In vitro activity of fusidic acid and mupirocin against coagulase-positive staphylococci from pets.

OBJECTIVES: Methicillin-resistant Staphylococcus aureus (MRSA) and multiresistant Staphylococcus pseudintermedius (MRSP) have emerged as important pathogens in animal infections. Associated therapeutic problems and the zoonotic potential of staphylococci have renewed interest in topical antibiotics for treatment and carrier decolonization. Fusidic acid and mupirocin are used topically in humans and animals but resistant strains isolated from people are increasing. This study investigates the in vitro activity of fusidic acid and mupirocin against coagulase-positive staphylococci from pets. METHODS: A collection of 287 staphylococci was examined, comprising 102 MRSA, 102 methicillin-susceptible S. aureus, 71 S. pseudintermedius and 12 MRSP from canine and feline infections and carrier sites isolated in the UK and Germany. MICs were determined by the agar dilution method according to CLSI (formerly NCCLS) standards. RESULTS: The majority (89.7%) of all MICs were

Susceptibility of Streptococcus pneumoniae to penicillin, azithromycin and telithromycin (PROTEKT 1999-2003).

Isolates of Streptococcus pneumoniae collected over the first 4 years of the PROTEKT study were tested for susceptibility to penicillin, azithromycin and telithromycin. A total of 20,750 isolates were collected from 39 countries. Penicillin non-susceptibility rates were stable over the study period; overall, 21.8% of isolates were resistant. Azithromycin resistance increased from 31.0% in Year 1 to 36.3% in Year 4. Resistance rates for penicillin and azithromycin varied between countries and were highest in France, Spain, South Africa, USA and the Far East. Multidrug resistance in S. pneumoniae did not change significantly over the 4 years, with an overall rate of 38.6%. Telithromycin retained good activity against S. pneumoniae (0.1% of isolates resistant), including multidrug-resistant isolates.

Tigecyclin--the first glycylcycline to undergo clinical development: an overview of in vitro activity compared to tetracycline.

Tetracycline antimicrobials are characterised by a broad-spectrum of antibacterial activity which includes Gram-positive, most Gram-negative, anaerobic and "atypical" (Legionella pneumophila, Chlamydophila pneumoniae and Mycoplasma pneumoniae) species. However, the original clinical utility of the tetracyclines has been compromised as a result of increasing resistance to them among previously susceptible, common pathogens. Research into structure-activity relationships among various tetracycline derivatives resulted in discovery of the 9-t- butylglycylamido tetracyclines, now known as the glycylcyclines, which are not affected by either specific efflux pump or ribosomal protection mechanisms of resistance. Tigecycline, 9-t-butylglycylamido-minocycline, is the first in the glycylcycline class to undergo clinical development. This review of published in vitro data clearly demonstrates the potent activity of tigecycline against a wide range of common hospital and community bacterial pathogens including those having acquired mechanisms of resistance to older congeners (tetracycline, minocycline and doxycycline). Its activity against multiply-resistant Staphylococcus spp, including glycopeptide-intermediate strains (GISA), Streptococcus pneumoniae, Enterococcus spp. (including vancomycin-resistant strains) and some extended-spectrum, beta-lactamase producing isolates of species of the Enterobacteriaceae, is particularly noteworthy.

Results of the Alexander Project: a continuing, multicenter study of the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens.

In 1992, an ongoing, international multicenter study was established to investigate the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens: the Alexander Project. Isolates cultured from patients living in geographically separated areas, ten in the European Union (EU) and five in the United States (US), were collected and tested using standard methods in a central laboratory. A total of 4,155 isolates of Haemophilus influenzae was collected during the period 1992-1994. beta-lactamase production was the principal mechanism of resistance observed with overall rates in the US (1992 = 26.3%; 1993 = 28.2%; and 1994 = 30.1%) generally twice those seen in the EU (1992 = 12.3%; 1993 = 14.4%; and 1994 = 15.5%). Chloramphenicol resistance was generally low except in Spanish centers where rates ranging from 4.0 to 15.9% were observed during the study period. One thousand one hundred ninety-three isolates of Moraxella catarrhalis were tested. beta-lactamase production was the only mechanism of resistance of any importance detected, with the vast majority of isolates producing the enzyme. Two thousand eight hundred twenty-nine isolates of Streptococcus pneumoniae were tested. French and Spanish centers provided isolates with the highest rates of either low-level (intermediate) or high-level penicillin resistance, which in 1994 ranged from 10.2 to 31.4% and 30.4 to 40.1% for each resistance category, respectively. With the exception of the fluoroquinolones, rates of resistance to other antimicrobials including the macrolides, doxycycline, chloramphenicol, and trimethoprim/sulfamethoxazole were high, generally, in centers with a high prevalence of penicillin resistance. However, in some centers (Toulouse, France and Genoa, Italy) this association was not complete for the macrolides.

