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1.
Vox Sang ; 112(8): 713-722, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28960367

RESUMO

BACKGROUND AND OBJECTIVES: Interventions to prevent and detect bacterial contamination of platelet concentrates (PCs) have reduced, but not eliminated the sepsis risk. Standardized bacterial strains are needed to validate detection and pathogen reduction technologies in PCs. Following the establishment of the First International Reference Repository of Platelet Transfusion-Relevant Bacterial Reference Strains (the 'repository'), the World Health Organization (WHO) Expert Committee on Biological Standardisation (ECBS) endorsed further repository expansion. MATERIALS AND METHODS: Sixteen bacterial strains, including the four repository strains, were distributed from the Paul-Ehrlich-Institut (PEI) to 14 laboratories in 10 countries for enumeration, identification and growth measurement on days 2, 4 and 7 after low spiking levels [10-25 colony-forming units (CFU)/PC bag]. Spore-forming (Bacillus cereusPEI-B-P-07-S, Bacillus thuringiensisPEI-B-P-57-S), Gram-negative (Enterobacter cloacaePEI-B-P-43, Morganella morganiiPEI-B-P-74, PEI-B-P-91, Proteus mirabilisPEI-B-P-55, Pseudomonas fluorescensPEI-B-P-77, Salmonella choleraesuisPEI-B-P-78, Serratia marcescensPEI-B-P-56) and Gram-positive (Staphylococcus aureusPEI-B-P-63, Streptococcus dysgalactiaePEI-B-P-71, Streptococcus bovisPEI-B-P-61) strains were evaluated. RESULTS: Bacterial viability was conserved after transport to the participating laboratories with one exception (M. morganiiPEI-B-P-74). All other strains showed moderate-to-excellent growth. Bacillus cereus, B. thuringiensis, E. coli, K. pneumoniae, P. fluorescens, S. marcescens, S. aureus and S. dysgalactiae grew to >106 CFU/ml by day 2. Enterobacter cloacae, P. mirabilis, S. epidermidis, S. bovis and S. pyogenes achieved >106 CFU/ml at day 4. Growth of S. choleraesuis was lower and highly variable. CONCLUSION: The WHO ECBS approved all bacterial strains (except M. morganiiPEI-B-P-74 and S. choleraesuisPEI-B-P-78) for repository enlargement. The strains were stable, suitable for spiking with low CFU numbers, and proliferation was independent of the PC donor.


Assuntos
Plaquetas/microbiologia , Segurança do Sangue/normas , Transfusão de Plaquetas , Bancos de Espécimes Biológicos , Escherichia coli/crescimento & desenvolvimento , Humanos , Klebsiella pneumoniae/crescimento & desenvolvimento , Padrões de Referência , Staphylococcus aureus/crescimento & desenvolvimento , Staphylococcus epidermidis/crescimento & desenvolvimento , Organização Mundial da Saúde
2.
Transpl Infect Dis ; 17(2): 289-96, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25661804

RESUMO

Acinetobacter baumannii is an important cause of healthcare-associated infections, and is particularly problematic among patients who undergo organ transplantation. We describe a case of fulminant sepsis caused by carbapenem-resistant A. baumannii harboring the blaOXA-23 carbapenemase gene and belonging to international clone II. This isolate led to the death of a patient 6 days after simultaneous kidney-pancreas transplantation. Autopsy findings revealed acute mitral valve endocarditis, myocarditis, splenic and renal emboli, peritonitis, and pneumonia. This case highlights the severe nature of certain A. baumannii infections and the vulnerability of transplanted patients to the increasingly intractable "high-risk" clones of multidrug-resistant organisms.


