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PubMed2000

Benchmarking the in vitro activity of moxifloxacin against recent isolates of Streptococcus pneumoniae, Moraxella catarrhalis, and Haemophilus influenzae. A European multi-centre study.

To benchmark the activity of moxifloxacin, a European study comprising 900 Streptococcus pneumoniae, 1051 Haemophilus influenzae, and 226 Moraxella catarrhalis referred from 30 institutions during 1998 is described. For S. pneumoniae, moxifloxacin and trovafloxacin MIC(90) and modal MICs values were 0.12 microg/ml and independent of susceptibility to other drug classes, geography, or site of infection. MIC(90)/modal MICs were, respectively, 0.25/0.12 microg/ml for grepafloxacin, 0.25/0.25 microg/ml for sparfloxacin, and 1.0/0.5 microg/ml for levofloxacin. The moxifloxacin C(max):MIC ratio of 20.8-26.3 is higher than comparator fluoroquinolones. Five isolates were intermediate or resistant to grepafloxacin, sparfloxacin, or levofloxacin of which four and three remained susceptible to trovafloxacin and moxifloxacin, respectively. For moxifloxacin, > 90% of S. pneumoniae isolates demonstrated MICs > or =3 dilutions below the susceptibility breakpoint used. Modal MICs and MIC(90) for M. catarrhalis (both 0.03 microg/ml) and H. influenzae (0.03 microg/ml and 0.06 microg/ml) were independent of beta-lactamase production. These data demonstrate the in vitro activity of moxifloxacin and establish a baseline for future surveillance studies that will be important for detecting and tracking any trends in changing activity of this fluoroquinolone.

Anti-Infective Agents↗
PubMed2000

Antimicrobial activity and in vitro susceptibility test development for cefditoren against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus species.

Cefditoren, a third generation orally administered aminothiazolyl cephalosporin, has demonstrated bactericidal activity against many Gram positive and negative bacterial pathogens and stability against clinically important beta-lactamases. Cefditoren was compared to cefaclor, cefixime, and penicillins against 1 435 recently isolated strains of streptococci (312 Streptococcus pneumoniae, 165 viridans group streptococci, 142 beta-haemolytic streptococci), Haemophilus influenzae (521 strains), and Moraxella catarrhalis (295 strains). Streptococcus pneumoniae and viridans group streptococci had penicillin nonsusceptible rates of 37.8 and 35.8%, respectively. Cefditoren (MIC(90) in microg/ml/% susceptible) activity against all tested H. influenzae (0.03/100) and M. catarrhalis (0.06-0.5/100) was comparable to cefixime and significantly greater than cefaclor. Cefditoren (MIC(90), 0.5 microg/ml) was 4- to 128-fold more active than comparison beta-lactams against the pneumoococci and was the most potent beta-lactam (including penicillin) versus beta-haemolytic streptococci. Cefditoren pharmacokinetics demonstrate a T(1/2) of 1.5-2 h and C(max) values of 2.8 and 4.6 microg/ml, respectively with 200 or 400 mg doses of cefditoren pivoxil; plasma concentrations exceed 1 microg/ml for 4 to 6 hours (33-50% of dosing interval). Consequently, a susceptible MIC of </= 1 microg/ml or </= 2 microg/ml was proposed with zone diameter correlates of >/= 18 and >/= 15 mm (5-microg disk) for all cited fastidious species tested. Categorical agreement between MIC and disk tests was 94.6 to 100% with a correlation coefficient (r) range of 0.50 to 0.90 for streptococci. H. influenzae intermethod comparison results using the same interpretive criteria were in complete agreement, but exhibited a low r = 0.39. Cefditoren clearly possesses the most potent activity among currently studied oral cephalosporins or penicillin against commonly isolated bacterial pathogens causing bronchitis, pneumonia, sinusitis, or pharyngitis and was active against nearly all penicillin-resistant streptococci at </= 0.5 microg/ml. Expanded clinical investigations seem warranted.

Cefaclor↗
PubMed2001

Rapid discrimination between BRO beta-lactamases from clinical isolates of Moraxella catarrhalis using restriction endonuclease analysis.

An important feature of Moraxella catarrhalis is the production of beta-lactamases, which causes resistance to the penicillins. Restriction enzyme analysis was able to distinguish between the bro-1 and bro-2 beta-lactamase-encoding genes from 89 clinical isolates of M. catarrhalis. This is a rapid, simple and cost effective method of characterizing these genes.

Costs and Cost Analysis↗
PubMed2001

Activity of BMS284756 against 2,681 recent clinical isolates of Haemophilus influenzae and Moraxella catarrhalis: Report from The SENTRY Antimicrobial Surveillance Program (2000) in Europe, Canada and the United States.