In vitro activity of lomefloxacin and other antimicrobials against bacterial enteritis pathogens.

Lomefloxacin is a new, difluoroquinolone. In this study, the in vitro activity of lomefloxacin against clinical isolates of a variety of bacterial species associated with acute diarrheal disease was determined and compared with that of ciprofloxacin, ofloxacin, amoxicillin, sulphamethoxazole, trimethoprim, tetracycline, and chloramphenicol. Bacterial isolates were obtained from different geographical areas, including Western Europe and the United Kingdom, Southern Europe, Africa, the Middle East, South and Southeast Asia, and South America, and were included to reflect the range of susceptibility seen throughout the world. Minimum inhibitory concentrations (MICs) were determined using an agar incorporation technique in Mueller-Hinton medium supplemented when necessary with saponin-lysed horse blood at a final concentration of 10% vol/vol. Lomefloxacin was highly active against all the species examined which included Salmonella spp., Shigella spp., Escherichia coli enterotoxigenic [(ETEC), enteroinvasive (EIEC), and enteropathogenic (EPEC) strains], Yersinia enterocolitica, Campylobacter jejuni, Vibrio spp., and Aeromonas hydrophila, with all isolates inhibited by 1 mg/L or less. This activity was similar to ofloxacin and slightly less than that of ciprofloxacin. By contrast, many of the isolates were resistant to one or more of the other, unrelated animicrobials. No cross-resistance between lomefloxacin and any of the nonfluoroquinolone antimicrobials examined in the study was observed.

European Glycopeptide Susceptibility Survey of gram-positive bacteria for 1995. European Glycopeptide Resistance Survey Study Group.

In the European Glycopeptide Susceptibility Survey 7078 Gram-positive isolates collected in 1995 from 70 centers in 9 countries of Western Europe were examined, using a standardized, quantitative susceptibility testing method. Of the 7078 isolates, 6824 (96.4%) were tested by the national coordinating centers. Teicoplanin (mode MIC 0.5 microgram/mL) was generally twice as active as vancomycin (mode MIC 1 microgram/mL) against Staphylococcus aureus (n = 2852). All isolates were susceptible to vancomycin (MIC < or = 4 micrograms/mL) and all but four to teicoplanin (MIC < or = 8 micrograms/mL); these four isolates were of intermediate susceptibility (MIC 16 micrograms/mL). With coagulase-negative staphylococci (n = 1444), the distribution of MIC of teicoplanin was wider than for vancomycin. Two and two-tenths percent of coagulase-negative staphylococci excluding Staphylococcus haemolyticus required 16 micrograms/mL teicoplanin for inhibition (intermediate) and 0.4% > or = 32 micrograms/mL (resistant). Among isolates of S. haemolyticus, 4.4% were of intermediate susceptibility (MIC 16 micrograms/mL) and 3.3% were resistant (MIC > or = 32 micrograms/mL) to teicoplanin. However, this species represented only 6.3% of the isolates of coagulase-negative Staphylococcus spp. Generally, teicoplanin (mode MIC < or = 0.12 microgram/mL) was four to eight times more active than vancomycin (mode MIC < or = 0.5 microgram/mL) against the 770 streptococcal isolates. Glycopeptide-susceptible Enterococcus spp. (n = 1695) were generally four times more susceptible to teicoplanin (mode MIC 0.25 microgram/mL) than to vancomycin (mode MIC 1 microgram/mL). Combined vancomycin and teicoplanin (VanA phenotype) resistance was observed more frequently (9.3%) in isolates of Enterococcus faecium than in Enterococcus faecalis (0.8%). Four isolates of unspeciated enterococci (1.4%) also expressed this resistance phenotype. Four isolates of E. faecium and four of E. faecalis expressed the VanB-type (low-level, vancomycin only) resistance. Spain was the only country not to submit resistant E. faecium strains while resistant E. faecalis isolates came only from Spain and Italy.