Assuntos
Infecções por Acinetobacter , Diabetes Mellitus Tipo 1/cirurgia , Endocardite Bacteriana , Falência Renal Crônica/cirurgia , Transplante de Rim , Transplante de Pâncreas , Complicações Pós-Operatórias , Acinetobacter baumannii/genética , Bacteriemia , Proteínas de Bactérias/genética , Carbapenêmicos , Farmacorresistência Bacteriana/genética , Humanos , Masculino , Pessoa de Meia-Idade , beta-Lactamases/genética
3.
J Clin Microbiol ; 52(11): 3928-32, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25165083

RESUMO

Sepsis caused by Staphylococcus aureus is a major health problem worldwide. Better outcomes are achieved when rapid diagnosis and determination of methicillin susceptibility enable early optimization of antimicrobial therapy. Eight large clinical laboratories, seven from the United States and one from Scotland, evaluated the combination of the Staphylococcus QuickFISH BC and the new mecA XpressFISH assay (both AdvanDx, Woburn, MA, USA) for the detection of methicillin-resistant S. aureus in positive blood cultures. Blood cultures flagged as positive by automated blood culture instruments and demonstrating only Gram-positive cocci in clusters on Gram stain were tested by QuickFISH, a 20-min assay. If only S. aureus was detected, mecA XpressFISH testing followed. The recovered S. aureus isolates were tested by cefoxitin disk diffusion as the reference method. The QuickFISH assay results were concordant with the routine phenotypic testing methods of the testing laboratories in 1,211/1,221 (99.1%) samples and detected 488/491 S. aureus organisms (sensitivity, 99.4%; specificity, 99.6%). Approximately 60% of the samples (730) contained coagulase-negative staphylococci or nonstaphylococci as assessed by the QuickFISH assay and were not tested further. The 458 compliant samples positive exclusively for S. aureus by the QuickFISH assay were tested by the mecA XpressFISH assay, which detected 209 of 211 methicillin-resistant S. aureus organisms (sensitivity, 99.1%; specificity, 99.6%). The mecA XpressFISH assay also showed high reproducibility, with 534/540 tests performed by 6 operators over 5 days achieving reproducible results (98.9% agreement). The combination of the Staphylococcus QuickFISH BC and mecA XpressFISH assays is sensitive, specific, and reproducible for the detection of methicillin-resistant S. aureus and yields complete results in 2 h after the blood culture turns positive.


Assuntos
Sangue/microbiologia , Hibridização in Situ Fluorescente/métodos , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Técnicas de Diagnóstico Molecular/métodos , Sepse/diagnóstico , Infecções Estafilocócicas/diagnóstico , Infecções Estafilocócicas/microbiologia , Técnicas Bacteriológicas/métodos , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Reprodutibilidade dos Testes , Escócia , Sensibilidade e Especificidade , Sepse/microbiologia , Estados Unidos
4.
Transpl Infect Dis ; 16(5): 830-7, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24995715

RESUMO

We describe the first case, to our knowledge, of disseminated Mycobacterium bovis Bacillus Calmette-Guérin infection in a child with Bare Lymphocyte Syndrome type II after undergoing hematopoietic stem cell transplantation (HSCT). The patient presented 30 days post HSCT with fever and lymphadenitis. Lymph node, blood, and gastric aspirates were positive for M. bovis. The patient received a prolonged treatment course with a combination of isoniazid, levofloxacin, and ethambutol. Her course was further complicated by granulomatous lymphadenitis and otitis media associated with M. bovis that developed during immune suppression taper and immune reconstitution. Ultimately, the patient recovered fully, in association with restoration of immune function, and has completed 12 months of therapy.


Assuntos
Vacina BCG/efeitos adversos , Transplante de Células-Tronco Hematopoéticas , Infecções por Mycobacterium/microbiologia , Mycobacterium bovis , Feminino , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Lactente , Infecções por Mycobacterium/tratamento farmacológico , Imunodeficiência Combinada Severa/complicações , Imunodeficiência Combinada Severa/terapia
6.
Vox Sang ; 102(3): 212-20, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21967170