Although the isolation and detection of fluoroquinolone-resistant Haemophilus influenzae and Moraxella catarrhalis has been a very rare occurrence, newer agents in the quinolone class must be evaluated to determine their comparative potencies and to develop in vitro testing methods. BMS284756 is an investigational desfluoro(6)-quinolone with a spectrum of activity most similar to recently introduced agents such as gatifloxacin and trovafloxacin. This compound was compared to levofloxacin, gatifloxacin, ciprofloxacin and moxifloxacin, as well as other orally administered antimicrobials against 1,872 H. influenzae and 810 M. catarrhalis isolates. Two Canadian H. influenzae strains had ciprofloxacin MICs elevated above the normal wild type susceptible MIC population (> 0.06 microg/mL). All other strains of H. influenzae and M catarrhalis were highly susceptible to the tested quinolones (MIC(90,) < or = 0.016 or 0.03 microg/mL). For the two H. influenzae isolates with elevated quinolone MICs the potency rank order was: gatifloxacin and BMS284756 (MICs, 0.25 and 1 microg/mL) > levofloxacin and moxifloxacin > ciprofloxacin (MICs, 0.5 and > 2 microg/mL). The comparison of Etest (AB BIODISK, Solna, Sweden) and disk diffusion results to the reference broth microdilution values produced acceptable intermethod accuracy when applied to BMS284756. This novel desfluoro compound possesses promising activity against fastidious Gram-negative respiratory tract pathogens and further clinical development is underway.

Anti-Infective Agents↗
PubMed2002

In vitro assessment of gatifloxacin spectrum and potency tested against Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pneumoniae isolates from the Asia-Western Pacific component of the SENTRY antimicrobial surveillance program (1998-1999).

Fluoroquinolones, especially the newer agents, have an increased role in the management of respiratory tract infections worldwide. In the SENTRY Antimicrobial Surveillance Program for the Asia-Pacific Region for 1998 and 1999, 630 Streptococcus pneumoniae, 583 Hemophilus influenzae and 274 Moraxella catarrhalis isolates were examined to determine the comparative activity of the new fluoroquinolone, gatifloxacin, compared with those of ciprofloxacin, levofloxacin and trovafloxacin. Gatifloxacin was highly active against all three species. Decreased susceptibility (MIC >/=2 microg/mL) to gatifloxacin was noted in only seven strains of S. pneumoniae (3 of which were resistant); in three strains of H. influenzae (MIC >/= 0.12 microg/mL), and 2 M. catarrhalis (MIC > 2 microg/mL).

Anti-Infective Agents↗
PubMed2003

Susceptibility trends of haemophilus influenzae and Moraxella catarrhalis against orally administered antimicrobial agents: five-year report from the SENTRY Antimicrobial Surveillance Program.

The assessment of orally administered antimicrobial susceptibilities of common pathogens that cause community-acquired respiratory tract infections (CARTI) has become exceedingly important due to the number of office visits for this indication. Numerous local, regional and global studies have documented the susceptibilities of Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis, the most common CARTI pathogens. SENTRY Antimicrobial Surveillance Program sites in North and Latin America, and Europe were requested to send a combined total of 100 isolates of these pathogens to the local monitor for reference broth microdilution testing (1997-2001). This study compared the susceptibility profiles of H. influenzae and M. catarrhalis isolates (13,370 strains) from the three geographic regions over a five year period. beta-lactamase mediated ampicillin resistance among H. influenzae was highest among North American isolates (27.9%) compared to Latin America and Europe (16.2 to 16.3%), although it was noted that during the five year study period, ampicillin resistance was steadily increasing in the latter two regions. Cefprozil (84.3% susceptible) and clarithromycin (81.1% susceptible) were also less active against North American H. influenzae isolates. Latin American isolates were much less susceptible to trimethoprim/sulfamethoxazole (T/S; 59.3%) compared to the other regions (75.8 to 78.6%). M. catarrhalis isolates were also significantly less susceptible to T/S in Latin America (10.5% resistance). The production of beta-lactamase enzymes among the M. catarrhalis isolates exceeded >95% in all three regions during the five year period. The fluoroquinolones (FQ) remained very active against these two respiratory pathogens with rare isolates with elevated FQ MIC results. It is apparent from this investigation that many commonly prescribed empiric treatments remain viable therapeutic options for CARTI caused by these two Gram-negative respiratory tract pathogens.