Comparative in vitro activity of lomefloxacin, a difluoro-quinolone.

Lomefloxacin is a new difluoro-quinolone. In this study, we have determined the in vitro activity of lomefloxacin against a wide range of clinical bacterial isolates and compared it with that of other fluoro-quinolones and some unrelated antimicrobials. Lomefloxacin was very active against Enterobacteriaceae (MIC90, 0.5 micrograms/ml) with activity comparable to that of ofloxacin (MIC90, 0.25 micrograms/ml). Lomefloxacin was moderately active against isolates of Pseudomonas aeruginosa (MIC90, 4 micrograms/ml), and again the activity was comparable to ofloxacin (MIC90, 4 micrograms/ml) but was eightfold less than ciprofloxacin (MIC90, 0.5 micrograms/ml). Lomefloxacin was also active against isolates of Staphylococcus aureus (MIC90, 1 micrograms/ml), irrespective of methicillin susceptibility, and this activity was most comparable to ofloxacin (MIC90, 0.5 micrograms/ml) and ciprofloxacin (MIC90, 0.5 micrograms/ml). Lomefloxacin was fourfold less active than either ofloxacin or ciprofloxacin against isolates of Enterococcus faecalis (MIC90, 8 micrograms/ml) and Streptococcus pneumoniae (MIC90, 8 micrograms/ml). In common with ofloxacin and ciprofloxacin, lomefloxacin was very active against isolates of Neisseria spp. (MIC90, less than or equal to 0.06 micrograms/ml), Haemophilus spp. (MIC90, less than or equal to 0.06 micrograms/ml), Legionella spp. (MIC90, less than or equal to 0.06 micrograms/ml), Vibrio spp. (MIC90, less than or equal to 0.06 micrograms/ml), and Campylobacter jejuni (MIC90, 1 microgram/ml). Lomefloxacin showed poor activity against isolates of Bacteroides spp. (MIC90, 16 micrograms/ml) or Clostridium difficile MIC90, 32 micrograms/ml) and was only moderately active against isolates of Clostridium perfringens (MIC90, 2 micrograms/ml), Peptostreptococcus spp. (MIC90, 4 micrograms/ml), Chlamydia trachomatis (MIC90, 4 micrograms/ml), Mycoplasma hominis (MIC90, 2 micrograms/ml), and Urea-plasma urealyticum (MIC90, 8 micrograms/ml). Lomefloxacin was found to be bactericidal at concentrations generally close to the MIC with greater than 3 log10 reduction in viability of exponentially dividing cultures of Escherichia coli and S. aureus within 5 hr of exposure to concentrations at eight times the MIC. These results indicate a potential clinical role for lomefloxacin in the treatment of genitourinary tract infections caused by Gram-positive and Gram-negative bacteria, respiratory tract infections caused by susceptible organisms, and soft tissue infections caused by S. aureus.

Microbiological profile of telithromycin, the first ketolide antimicrobial.

Telithromycin, the first of the ketolide antimicrobials, has been specifically designed to provide potent activity against common and atypical/intracellular or cell-associated respiratory pathogens, including those that are resistant to beta-lactams and/or macrolide-lincosamide-streptograminB (MLS(B)) antimicrobials. Against gram-positive cocci, telithromycin possesses more potent activity in vitro and in vivo than the macrolides clarithromycin and azithromycin. It retains its activity against erm-(MLS(B)) or mef-mediated macrolide-resistant Streptococcus pneumoniae and Streptococcus pyogenes and against Staphylococcus aureus resistant to macrolides through inducible MLS(B) mechanisms. Telithromycin also possesses high activity against the Gram-negative pathogens Haemophilus influenzae and Moraxella catarrhalis, regardless of beta-lactamase production. In vitro, it shows similar activity to azithromycin against H. influenzae, while in vivo its activity against H. influenzae is higher than that of azithromycin. Telithromycin's spectrum of activity also extends to the atypical, intracellular and cell-associated pathogens Legionella pneumophila, Mycoplasma pneumoniae and Chlamydia pneumoniae. In vitro, telithromycin does not induce MLS(B) resistance and it shows low potential to select for resistance or cross-resistance to other antimicrobials. These characteristics indicate that telithromycin will have an important clinical role in the empirical treatment of community-acquired respiratory tract infections.

