Non-susceptibility trends and serotype distributions among Streptococcus pneumoniae from community-acquired respiratory tract infections and from bacteraemias in the UK and Ireland, 1999 to 2007.

OBJECTIVES: Pneumococcal disease is prevalent and is a cause of significant morbidity and mortality in the UK and Ireland. We describe the antimicrobial susceptibility and serotype distributions of Streptococcus pneumoniae causing bacteraemia and community-acquired pneumonia in these countries from 1999/2000 to 2006/7, predominantly prior to the introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) into the standard vaccination schedule in September 2006. METHODS: The BSAC Respiratory and Bacteraemia Resistance Surveillance Programmes collected S. pneumoniae from sentinel laboratories distributed across the UK and Ireland. A central laboratory for each programme re-identified the isolates, determined their serotypes and measured MICs by the BSAC agar dilution method. RESULTS: The prevalence of antimicrobial non-susceptibility, although significant, was generally below the global average. There was no convincing evidence of increasing non-susceptibility over time in either study. The results showed clear differences in the serotype distribution between respiratory and blood isolates, but suggested that PCV7 would provide adequate coverage of invasive isolates in the UK and Ireland. A significant and rapid increase of the non-vaccine serotype 1 among blood isolates from 2001 to 2006 was worrying, given the spread of hypervirulent serotype 1 clones elsewhere in the world. CONCLUSIONS: Continued surveillance of both antimicrobial non-susceptibility and serotype distribution changes following the introduction of PCV7 into the routine immunization schedule in the UK and Ireland is imperative. The data presented here, largely obtained prior to the introduction of PCV7 in the UK, provide a valuable baseline against which to monitor changes in antimicrobial non-susceptibility and serotype distribution and hence to identify the expansion of any significant clones.

Non-susceptibility trends among Haemophilus influenzae and Moraxella catarrhalis from community-acquired respiratory tract infections in the UK and Ireland, 1999-2007.

OBJECTIVES: To determine the antimicrobial susceptibility of Haemophilus influenzae and Moraxella catarrhalis causing community-acquired respiratory tract infections in the UK and Ireland from 1999/2000 to 2006/07. METHODS: Sentinel laboratories across the UK and Ireland contributed up to a fixed quota of isolates of defined organisms per annum. A central laboratory confirmed the isolates' identities, measured MICs by the BSAC agar dilution method and undertook further testing by standard methods. The variability of the MIC method was assessed by repeated annual testing of control isolates. BSAC and EUCAST breakpoints were used. Statistical analysis adjusted for inter-centre variation by random effects logistic regression. RESULTS: A total of 7371 H. influenzae and 2529 M. catarrhalis isolates were investigated. Over 90% of the H. influenzae isolates were susceptible to most of the antimicrobials tested, the exceptions being ampicillin (84.6% susceptible), trimethoprim (84.0%), cefuroxime (82.9%), amoxicillin (77.2%) and cefaclor (11.7%). For M. catarrhalis, resistance was solely due to beta-lactamase (prevalence over 91%) reducing susceptibility to penicillins only. There was little evidence of decreased antimicrobial susceptibility between 1999 and 2007 in either pathogen, except for a reduction in susceptibility to trimethoprim in H. influenzae (90.3% to 82.6%, P < 0.00001). On the other hand, tetracycline susceptibility in H. influenzae increased over this period in the UK and Ireland (96.5 to 98.8%, P = 0.00008). CONCLUSIONS: Despite increased resistance in respiratory pathogens from other parts of the world, the susceptibility of H. influenzae and M. catarrhalis to all agents, except tetracycline and trimethoprim in the case of H. influenzae, has remained constant during this longitudinal study.

Regional trends in beta-lactam, macrolide, fluoroquinolone and telithromycin resistance among Streptococcus pneumoniae isolates 2001-2004.