Administration, Oral↗
PubMed1996

In vitro activity of sanfetrinem (GV104326), a new trinem antimicrobial agent, versus Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

Sanfetrinem, formerly GV104326, is a new trinem antimicrobial agent with extensive in vitro activity for a variety of different bacteria. The activity of sanfetrinem was determined using a broth microdilution MIC method versus a large number of clinical isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis obtained in a recent 30-center United States surveillance study. The sanfetrinem MIC50 and MIC90 values for these three organism groups were 0.015 and 0.5 microgram/ml, 0.25, and 0.5 microgram/ml, and 0.015 and 0.03, respectively.

Anti-Bacterial Agents↗
PubMed1997

Surveillance of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis in the United States in 1996-1997 respiratory season. The Laboratory Investigator Group.

A U.S. surveillance study of antimicrobial resistance in respiratory tract pathogens in the respiratory season (1996-1997) is reported that included 11,368 isolates from 434 institutions in 45 states and the District of Columbia. beta-lactamase was produced by 33.4% of Haemophilus influenzae and 92.7% of Moraxella catarrhalis. Of the 9,190 Streptococcus pneumoniae isolates tested, 33.5% were not susceptible to penicillin (MIC > or = 0.12 microgram/mL), with 13.6% having high-level resistance (MICs > 1 microgram/mL). For H. influenzae, the most active antimicrobials (based on percent of strains susceptible) were levofloxacin (100%) and ceftriaxone (99.9%); the least active were ampicillin (67.2%) and clarithromycin (58.1%). For M. catarrhalis, the most active drugs were amoxicillin-clavulanate, ceftriaxone, and levofloxacin (100%); the least active was ampicillin. The order of the activity of the drugs against S. pneumoniae were levofloxacin (97.3%) > ceftriaxone (87.1%) > amoxicillin-clavulanate (81.7%) = clarithromycin (80.9%) > cefuroxime (74.5%) > penicillin (66.5%). The activity of the beta-lactams and clarithromycin against isolates of S. pneumoniae was closely associated with the resistance to penicillin. Levofloxacin was more active against S. pneumoniae overall, because it exhibited no cross-resistance. These data indicate that the incidence of beta-lactamase production in H. influenzae (33.4%) and M. catarrhalis (92.7%) is similar to other recent studies, and that the incidence of penicillin-intermediate and -resistant S. pneumoniae is increasing, particularly the high-level penicillin-resistant (MICs > 1 microgram/mL) strains, which were often multi-resistant.

Amoxicillin-Potassium Clavulanate Combination↗
PubMed1998

Comparative antimicrobial activity and kill-curve investigations of novel ketolide antimicrobial agents (HMR 3004 and HMR 3647) tested against Haemophilus influenzae and Moraxella catarrhalis strains.

The activity of two ketolide compounds, HMR 3004 and 3647, were compared to those of five macrolides, quinupristin/dalfopristin, ciprofloxacin, and ampicillin. The rate of killing for the ketolides was also assessed against Haemophilus influenzae and Moraxella catarrhalis. One hundred H. influenzae and 148 M. catarrhalis isolates were tested using broth microdilution and appropriate growth media. The killing rates of HMR 3004 and 3647 were analyzed using the time-kill method against five strains from each of the two species. Against H. influenzae, the activity of the ketolides (MIC90, 2 or 4 microg/mL) resembled that of azithromycin and quinupristin/dalfopristin and was more active than any tested macrolide. Against M. catarrhalis, HMR 3004 and 3647 were equally potent as azithromycin and clarithromycin (MIC50, 0.06 microg/mL and MIC90, 0.12 microg/mL) and more potent than all other macrolides or quinupristin/dalfopristin. Time-kill kinetic studies revealed that like the macrolide compounds, the ketolides are bacteristatic at or near the MIC for both H. influenzae and M. catarrhalis. This activity can be increased to a bactericidal level if the concentration is increased four- or eightfold the MIC for H. influenzae. In conclusion, HMR 3004 and 3647 have bacteristatic activity against tested respiratory pathogens and may prove to have an important role against macrolide-resistant isolates.

Anti-Bacterial Agents↗
PubMed1998

Fluoroquinolone-resistant Moraxella catarrhalis in a patient with pneumonia: report from the SENTRY Antimicrobial Surveillance Program (1998).

Fluoroquinolone resistance in Moraxella catarrhalis isolates has been quite rare. This report presents a case history of a 22-year-old man with compromised immune status and severe pneumonia caused by M. catarrhalis. The organism was markedly resistant (MICs, 1.5- > 32 micrograms/mL) to several marketed fluoroquinolones including the agent (levofloxacin) used for concurrent and prior therapy. The emergence of this problematic strain seems related to chronic exposure of the patient to compounds in the class and poor patient compliance to prescribed medications. The strain was not clonally related to other M. catarrhalis strains isolated in the same hospital during early 1998. This second documented case of a fluoroquinolone-resistant M. catarrhalis clinical isolate presents a warning that resistances can emerge in at-risk patients, and that surveillance systems (SENTRY) will be necessary to monitor for unusual organisms and spread of resistance phenotypes among commonly isolated respiratory tract pathogens.