Clinical and bacteriological efficacy of the ketolide telithromycin against isolates of key respiratory pathogens: a pooled analysis of phase III studies.

A pooled analysis of data from 13 phase III studies of telithromycin in the treatment of community-acquired pneumonia, acute exacerbations of chronic bronchitis, acute sinusitis or group A beta-haemolytic streptococcal pharyngitis and tonsillitis was undertaken. Causative key respiratory tract pathogens (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, Staphylococcus aureus and Streptococcus pyogenes) were isolated at entry to the studies from cultures of relevant respiratory samples and tested for their susceptibility to telithromycin, penicillin and macrolides (erythromycin A). The combined clinical and bacteriological efficacy of telithromycin at the post-therapy, test-of-cure visit (days 17-24) was assessed in patients from whom a microbiologically evaluable pathogen was isolated at entry. More than 98% of key respiratory pathogens isolated, including penicillin G- and macrolide (erythromycin A)-resistant strains of S. pneumoniae, demonstrated full or intermediate susceptibility to telithromycin in vitro at the breakpoints of < or = 1.0 mg/L (susceptible) and 2.0 mg/L (intermediate) used for the purpose of evaluating the susceptibility of isolates recovered during the clinical trials. Treatment with telithromycin 800 mg once-daily for 5, 7 or 7-10 days resulted in high rates of clinical cure (88.5%) and a satisfactory bacteriological outcome (88.9%), similar to the figures seen with comparator antibacterial agents. Clinical cure and eradication rates were good for all key respiratory pathogens, including penicillin G- and macrolide (erythromycin A)-resistant S. pneumoniae. The results suggest that telithromycin will provide effective empirical therapy for community-acquired upper and lower respiratory tract infections.

Antimicrobial resistance of Streptococcus pneumoniae and Haemophilus influenzae in Sao Paulo, Brazil from 1996 to 2000.

This study was undertaken to assess the in vitro activity of several antimicrobial agents against Brazilian isolates of Streptococcus pneumoniae and Haemophilus influenzae from 1996 to 2000. The antibiotics used were penicillin, amoxicillin/clavulanic acid (A/C), ampicillin, amoxicillin, cefaclor, cefdinir, cefixime, cefprozil, ceftriaxone, cefuroxime, azithromycin, clarithromycin, erythromycin, ciprofloxacin, levofloxacin, ofloxacin, chloramphenicol, clindamycin, doxycycline and trimethoprim/sulphamethoxazole (T/S). MICs were determined by the National Committee for Clinical Laboratory Standards (NCCLS) method and interpreted using NCCLS and PK/PD breakpoints. For S. pneumoniae 80.0% were penicillin susceptible, 18.3% intermediate, 1.7% resistant; most active agents were amoxicillin, A/C, ceftriaxone and levofloxacin; T/S was the least active agent. Beta-lactamase was produced by 13.7% of H. influenzae. All were susceptible to A/C, cefdinir, cefixime, ceftriaxone and quinolones. The least active agents were T/S and macrolides.

The Nearchus project: antibiotic susceptibility of respiratory pathogens and clinical outcome in lower respiratory tract infections at 27 centres in the UK.