OBJECTIVES: To determine global antibacterial resistance rates among community-acquired isolates of Streptococcus pneumoniae. METHODS: Between 2001 and 2004, 20,142 S. pneumoniae isolates from 151 centres in 40 countries were collected and tested for susceptibility to common antibacterials in the PROTEKT surveillance study. RESULTS: The prevalence of beta-lactam and macrolide resistance did not change, but there was marked geographic variability. The most common macrolide resistance mechanism was ribosomal methylation mediated by erm(B), except in Canada, Greece and the USA where drug efflux mediated by mef(A) was predominant. The erythromycin minimum inhibitory concentration for mef(A) isolates increased significantly (P<0.001; chi2 test). The global prevalence of macrolide-resistant isolates positive for both erm(B) and mef(A) was 12.0% in 2003-2004; erm(B)+mef(A) strains were particularly common in South Korea (40.8%), South Africa (46.4%) and the USA (29.6%). Telithromycin was the most active antibacterial tested. Over the studied period, > or = 99.7% of all isolates and > 99% of erythromycin-resistant isolates, irrespective of genotype, were susceptible to telithromycin. CONCLUSIONS: These results confirm the high worldwide prevalence of resistance to commonly used antibacterial agents and multiple resistance phenotypes among clinical isolates of S. pneumoniae and suggest that high-level macrolide resistance is continuing to increase in most countries.

Trends in penicillin and macrolide resistance among pneumococci in the UK and the Republic of Ireland in relation to antibiotic sales to pharmacies and dispensing doctors.

It is widely believed that reducing antimicrobial usage should reduce resistance, although observational evidence is mixed. Pneumococci make ideal subjects to test this belief as they are widely surveyed and lack an animal reservoir. Accordingly, susceptibility data for pneumococci in the UK and Ireland were retrieved from the Health Protection Agency's LabBase/CoSurv system and from the European Antimicrobial Resistance Surveillance System (EARSS) and British Society for Antimicrobial Chemotherapy (BSAC) databases. The BSAC surveillance examines respiratory pneumococci; the other systems focus upon invasive organisms only, with the LabBase/CoSurv system being the most comprehensive, capturing data on most bacteraemias in England and Wales. National pharmacy sales data were obtained from the IMS Health MIDAS database and were modelled to the resistance data by logistic and linear regression analysis. All systems except for the BSAC respiratory surveillance data indicated that penicillin resistance has fallen significantly since 1999 in the UK, whereas macrolide resistance has been essentially stable, or has risen slightly. The data for Ireland were based on smaller sample sizes but suggested a fall in penicillin non-susceptibility from 1999 to 2004, with conflicting evidence for macrolide resistance. The recent decreasing trend in penicillin resistance is in contrast to a rising trend in England and Wales until (at least) 1997 and strongly rising macrolide resistance from 1989 to 1993. UK pharmacy sales of macrolides and oral beta-lactams fell by ca. 30% in the late 1990s following increased concern about resistance, before stabilising or rising weakly; sales in Ireland were stable or rose slightly in the study period. We conclude that falling penicillin resistance in pneumococci followed reduced sales of oral beta-lactams to pharmacies in the UK, but a similar fall in macrolide sales was not associated with any fall in resistance. Stabilisation or decline in penicillin resistance has occurred in Ireland despite stable or increasing oral beta-lactam sales.

The Alexander Project: the benefits from a decade of surveillance.

The Alexander Project, initiated in 1992 as an international, multicentre, longitudinal surveillance study of antimicrobial susceptibility among common respiratory pathogens, has been pivotal in defining the role of global surveillance. At the time, there were few studies in which data were collected in a way that allowed meaningful comparisons to be made between studies, locations or over time. The project instituted the use of a central laboratory and standardized methods for the collection of isolates and determination of susceptibility, and this was continued with the addition of two further reference laboratories. Data from the study have provided a resource for measuring trends in the susceptibility patterns of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis at country, regional and global levels. Determination and publication of quantitative MICs enabled detailed assessment of changes in susceptibility distributions and assessment of microbiological and potential clinical susceptibility using different breakpoints, including those based on pharmacokinetic/pharmacodynamic parameters. Comparisons of antimicrobial usage patterns and resistance prevalences over time allowed hypotheses to be examined with respect to the role of quantity and type of antimicrobial use in the selection and spread of resistance. The resulting collection of isolates has provided a valuable resource for molecular studies into the evolution of resistance over time and location; a substantial proportion of this collection is now in the public domain. This paper reviews the 10 years of the Alexander Project and the benefits it has brought to an understanding of the evolution of antibacterial resistance in community respiratory bacteria.

