DIAGN MICROBIOL1NFECTDIS 1990;13:345-348

345

In vitro Activity of Sparfloxacin (AT-4140, CI-978, PD 131501), a New Quinolone Antimicrobial Agent George M. Eliopoulos, Karin Klimm, and M. Lindsay Grayson

In vitro activity of sparfloxacin (AT-4140, CI-978, PD 131501) against clinical bacterial isolates was compared with those of ciprofloxacin and vancomycin or imipenem. Sparfloxacin was more active or equal to ciprofloxacin against most

Gram-positive species and against Bacteroides fragilis, and it inhibited virtually all Enterobacteriaceae at 1.0 Izg/ml or less.

Sparfloxacin (AT-4140, CI-978, PD 131501) is a new fluoroquinolone antimicrobial agent with activity against a broad spectrum of Gram-positive and -negative bacteria (Kojima et al. 1989; Nakamura et al. 1989). Promising activities against Mycobacterium spp., Mycoplasma spp., and Chlamydia spp. have also been noted (Nakamura et al., 1989). The drug is well absorbed following oral administration and has a serum elimination half-life in humans of - 1 6 hr (Kanamaru et al., 1988). The present study compared activities of this agent with those of ciprofloxacin and either vancomycin or imipenem against >550 bacterial isolates of clinical origin. Most bacterial strains used in this study were collected at the N e w England Deaconess Hospital or Massachusetts General Hospital (Boston, MA). Additional isolates with unusual resistance profiles that had been referred to our laboratory were included as specifically noted below (Farber et al., 1983). Standard laboratory grade susceptibility testing powders were gifts from the following

sources: Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, Ann Arbor, MI (sparfloxacin), Miles Pharmaceuticals, West Haven, CT (ciprofloxacin), Eli Lilly and Company, Indianapolis, IN (vancomycin), and Merck, Sharp and Dohme Research Laboratories, West Point, PA (imipenem).

From the Department of Medicine (G.M.E., K.K., M.L.G.), New England Deaconess Hospital, Boston, Massachusetts; Harvard Medical School (G.M.E., M.L.G.), Boston, Massachusetts. Address reprint requests to: G.M. Eliopoulos, M.D., Department of Medicine, New England Deaconess Hospital, 185 Pilgrim Road, Boston, MA 02115. Received March 12, 1990; revised and accepted March 13, 1990. © 1990Elsevier Science Publishing Co., Inc. 655 Avenues of the Americas, New York, NY 10010 0732-8893/90/$3.50

Antimicrobial activity was determined by a standard agar plate dilution technique (NCCLS, 1988) employing Mueller-Hinton agar (BBL Microbiology Systems, Cockeysville, MD) for most organisms, with modifications for fastidious organisms and anaerobes as described previously (Grayson et al., 1989; Sentochnik et al., 1989). Minimal inhibitory concentrations (MICs) were recorded after 18 hr of incubation, except for the following: Diphtheroids, Bacteroides fragilis, and Campylobacter jejuni were incubated for 48 hr; Helicobacter (Campylobacter) pylori growth was determined after 3 days of incubation. Susceptibilities of mycobacteria were determined by broth microdilution in 7Hll broth (Yajko et al., 1987). Plates were inspected for growth after both 4 and 7 days of incubation; day 7 results are presented. Results of in vitro susceptibility studies are shown in Table 1. Against most Gram-positive organisms, MIC90s of sparfloxacin were within one dilution of those of ciprofloxacin. Sparfloxacin was fourfold more active (MIC90) than ciprofloxacin against pneumococci and penicillin-resistant strains of viridans streptococci. All members of the family En-

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G.M, Eliopoulos et al.

terobacteriaceae tested, except for one strain of Serratia marcescens, w e r e inhibited b y sparfloxacin at concentrations ~ 1 p~g/ml. Ciprofloxacin w a s twoto eightfold more active against these organisms a n d against Pseudomonas aeruginosa. Sparfloxacin w a s

TABLE 1.

m o r e active t h a n ciprofloxacin against Acinetobacter calcoaceticus subsp, anitratus, B. fragilis a n d C. jejuni. The t w o f l u o r o q u i n o l o n e s w e r e equally active against Mycobacterium avium-intracellulare, and both w e r e s u p e r i o r in activity to i m i p e n e m .

C o m p a r a t i v e in vitro Activity of Sparfloxacin MIC (lag/ml)

Organism (No.)