RESUMO

BACKGROUND AND OBJECTIVES: Serratia marcescens is a gram-negative bacterium that has been implicated in adverse transfusion reactions associated with contaminated platelet concentrates. The aim of this study was to investigate whether the ability of S. marcescens to form surface-attached aggregates (biofilms) could account for contaminated platelet units being missed during screening by the BacT/ALERT automated culture system. MATERIALS AND METHODS: Seven S. marcescens strains, including biofilm-positive and biofilm-negative control strains and five isolates recovered from contaminated platelet concentrates, were grown in enriched Luria-Bertani medium and in platelets. Biofilm formation was examined by staining assay, dislodging experiments and scanning electron microscopy. Clinical strains were also analysed for their ability to evade detection by the BacT/ALERT system. RESULTS: All strains exhibited similar growth in medium and platelets. While only the biofilm-positive control strain formed biofilms in medium, this strain and three clinical isolates associated with transfusion reactions formed biofilms in platelet concentrates. The other two clinical strains, which had been captured during platelet screening by BacT/ALERT, failed to form biofilms in platelets. Biofilm-forming clinical isolates were approximately three times (P<0·05) more likely to be missed by BacT/ALERT screening than biofilm-negative strains. CONCLUSION: S. marcescens strains associated with transfusion reactions form biofilms under platelet storage conditions, and initial biofilm formation correlates with missed detection of contaminated platelet concentrates by the BacT/ALERT system.


Assuntos
Biofilmes/crescimento & desenvolvimento , Plaquetas/microbiologia , Preservação de Sangue , Transfusão de Plaquetas/efeitos adversos , Serratia marcescens/crescimento & desenvolvimento , Serratia marcescens/isolamento & purificação , Plaquetas/ultraestrutura , Contagem de Colônia Microbiana/métodos , Feminino , Humanos , Masculino , Infecções por Serratia/sangue , Infecções por Serratia/microbiologia , Infecções por Serratia/transmissão , Serratia marcescens/ultraestrutura
7.
Vox Sang ; 102(1): 22-31, 2012 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-21732948

RESUMO

BACKGROUND: Bacterial contamination of platelet concentrates (PCs) still remains a significant problem in transfusion with potential important clinical consequences, including death. The International Society of Blood Transfusion Working Party on Transfusion-Transmitted Infectious Diseases, Subgroup on Bacteria, organised an international study on Transfusion-Relevant Bacteria References to be used as a tool for development, validation and comparison of both bacterial screening and pathogen reduction methods. MATERIAL AND METHODS: Four Bacteria References (Staphylococcus epidermidis PEI-B-06, Streptococcus pyogenes PEI-B-20, Klebsiella pneumoniae PEI-B-08 and Escherichia coli PEI-B-19) were selected regarding their ability to proliferate to high counts in PCs and distributed anonymised to 14 laboratories in 10 countries for identification, enumeration and bacterial proliferation in PCs after low spiking (0·3 and 0·03 CFU/ml), to simulate contamination occurring during blood donation. RESULTS: Bacteria References were correctly identified in 98% of all 52 identifications. S. pyogenes and E. coli grew in PCs in 11 out of 12 laboratories, and K. pneumoniae and S. epidermidis replicated in all participating laboratories. The results of bacterial counts were very consistent between laboratories: the 95% confidence intervals were for S. epidermidis: 1·19-1·32 × 10(7) CFU/ml, S. pyogenes: 0·58-0·69 × 10(7) CFU/ml, K. pneumoniae: 18·71-20·26 × 10(7) CFU/ml and E. coli: 1·78-2·10 × 10(7) CFU/ml. CONCLUSION: The study was undertaken as a proof of principle with the aim to demonstrate (i) the quality, stability and suitability of the bacterial strains for low-titre spiking of blood components, (ii) the property of donor-independent proliferation in PCs, and (iii) their suitability for worldwide shipping of deep frozen, blinded pathogenic bacteria. These aims were successfully fulfilled. The WHO Expert Committee Biological Standardisation has approved the adoption of these four bacteria strains as the first Repository for Transfusion-Relevant Bacteria Reference Strains and, additionally, endorsed as a project the addition of six further bacteria strain preparations suitable for control of platelet contamination as the next step of enlargement of the repository.


