In vitro activity of roxithromycin against Moraxella catarrhalis

DIAGN MICROBIOL INFECT DIS ~ c 1992;15:63S-655

A ONCE-DAILY ORAL ANTIBIOTIC: THE WAY AHEAD IN COMMUNITY- ACQUIRED INFECTION A Roxithromycin Symposium Presented at the 17th International Congress of Chemotherapy, Berlin, Germany, 23-27 June 1991

In vitro Activity of Roxithromycin Against Moraxella catarrhalis

Robert C. Spencer and Philip F. Wheat

The in vitro activity of roxithromycin was compared with that of the other antimicrobial agents (erythromycin, tetracycline, arapicillin, and cot" i. ~oxazole) against 188 distinct clinical iso- lates of Moraxella ca~rrhalis. Of these, 106 strains (66%) produced g-lactamase. The MICgo of roxithromycin was 0.25 ~g/ml compared with values of 0.5, 1, >8, >8:0.4 I~g/ml for

I N T R O D U C T I O N

Roxithromycin (Fi~are 1) is a new oral ether oxime derivative of erythromycin with an in vitro activity comparable to that of erythromycin (Jone3 et al., 1983~ Barlam and Neu, 1984_). It possesses improved pharmacokinetic properties: resistant to gastric acid hydrolysis, rapid absorption by the gastrointestinal tract, high serum concentrations, and a long half- life of ~13 hr (Wise et al., 1987). Because of these properties, together with its spectrum of activity, roxithromycin appears to offer advantages for the treatment of respiratory tract infections (Gentry, 1987).

Moraxella catarrhalis is now increasingly recog- nized as an important pathogen in infections of the respiratory tract, including acute exacerbations of chronic bronchitis, sinusitis, conjunctivitis, and acute otitis media, especially in children (Catlin, 1990). This microorganism can also behave as an opportunistic

From the Department of Bacteriology, Royal Hallamshiro Hospital, Sheffield, United Kingdom.

Addilional copies of this supplement are available from Roussel UCLAF, Domain~ Th~rapeut~que Antibioth~rapie, 35 Boulevard des lnvalides, 75007 Paris, France.

Received 8 October 1991; revised and accepted 20 December 1991. © 1992 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010 0732-8893/92/$5.00

erythromycin, tetracycline, ampieiltin, and sulfamethoxazole- trimethoprim, respectively. These results, allied with its im- proved pharmacokinetic properties, suggest that roxithromycin should be an effective treatment in children and adults for up- per and lower respiratory tract infections caused by M. catar- rhalis.

pulmonary invader caushng frank bacterial pneu- monia in immunologically compromised patients (McNeely et al., 1976). Information regarding the in vitro activity of roxithromycin against M. catarrhalis, however, is sparse. It was therefore decided to com- pare the activity of roxithromycin with that of other antibiotics commonly used in the treatment of re- spiratory tract infections.

MATERIALS A N D M E T H O D S

Bacteria

A total of 180 distinct clinical isolates ofM. catarrhalis were collected (86% isolated from sputum specimens and 14% from conjunctival swabs). Of these 106 (66%) were ~-lactamase producers, as demonstrated by a microbiologic n-lethod (Selv,~'n, 1977). Strains of M. catarrhalis were identified by the hydrolysis of tributyrin by butyrate esterase (Richards, 1988).

Antibiotics Tested

Antibiotics studied were ~ c , ~ , ~ y ~ - , erythro- mycin, tetracycline, ampicillin, and cotrimoxazole (sulfamethoxazole-trimethoprim, ratio 19:1).

64S R.C. Spencer and P.F. Wheat

N /OCH~OCH2CH2OCH3

H~C ~ CH3

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,cff- : o

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FIGURE 1 Structure of roxithromycin.

Susceptibi l i ty Tests

Minimum inhibitory concentrations (MICs) were de- termined by using an agar dilution method with an inoculum of 104-10 s colony-forming units (CFU) de- livered onto Diagnostic Sensitivity Test agar (Oxoid) with a multipoint inoculator (Denley). Agar was supplemented with 5% lysed horse blood. The MIC was defined as the lowest concentration of antibiot-

TABLE 1 In vitro Susceptibility of 188 Strains of Moraxella catarrhalis

MIC (,g/nd)

Antibiotic Range MICs0 MICg0

Roxit-hromycin 0.06-0.25 0.125 0.25 Erythromycin 0.06-0.5 0.25 0.5 Tetracycline 0.25-->8 1 1 Ampiciilin 0.06->8 >8 >8 Suifamethoxazole- 0.5:0.025 2:0.1 >8:0.4 trimethoprim to (19:1) >8:0.4

MIC, minimum inhibitory concentration.

ics showing no visible growth after 18 hr of incu- batic.n at 37°C in air.

RESULTS AND DISCUSSION

The results of the in vitro study are shown in Table 1. All isolates were susceptible to roxlti~roP~ydn (MIC, 0.06-0.25 p,g/ml) and erythromycin (MIC, 0.06-0.5 p,g/ml). The majority of strains were susceptible to tetracycline (MICgo, 1 ~g/ml) and also to sulfame- thoxazole-trimethoprim (MICgo, 2>8:0.4 p,g/ml). As expected, the majority of strains were resistant to ampicillin (MICso and MICg0, >8 ttg/ml).

These results show that roxithromydn has in vitro antibacterial activity similar to that of erythromydn against both [3-1actamase-positive and negative strains of M. catarrhalis. The MICg0 of 0.25 ttg/ml is some- what lower than the value of 1 ttg/ml reported by Hardy et al. (1988), though their study only involved the examination of 17 strains. The high susceptibility of M. catarrhalis to erythromycin is related to the considerable hydrophobicity of its cell surface (Go- toh et al., 1989).

The increasing number of strains that produce the IMactamases, BRO-1 and BRO-2 (Wallace et al., 1989), have correspondingly reduced the effectiveness of the ampicillin antibiotics. In his worldwide review of 22 published papers, Catlin (1990) reported prev- alence rates of I~-lactamase-produdng strains as high as 87%. In a survey of children with acute otitis media, 75% of strains were [3-1actamase positive (Ko- vatch et al., 1983).

Tetracyclines cannot be used in pediatric cases and there have been reports of tetracycline-resistant strains (Roberts et al., 1990). A study by Brumfitt and colleagues (1985) could not detect any sulfa- methoxazole in saliva or sputum during and follow- ing treatment with cotrimoxazole. As a result of such findings, trimethoprim alone is now recommended for use in respiratory tract infections (Lacey et al., 1980), but trimethoprim is totally ineffective in vitro against M. catarrhalis (Winstanley and Spencer, 1986).

Volunteer studies have shown higher concentra- tions of roxithromycin in serum than would have been achieved with a comparable dose of oral eryth- romycin (Wise et al., 1987). Comparing such levels with in vitro activity against M. catarrhalia, it is to be expected that roxithromycin given 150 mg twice daily would be effective. In view of these favorable phar- macokinetic properties, when compared with other currently marketed macrolides, roxithromycin with its convenient dosing schedule should be an effec- tive antibiotic for use in respiratory infections caused by M. catarrhalis.

In vitro Roxithromycin Against MoraxeUa 65S

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