Demographic analysis of antimicrobial resistance among Streptococcus pneumoniae: worldwide results from PROTEKT 1999-2000.

DESIGN: The influence of demographic factors upon antimicrobial resistance among 3362 isolates of Streptococcus pneumoniae from 25 countries was investigated, using univariate comparison and multivariate logistic regression. RESULTS: Eleven countries had significantly higher rates (Odds ratios [OR]: 2.50-64.79) of penicillin and/or erythromycin resistance than the UK. After taking country effects into account, rates of penicillin resistance (OR 1.98) and erythromycin resistance (OR 1.89) were significantly higher among infants than adults. Fewer (OR 0.69) erythromycin-resistant isolates were collected from male than female patients. There was no difference in the incidence of penicillin or erythromycin resistance among inpatients or outpatients. Penicillin resistance was more prevalent among ear swabs than blood cultures (OR 2.07). Erm(B), the predominant macrolide resistance mechanism across all age groups, was particularly prevalent among bronchoalveolar lavage (69.1%) and sinus (68.8%) isolates. Isolates possessing both erm(B) and mef(A) were generally collected from South Korea and were most common among infants and children (10.3%) and ear samples (17.3%). Telithromycin susceptibility was >99.5%, irrespective of demography. CONCLUSIONS: Although demography had a significant impact on antimicrobial resistance of pneumococci, telithromycin remained highly active across all demographic groups.

Comparative antimicrobial susceptibility of respiratory tract pathogens.

Bacterial respiratory tract infections (RTIs), whether primary or subsequent to viral infection, are a frequent cause of morbidity and mortality worldwide. Treatment of these infections is most often empirical. Therefore, an antimicrobial's antibacterial spectrum must include the most likely pathogens: Streptococcus pneumoniae, the most frequent cause of community-acquired pneumonia (CAP), Haemophilus influenzae, Moraxella catarrhalis, and Staphylococcus aureus, as well as atypicals such as Mycoplasma pneumoniae, Legionella pneumophila and Chlamydophila (Chlamydia) pneumoniae. In addition, knowledge of antimicrobial resistance among these key pathogens is imperative for physicians to choose the most appropriate therapeutic agent. The latest data from global surveillance studies indicates that high-level resistance to penicillin (MIC > or =2 mg/l) among isolates of S. pneumoniae varies widely by geographic location. Rates exceed 20% in the USA, Mexico, Japan, Saudi Arabia, Israel, Spain, France, Greece, Hungary, and the Slovak Republic. In South Africa, Hong Kong, Taiwan, and South Korea rates exceed 50%. Penicillin non-susceptibility--including isolates exhibiting high-level resistance and intermediate susceptibility (MIC 0.12-1 mg/l)--is frequently found in association with macrolide resistance, which is found at a prevalence of 70-80% in some Asian countries. Trimethoprim-sulfamethoxazole (TMP-SMX) and tetracycline resistance, either individually or combined with macrolide resistance as multiple resistance, is also associated with reduced susceptibility to penicillin. Another concern about antimicrobial resistance in respiratory tract pathogens is beta-lactamase production among isolates of H. influenzae and M. catarrhalis. However, respiratory fluoroquinolones, of which levofloxacin has been available for the longest time, currently remain active against the great majority of common bacterial respiratory pathogens, including atypicals.

Activity of telithromycin and comparators against bacterial pathogens isolated from 1,336 patients with clinically diagnosed acute sinusitis.

