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Moraxella catarrhalis is a common pathogen found in children with upper respiratory tract infections and in patients with chronic obstructive pulmonary disease during exacerbations. The bacterial species is often isolated together with Streptococcus pneumoniae and Haemophilus influenzae . Outer membrane vesicles (OMVs) are released by M. catarrhalis and contain phospholipids, adhesins, and immunomodulatory compounds such as lipooligosaccharide. We have recently shown that M. catarrhalis OMVs exist in patients upon nasopharyngeal colonization. As virtually all M. catarrhalis isolates are β-lactamase positive, the goal of this study was to investigate whether M. catarrhalis OMVs carry β-lactamase and to analyze if OMV consequently can prevent amoxicillin-induced killing. Recombinant β-lactamase was produced and antibodies were raised in rabbits. Transmission electron microscopy, flow cytometry, and Western blotting verified that OMVs carried β-lactamase. Moreover, enzyme assays revealed that M. catarrhalis OMVs contained active β-lactamase. OMVs (25 μg/ml) incubated with amoxicillin for 1 h completely hydrolyzed amoxicillin at concentrations up to 2.5 μg/ml. In functional experiments, preincubation of amoxicillin (10× MIC) with M. catarrhalis OMVs fully rescued amoxicillin-susceptible M. catarrhalis , S. pneumoniae , and type b or nontypeable H. influenzae from β-lactam-induced killing. Our results suggest that the presence of amoxicillin-resistant M. catarrhalis originating from β-lactamase-containing OMVs may pave the way for respiratory pathogens that by definition are susceptible to β-lactam antibiotics.

The in vitro activities of modithromycin against Gram-positive and -negative respiratory pathogens, including macrolide-resistant cocci with different resistance mechanisms, were compared with those of other macrolide and ketolide agents. MICs were determined by the broth microdilution method. All 595 test strains used in this study were isolated from Japanese medical facilities. The erm (ribosome methylase) and/or mef (efflux pump) gene, which correlated with resistance to erythromycin as well as clarithromycin and azithromycin, was found in 81.8%, 21.3%, and 23.2% of Streptococcus pneumoniae , Streptococcus pyogenes , and methicillin-susceptible Staphylococcus aureus (MSSA) strains, respectively. Modithromycin showed MIC 90 s of 0.125 μg/ml against these three cocci, including macrolide-resistant strains. In particular, the MIC of modithromycin against ermB -carrying S. pyogenes was ≥32-fold lower than that of telithromycin. The activities of modithromycin as well as telithromycin were little affected by the presence of mefA or mefE in both streptococci. Against Gram-negative pathogens, modithromycin showed MIC 90 s of 0.5, 8, and 0.031 μg/ml against Moraxella catarrhalis , Haemophilus influenzae , and Legionella spp., respectively. The MICs of modithromycin against M. catarrhalis and H. influenzae were higher than those of telithromycin and azithromycin. However, modithromycin showed the most potent anti- Legionella activity among the macrolide and ketolide agents tested. These results suggested that the bicyclolide agent modithromycin is a novel class of macrolides with improved antibacterial activity against Gram-positive cocci, including telithromycin-resistant streptococci and intracellular Gram-negative bacteria of the Legionella species.

AFN-1252, a potent inhibitor of enoyl-acyl carrier protein reductase (FabI), inhibited all clinical isolates of Staphylococcus aureus ( n = 502) and Staphylococcus epidermidis ( n = 51) tested, including methicillin (meticillin)-resistant isolates, at concentrations of ≤0.12 μg/ml. In contrast, AFN-1252 was inactive (MIC 90 , >4 μg/ml) against clinical isolates of Streptococcus pneumoniae , beta-hemolytic streptococci, Enterococcus spp., Enterobacteriaceae , nonfermentative gram-negative bacilli, and Moraxella catarrhalis . These data support the continued development of AFN-1252 for the treatment of patients with resistant staphylococcal infections.

