethoxazole-trimethoprim, 10.8 mm. These resistant strains were susceptible to cefotaxime, moxalactam, cefoperazone, cefuroxime, rifampin, and gentamicin. Our data suggest that in Spain the resistance of H. influenzae to ampicillin and chloramphenicol is endemic and that other effective therapeutic modalities are needed.     

Susceptibility of Haemophilus influenzae Type b to Rifampin and Sulfisoxazole

A total of 100 and 97% of Haemophilus influenzae type b strains from major infections were susceptible, respectively, to levels of rifampin and sulfisoxazole attainable in saliva. It is theoretically feasible to eliminate Haemophilus influenzae from the nasopharynx with these drugs.     

Susceptibility of Haemophilus influenzae to chloramphenicol and eight beta-lactam antibiotics

We examined the minimal inhibitory concentrations and minimal bactericidal concentrations of chloramphenicol, ampicillin, ticarcillin, cefamandole, cefazolin, cefoxitin, cefotaxime, ceforanide, and moxalactam for 100 isolates of Haemophilus influenzae, 25 of which produced beta-lactamase. Susceptibility was not influenced by the capsular characteristic of the organism. The mean minimal inhibitory concentrations of cefamandole, ticarcillin, and ampicillin for beta-lactamase-producing strains were 3-, 120-, and 400-fold higher than their respective mean minimal inhibitory concentrations for beta-lactamase-negative strains. No such difference was noted for the other antibiotics. We performed time-kill curve studies, using chloramphenicol, ampicillin, cefamandole, cefotaxime, and moxalactam with two concentrations of the antimicrobial agents (4 or 20 times the minimal inhibitory concentrations) and two inoculum sizes (10(4) or 10(6) colony-forming units per ml). The inoculum size had no appreciable effect on the rate of killing of beta-lactamase-negative strains. The rates at which beta-lactamase-producing strains were killed by chloramphenicol, cefotaxime, and moxalactam was not influenced by the inoculum size. Whereas cefamandole in high concentrations was able to kill at 10(6) colony-forming units/ml of inoculum, it had only a temporary inhibiting effect at low drug concentrations. Methicillin and the beta-lactamase inhibitor CP-45,899 were able to neutralize the inactivation of cefamandole by a large inoculum of beta-lactamase-producing H. influenzae.     

Resistance surveillance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in the United States, 1997-1998

A national antimicrobial resistance surveillance study was conducted from December 1997 to May 1998 to determine the prevalence of antimicrobial resistance in 6620 clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. In this centralized study, which involved 163 institutions located in 43 states, we determined MICs for representatives of five antimicrobial classes: beta-lactams (penicillin, co-amoxiclav, cefuroxime, ceftriaxone), macrolides (azithromycin, clarithromycin), co-trimoxazole, glycopeptides (vancomycin) and fluoroquinolones (levofloxacin). In most S. pneumoniae isolates, all antimicrobials were to be found active, but amongst penicillin-resistant isolates (MICs > or = 2 mg/L), resistance to other beta-lactams, macrolides and co-trimoxazole was common. For vancomycin and levofloxacin, however, activity was not associated with penicillin resistance. The prevalence of penicillin-nonsusceptible (intermediate and resistant) pneumococci was highest in the South Atlantic (44%) and East South Central (43%) regions and lowest in the Mid-Atlantic (28%) and New England (28%) regions. Resistance to beta-lactams, macrolides and co-trimoxazole was more commonly found amongst respiratory isolates than blood isolates and in strains from patients < or = 12 years old than from older patients. beta-lactamase, which was detected in 33% of H. influenzae and 92% of M. catarrhalis strains, did not affect the activity of the beta-lactams under study other than ampicillin. Certain agents, such as vancomycin and the fluoroquinolones, remain highly active, and well-designed surveillance systems that monitor MIC distributions would be needed to detect a potential for reduced susceptibility. In addition, surveillance programmes should be designed to collect information about associated resistance as well as differences in prevalence associated with region, specimen source and patient age.     

Resistance surveillance of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolated in Asia and Europe, 1997-1998

A multicentre, collaborative study was performed in Asia and Europe during the winter of 1997-1998 to determine the in vitro activity of selected antimicrobial agents against common respiratory pathogens. Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis isolates were collected from 48 sites in China, France, Germany, Italy, Japan, Spain and the UK and tested in a central laboratory in the USA. Broth microdilution MICs were determined for beta-lactams (penicillin, amoxycillin/clavulanate, cefuroxime, ceftriaxone), macrolides (azithromycin, clarithromycin), sulphonamides (co-trimoxazole), glycopeptides (vancomycin) and fluoroquinolones (levofloxacin). The percentage of isolates susceptible to each antimicrobial class varied substantially by country. Penicillin susceptibility amongst pneumococci ranged from 34% in France and Spain to 92% in Germany, and macrolide susceptibility varied between 26% in China and 91% in the UK. In most countries beta-lactam, macrolide and cotrimoxazole resistance was more prevalent amongst penicillin-intermediate and -resistant S. pneumoniae isolates. However, little or no resistance was detected to levofloxacin (0.3% intermediate and resistant) or vancomycin (0% intermediate and resistant). For H. influenzae the prevalence of beta-lactamase production varied from 6% in China and Germany to 32% in Spain, and for M. catarrhalis, from 79% in Germany to 98% in Japan. With the exception of ampicillin, beta-lactamase production had a minimal effect on beta-lactam activity against H. influenzae or M. catarrhalis. Our findings demonstrate that antimicrobial resistance profiles of common respiratory isolates differ dramatically between countries in Asia and Europe.     

