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Recent Declines in ß-Lactam and MLSB Resistances Among S. pneumoniae and Age-Related Effects:
Report from the SENTRY Antimicrobial Surveillance Program (North America, 1997 - 2002)
The JONES Group/JMI Laboratories, North Liberty, IA
D S ( C o n t i n u e d )
Background: The SENTRY Program has monitored emerging resistance (R) in S. pneumoniae (SPN) since 1997.
prepare a suspension equal to a 0.5 MacFarland turbidity standard. Using an autoinoculator, 100 µl of the inoculum Consistent increases in penicillin (PEN), erythromycin (ER) and clindamycin (CC) R have been documented each suspension was diluted in an appropriate broth for delivery of 5 x 104 CFU/well. Cation-adjusted Mueller-Hinton Change in macrolide resistance phenotype occurrence among S. pneumoniae isolates from North year, however year 2002 results indicate a shift to greater susceptibility (S). Details of this change were analyzed Activity and susceptibility rates for 6-7 selected antimicrobial agents against H. influenzae, M. catarrhalis, and S. pneumoniae broth with lysed horse blood for S. pneumoniae was dispensed into the wells of validated panels (TREK Diagnostics, America (2001 to 2002) listed by patient age group.
in the SENTRY Program-North America (2000-2002).
to determine patient populations and other demographics contributing to these reductions in R.
Cleveland, Ohio, USA). Panels were incubated in ambient air for 20 - 24 hours. MIC endpoints were determined as a lack of visible growth as outlined in the NCCLS approved standard. Interpretive criteria used were those of Methods: Among 16,489 community-acquired respiratory tract (CARTI) pathogens processed from North America
NCCLS M100-S13. Daily quality control was performed by the routine testing of ATCC strains including S. pneumoniae (NA) (1997 - 2002), a total of 6,562 SPN (1001 - 1201/year from > 30 sites) were tested by reference broth microdilution method against 27 - 32 drugs/year. All tests were interpreted by NCCLS criteria (2003) for S, R and intermediate (I). SPN was recovered from 38 - 42% of CARTI samples, similar to that of H. influenzae (39 - 42%) and 2-fold greater than M. catarrhalis (18 - 22%) that remained unchanged over the six year period.
Impact of age on susceptibility profiles. Demographic information obtained with each isolate was grouped by subset analysis into three age classes (0 - 5 years, 6 - 64 years and ≥ 65 years) and compared with trends in antimicrobial Results: The results follow in the table:
susceptibility patterns, specifically examining results for ß-lactam and macrolide agents during each of the last three MLS resistance phenotype, representing resistance to macrolides, lincosamides, and streptogramin B agents. Conferred by methylation of a single adenine in the bacterial 50s ribosome (erm genes).
M-phenotype representing resistance to macrolides, but not clindamycin, which involves a macrolide efflux pump (mef).
S. pneumoniae was isolated from 38 - 42% of community-acquired respiratory tract infections, varying by year (p >0.05). The rates of occurrence for H. influenzae and M. catarrhalis were 39 - 42% and 18 - C O N C L U S I O N S
• Resistance to penicillin and other ß-lactams among S. pneumoniae, decreased in 2002 • Resistance rates among H. influenzae and M. catarrhalis CARTI isolates remained stable over the last for the first time in the six-year interval driven by a reduction in high-level resistant isolates.
six respiratory disease seasons. Ampicillin-resistant (ß-lactamase-positive) H. influenzae averaged 29%, The extreme age groups (0-5 and ≥ 65 years) showed the greatest reduction in R to PEN, ER and CC with minimal change occurring in isolates from those 6-64 years.
slightly less in the last three years. ß-lactamase production by M. catarrhalis isolates consistently exceeded • Macrolide resistance decreased in 2002 via combined decreases in all MLS but showed a slight increase in the M-phenotype strains (69.6%).