Ceftobiprole, a broad-spectrum pyrrolidinone-3-ylidenemethyl cephem currently in phase III clinical trials, had MICs between 0.008 μg/ml and 8.0 μg/ml for 321 clinical isolates of Haemophilus influenzae and between ≤0.004 μg/ml and 1.0 μg/ml for 49 clinical isolates of Moraxella catarrhalis . Ceftobiprole MIC 50 and MIC 90 values for H. influenzae were 0.06 μg/ml and 0.25 μg/ml for β-lactamase-positive strains ( n = 262), 0.03 μg/ml and 0.25 μg/ml for β-lactamase-negative strains ( n = 40), and 0.5 μg/ml and 2.0 μg/ml for β-lactamase-negative ampicillin-resistant strains ( n = 19), respectively. Ceftobiprole MIC 50 and MIC 90 values for β-lactamase-positive M. catarrhalis strains ( n = 40) were 0.12 μg/ml and 0.5 μg/ml, respectively, whereas the ceftobiprole MIC range for β-lactamase-negative M. catarrhalis strains ( n = 9) was ≤0.004 to 0.03 μg/ml. Ceftriaxone MICs usually were generally at least twofold lower than those of ceftobiprole, whereas amoxicillin-clavulanate MICs usually were higher than those of ceftobiprole. Azithromycin and telithromycin had unimodal MIC distributions against H. influenzae , with MIC 90 values of azithromycin and telithromycin of 2 μg/ml and 4 μg/ml, respectively. Except for selected quinolone-nonsusceptible H. influenzae strains, moxifloxacin proved highly active, with MIC 90 values of 0.12 μg/ml. Time-kill analyses showed that ceftobiprole, ceftriaxone, cefpodoxime, amoxicillin-clavulanate, azithromycin, telithromycin, and moxifloxacin were bactericidal at 2× MIC by 24 h against all 10 H. influenzae strains surveyed. Only modest increases in MICs were found for H. influenzae or M. catarrhalis clones after 50 serial passages in the presence of subinhibitory concentrations of ceftobiprole, and single-passage selection showed that the selection frequency of H. influenzae or M. catarrhalis clones with elevated ceftobiprole MICs is quite low.

Among respiratory tract isolates of Streptococcus pneumoniae from children, resistance to penicillins, cephalosporins, macrolides, and trimethoprim-sulfamethoxazole (SXT) increases on an annual basis. Pediatric patients who do not respond to conventional therapy for respiratory tract infections someday may be treated with fluoroquinolones. In this study, MICs of β-lactams, azithromycin, SXT, and levofloxacin were determined and interpreted by using NCCLS guidelines for isolates of S. pneumoniae (2,834 from children and 10,966 from adults), Haemophilus influenzae (629 from children and 2,281 from adults), and Moraxella catarrhalis (389 from children and 1,357 from adults) collected during the 2000-2001 and 2001-2002 respiratory illness seasons in the United States as part of the ongoing TRUST surveillance studies. Rates of resistance to penicillin, azithromycin, and SXT were ≥7.5% higher among patients ≤4 years old than among patients 5 to 10, 11 to 17, and ≥18 years old in both the 2000-2001 and the 2001-2002 respiratory illness seasons. Levofloxacin resistance was detected in 2 of 2,834 isolates (0.07%) from patients 64 years old. Multidrug resistance was twice as common among patients ≤4 years old (25.3%) as among patients 5 to 10 years old (13.7%), 11 to 17 years old (11.9%), 18 to 64 years old (12.1%), and >64 years old (12.4%). The most common multidrug resistance phenotype in S. pneumoniae isolates for all age groups was resistance to penicillin, azithromycin, and SXT (70.3 to 76.6%). For H. influenzae and M. catarrhalis isolates from patients 64 years old, levofloxacin MICs at which 90% of the isolates were inhibited were 0.015 and 0.03 to 0.06 μg/ml, respectively, in the 2000-2001 and 2001-2002 respiratory illness seasons. In the 2000-2001 and 2001-2002 respiratory illness season surveillance studies in the United States, 99.9% of pediatric isolates of S. pneumoniae were susceptible to levofloxacin. If fluoroquinolones become a treatment option for pediatric patients, careful monitoring of fluoroquinolone susceptibilities will be increasingly important in future surveillance studies.