Community-acquired respiratory infections are usually treated empirically by the primary care physician. Increasing antibiotic resistance, for example, in pneumococci, prompted a UK survey of antibiotic susceptibility of three major lower respiratory tract pathogens, Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Each of 27 centres was asked to collect up to 100 isolates of the three species and submit them for confirmation of identity and for susceptibility testing to a central laboratory. In addition, general practitioners were asked for demographic details on the patient, their treatment and the clinical outcome. Of 1689 viable pathogens collected, there were 1078 (64%) strains of H. influenzae, 258 (15%) of M. catarrhalis and 353 (21%) of S. pneumoniae. Production of beta-lactamase was detected in 163 (15%) of 1078 isolates of H. influenzae and in 243 (94%) isolates of M. catarrhalis. For S. pneumoniae, moderate resistance to penicillin (MIC 0.12-1 mg/l) was found in 12 (3.4%) isolates and high level resistance (MIC > or = 2 mg/l) in 13 (3.7%) isolates. The most common individual treatments were amoxycillin, amoxycillin/clavulanate (amoxyclav) , and erythromycin. Complete or partial clinical resolution was achieved in 88% of 809 patients infected with H. influenzae, 83% of 197 infected with M. catarrhalis and 90% of 255 infected with S. pneumoniae.

Disinfection of gastrointestinal fibrescopes: an evaluation of the Pauldrach Endocleaner, and various chemical agents.

The Pauldrach Endocleaner was evaluated for the disinfection of gastrointestinal fibrescopes, and found to be a convenient, relatively inexpensive machine for use in endoscopy clinics. An experimental procedure was designed, for use with the endocleaner, which allowed application of an inoculum of Pseudomonas aeruginosa to a Fujinon OX52 endoscope and its subsequent quantitation before and after disinfection procedures. Using aldehyde based disinfectants ('Cidex', 'Kohrsolin' and 'Gigasept') it was possible to achieve a 99.999% reduction in the recovery of viable Ps. aeruginosa with a minimum exposure time of 20 min 'Dettox ABC' and buffered hypochlorite (100 ppm) were less effective achieving an approximately 99% reduction with a minimum exposure time of 30 min. Following apparently adequate disinfection and irrespective of the disinfectant used, the endoscope was found to be heavily contaminated with Ps. aeruginosa when examined after overnight storage at room temperature thus emphasising the need for meticulous disinfection of instruments prior to use in a day's list.

Contamination of blood during cardiopulmonary bypass: the effect of antibiotic prophylaxis.

Despite antibiotic prophylaxis in cardiac surgery, gram-positive bacteria can be isolated in up to 10% of intraoperative blood cultures. During a prospective randomized trial, blood was collected from the oxygenator at the end of bypass in 58 patients given teicoplanin and in 60 others given flucloxacillin and tobramycin. Coagulase-negative staphylococci were cultured from 16 patients given teicoplanin but in only four cases after flucloxacillin and tobramycin (Fisher's exact test, P = 0.005). In contrast, Propionibacterium spp. or coryneforms were isolated from 22 patients given flucloxacillin and tobramycin and from only one patient in the teicoplanin group. There were no cases of prosthetic valve endocarditis. After 3 h exposure to 4 x MIC of teicoplanin there was only a 10-60 fold reduction in cfus of Staphylococcus epidermidis, which may partly explain the excess of these organisms.

Aminosidine (paromomycin) in the treatment of leishmaniasis imported into the United Kingdom.

We report 11 patients with leishmaniasis from different endemic areas, treated in the UK with intravenous aminosidine alone or in combination with other drugs. Clinical and parasitological cures were achieved in all 7 patients from the Mediterranean zone who had visceral disease, with one relapse. Two of 4 patients with cutaneous or mucosal disease were cured; the other 2, from Iraq and Iran, did not respond. Toxic effects were high-tone deafness in 2 patients, one of whom had pre-existing renal impairment, and transient, mild elevation of serum creatinine in 3. Aminosidine is an effective, tolerable and relatively non-toxic alternative to existing antileishmanial drugs for the treatment of visceral leishmaniasis. Further studies will be needed to assess its place in cutaneous and mucosal disease.

Evolving resistance patterns in community-acquired respiratory tract pathogens: first results from the PROTEKT global surveillance study. Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin.