Assuntos
Plaquetas/microbiologia , Transfusão de Sangue , Infecções Bacterianas/prevenção & controle , Técnicas de Tipagem Bacteriana/métodos , Técnicas Bacteriológicas , Bancos de Espécimes Biológicos , Transfusão de Componentes Sanguíneos/métodos , Plaquetas/citologia , Escherichia coli/metabolismo , Humanos , Cooperação Internacional , Klebsiella pneumoniae/metabolismo , Garantia da Qualidade dos Cuidados de Saúde/métodos , Reprodutibilidade dos Testes , Staphylococcus epidermidis/metabolismo , Streptococcus pyogenes/metabolismo
8.
Antimicrob Agents Chemother ; 55(9): 4430-1, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21730123

RESUMO

The triple combination trimethoprim, EDTA, and ethanol (B-Lock), is an antimicrobial lock solution for use in indwelling intravascular catheters to prevent and treat catheter-associated infections. B-Lock demonstrated MICs of ≤0.05% (percentage of solution) against Candida spp. (n = 125) and 0.003% to 25% against bacterial strains (n = 175). B-Lock was also fungicidal against the majority of the Candida strains at 6% to 25%. B-Lock demonstrates potential value for the prevention and treatment of catheter-associated infections.


Assuntos
Anti-Infecciosos/farmacologia , Candida/efeitos dos fármacos , Infecções Relacionadas a Cateter/prevenção & controle , Ácido Edético/farmacologia , Etanol/farmacologia , Trimetoprima/farmacologia , Bactérias/efeitos dos fármacos , Infecções Relacionadas a Cateter/microbiologia , Cateteres de Demora/microbiologia , Combinação de Medicamentos , Testes de Sensibilidade Microbiana
9.
Surg Endosc ; 25(7): 2224-9, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21298542

RESUMO

BACKGROUND: Biologic grafts used in ventral hernia repair are derived from various sources and undergo different post-tissue-harvesting processing, handling, and sterilization techniques. It is unclear how these various characteristics impact graft response in the setting of contamination. We evaluated four materials in an infected hernia repair animal model using fluorescence imaging and quantitative culture studies. METHODS: One hundred seven rats underwent creation of a chronic hernia. They were then repaired with one synthetic polyester control material (n = 12) and four different biologic grafts (n = 24 per material). Biologic grafts evaluated included Surgisis (porcine small intestinal submucosa), Permacol (crosslinked porcine dermis), Xenmatrix (noncrosslinked porcine dermis), and Strattice (noncrosslinked porcine dermis). Half of the repairs in each group were inoculated with Staphylococcus aureus at 10(4) CFU/ml and survived for 30 days without systemic antibiotics. Animals then underwent fluorescence imaging and quantitative bacterial studies. RESULTS: All clean repairs remained sterile. Rates of bacterial clearance were as follows: polyester synthetic 0%, Surgisis 58%, Permacol 67%, Xenmatrix 75%, and Strattice 92% (P=0.003). Quantitative bacterial counts had a similar trend in bacterial clearance: polyester synthetic 1×10(6) CFU/g, Surgisis 4.3×10(5) CFU/g, Permacol 1.7×10(3) CFU/g, Xenmatrix 46 CFU/g, and Strattice 31 CFU/g (P=0.001). Fluorescence imaging was unable to detect low bacterial fluorescence counts observed on bacterial studies. CONCLUSION: Biologic grafts, in comparison to synthetic material, are able to clear a Staphylococcus aureus contamination; however, they are able to do so at different rates. Bacterial clearance correlated to the level of residual bacterial burden observed in our study. Post-tissue-harvesting processing, handling, and sterilization techniques may contribute to this observed difference in ability to clear bacteria.


Assuntos
Bioprótese/microbiologia , Hérnia Abdominal/cirurgia , Animais , Carga Bacteriana , Colágeno , Modelos Animais de Doenças , Contaminação de Equipamentos , Feminino , Hérnia Abdominal/microbiologia , Microscopia de Fluorescência , Poliésteres , Ratos , Ratos Sprague-Dawley , Estatísticas não Paramétricas , Suínos
10.
Microb Drug Resist ; 13(1): 21-8, 2007.
Artigo em Inglês | MEDLINE | ID: mdl-17536930