BACKGROUND: Increasing antimicrobial resistance among the key pathogens responsible for community-acquired respiratory tract infections has the potential to limit the effectiveness of antibiotics available to treat these infections. Since there are regional differences in the susceptibility patterns observed and treatment is frequently empirical, the selection of antibiotic therapy may be challenging. PROTEKT, a global, longitudinal multicentre surveillance study, tracks the activity of telithromycin and comparator antibacterial agents against key respiratory tract pathogens. METHODS: In this analysis, we examine the prevalence of antibacterial resistance in 1,336 bacterial pathogens, isolated from adult and paediatric patients clinically diagnosed with acute bacterial sinusitis (ABS). RESULTS AND DISCUSSION: In total, 58.0%, 66.1%, and 55.8% of S. pneumoniae isolates were susceptible to penicillin, cefuroxime, and clarithromycin respectively. Combined macrolide resistance and reduced susceptibility to penicillin was present in 200/640 (31.3 %) of S. pneumoniae isolates (128 isolates were resistant to penicillin [MIC > or = 2 mg/L], 72 intermediate [MIC 0.12-1 mg/L]) while 99.5% and 95.5% of isolates were susceptible to telithromycin and amoxicillin-clavulanate, respectively. In total, 88.2%, 87.5%, 99.4%, 100%, and 100% of H. influenzae isolates were susceptible to ampicillin, clarithromycin, cefuroxime, telithromycin, and amoxicillin-clavulanate, respectively. In vitro, telithromycin demonstrated the highest activity against M. catarrhalis (MIC50 = 0.06 mg/L, MIC90 = 0.12 mg/L). CONCLUSION: The high in vitro activity of against pathogens commonly isolated in ABS, together with a once daily dosing regimen and clinical efficacy with 5-day course of therapy, suggest that telithromycin may play a role in the empiric treatment of ABS.

In vitro activities of telithromycin, linezolid, and quinupristin-dalfopristin against Streptococcus pneumoniae with macrolide resistance due to ribosomal mutations.

To date, 86 of 7,746 macrolide-resistant Streptococcus pneumoniae isolates from 1999 to 2002 PROTEKT (Prospective Resistant Organism Tracking and Epidemiology for the Ketolide Telithromycin) surveillance studies were negative for methylase and efflux mechanisms. Mutations in 23S rRNA or the genes encoding riboprotein L4 or L22 were found in 77 of 86 isolates. Six isolates were resistant to quinupristin-dalfopristin and two were resistant to linezolid, while telithromycin demonstrated good activities against all isolates.

Activity of telithromycin against key pathogens associated with community-acquired respiratory tract infections.

OBJECTIVES: To investigate the correlation between in vitro susceptibility of isolates and clinical outcomes with telithromycin in respiratory tract infections. METHODS: The activity of telithromycin was determined by in vitro susceptibility testing of key respiratory tract pathogens isolated from patients with community-acquired pneumonia, acute exacerbations of chronic bronchitis or acute maxillary sinusitis enrolled in 14 Phase III/IV clinical trials evaluating the clinical efficacy of telithromycin. RESULTS: In this pooled analysis, telithromycin mode minimum inhibitory concentration (MIC) and MIC90, respectively, were: 0.016 and 0.03 mg/l against Streptococcus pneumoniae (n=626); 0.03 and 0.5 mg/l for penicillin-resistant S. pneumoniae (n=56); 0.03 and 1 mg/l for erythromycin-resistant S. pneumoniae (n=81); 2 and 4 mg/l against Haemophilus influenzae (including beta-lactamase producers; n=627); both 0.12 mg/l for Moraxella catarrhalis (n=159) and both 0.25 mg/l for Staphylococcus aureus (n=124). Telithromycin (5 or 7-10 days) resulted in overall clinical and bacteriologic success rates of 88.1% (1593/1808) and 89% (1593/1789), respectively. CONCLUSIONS: High levels of in vitro susceptibility to telithromycin are paralleled by high rates of clinical cure and bacteriologic eradication.

Activities of telithromycin against 13,874 Streptococcus pneumoniae isolates collected between 1999 and 2003.