Staphylococcus aureus (15) (Methicillin-susceptible)

Staphylococcus aureus (15) (Methicillin-resistant)

Staphylococcus epiderrnidis (15) (Methicillin-susceptible)

Staphylococcus epidermidis (15) (Methicillin-resistant)

Enterococcus faecalis (30) Enterococcus faecium (20) Enterococcus avium (10) Streptococci, group A,B,C,G (30)

Streptococcus pneumoniae (10) (Penicillin-susceptible)

Streptococcus pneumoniae (10) (Penicillin-resistant) Viridans group Streptococci (20) (Penicillin-susceptible) Viridans group Streptococci (10) (Penicillin-resistant) JK group diphtheroids (10)

Listeria monocytogenes (10) Acinetobacter calcoaceticus subsp, anitratus (10)

Antimicrobial Agent

Range

50%

AT-4140 Ciprofloxacin Vancomycin AT-4140 Ciprofloxacin Vancomycin AT-4140 Ciprofloxacin Vancomycin AT-4140 Ciprofloxacin Vancomycin AT-4140 Ciprofloxacin Vancomycin AT-4140 Ciprofloxacin Vancomycin AT-4140 Ciprofloxacin Vancomycin AT-4140 Ciprofloxacin Vancomycin AT-4140 Ciprofloxacin Vancomycin AT-4140 Ciprofloxacin Vancomycin AT-4140 Ciprofloxacin Vancornycin AT-4140 Ciprofloxacin Vancomycin AT-4140 Ciprofloxacin Vancomycin AT-4140 Ciprofloxacin Vancomycin AT-4140 Ciprofloxacin Imipenem

0.06-0.25 0.25-O.5 1-2 0.12-0.25 0.5 1-2 0.12-0.5 0.25-1 1-4 0.03-1 0.25-1 1-4

0.25 0.5 2 0.25 0.5 1 0.25 0.5 2 0.25 0.5 4 1 1 4 1 4 2 1 1 1 0.5 0.5 1 0.5 2 1 0.5 2

0.5-1

0.25-2 2-4 0.54 0.25-8 1-4 1-2 0.5-1 1-2 0.5-1 0.5-2

0.5-1 0.25-1 1-4 0.5-1 0.25--1 1-4 0.5-1 0.25-1 1-2 0.5-1 0.25-0.5 1-4 0.5 0.12-0.25 0.25-0.5 0.5-1 1

1-2 0.12-0.5 0.06-0.25 0.06-0.5 0.25-4

1

0.5 1 1 0.25 1 0.5 0.25 0.25 1 1 1 0.25 0.06 0.5 0.5

90% 0.25 0.5 2 0.25 0.5 2 0.5 0.5 4 0.25 0.5 4 1 1 4 4 4 4 2 1 2 1

1 1 1 4 1 1

4 1 1 2 1 0.5 4 0.5 0.25 0.5 1 1 1 0.5 0.12 0.5 1

Notes

347

TABLE 1.

Continued MIC (Izg/ml)

Organism (No.) Aeromonas hydrophila (10)

Campylobacter jejuni (10)

Campylobacter pylori (25)

Citrobacter freundii (20)

Enterobacter spp. a (30)

Escherichia colib (30)

Klebsiella pneumoniae ~ (30)

Pasteurella multocida (8)

Proteus spp. a (20)

Pseudomonas aeruginosa (15)

Pseudomonas cepacia (10)

Serratia marcescens (20)

Xanthomonas maltophilia (14)

Bacteroides fragilis (30)

Mycobacterium aviumintracellulare complex (20) qncludes bIndudes qncludes qncludes

Antimicrobial Agent AT-4140 Ciprofloxacin Imipenem AT-4140 Ciprofloxacm Irnipenem AT-4140 Ciprofloxacrn Imipenern AT-4140 Ciprofloxacin Imipenern AT-4140 Ciprofloxacin Imipenern AT-4140 Ciprofloxacin Imipenem AT-4140 Ciprofloxacin Irnipenern AT-4140 Ciprofloxacin Imipenern AT-4140 Ciprofloxacm Imipenem AT-4140 Ciprofloxacin Irnipenem AT-4140 Ciprofloxacin Imipenem AT-4140 Ciprofloxacin Imipenem AT-4140 Ciprofloxacin Imipenem AT-4140 Ciprofloxacin Imipenern AT-4140 Ciprofloxacin Irnipenem

Range 0.06-0.25 ~