RESUMO

There are little data on the genetic relatedness between antibiotic-resistant pneumococcal isolates colonizing the Ugandan population. Penicillin-intermediate pneumococci of serogroups or serotypes rarely or not previously reported as being penicillin nonsusceptible were selected out of 166 isolates representing 26 capsular serogroups or serotypes isolated from Ugandan children in 1995 and human immunodeficiency virus (HIV) infected Ugandan adults in 2004-2005. Pairs of penicillin-intermediate pneumococci of the same serogroup or serotype present in both patient populations were characterized further by pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST). Seven such pairs of isolates were found and included serogroups 7, 11, 15B/C, and 16 as well as serotypes 13, 21, and 35B. PFGE of these seven pairs showed no clonality between serogroups or serotypes, and clonality only within serogroup 11 and serotype 13. MLST of the 14 individual isolates revealed 13 different sequence types (STs), 11 of which had not previously been recorded. Comparisons with all known STs revealed that most of these strains were related only to strains of the same serotype in other countries, with these related strains frequently also being penicillin intermediate. These findings suggest that penicillin nonsusceptibility in Uganda is likely due to the introduction of antibiotic-resistant pneumococcal clones into Uganda rather than development of resistance within the country.


Assuntos
Antibacterianos/farmacologia , Portador Sadio , Infecções por HIV/microbiologia , Penicilinas/farmacologia , Infecções Pneumocócicas/microbiologia , Streptococcus pneumoniae/genética , Adulto , Pré-Escolar , Eletroforese em Gel de Campo Pulsado , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Humanos , Lactente , Recém-Nascido , Resistência às Penicilinas , Infecções Pneumocócicas/complicações , Infecções Pneumocócicas/epidemiologia , Prevalência , Sorotipagem , Streptococcus pneumoniae/isolamento & purificação , Uganda/epidemiologia
11.
S Afr Med J ; 97(11 Pt 3): 1133-40, 2007 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18250924

RESUMO

Despite increasing resistance in the pneumococcus over the past 30 years, there are few cases of treatment failure of non-meningeal infections with high-dosage parenteral penicillin G, which still remains highly effective for many pneumococcal diseases. This is reflected by the new 2008 CLSI breakpoints for parenteral penicillin G of susceptible, /=8 microg ml, for non-meningeal infections. For meningitis and oral penicillin V use, the old penicillin breakpoints of susceptible, /=2 microg/ml, will remain in place. Clinically relevant susceptibility breakpoints have also been developed for virtually all relevant antimicrobial agents used to treat pneumococcal diseases, based on clinical studies and pharmacokinetic and pharmacodynamic parameters. Although pneumococcal resistance to beta-lactams, macrolides and co-trimoxazole is now common worldwide, we are still able to treat almost all pneumococcal infections adequately. An exception is the oral treatment of multidrug-resistant serotype 19A strains in children in the USA, as these are resistant to amoxicillin, oral cephalosporins, macrolides, clindamycin and co-trimoxazole. While there is a need to develop new agents, judicious use of antimicrobial agents is the best long-term approach. Empiric treatment guidelines should reflect the emerging threats from increased drug resistance and the possibility of increased virulence in replacement serotypes following vaccine use. Compliance with guidelines by physicians and patients is important to prevent further development of resistance.


Assuntos
Infecções Pneumocócicas/tratamento farmacológico , Streptococcus pneumoniae/efeitos dos fármacos , Infecções Comunitárias Adquiridas/tratamento farmacológico , Farmacorresistência Bacteriana , Farmacorresistência Bacteriana Múltipla , Humanos , Meningite Pneumocócica/tratamento farmacológico , Pneumonia Bacteriana/tratamento farmacológico , Sinusite
12.
Clin Microbiol Infect ; 11(1): 9-14, 2005 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-15649298