The in vitro activities of faropenem and other antimicrobial agents were determined against 4,725 Streptococcus pneumoniae isolates, 2,614 Haemophilus influenzae isolates, and 1,193 Moraxella catarrhalis isolates collected from 273 U.S. laboratories during 1999. Faropenem MICs at which 90% of isolates are inhibited were 0.008, 0.25, and 1 μg/ml for penicillin-susceptible, -intermediate, and -resistant S. pneumoniae strains, respectively; 0.5 and 1 μg/ml for β-lactamase-positive and -negative H. influenzae strains, respectively; and 0.12 and 0.5 μg/ml for β-lactamase-negative and -positive M. catarrhalis strains, respectively. Faropenem holds promise as an oral therapy for community-acquired respiratory tract infections.

The antimicrobial activity of BMS 284756, a novel des-F(6)-quinolone, was comparatively evaluated against 257 Streptococcus pneumoniae , 198 Haemophilus influenzae , and 88 Moraxella catarrhalis strains isolated in Latin America between July and September of 1999 as part of the SENTRY Antimicrobial Surveillance Program. Nearly 28.0% of S. pneumoniae strains were nonsusceptible to penicillin. The rank order of quinolone potency versus S. pneumoniae was BMS 284756 (MIC at which 90% of isolates were inhibited [MIC 90 ], 0.12 μg/ml) > trovafloxacin (MIC 90 , 0.25 μg/ml) > gatifloxacin (MIC 90 , 0.5 μg/ml) > levofloxacin and ciprofloxacin (MIC 90 , 1 to 2 μg/ml). All S. pneumoniae strains that were not susceptible to other quinolones were inhibited by BMS 284756 at ≤2 μg/ml. The overall prevalence of β-lactamase production was 15.2% in H. influenzae and 98.9% in M. catarrhalis. BMS 284756 showed excellent potency and spectrum against this group of pathogens, inhibiting all isolates at ≤0.12 μg/ml. BMS 284756 exhibited activity similar to those displayed by the new fluoroquinolones, such as levofloxacin, trovafloxacin, or gatifloxacin, and could be a therapeutic option for empirical treatment of community-acquired respiratory tract infections.

An antimicrobial susceptibility surveillance study of Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis isolates was performed during the winter of 1996–1997 in order to determine their susceptibilities to 5 fluoroquinolones and 21 other antimicrobial agents. Broth microdilution MICs were determined for 2,752 isolates from 51 U.S. medical centers. Of the 1,276 S. pneumoniae isolates, 64% were susceptible, 17% were intermediate, and 19% were highly resistant to penicillin. On the basis of the MICs at which 90% of isolates are inhibited and modal MICs, the hierarchy of the five fluoroquinolones from most to least active was grepafloxacin > sparfloxacin > levofloxacin = ciprofloxacin > ofloxacin. For S. pneumoniae isolates for which penicillin MICs were elevated, the MICs of the cephalosporins, macrolides, clindamycin, tetracycline, and trimethoprim-sulfamethoxazole were also elevated, but the MICs of the fluoroquinolones, vancomycin, and rifampin were not. The prevalence of penicillin-susceptible pneumococci varied by U.S. Bureau of the Census region (range, 44% in the East South Central region to 75% in the Pacific region). In addition, S. pneumoniae isolates from blood were significantly more susceptible to penicillin than those from respiratory, ear, or eye specimens, and pneumococci from patients ≤2 years old were significantly more resistant to penicillin than those from older patients (by chi-square analysis, P < 0.05). β-Lactamase was produced by 35% of H. influenzae isolates and 93% of M. catarrhalis isolates, resulting in increased MICs of amoxicillin and certain cephalosporins. We noted that the antimicrobial resistance patterns of S. pneumoniae isolates, which correlate with the penicillin susceptibility phenotype, vary by site of infection, age group of the patient, and geographic source of the isolate.

The β-lactamases from 403 Moraxella ( Branhamella ) catarrhalis clinical isolates obtained during 1994–1995 and 1997–1998 U.S. multicenter surveillance studies were characterized by isoelectric focusing. The overall prevalences of the BRO-1 and BRO-2 enzymes among β-lactamase-positive isolates were estimated to be 97.5 and 2.5%, respectively. The minimum inhibitory concentrations (MICs) of ampicillin for all BRO-2-producing isolates were ≤1 μg/ml; however, numerous β-lactamase-positive isolates for which the ampicillin MICs were ≤1 μg/ml produced the BRO-1 enzyme (88.1%).