Telithromycin MICs for 13,874 Streptococcus pneumoniae isolates collected in the first 3 years of the global PROTEKT study (1999 to 2003) were studied. There was no change in the distribution of telithromycin MICs over this period, even in countries where telithromycin is in use. The telithromycin MICs for 10 isolates (0.07%) were >/=4 micro g/ml, and these 10 isolates contained erm(B); there was no evidence of reproducible clonal spread between centers.

Molecular epidemiology of multiresistant Streptococcus pneumoniae with both erm(B)- and mef(A)-mediated macrolide resistance.

Of a total of 1043 macrolide-resistant Streptococcus pneumoniae isolates collected from 24 countries as part of PROTEKT 1999-2000, 71 isolates tested positive for both the mef(A) and erm(B) genes. Of 69 isolates subjected to further molecular investigations, all were resistant to tetracycline, 63 (91.3%) were resistant to penicillin, and 57 (82.6%) were resistant to trimethoprim-sulfamethoxazole. One isolate was also fluoroquinolone resistant, and another was resistant to quinupristin-dalfopristin. The ketolide telithromycin retained activity against all of the isolates. Of the 69 of these 71 isolates viable for further testing, 46 were from South Korea, 13 were from the United States, 8 came from Japan, and 1 each came from Mexico and Hungary. One major clonal complex (59 [85.5%] of 69 isolates) was identified by serotyping (with 85.5% of the isolates being 19A or 19F), pulsed-field gel electrophoresis, and multilocus sequence typing. The remaining isolates were less clonal in nature. Representative isolates were shown to carry the mobile genetic elements Tn1545 and mega, were negative for Tn1207.1, had tetracycline resistance mediated by tet(M), and contained the mef(E) variant of mef(A). All isolates were positive for mel, a homologue of the msr(A) efflux gene. These clones are obviously very efficient at global dissemination, and hence it will be very important to monitor their progress through continued surveillance. Telithromycin demonstrated high levels of activity (MIC for 90% of the strains tested, 0.5 micro g/ml; MIC range, 0.06 to 1 micro g/ml) against all isolates.

PROTEKT 1999-2000: a multicentre study of the antibiotic susceptibility of respiratory tract pathogens in Hong Kong, Japan and South Korea.

A multicentre surveillance study performed in the Far East during 1999-2000 investigated the in vitro activity of >20 antibacterials against common respiratory pathogens. In Hong Kong, Japan, and South Korea, 57.1, 44.5 and 71.5% Streptococcus pneumoniae were penicillin-resistant and 71.4, 77.9 and 87.6% were erythromycin-resistant, respectively. Overall, >90% of penicillin-resistant strains were also macrolide-resistant. All strains were susceptible to telithromycin. Fluoroquinolone-resistant isolates in Japan (1.3%), Hong Kong (14.3%) and South Korea (2.9%) were mostly co-resistant to penicillin, macrolides and tetracycline. Beta-lactamase production by Haemophilus influenzae isolates was 8.5% in Japan, 17.1% in Hong Kong and 64.7% in strains from South Korea. A single (0.27%) BLNAR isolate was obtained in Japan. There was no fluoroquinolone resistance. Moraxella catarrhalis was inhibited by telithromycin at

Comparison of BSAC agar dilution and NCCLS broth microdilution MIC methods for in vitro susceptibility testing of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis: the BSAC Respiratory Resistance Surveillance Programme.