Conclusions: The increase in PEN S was mainly associated with a decrease in the occurrence of isolates with
high level R (MIC,
≥2 µg/ml). The net increase in S to macrolides and lincosamides was due to a simultaneous • A consistent trend toward increasing resistance in S. pneumoniae to ß-lactams and MLS agents was MIC and MIC in µg/ml at which 50 and 90% of the isolates, respectively, MIC <0.06 negative ß-lactamase production; MIC > 0.06 is positive for reduction in the MLS phenotype (ER- and CC-R) and a lesser magnitude increase in the M-phenotype (ER-R and were inhibited. % S, percent of isolates susceptible and % R, percent of • Reductions in resistance was greatest in age groups at the extremes of life, e.g. 0 - 5 observed from 1999 through 2001 (Figure 1). However, in 2002 the non-susceptible rates for penicillin CC-S). The potential impact of vaccine usage and prescription discipline on changes to the susceptibility pattern isolates resistant using NCCLS criteria. Resistance rates in parenthesis are based on Chen et al. criteria (1999) Interpretative criteria not established by the NCCLS.
and erythromycin decreased 5.8 and 4.3%, respectively. In contrast, levofloxacin resistance increased of SPN in NA should be further investigated.
from 0.9 in 2000 to 1.4% in 2002 (Table 1).
• Resistance reductions appears to be related in time to pneumococcal vaccination Susceptibilities of select antimicrobials tested against S. pneumoniae isolates from North America (2001-2002) listed by patient • The other ß-lactams (oral agents amoxicillin/clavulanate, cefdinir, cefuroxime axetil) also showed improved success in the two targeted age groups.
spectrums versus S. pneumoniae in 2002 (Table 1).
• Further investigations are urged into the continued impact of vaccine usage and Penicillin resistance among S. pneumoniae has increased continuously in the USA in the last decade. Additionally,penicillin-resistant strains have become increasingly more resistant to other antimicrobial agents. Rates may vary • Age group related changes in resistance for 2002 were most evident in the young (0 - 5 years) and the prescription discipline on pneumococcal resistance rates in CARTI and hospitalized according to the geographic region and in some areas more than one-third of S. pneumoniae isolates have resistance elderly (≥ 65 years) with susceptibility increases for ß-lactams. Macrolides showed a decrease in to penicillin. Resistance rates may also vary according to patient age group, the higher rates have usually been susceptibility for the young children (-2.1% for erythromycin) compared to favorable increases in found in children and in the elderly. The continuous increase in the resistance rates among pneumococci has been susceptibility for the isolates from adult patients (Table 2).
attributed to several factors, mainly the dissemination of resistant clones and local or national patterns of antimicrobial use. Moreover, the influence of the increasing use of the pneumococcal conjugate vaccine on the pneumococcal S E L E C T E D R E F E R E N C E S
resistance rates has not been fully evaluated. Since the vaccine has shown to be highly effective against invasive • Table 3 shows the resistance variation among 2001 and 2002 pneumococcal isolates by age and level disease in young children and elderly people, and the serotypes included in the 7- or 23-valent vaccines account of penicillin susceptibility. The greatest decrease in resistance occurred among the elderly patient isolates American Academy of Pediatrics. Policy Statement: Recommendations for the Prevention of Pneumococcal Infections, Including the Use of Pneumococcal Conjugate Vaccine (Prevnar), Pneumococcal Polysaccharide Vaccine, and Antibiotic Prophylaxis (RE9960). Pediatrics 2000; 106:362-366.
for most penicillin-resistant or multi-resistant clones causing infection in the USA, we may expect a reduction in and the proportion of high-level resistant strains (penicillin MIC, ≥ 2 µg/ml).
resistant pneumococci as the vaccine becomes widely used.
Center for Disease Control and Prevention. Facilitating influenza and pneumococcal vaccination through standing orders programs. Morbidity and Mortality Weekly Report. 2003; 52:68-69.
• Changes in 2002 for MLS resistance phenotypes indicated an increase in mef A, efflux M-phenotypes The objective of this presented study was to evaluate the contemporary in vitro activity and spectrum for leading Chen DK, McGeer A, De Azavedo JC, Low DE. Decreased susceptibility of Streptococcus pneumoniae to fluoroquinolones in Canada. New England Journal of orally administered antimicrobials available for the treatment of community-acquired respiratory tract infections in the children (60.9 to 67.4%) and in the elderly (69.2 to 74.3%), see Table 4.