The in vitro activity of a new orally administered carbacephem analog of cefaclor, loracarbef (LY163892), was compared with those of cefaclor and several other oral antimicrobial agents against recent clinical isolates of Haemophilus influenzae and Moraxella catarrhalis. Loracarbef was found to be slightly more active than cefaclor against H. influenzae and had activity essentially equivalent to that of cefaclor for M. catarrhalis. Resistance to loracarbef was uncommon and was noted only with rare beta-lactamase-producing strains of H. influenzae. On the basis of these observations, loracarbef may be of utility in the management of localized, non-life-threatening infections caused by H. influenzae and M. catarrhalis.

The association between trimethoprim-sulfamethoxazole use and resistance among the major respiratory tract pathogens was investigated by comparing regional consumption of the drug to regional resistance in the following year in 21 central hospital districts in Finland. A total of 23,530 Streptococcus pneumoniae isolates, 28,320 Haemophilus influenzae isolates, and 14,138 Moraxella catarrhalis isolates were tested for trimethoprim-sulfamethoxazole susceptibility during the study period (1998-2004). Among the S. pneumoniae isolates, a statistically significant connection was found between regional consumption and resistance. No statistically significant connection was found between regional trimethoprim-sulfamethoxazole use and resistance among H. influenzae and M. catarrhalis isolates. According to our results, it seems that only in pneumococci can the development of trimethoprim-sulfamethoxazole resistance be influenced by restricting its use. However, trimethoprim-sulfamethoxazole remains an important antimicrobial agent because of its reasonable price. Hence, resistance to trimethoprim-sulfamethoxazole among these pathogens needs continuous monitoring.

The in vitro activity of sparfloxacin (CI-978; AT-4140) was compared with those of other antimicrobial agents against isolates of staphylococci, enterococci, and various respiratory tract pathogens. Sparfloxacin was the most active drug tested against staphylococci (MIC for 90% of the strains tested [MIC90], 0.125 micrograms/ml) and enterococci (MIC90, 1.0 microgram/ml). It was also active against Haemophilus influenzae (MIC90, less than or equal to 0.06 microgram/ml), Moraxella (Branhamella) catarrhalis (MIC90, 0.125 microgram/ml), Streptococcus pneumoniae (MIC90, 0.5 microgram/ml), and Streptococcus pyogenes (MIC90, 1.0 microgram/ml).

Faropenem was tested against 1,188 middle ear fluid pathogens from children in Israel and Costa Rica. Against Streptococcus pneumoniae and Haemophilus influenzae , faropenem was the most active β-lactam, with activity that was similar to or greater than of the other oral antimicrobial classes studied. Faropenem was also active against Moraxella catarrhalis and Streptococcus pyogenes .

The microdilution MICs of HMR 3647, erythromycin A, azithromycin, clarithromycin, roxithromycin, and pristinamycin against 50/90% of 249 Haemophilus influenzae and 50 Moraxella catarrhalis isolates were 2/4, 0.06/0.125; 8/16, 0.25/0.25; 2/4, 0.06/0.125; 16/16, 0.25/0.25; 32/>32, 1/2; and 2/4, 0.5/0.5 μg/ml. Azithromycin was bactericidal against all 10 H. influenzae and 3 of 5 M. catarrhalis isolates and HMR 3647, erythromycin A, clarithromycin, roxithromycin, and pristinamycin were bacteriostatic, against all 15 strains after 24 h at the MIC.

The purpose of this study was to compare the mutant prevention concentration (MPC) of ABT-492 to those of levofloxacin, moxifloxacin, and gatifloxacin against Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis . The fluoroquinolones had comparable mutation selection windows, which is the ratio of MPC/MIC, for all isolates.

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 β-lactamase, while 92.4% of the 2,314 M. catarrhalis isolates produced β-lactamase. The incidence of β-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 β-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 ≤0.03 μg/ml. The MIC 90 s of the investigational ketolides telithromycin and ABT-773 were 2 and 4 μg/ml, respectively, and the MIC 90 of the investigational glycylcycline GAR-936 (tigecycline) was 4 μg/ml. Among the M. catarrhalis isolates tested, the resistance rates derived by using the NCCLS breakpoint criteria for H. influenzae were H. influenzae strains in Canada is decreasing (18.6% in 2001-2002), while the incidence of β-lactamase-positive M. catarrhalis strains has remained constant (90.0% in 2001-2002).