OBJECTIVE: The aim of this study was to establish the degree of comparability between the NCCLS broth microdilution and BSAC agar dilution MIC methods of antimicrobial susceptibility testing. METHODS: Six hundred and sixty-one clinical isolates of Streptococcus pneumoniae, 936 Haemophilus influenzae and 421 Moraxella catarrhalis, collected in the winter of 1999-2000 by 20 laboratories in the UK and Eire from patients with presumed community-acquired lower respiratory infections, were tested by the two methods. MIC agreement was defined as excellent (good) if results were within +/- 1 doubling dilution for > or =90% (> or =80%) of isolates and within +/- 2 doubling dilutions for > or =95%. Isolates were categorized as susceptible, intermediate or resistant using the breakpoints appropriate to the testing method. RESULTS: MIC agreement was good or excellent in 27 of 36 organism-agent combinations. Agreement was less for M. catarrhalis than for other species, and lower in all three species for cefaclor and trimethoprim than for other antimicrobials. Discrepancies in categorization occurred only occasionally, and were generally explained by differences in breakpoints rather than in measured MICs. One exception was S. pneumoniae with penicillin. Despite excellent MIC agreement and identical breakpoints, 9% of these had minor discrepancies, mainly because 7% of isolates were found intermediate by the BSAC method but resistant by the NCCLS method. CONCLUSION: There is generally very good agreement between the MICs obtained by the BSAC agar dilution and NCCLS broth microdilution methods in this population of isolates, comparable to the level of agreement achieved between different laboratories using a single method. Breakpoint differences contribute to most of the discrepancies in susceptibility categorization.

Antimicrobial susceptibility of lower respiratory tract pathogens in Great Britain and Ireland 1999-2001 related to demographic and geographical factors: the BSAC Respiratory Resistance Surveillance Programme.

OBJECTIVE: The aim of this study was to assess the antimicrobial susceptibility of community-acquired lower respiratory pathogens in Great Britain and Ireland, and investigate its relationship with demographic and geographical factors using multiple logistic regression analysis. METHODS: A total of 1328 isolates of Streptococcus pneumoniae, 1894 Haemophilus influenzae and 845 Moraxella catarrhalis were collected from lower respiratory clinical specimens (primarily sputum) by 20 laboratories in Great Britain (England, Wales and Scotland) and Ireland (Northern Ireland and Eire) between 1999 and 2001. RESULTS: Of 1154 S. pneumoniae from Great Britain, 92-100% were susceptible to beta-lactams (only 0.2% having penicillin MICs > or =2 mg/L), 89% were susceptible to erythromycin, 93% susceptible to tetracycline, and 94-100% intermediate or susceptible to fluoroquinolones. Susceptibility to agents other than fluoroquinolones was less frequent in the 174 isolates from Ireland: beta-lactam susceptibility was 68-99% (3.4% having penicillin MICs > or =2 mg/L), erythromycin susceptibility was 78% and tetracycline susceptibility was 82%. In multivariate analysis, susceptibility in S. pneumoniae was associated with country and patient age, being most common overall in the 20-49 years age group. Of 1894 H. influenzae, 15% produced beta-lactamase and 79-100% were susceptible to beta-lactams other than cefaclor. Ninety-six per cent were intermediate and 1% susceptible to erythromycin, 97% susceptible to tetracycline, and 89% susceptible to trimethoprim. Only one isolate showed resistance to ciprofloxacin. H. influenzae from sputum were more likely to be susceptible than isolates from other sources. Of 845 M. catarrhalis, 92% produced beta-lactamase and 9% were susceptible to ampicillin, >99% were susceptible to co-amoxiclav, cefotaxime, erythromycin and fluoroquinolones. CONCLUSIONS: Clinically relevant demographic factors predictive of susceptibility were country and patient age in S. pneumoniae, and specimen type (sputum/non-sputum) in H. influenzae. Susceptibility to most antimicrobials remains high in Ireland and very high in Great Britain.

The Alexander Project 1998-2000: susceptibility of pathogens isolated from community-acquired respiratory tract infection to commonly used antimicrobial agents.