(CARTI) caused by S. pneumoniae as a component of the SENTRY Antimicrobial Surveillance Program. In addition, Dagan R. Streptococcus pneumoniae in the potential effects of new vaccines on the pattern of antibiotic drug usage in pediatrics. Current Therapeutic Research we evaluated the current resistance trends based on the annual results obtained from 1997 to 2002 and the influence • These changes in resistance appear to correspond to literature cited expansion of the use of pneumococcal Hoban D, Doern G, Fluit A, Roussel-Delvallez M, Jones RN. Worldwide prevalence of antimicrobial resistance in Streptococcus pneumoniae, Haemophilus of patient age on S. pneumoniae susceptibility patterns during the monitored 6-year period (16,489 isolates).
vaccines in the most effected populations of patients illustrated in this report (0 - 5 and ≥ 65 years).
influenzae, and Moraxella catarrhalis in the SENTRY Antimicrobial Surveillance Program, 1997-1999. Clinical Infectious Disease 2001; 32(Suppl 2):S81-93.
Jones RN, Pfaller MA. In vitro activity of newer fluoroquinolones for respiratory tract infections and emerging patterns of antimicrobial resistance: Data from the M A T E R I A L S A N D M E T H O D S
SENTRY Antimicrobial Surveillance Program. Clinical Infectious Disease 2000; 31:S16-23.
Figure 1: Trends in the susceptibility patterns of S. pneumoniae isolates in the SENTRY Program (1997 - 2002).
Jones RN, Biedenbach DJ, Beach ML. Influence of patient age on the susceptibility patterns of Streptococcus pneumoniae isolates in North America (2000- 2001): Report from the SENTRY Antimicrobial Surveillance Program. Diagnostic Microbiology and Infectious Disease 2003; 46:77-80.
Bacterial isolate collection. A total of 16,489 contemporary CARTI isolates were gathered from > 40 medical centers Criteria for susceptibility applied from NCCLS tables.
(approximately 35/year) in North America during 1997 to 2002. Isolates were identified by the originating laboratories Low DE. The new oral cephalosporins in community-acquired infections. Clinical Microbiology and Infection 2000; 6(Suppl 3):64-69.
and pure cultures were then forwarded in a semisolid transport medium containing charcoal to a central monitoring National Committee for Clinical Laboratory Standards. (2003). Methods for dilution antimicrobial tests for bacteria that grows aerobically. Approved standard site (JMI Laboratories, North Liberty, IA). Upon arrival, isolates were subcultured onto appropriate media to ensure viability and purity, and incubated in a 3 - 5% CO environment. S. pneumoniae isolates were identified by examination Change in the rate of penicillin resistance among S. pneumoniae isolates from North America (2001 to 2002) listed by patient National Committee for Clinical Laboratory Standards. (2003). Performance standards for antimicrobial susceptibility testing. Supplemental tables, M100-S13.
of typical colonial characteristics and use of the bile (2% sodium desoxycholate) solubility test.
Whitney CG, Farley MM, Hadler J, Harrison LH, Bennett NM, Lynfield R, Reingold A, Cieslak PR, Pilishvili T, Jackson D, Facklam RR, Jorgensen JH, Schuchat Determination of MICs. Susceptibility testing utilizing the National Committee for Clinical Laboratory Standards A, for the Active Bacterial Core Surveillance of the Emerging Infections Program Network. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. New England Journal of Medicine 2003; 348:1737-1746.
(NCCLS) reference broth microdilution method was performed with a battery of broad-spectrum antimicrobial agents (27 - 32 drug/year): penicillin, amoxicillin/clavulanic, numerous oral cephalosporins, macrolides, ampicillin, clindamycin, Whitney CG, Farley MM, Hadler J, Harrison LH, Lexau C, Reingold A, Lefkowitz L, Cieslak PR, Cetron M, Zell ER, Jorgensen JH, Schuchat A, The Active Bacterial Core Surveillance Program of the Emerging Infections Program Network. Increasing prevalence of multidrug-resistant Streptococcus pneumoniae in the United ciprofloxacin and levofloxacin will be presented here. Colonies from fresh (< 24 hours) subcultures were used to States. New England Journal of Medicine 2000; 343:1917-1924.



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Efficacy of Hydroxyurea in Providing Transfusion Saqib H. Ansari, MBBS, DCH, DPGN, MPhil, Tahir S. Shamsi, MBBS, FRCPath, Mushtaq Ashraf, MBBS, MD, Kousar Perveen, BSc, MBA, CRA, Tasneem Farzana, MBBS, MCPS, Munira Borhany, MBBS, FCPS, Sajida Erum, Pharm D, CCRP, and Tabassum Mehboob, PhD in the general population with an increased risk of Background: Packed red blood cell (PRC) transfusion

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