The in vitro activity of ABT-773 was evaluated against Streptococcus pneumoniae , Haemophilus influenzae , and Moraxella catarrhalis isolates. ABT-773 was the most active antimicrobial tested against S. pneumoniae . ABT-773 and azithromycin were equivalent in activity against H. influenzae and M. catarrhalis and more active than either clarithromycin or erythromycin.

Two tetracycline-resistant (Tcr) Moraxella (Branhamella) catarrhalis strains from England were compared with two previously characterized Tcr Texas strains. Both pairs carried the Tet B determinant, which was nontransferable. Pulsed-field gel electrophoresis of their genomic DNA restriction fragments demonstrated that the strains from the same area were identical (clonal); however, the Texas and English strains differed from each other.

MICs of 10 oral antibiotics were determined for 105 Moraxella catarrhalis and 96 Haemophilus influenzae isolates from adults. A two- to fourfold increase in MICs of oral cephalosporins was seen in the presence of BRO-1 but not with TEM-1 or BRO-2. The MICs of cefixime for 90% of strains of H. influenzae (0.125 microgram/ml) and M. catarrhalis (0.25 microgram/ml) were 8- to 64-fold lower than those of other oral cephalosporins.

The majority of clinical isolates of Moraxella catarrhalis produce β-lactamase. The role of this enzyme in the phenomenon of indirect pathogenicity, in which a true pathogen such as Streptococcus pneumoniae is protected from the action of certain β-lactam antibiotics, is well recognized. By using a simple continuous-culture biofilm system, it has been shown that the pneumococcus attains high titers in excess of 10 12 CFU/biofilm; furthermore, the penicillin-sensitive pneumococcus used remained susceptible to a range of β-lactam antibiotics in these biofilms (R. K. Budhani and J. K. Struthers, J. Antimicrob. Chemother. 40:601–602, 1997). This system was used to characterize the antibiotic susceptibility of this isolate when grown with β-lactamase-negative or -positive moraxellae. When grown with β-lactamase-producing moraxellae in the presence of either benzylpenicillin or amoxicillin, the pneumococcus was protected in the range of the antibiotic concentrations to which it would be considered resistant. With amoxicillin-clavulanic acid the titers of the two organisms collapsed at the antibiotic concentration at which moraxellae became susceptible. The levels of β-lactamase activity in cell-free supernatants of broth culture, in biofilm, and in biofilm effluent revealed distinct differences in this activity; levels in biofilm were significantly lower than those in broth culture supernatants. The system appears suitable for studying organisms under antibiotic stress and for investigating the interactions of bacteria under such conditions.

The postantibiotic effect (PAE) of amoxicillin-clavulanate was studied for strains of Staphylococcus aureus, Haemophilus influenzae, Moraxella catarrhalis, Klebsiella pneumoniae, and Escherichia coli. A PAE of approximately 2 h was seen for beta-lactamase-positive and -negative strains of S. aureus following 2 h of exposure to twice the MIC and did not increase at 16 times the MIC. The PAE observed with H. influenzae was clearly related to the growth rate of the organism. A PAE of 0.8 h was found for amoxicillin (four times the MIC) against a beta-lactamase-negative strain of H. influenzae (generation time, 26.3 min) and a PAE of 1.74 h was found for amoxicillin-clavulanate (twice the MIC) against a beta-lactamase-positive strain (generation time, 32.2 min). When the beta-lactamase-positive strain was growing more slowly (generation time, 120 min), the PAE of amoxicillin-clavulanate increased to > 3.32 h. The PAE of amoxicillin-clavulanate at 2/1 micrograms/ml on a beta-lactamase-producing strain of M. catarrhalis was > 2.9 h, and, as expected, the PAEs of twice the MIC on K. pneumoniae and E. coli were generally short (< 1 h). The post-beta-lactamase inhibitor effect (PLIE), determined after removal of only clavulanate, was also examined for beta-lactamase-positive strains. This was more prolonged (approximately 3 to 4 h) than the corresponding PAE for S. aureus, H. influenzae, and M. catarrhalis. The PLIE was related to the amount of beta-lactamase produced and required the presence of amoxicillin in the initial exposure period. These data may have implications for reducing the dosage of amoxicillin-clavulanate.