RESUMO

The activity of WCK 771, a new experimental quinolone being developed to overcome quinolone resistance in staphylococci, against quinolone-susceptible and -resistant pneumococci was determined. Comparative activities of ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, clinafloxacin, vancomycin, linezolid, amoxycillin, cefuroxime, azithromycin and clarithromycin were determined with MIC and time-kill experiments. Animal experiments were also performed to test the in-vivo anti-pneumococcal activity of WCK 771 compared to levofloxacin. WCK 771 MIC50/90 values for 300 quinolone-susceptible Streptococcus pneumoniae isolates (108 penicillin-susceptible, 92 penicillin-intermediate and 100 penicillin-resistant) were 0.5/0.5 mg/L; the MICs of beta-lactams and macrolides rose with those of penicillin G, and all isolates were susceptible to vancomycin and linezolid. WCK 771 MIC50/90 values for 25 quinolone-resistant pneumococcal isolates were 4/8 mg/L, compared to 0.5/1 mg/L for clinafloxacin, 2/4 mg/L for gatifloxacin and moxifloxacin, 8/16 mg/L for levofloxacin, and 16/>32 mg/L for ciprofloxacin. Time-kill studies showed that WCK 771 was bactericidal against pneumococci after 24 h at 4 x MIC, as were the other quinolones tested. Animal model studies showed that WCK 771 had efficacy comparable to that of levofloxacin, by both the oral and subcutaneous routes, for systemic infection caused by three quinolone-susceptible isolates of pneumococci. Overall, WCK 771 was potent both in vivo and in vitro against quinolone-susceptible, but not quinolone-resistant, S. pneumoniae, regardless of penicillin susceptibility.


Assuntos
Bacteriemia/tratamento farmacológico , Fluoroquinolonas/farmacologia , Pneumonia Pneumocócica/tratamento farmacológico , Streptococcus pneumoniae/efeitos dos fármacos , Animais , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/microbiologia , Farmacorresistência Bacteriana , Fluoroquinolonas/uso terapêutico , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Pneumonia Pneumocócica/microbiologia , Resultado do Tratamento
13.
Antimicrob Agents Chemother ; 48(10): 4020-2, 2004 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-15388470

RESUMO

Penicillin-binding proteins (PBPs) of 15 selected penicillin- and amoxicillin-resistant Streptococcus pneumoniae isolates (MICs of 2 to 8 and 8 to 16 microg/ml, respectively) were studied. In addition to typical changes in PBPs 1A and 2X, these strains had 10 unique changes in PBP 2B, including a (618)A-G substitution, which may be the key alteration associated with amoxicillin resistance.


Assuntos
Amoxicilina/farmacologia , Proteínas de Ligação às Penicilinas/metabolismo , Penicilinas/farmacologia , Streptococcus pneumoniae/efeitos dos fármacos , Primers do DNA , Testes de Sensibilidade Microbiana , Proteínas de Ligação às Penicilinas/química , Infecções Pneumocócicas/microbiologia , Vigilância da População , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Streptococcus pneumoniae/metabolismo
14.
Int J Antimicrob Agents ; 23(4): 356-61, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15081084

RESUMO

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.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Infecções por Haemophilus/epidemiologia , Haemophilus influenzae/efeitos dos fármacos , Infecções Pneumocócicas/epidemiologia , Streptococcus pneumoniae/efeitos dos fármacos , Adolescente , Adulto , Brasil , Criança , Infecções por Haemophilus/microbiologia , Humanos , Testes de Sensibilidade Microbiana/métodos , Testes de Sensibilidade Microbiana/normas , Infecções Pneumocócicas/microbiologia , Vigilância da População
15.
Clin Microbiol Infect ; 10 Suppl 2: 18-27, 2004 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-14759230

RESUMO

The development of our understanding of the pharmacokinetic (PK) and pharmacodynamic (PD) principles that determine antimicrobial efficacy has advanced substantially over the last 10 years. We are now in a position to use PK/PD principles to set targets for antimicrobial design and optimisation so that we can predict eradication of specific pathogens or resistant variants when agents are used clinically. Optimisation of PK/PD parameters to enable the treatment of resistant pathogens with oral agents may not be possible with many current agents, such as some cephalosporins, macrolides and fluoroquinolones. Aminopenicillins, however, such as amoxicillin, have linear PK and have a good safety profile even at high doses. The new pharmacokinetically enhanced oral formulation of amoxicillin/clavulanate, 2000/125 mg twice daily, was designed using PK/PD principles to be able to eradicate Streptococcus pneumoniae with amoxicillin MICs of up to and including 4 mg/L, which includes most penicillin-resistant isolates. For amoxicillin and amoxicillin/clavulanate, a time above MIC (T > MIC) of 35-40% of the dosing interval (based on blood levels) is predictive of high bacteriological efficacy. This target was met by the design of a unique bilayer tablet incorporating 437.5 mg of sustained-release sodium amoxicillin in one layer plus 562.5 mg of immediate-release amoxicillin trihydrate and 62.5 mg of clavulanate potassium in the second layer, with two tablets administered for each dose. This unique design extends the bacterial killing time by increasing the T > MIC to 49% of the dosing interval against pathogens with MICs of 4 mg/L, and 60% of the dosing interval against pathogens with MICs of 2 mg/L. Based on these results, this new amoxicillin/clavulanate formulation should be highly effective in treating respiratory tract infections due to drug-resistant S. pneumoniae as well as beta-lactamase-producing pathogens, such as Haemophilus influenzae and Moraxella catarrhalis.