Adult↗
PubMed1999

In vitro activity of the novel ketolide HMR 3647 and comparative oral antibiotics against Canadian respiratory tract isolates of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis.

The in vitro activities of HMR 3647, erythromycin A, clarithromycin, azithromycin, roxithromycin, penicillin G, ampicillin, cefuroxime, trimethoprim/sulfamethoxazole, tetracycline, ciprofloxacin, and levofloxacin were determined for 1179 Streptococcus pneumoniae, 1438 Haemophilus influenzae, and 428 Moraxella catarrhalis isolated from respiratory tract specimens by 18 medical centers across Canada during 1997-1998. On a per weight basis, HMR 3647 was the most active agent tested against S. pneumoniae with MIC90s of < or = 0.12 microgram/mL for both penicillin susceptible and penicillin intermediate isolates and 0.25 microgram/mL for penicillin-resistant isolates. HMR 3647 was also highly active against M. catarrhalis (MIC90, < or = 0.12 microgram/mL), but less active against H. influenzae (MIC90, 4 micrograms/mL).

Administration, Oral↗
PubMed1986

Moraxella septic arthritis of the knee joint: a case report.

Moraxella osloensis pyarthrosis of the knee joint is an unusual infection. The diagnosis can be quite difficult since the organism is fastidious in its growth characteristics. This case report presents an adult with M. osloensis sepsis of the knee, which could only be diagnosed by arthroscopic synovial biopsy and culture. Moreover, arthroscopy played a critical role in the definitive therapy.

Arthritis, Infectious↗
PubMed2001

Susceptibility of Canadian isolates of Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae to oral antimicrobial agents.

We measured the susceptibility of Canadian isolates of three respiratory tract pathogens (Haemophilus influenzae, Moraxella catarrhalis and Streptococcus pneumoniae) to several currently approved antimicrobial agents by two different methods. We also measured the susceptibility of isolates to seven fluoroquinolones. Beta-lactamase was produced by 123/566 (21.7%) of H. influenzae isolates compared with 178/200 (89%) of M. catarrhalis isolates. For S. pneumoniae 83/374 (22.2%) isolates were penicillin resistant and of these 2.1% (8/374) showed high level resistance (MIC > or = 2 mg/l). Regardless of methodology, all fluoroquinolones were highly active against H. influenzae (MIC(90) < or = 0.031 mg/l) and M. catarrhalis (MIC(90) < or = 0.064 mg/l) isolates. Susceptibility of H. influenzae to cefuroxime and amoxycillin/clavulanic acid was 99-100% whereas 84-85.5% were susceptible to cefaclor and cefprozil. Azithromycin susceptibility ranged from 82.6 to 99.2% depending on the method. M. catarrhalis isolates were uniformly susceptible to all agents tested except amoxycillin. Cross-resistance in S. pneumoniae to all non-quinolone agents was concurrent with increasing penicillin resistance as shown by increasing MIC90 values. For the fluoroquinolones tested, the rank order of potency based on MIC(90) values was as follows: gemifloxacin (0.031-0.063 mg/l), trovafloxacin (0.125 mg/l), moxifloxacin (0.125-0.25 mg/l), grepafloxacin (0.125-0.25 mg/l), gatifloxacin (0.5 mg/l), levofloxacin (1 mg/l) and ciprofloxacin (2 mg/l). Our study confirms either a high or increasing prevalence of antimicrobial resistant respiratory pathogens in Canada and also compares the new and old fluoroquinolones and their potential role as therapy for community-acquired infections. The prevalence of beta-lactamase positive H. influenzae may have decreased from levels reported in previous studies.

Administration, Oral↗
PubMed2002

Comparative in vitro activity of gemifloxacin to other fluoroquinolones and non-quinolone agents against Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis in the United States in 1999-2000.