A rapid increase in the prevalence of beta-lactamase-producing Moraxella (Branhamella) catarrhalis strains has been noticed during the last decades. Today, more than 80% of strains isolated worldwide produce beta-lactamase. To investigate beta-lactamase(s) of M. catarrhalis at the molecular level, the BRO-1 beta-lactamase gene (bla) was isolated as part of a 4,223-bp HindIII fragment. Sequence analysis indicated that bla encodes a polypeptide of 314 amino acid residues. Insertional inactivation of bla in M. catarrhalis resulted in complete abrogation of beta-lactamase production and ampicillin resistance, demonstrating that bla is solely responsible for beta-lactam resistance. Comparison with other beta-lactamases suggested that M. catarrhalis beta-lactamase is a unique enzyme with conserved residues at the active sites. The presence of a signal sequence for lipoproteins suggested that it is lipid modified at its N terminus. In keeping with this assumption was the observation that 10% of beta-lactamase activity was found in the membrane compartment of M. catarrhalis. M. catarrhalis strains produce two types of beta-lactamase, BRO-1 and BRO-2, which differ in their isoelectric points. The BRO-1 and BRO-2 genes from two ATCC strains of M. catarrhalis were sequenced, and only one amino acid difference was found between the predicted products. However, there was a 21-bp deletion in the promoter region of the BRO-2 gene, possibly explaining the lower level of production of BRO-2. The G + C content of bla (31%) was significantly lower than those of the flanking genes (47 and 50%), and the overall G + C content of the M. catarrhalis genome (41%). These results indicate that bla was acquired by horizontal gene transfer from another, still unknown species.

In vitro activities of the ketolides HRM 3647 and HRM 3004 against pathogenic Neisseria gonorrhoeae and N. meningitidis , saprophytic Neisseria isolates, and Moraxella catarrhalis were determined. The comparison of ketolide activities with those of the other macrolides shows a much better activity in the majority of species, with macrolide MICs at which 90% of the isolates are inhibited between 8- and 10-fold higher.

Two-high-level-tetracycline-resistance Moraxella (Branhamella) catarrhalis strains were shown to carry DNA sequences which hybridized with the Tet B probe. The determinant appeared to be located in the chromosome and was nontransferable.

A total of 74 clinical isolates of Branhamella catarrhalis were characterized with respect to their ampicillin, amoxicillin-clavulanate, cephalothin, cefaclor, erythromycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole MICs and zones of inhibition. Disk diffusion tests were performed according to the guidelines of the National Committee for Clinical Laboratory Standards with two different media (Mueller-Hinton agar and chocolate Mueller-Hinton agar) and plates incubated under two atmospheric conditions (ambient air and 5 to 7% CO2). Optimum disk diffusion test results were obtained with Mueller-Hinton agar plates incubated in ambient air with all eight antimicrobial agents. On the basis of comparisons of MICs versus zones of inhibition, the following zone diameter interpretive criteria were defined for testing B. catarrhalis with disks containing 10 micrograms of ampicillin: greater than or equal to 38 mm, susceptible; 20 to 37 mm, moderately susceptible; less than or equal to 19 mm, resistant. The respective MIC correlates were less than or equal to 0.06, 0.125 to 0.5, and greater than or equal to 1.0 micrograms/ml. Because of the absence of frankly resistant test organisms, it was not possible to make definitive recommendations pertaining to disk diffusion tests with amoxicillin-clavulanate, cephalothin, cefaclor, erythromycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole. Evidence is presented, however, which suggests that the current National Committee for Clinical Laboratory Standards disk diffusion interpretive criteria for nonfastidious bacteria can be applied to B. catarrhalis, at least as they pertain to the susceptible category with cephalothin, amoxicillin-clavulanate, erythromycin, tetracycline, chloramphenicol, and trimethoprim-sulfamethoxazole. With cefaclor, a zone diameter of greater than or equal to 21 mm was determined to adequately define the susceptible category.

The in vitro activities of 39 antimicrobial agents were assessed versus 74 clinical isolates of Branhamella catarrhalis. Resistance was observed only with penicillin and ampicillin and then only with beta-lactamase-producing strains. The results of in vitro susceptibility tests with agar dilution and broth microdilution procedures were found to be comparable. The results of broth tube macrodilution tests were, in general, one twofold-concentration increment higher.