OBJECTIVES: The Alexander Project is a continuing surveillance study, begun in 1992, examining the susceptibility of pathogens involved in adult community-acquired respiratory tract infections (CARTI) to a range of antimicrobial agents. MATERIALS AND METHODS: This study tested the susceptibility of isolates of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis collected between 1998 and 2000 to 23 antimicrobials. Minimum inhibitory concentrations of agents were determined using the broth microdilution method and interpreted according to NCCLS and pharmacokinetic/pharmacodynamic (PK/PD) breakpoints. RESULTS: In total, 8882 isolates of S. pneumoniae, 8523 isolates of H. influenzae and 874 isolates of M. catarrhalis were collected during 1998-2000 from centres in 26 countries. The world-wide prevalence of penicillin resistance (penicillin MICs > or = 2 mg/l) in isolates of S. pneumoniae was 18.2% over the study period, and the prevalence of macrolide resistance (erythromycin MICs > or = 1 mg/l) in this pathogen was 24.6%. Over the study period, macrolide resistance exceeded penicillin resistance in 19 of the 26 countries included in the study. Of the non-fluoroquinolone agents, the only oral agents to which over 90% of S. pneumoniae isolates were susceptible at both NCCLS and PK/PD breakpoints were amoxicillin (95.1%) and co-amoxiclav (95.5-97.9%). The prevalence of fluoroquinolone-resistant S. pneumoniae (ofloxacin MICs > or = 8 mg/l) was 1.1%. Gemifloxacin was the most potent fluoroquinolone tested against S. pneumoniae (99.9% susceptible). In isolates of H. influenzae, beta-lactamase production was 16.9%, whereas the prevalence of beta-lactamase-negative, ampicillin-resistant strains was low (0.2%). beta-Lactamase production in M. catarrhalis world-wide remained high over the period studied (92.1%). Using PK/PD breakpoints, the most active non-fluoroquinolone agents against H. influenzae were ceftriaxone (100% susceptible), cefixime (99.8%) and co-amoxiclav (98.1-99.6%). Co-amoxiclav, cefdinir and cefixime (100%) were the most active beta-lactams against M. catarrhalis. Both H. influenzae and M. catarrhalis were highly susceptible to the fluoroquinolones. CONCLUSIONS: These data demonstrate the continued evolution of and geographical variation in bacterial resistance and highlight the need for appropriate prescribing of antimicrobials in CARTI, using agents with adequate activity, based on local susceptibility profiles and PK/PD parameters.

Infecções do trato respiratório: principais agentes bacterianos e padrões de resistência Dados brasileiros do estudo internacional PROTEKT / Respiratory tract infections: major bacterial pathogens and patterns of resistance. Brazilian results from PROTEKT surveillance study

As infecções da trato respiratório (ITR) são responsáveis por significativa morbidade e mortalidade. Devido a sua diversificada etiologia e dificuldades diagnósticas, muitas vezes, o tratamento destas infecções é iniciado empiricamente.

Antimicrobial susceptibility of community-acquired respiratory tract pathogens in North America in 1999-2000: findings of the PROTEKT surveillance study.

The PROTEKT surveillance study commenced in 1999 to examine the antimicrobial susceptibility of community-acquired respiratory pathogens. We report here the results from 2371 isolates collected during 2000 by North American centers (Canada, n = 7; USA, n = 8). Overall, 21.3% of pneumococci (n = 687) were penicillin G-resistant (Canada, 10.3%; USA, 32.6%). Corresponding rates of erythromycin resistance were 16.3% and 31.5%. Telithromycin inhibited all penicillin- and erythromycin-resistant isolates at < or =1 microg/ml. Among 612 Hemophilus influenzae isolates, 22.4% were beta-lactamase-positive. Antimicrobial susceptibility of H. influenzae varied between 82.4% (clarithromycin) and 100% (cefpodoxime, levofloxacin). Importantly, one isolate was found to be resistant to both moxifloxacin and ciprofloxacin. Most Moraxella catarrhalis isolates were highly susceptible to the antimicrobials tested, except ampicillin. All Streptococcus pyogenes isolates (n = 382) were penicillin-susceptible and 5.2% were non-susceptible to erythromycin. S. pyogenes showed cross-resistance to other macrolides yet remained inhibited by telithromycin at < or =0.5 microg/ml. Methicillin resistance among Staphylococcus aureus was common (19.9%), particularly in the USA. The PROTEKT study confirms the widespread prevalence of antimicrobial resistance among common respiratory pathogens in North America, and hence the need for continued surveillance to guide optimal empiric therapy for community-acquired respiratory tract infections.