This study was undertaken to assess the in vitro activity of gemifloxacin, five other fluoroquinolone antimicrobial agents (ciprofloxacin, gatifloxacin, levofloxacin, moxifloxacin and ofloxacin) and other non-quinolone comparator agents (ampicillin, erythromycin, clindamycin, doxycycline, penicillin and trimethoprim/sulphamethoxazole) against Streptococcus pneumoniae collected in the United States. Susceptibility testing of 550 S. pneumoniae, 290 Haemophilus influenzae and 205 Moraxella catarrhalis showed that 38.2% of pneumococci were penicillin nonsusceptible, while 26.2 and 95.6% of H. influenzae and M. catarrhalis, respectively, produced beta-lactamase. Overall new fluoroquinolones were the most active agents. The in vitro activity (based on MIC90 in mg/l) of the six fluoroquinolones was gemifloxacin>moxifloxacin>gatifloxacin>levofloxacin>ciprofloxacin and ofloxacin.

Adolescent↗
PubMed2002

Apparent plateau in beta-lactamase production among clinical isolates of Haemophilus influenzae and Moraxella catarrhalis in the United States: results from the LIBRA Surveillance initiative.

Haemophilus influenzae (n=2791) and Moraxella catarrhalis (n=1249) isolated from patient specimens during 1999 were collected from 290 laboratories participating in a moxifloxacin surveillance study as part of the LIBRA Surveillance initiative. Isolates were tested for in vitro susceptibility to a panel of agents suitable for the treatment of respiratory tract infections. beta-Lactamase production was identified in 32.2% of H. influenzae and 94.2% of M. catarrhalis. These percentages differed by less than 1.5% from results of a study conducted in 1997-1998 and were similar to results from other recent US surveillance studies. Resistance among H. influenzae to trimethoprim-sulphamethoxazole increased considerably, from 2% in the 1997-1998 study (n=6588 H. influenzae) to 15.5% in the current study. One isolate of H. influenzae had an MIC of 8 mg/l to both levofloxacin and moxifloxacin; all other isolates had MICs of < or =0.5 mg/l and < or =0.25 mg/l, respectively. beta-Lactamase production was found to confer ampicillin resistance in nearly all isolates. For M. catarrhalis, beta-lactamase-negative isolates had MICs < or =0.12-0.25 mg/l for ampicillin and < or =0.03-0.12 mg/l for ceftriaxone. In contrast, beta-lactamase production resulted in MICs of < or = 0.12->16 mg/l for ampicillin and < or = 0.03-4 mg/l for ceftriaxone. All M. catarrhalis had MICs < or =0.12 mg/l for moxifloxacin and < or =1 mg/l for levofloxacin. In summary, antimicrobial susceptibilities and the prevalence of beta-lactamase production in H. influenzae and M. catarrhalis in the United States has remained essentially unchanged from 1997-1998 to 1999.

Anti-Bacterial Agents↗
PubMed2002

Prevalence of antimicrobial resistance in Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis and Streptococcus pyogenes: results of a multicentre study in Turkey.

The in vitro activities of several antimicrobial agents against clinical isolates of Streptococcus pneumoniae (283), Haemophilus influenzae (272), Moraxella catarrhalis (179) and Streptococcus pyogenes (256) were determined in a multicentre study with the participation of five hospitals from four cities in Turkey. Penicillin resistance in S. pneumoniae was evaluated using the E-test and the remaining agents by disk diffusion. For S. pneumoniae overall 25.8% of the isolates were intermediately and 3.9% were highly resistant to penicillin and resistance to chloramphenicol, azithromycin and trimethoprim/sulphamethoxazole (TMP/SMX) was 3.8, 2.1 and 55.4%, respectively. Seven percent of H. influenzae produced beta-lactamase and all were susceptible to cefotaxime and azithromycin; the highest rate of resistance, 23.5%, was for TMP/SMX. Eighty-one percent of M. catarrhalis isolates produced beta-lactamase, 18.4% were resistant to TMP/SMX and all were susceptible to sulbactam/ampicillin combination. Resistance to chloramphenicol and azithromycin of S. pyogenes was 2.2 and 1.9%, respectively.

Anti-Bacterial Agents↗
PubMed2002

Oral antimicrobial susceptibilities of Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis isolates from Japanese children.

The minimum inhibitory concentrations (MICs) of 11 oral antibiotics were measured for 140 Streptococcus pneumoniae, 115 Haemophilus influenzae, and 46 Moraxella catarrhalis strains isolated from Japanese children. The antibiotics selected included a range of commonly prescribed agents together with a selection of new cefems and a penem. Cefditoren was most active against the highly penicillin resistant S. pneumoniae, beta-lactamase-producing H. influenzae and beta-lactamase-negative ampicillin-resistant H. influenzae. However, amoxycillin retained good activity against the penicillin-susceptible or -intermediately resistant S. pneumoniae (88.6%) and most of ampicillin-susceptible or -intermediately resistant H. influenzae (87.9%). We thus consider that amoxycillin remains a useful initial choice for the treatment of paediatric respiratory infections in Japan.

Administration, Oral↗