Assuntos
Combinação Amoxicilina e Clavulanato de Potássio/uso terapêutico , Antibacterianos/uso terapêutico , Desenho de Fármacos , Farmacorresistência Bacteriana , Pneumonia Pneumocócica/tratamento farmacológico , Streptococcus pneumoniae/efeitos dos fármacos , Combinação Amoxicilina e Clavulanato de Potássio/administração & dosagem , Combinação Amoxicilina e Clavulanato de Potássio/farmacocinética , Animais , Antibacterianos/administração & dosagem , Antibacterianos/farmacologia , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Pneumonia Pneumocócica/microbiologia , Fatores de Tempo , Resultado do Tratamento
16.
Clin Microbiol Infect ; 9(7): 653-61, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12925106

RESUMO

OBJECTIVE: To test the activity of telithromycin against 1034 Streptococcus pneumoniae isolates from pediatric patients in ten centers from ten central and eastern European countries during 2000-2001, and to compare it with the activities of erythromycin A, azithromycin, clarithromycin, clindamycin, and quinupristin-dalfopristin. METHODS: The minimum inhibitory concentrations (MICs) of telithromycin, erythromycin A, azithromycin, clarithromycin, clindamycin, levofloxacin, quinupristin-dalfopristin and penicillin G were tested by the agar dilution method with incubation in air, and mechanisms of resistance to macrolides and quinolones were investigated. RESULTS: Strains were isolated from sputum, tracheal aspirates, ear, eye, blood, and cerebrospinal fluid. Among S. pneumoniae strains tested, 36% had raised penicillin G MICs (>/= 0.12 mg/L). Susceptibilities were as follows: telithromycin, quinupristin-dalfopristin and levofloxacin, >/= 99%; clindamycin, 83%; and erythromycin A, azithromycin and clarithromycin, 78%. Of 230 (22.3%) erythromycin A-resistant S. pneumoniae strains, 176 (79.6%) had erm(B), 38 (16.1%) had mef(A), and 10 (4.3%) had mutations in 23S ribosomal RNA or in ribosomal protein L4. The rates of drug-resistant S. pneumoniae are high in all centers except Kaunas, Riga, and Prague. CONCLUSION: Telithromycin had low MICs against all strains, irrespective of macrolide, azalide or clindamycin resistance. Ribosomal methylation was the most prevalent resistance mechanism among all resistant strains, except in Sofia, where the prevalence of the efflux mechanism was higher.


Assuntos
Antibacterianos/farmacologia , Cetolídeos , Macrolídeos , Streptococcus pneumoniae/efeitos dos fármacos , Adolescente , Criança , Pré-Escolar , Farmacorresistência Bacteriana/fisiologia , Eletroforese em Gel de Campo Pulsado , Humanos , Lactente , Recém-Nascido
17.
Clin Microbiol Infect ; 9(7): 741-5, 2003 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-12925122

RESUMO

In total, 1039 pediatric Streptococcus pyogenes isolates from Bulgaria, Croatia, the Czech Republic, Hungary, Latvia, Lithuania, Poland, Romania, Slovakia and Slovenia were studied. All strains were susceptible to penicillin G, levofloxacin, and quinupristin-dalfopristin, 91-100% to telithromycin, and 82-100% to erythromycin, azithromycin, and clarithromycin, and 90-100% to clindamycin. Macrolide resistance occurred mainly in Slovakia (25%), the Czech Republic (17.3%), and Croatia (15.8%). Overall, 9.7% of S. pyogenes isolates were erythromycin resistant due to erm(B)- or erm(A)-encoded methylases (72.3%) or to a mef(A)-encoded efflux pump (25.7%). One strain had alterations of both 23S rRNA (A2058G Escherichia coli numbering) and ribosomal protein L22 (G95D).