In recent years, antibacterial resistance among respiratory pathogens implicated in community-acquired respiratory tract infections (RTIs) has spread worldwide at an alarming rate. Thus, there is a pressing need for new antibacterials that retain activity against resistant organisms, have a low potential to select for resistance and do not induce cross-resistance. Telithromycin is the first of a new class of antibacterials - the ketolides - that have been designed specifically to overcome resistance among respiratory tract pathogens. This paper presents the first results of the PROTEKT study (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin), a worldwide surveillance study initiated to chart the prevalence of important resistance phenotypes and genotypes and the comparative activity of telithromycin against such strains. Analysis of over 7,000 bacterial isolates by April 2001 has confirmed the notable prevalence of strains resistant to commonly prescribed RTI antibacterials for all the pathogens studied. Telithromycin demonstrates high activity against isolates of Streptococcus pneumoniae, irrespective of penicillin G, macrolide or fluoroquinolone resistance. Telithromycin is also highly active against other respiratory tract pathogens, including Streptococcus pyogenes and beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis. These data justify the assertion that telithromycin is a promising new candidate for the empirical treatment of community-acquired RTIs, particularly in the face of increasing antibacterial resistance.

Antibacterial resistance among children with community-acquired respiratory tract infections (PROTEKT 1999-2000).

OBJECTIVE: To determine the susceptibility of bacterial respiratory tract pathogens, isolated from children (0-12 years) as part of the global PROTEKT surveillance study (1999-2000), to a range of antibacterials, including the ketolide telithromycin. METHODS: Minimum inhibitory concentrations of the antibacterials studied were determined at a central laboratory using the NCCLS microdilution broth method. Macrolide resistance mechanisms were detected by PCR. RESULTS: Of 779 Streptococcus pneumoniae isolates worldwide, 43% were non-susceptible to penicillin (18% intermediate; 25% resistant) and 37% were resistant to erythromycin, with considerable intercountry variation. Eighteen per cent of 653 Haemophilus influenzae and >90% of 316 Moraxella catarrhalis isolates produced beta-lactamase. Of 640 Streptococcus pyogenes isolates, 10% were resistant to erythromycin, with considerable intercountry variation. All S. pneumoniae and 99.8% of H. influenzae isolates were susceptible to telithromycin using breakpoints proposed to the NCCLS (

A UK multicentre study of the antimicrobial susceptibility of bacterial pathogens causing urinary tract infection.

OBJECTIVES: To determine the prevalence of resistance amongst urinary tract pathogens against antimicrobials used to treat urinary tract infections (UTIs) in the UK to provide data to help direct empirical therapy. METHOD: During 1999-2000, a total of 1291 bacterial isolates causing UTI were collected from 8 centres in the UK. Isolates were cultured from patients with (1). community-acquired UTI in those less than 65 years old (397), (2). hospital-acquired UTI other than those admitted with pyelonephritis (394), (3). pyelonephritis (108) and (4). community-acquired UTI in those greater than 65 years old (392). After re-identification, MICs for a range of antimicrobials were determined and interpreted using NCCLS procedures and interpretive guidelines. RESULTS: Escherichia coli was the predominant pathogen in all categories but the total percentage for each category varied (56.3-77.3%). The next three pathogens of importance were Enterococcus faecalis, Klebsiella pneumoniae and Proteus mirabilis which varied in prevalence slightly from category to category. The activity of amoxycillin against E. coli (51.3% susceptible) was greatly reduced as a result of beta-lactamase production and only partially restored by the addition of clavulanic acid (78.8% susceptible). Cefuroxime was very active against E. coli using parenteral form breakpoints (97.1% susceptible) but less so using oral form breakpoints (68.6% susceptible). Cefuroxime was inactive against Enterococcus spp. and Pseudomonas spp. Nitrofurantoin was very active against isolates of E. coli (96.3% susceptible) and E. faecalis but not against K. pneumoniae, P. mirabilis or Pseudomonas aeruginosa. Overall susceptibility to trimethoprim ranged from 58.1% to 84.5% for the most prevalent pathogens. Ciprofloxacin was highly active against the UTI pathogens examined in this study with susceptibilities of between 88.6% and 97.7% for the most prevalent pathogens (E. coli, n=864, 97.7% susceptible) and was the only oral agent tested with activity against Pseudomonas spp. CONCLUSION: These data provide much needed information on the prevalence of antimicrobial resistance amongst pathogens currently causing UTI in the UK.