High levels of multiple antibiotic resistance among 938 Haemophilus influenzae type b meningitis isolates from Cuba (1990-2002)

OBJECTIVES: A national surveillance study to determine antimicrobial susceptibility in Haemophilus influenzae type b isolated from cerebrospinal fluid was carried out in Cuba from 1990 to 2002. METHODS: Susceptibility to ampicillin, co-amoxiclav, cefotaxime, ceftriaxone, co-trimoxazole, tetracycline, chloramphenicol and rifampicin was tested by the microdilution method according to the NCCLS guidelines. RESULTS: The 34 participating laboratories recovered 938 consecutive, non-identical isolates. All the isolates were retrieved from children aged <5 years. The mean number of isolates collected by year in the pre-vaccination era (1990-1998) was 93; after vaccination, 57 isolates were reported in 1999, 31 in 2000, four in 2001 and five in 2002. Resistance to ampicillin, co-trimoxazole, tetracycline and chloramphenicol was 46.3% (all beta-lactamase-positive), 51.3%, 33.2% and 44.0%, respectively. Ampicillin-resistant beta-lactamase-negative strains were not detected. All strains were susceptible to co-amoxiclav, cefotaxime, ceftriaxone and rifampicin. Ampicillin resistance was strongly associated with resistance to tetracycline, co-trimoxazole and chloramphenicol (P<0.001). Multidrug resistance was present in 43.8% of isolates. The most prevalent phenotype was resistance to ampicillin/chloramphenicol/tetracycline/co-trimoxazole, which was detected in 29.2% of strains overall. An increase in the prevalence of resistance to these antibiotics was observed from 1990 to 2000 in the range 40.7%-54.8% for ampicillin, 40.1%-51.6% for chloramphenicol, 45.4%-58.1% for co-trimoxazole and 23%-45.2% for tetracycline. CONCLUSIONS: In Cuba, the widespread vaccination against Haemophilus influenzae type b prevented a large number of meningitis cases in children caused by strains resistant to multiple antibiotics.     

Amoxicillin-clavulanic acid in the treatment of lower respiratory tract infections caused by beta-lactamase-positive Haemophilus influenzae and Branhamella catarrhalis.

Twenty-one adult patients hospitalized with lower respiratory tract infections due to Branhamella catarrhalis or Haemophilus influenzae or both were treated with the combination of oral amoxicillin and potassium clavulanate (Augmentin) in an open, noncomparative clinical trial. Diseases included pneumonia, empyema, and exacerbations of bronchiectasis and chronic lung disease. Thirteen of 16 B. catarrhalis and six of nine H. influenzae isolates were beta-lactamase positive. The patients with B. catarrhalis were treated for a mean of 5.3 days, and those with H. influenzae were treated for a mean of 7.0 days. The overall response to therapy was excellent, with 18 of 19 beta-lactamase-producing strains eradicated on therapy. One patient secondarily infected with Pseudomonas aeruginosa was a clinical failure, and two patients with H. influenzae who became culture positive again after therapy were considered microbiologic failures. Gastrointestinal side effects (especially nausea) were common, although all patients completed a course of therapy. Sputum levels of amoxicillin were surprisingly low (less than 0.05 to 0.54 micrograms/ml), a finding which may explain the high relapse rate (22%) seen with H. influenzae, as these are below the usual MICs of amoxicillin for this organism. The combination of amoxicillin plus potassium clavulanate appears to be an excellent drug for treatment of beta-lactamase-producing strains of these two species, although mild gastrointestinal side effects are common.     

Antibiotic susceptibility of blood and cerebrospinal fluid isolates of Haemophilus influenzae

One hundred and sixty-nine blood and cerebrospinal fluid isolates of Haemophilus influenzae, collected in the Province of Ontario from children and adults from 1976 to 1983, were tested for susceptibility to six conventional and eight newer antibacterial drugs. Most active were ceftriaxone, ceftizoxime and cefotaxime (MIC90 less than or equal to 0.02 mg/l); latamoxef (moxalactam), acrosoxacin and ceftazidime were close behind with MIC90s in the 0.05-0.09 mg/l range. Twenty-five strains (14.8%) were beta-lactamase-producing and thus resistant to ampicillin. There were no chloramphenicol-resistant strains. The isolates showed intermediate but still clinically useful susceptibility to trimethoprim, rifampicin, cefuroxime, piperacillin and chloramphenicol and were least susceptible to gentamicin and sulphamethoxazole.     

Rapid Detection of Ampicillin-Resistant Haemophilus influenzae and Their Susceptibility to Sixteen Antibiotics

Ampicillin-resistant and -susceptible strains of Haemophilus influenzae were tested for susceptibility to 16 antibiotics. Chloramphenicol and a new cephalosporin, cefamandole, were most active with minimal inhibitory concentrations (MICs) for all bacteria tested between 0.5 to 2.0 μg/ml. All but two organisms were susceptible to tetracycline. Ampicillin-resistant strains of H. influenzae were less susceptible (MIC, 4 to 32 μg/ml) to carbenicillin and ticarcillin than ampicillin-susceptible organisms (MIC, 0.25 to 1.0 μg/ml). A rapid assay for β-lactamase, utilizing a chromogenic cephalosporin substrate, detected enzyme production in all 17 ampicillin-resistant strains of H. influenzae.