Assuntos
Antibacterianos/farmacologia , Cetolídeos , Macrolídeos , Infecções Estreptocócicas/tratamento farmacológico , Streptococcus pyogenes/efeitos dos fármacos , Adolescente , Criança , Pré-Escolar , Farmacorresistência Bacteriana , Europa (Continente)/epidemiologia , Humanos , Lactente , Recém-Nascido , Metilação , Ribossomos/metabolismo , Infecções Estreptocócicas/epidemiologia , Streptococcus pyogenes/isolamento & purificação
18.
Antimicrob Agents Chemother ; 47(9): 3012-4, 2003 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-12937016

RESUMO

Daptomycin mean staphylococcal postantibiotic effects (PAEs) were 1.1 to 6.2 h, with a mean of 2.5 h. The mean pneumococcal PAEs were 1.7 h, ranging between 1.0 and 2.5 h. The staphylococcal and pneumococcal postantibiotic sub-MIC effects at 0.4 times the MIC ranged from 3.0 to >12.0 h and 1.9 to >12.0 h, respectively.


Assuntos
Antibacterianos/farmacologia , Daptomicina/farmacologia , Staphylococcus/efeitos dos fármacos , Streptococcus pneumoniae/efeitos dos fármacos , Contagem de Colônia Microbiana , Humanos , Resistência a Meticilina , Testes de Sensibilidade Microbiana , Infecções Pneumocócicas/microbiologia , Infecções Estafilocócicas/microbiologia
19.
Antimicrob Agents Chemother ; 47(3): 1140-2, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12604557

RESUMO

Conventional in vitro methods were used to determine the postantibiotic effects (PAEs), sub-MIC effects (SMEs), and postantibiotic sub-MIC effects (PA-SMEs) of garenoxacin for a range of organisms. The mean PAEs of garenoxacin for pneumococci, staphylococci, and enterococci were 0.3 to 2.2 h. For Escherichia coli and Pseudomonas aeruginosa, the PAEs were 0.9 to 1.6 h. The mean PA-SMEs (0.4 times the MIC) for pneumococci, staphylococci, and enterococci were 3.0 to >10 h, 1.8 to >10.7 h, and 5.8 h, respectively, while those for E. coli and P. aeruginosa were 7.6 and 4.4 h, respectively.


Assuntos
Antibacterianos/farmacologia , Anti-Infecciosos/farmacologia , Fluoroquinolonas , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Indóis/farmacologia , Quinolonas/farmacologia , Contagem de Colônia Microbiana , Meios de Cultura , Testes de Sensibilidade Microbiana , Fatores de Tempo
20.
Int J Antimicrob Agents ; 20(2): 108-12, 2002 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-12297359

RESUMO

The mechanism of resistance was investigated in 39 macrolide-resistant clinical isolates of Streptococcus pneumoniae isolated from January 1997 to July 1999 in Santiago, Chile. Our results showed that 22 (56.5%) were macrolide-resistant, clindamycin-susceptible isolates (M phenotype) and 17 (43.5%) were macrolide and clindamycin resistant (MLS(B) phenotype). mefE gene was detected in all M phenotype, while ermB gene was detected in all MLS(B)-phenotype strains. Serotype 14 was the most frequent serotype among M-phenotype strains, and serotypes 19 and 23F were the most frequent serotypes in MLS(B) strains. These results demonstrate that both phenotypes of macrolide-resistant S. pneumoniae are found in Santiago, Chile, with the M phenotype predominating.


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana , Eritromicina/farmacologia , Proteínas de Membrana , Streptococcus pneumoniae/efeitos dos fármacos , Adulto , Proteínas de Bactérias/genética , Criança , Chile , Clindamicina/farmacologia , Farmacorresistência Bacteriana/genética , Humanos , Metiltransferases/genética , Testes de Sensibilidade Microbiana , Fenótipo , Sorotipagem , Streptococcus pneumoniae/classificação , Streptococcus pneumoniae/genética
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