The treatment of neonatal meningitis due to gram-negative bacilli with ciprofloxacin: evidence of satisfactory penetration into the cerebrospinal fluid.

We describe two cases of neonatal meningitis due to Gram-negative bacilli treated successfully with ciprofloxacin. Examination of serial samples of cerebrospinal fluid indicated the effect of meningeal inflammation on penetration of this drug into the CSF.

Trends in the antimicrobial susceptibility of bacterial respiratory tract pathogens--findings of the Alexander Project 1992-1996.

The Alexander Project is an ongoing, multicenter surveillance study of the antimicrobial susceptibility of community-acquired lower respiratory tract bacterial pathogens with testing undertaken in a central laboratory. During the period 1992-1995, isolates were collected from geographically separate centers in countries of the EU and various states in the USA. In 1996, the project was extended to centers in Mexico, Brazil, Saudi Arabia, South Africa, Hong Kong and other European countries not previously included. Within Europe, France and Spain are established as centers with a high prevalence of both penicillin-intermediate (MIC 0.12-1 mg/l) and resistant (MIC > or = 2 mg/l) strains of Streptococcus pneumoniae, with combined resistance rates in excess of 40% in Toulouse and Barcelona in 1996. Combined rates of intermediate and resistant strains in excess of 10% were found in 1996, the first year of sampling, in Belgium, Switzerland, the Slovak Republic and Hungary. Penicillin resistance has evolved in the USA during the period of study, with rates for combined pneumococcal isolates increasing from 5.6% in 1992 to 16.4% in 1996. Of the new, non-European centers joining the project in 1996, Mexico (intermediate 31.4%, resistant 15.7%) and, in particular, Hong Kong (intermediate 9.1%, resistant 50%) are centers with a high prevalence of penicillin resistance. Macrolide resistance has increased generally among pneumococcal isolates examined during the study period, both in penicillin-susceptible and resistant isolates, and was evident in 16.5% of the 2160 isolates collected during 1996. In four centers (London, UK; Genoa, Italy; Pokfulum, Hong Kong; Leuven, Belgium), macrolide resistance rates exceeded those of combined penicillin-intermediate and resistant strains; in 12/19 centers (63.2%) macrolide resistance was more prevalent than penicillin resistance. In 1996, macrolide resistance was found in excess of 10% of isolates in Poland, Hungary, London, UK, combined USA isolates, the Slovak Republic, Barcelona, Spain, Genoa, Italy, Mexico, Toulouse, France and Pokfulum, Hong Kong. beta-lactamase production was the principal mechanism of resistance found among isolates of Haemophilus influenzae, with rates in 1996 of around 20% or more in France, Belgium and Spain, and in excess of 10% in the UK and the Czech Republic. In the same year in non-European centers, Mexico (25%), Saudi Arabia (27.9%), Hong Kong (37.1%) and the USA (30.4% of combined isolates) had a high prevalence of beta-lactamase production. Isolates of beta-lactamase-negative, ampicillin-resistant H. influenzae were generally very uncommon, with only Barcelona, Spain consistently associated with rates in excess of 1%. beta-lactamase production in Moraxella catarrhalis was observed in over 90% of isolates tested in 1996.

Future trends in antimicrobial chemotherapy: expert opinion on the 43rd ICAAC.

The current document bestows an expert synopsis of key new information presented at the 43rd Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) meeting in 2003. Data is presented on the socio-political aspects of and policies on antimicrobial prescribing, novel mechanisms of resistance in Streptococcus pneumoniae, and current epidemiological trends in global resistance. Novel information on new (and existing) antimicrobial agents--new penicillins, cephalosporins, monobactams and oxipenem inhibitors, ketolides, glycopeptides, fluoroquinolones (and hybrids), peptides, daptomycin, aminomethylcyclines, glycylcyclines, and newer formulations of agents such as amoxycillin-clavulanate--provides renewed hope that resistant pathogens can be controlled through use of more potent agents. Improved strategies for the use of existing antimicrobial agents, such as the use of high-dose regimens, short-course therapy, also may delay or reduce the development of resistance and preserve the value of our antibiotic armamentarium.