RESUMO
This was a retrospective, multi-center study of patients admitted to hospital with community-acquired pneumonia, caused by Streptococcus pneumoniae, after failing to respond to >2 days of outpatient macrolide therapy. 122 cases, treated between 2000-2004, were enrolled from 31 North American sites between January 2004 - March 2005. Non-susceptible isolates (predominately low-level resistance: erythromycin MICs of 1-16 mcg/ml) were recovered from 87 patients (71%). Bacteremia was present in 63 patients (52%). The in-hospital mortality rate was 5.7 %; all 7 patients who died were bacteremic, 6 had a non-susceptible isolate. We report here the largest series of macrolide failures published to date. The patients were notable for their high rates of macrolide resistance, bacteremia, and mortality. High-level macrolide resistance remains rare among US patients failing outpatient macrolides. The majority of cases and virtually all of the mortality occurred in patients with low-level resistant strains.
Assuntos
Antibacterianos/uso terapêutico , Farmacorresistência Bacteriana , Macrolídeos/uso terapêutico , Pneumonia Pneumocócica/tratamento farmacológico , Pneumonia Pneumocócica/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia , Criança , Pré-Escolar , Infecções Comunitárias Adquiridas , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Pneumonia Pneumocócica/microbiologia , Estudos Retrospectivos , Falha de TratamentoRESUMO
Rashes are a common adverse event observed during antimicrobial therapy. Many rashes are mild to moderate in intensity, however some reactions can be the prelude to much more severe outcomes such as Stevens-Johnson Syndrome (SJS) or Toxic Epidermal Necolysis. Several risk or influencing factors are known such as female gender, age and concomitant viral infections, and these may apply to more than one drug class. The incidence of rashes and other cutaneous reactions vary, however rates of >3% are reported with the beta-lactams while serious reactions such as SJS are observed with trimethoprim-sulphamethoxazole. Newer fluoroquinolone agents are devoid of the moiety which caused phototoxic reactions, while rates of rash vary from < 1%-3% or higher if longer courses of therapy are given. Serious systemic events have not been reported with these agents unlike other older, well-accepted antimicrobials. Rashes, while occasionally itchy and sometimes transiently unsightly, have less of an impact on a patient's daily activities than diarrhea, nausea or other more profound adverse events. However, it is essential that any rash be carefully monitored for possible, but rare, serious systemic events ensuing.
Assuntos
Anti-Infecciosos/efeitos adversos , Toxidermias/etiologia , Pele/efeitos dos fármacos , HumanosRESUMO
Cutaneous adverse events are seen with many antimicrobials. A signal was observed with gemifloxacin in the original clinical research program, however subsequent studies and analysis demonstrated a mild-moderate self-limited macular-papular rash seen most frequently when the duration of exposure was beyond 7 days, a non-approved duration. Following administration for 5 days for community-acquired respiratory tract infections the rash rate is typically less than 1.5%, a rate similar to that for other fluoroquinolones and lower than other frequently used community antimicrobials. The rash associated with gemifloxacin has not been linked with cross or subclinical-sensitization nor any systemic manifestations such as Stevens-Johnson Syndrome or Toxic Epidermal Necrolysis. This review describes the extensive studies conducted to support the use of this agent for short durations in community infections.
Assuntos
Exantema/induzido quimicamente , Fluoroquinolonas/efeitos adversos , Naftiridinas/efeitos adversos , Infecções Respiratórias/tratamento farmacológico , Pele/efeitos dos fármacos , Ensaios Clínicos como Assunto , Gemifloxacina , Humanos , Fatores de RiscoAssuntos
Anti-Infecciosos/uso terapêutico , Infecções Comunitárias Adquiridas/tratamento farmacológico , Fluoroquinolonas/uso terapêutico , Infecções Respiratórias/tratamento farmacológico , Adulto , Anti-Infecciosos/efeitos adversos , Farmacorresistência Bacteriana , Exantema/induzido quimicamente , Feminino , Fluoroquinolonas/efeitos adversos , Humanos , MasculinoAssuntos
Ehrlichiose/complicações , Febre/etiologia , Esplenectomia/efeitos adversos , Adulto , Idoso , Antibacterianos/uso terapêutico , Confusão/etiologia , Doxiciclina/uso terapêutico , Ehrlichiose/sangue , Ehrlichiose/tratamento farmacológico , Febre/sangue , Humanos , Contagem de Leucócitos , Masculino , Recidiva , ZoonosesRESUMO
Antimicrobial resistance, including plasmid-mediated resistance, among the species of the Bacteroides fragilis group is well documented. An analysis of the in vitro susceptibility of B. fragilis group species referred between 1995 and 1996 as well as during a 7-year (1990 to 1996), prospective, multicenter survey of over 4,000 clinical isolates of B. fragilis group species was undertaken to review trends in the percent resistance to and geometric mean MICs of the antibiotics tested. There was a trend toward a decrease in the geometric mean MICs of most beta-lactam antibiotics, while the percent resistance to most agents was less affected. Within the species B. fragilis, the geometric mean MICs showed significant (P < 0.05) decreases for piperacillin-tazobactam, ticarcillin-clavulanate, piperacillin, ticarcillin, ceftizoxime, cefotetan, and cefmetazole; a significant increase was observed for clindamycin and cefoxitin. For the non-B. fragilis species, a significant decrease in the geometric mean MICs was observed for meropenem, ampicillin-sulbactam, ticarcillin-clavulanate, piperacillin, ticarcillin, ceftizoxime, and cefmetazole; a significant increase was observed for cefoxitin. Significant increases in percent resistance were observed within the B. fragilis strains for ticarcillin and ceftizoxime and within the non-B. fragilis isolates for cefotetan. Significant increases in percent resistance among all B. fragilis group species were observed for clindamycin, while imipenem showed no significant change in resistance trends. The trend analysis for trovafloxacin was limited to 3 years, since the quinolone was tested only in 1994, 1995, and 1996. During the 7 years analyzed, there was no resistance to metronidazole or chloramphenicol observed. The data demonstrate that resistance among the B. fragilis group species has decreased in the past several years, the major exception being clindamycin. The majority of the resistance decrease has been for the beta-lactams in B. fragilis, compared to other species. The reasons for these changes are not readily apparent.
Assuntos
Antibacterianos/farmacologia , Bacteroides fragilis/efeitos dos fármacos , Bacteroides fragilis/fisiologia , Resistência Microbiana a Medicamentos/fisiologia , Humanos , Testes de Sensibilidade MicrobianaRESUMO
Antimicrobial resistance, including plasmid-mediated resistance, among Bacteroides fragilis group species is well documented. A 5-year (1990-1994) prospective, eight-center survey of 3,177 clinical isolates of Bacteroides species was undertaken to review trends in resistance, using the breakpoints for full and intermediate susceptibility established by the National Committee for Clinical Laboratory Standards. No documented resistance to either metronidazole or chloramphenicol was found in this survey. Among B. fragilis isolates virtually no resistance was seen to imipenem, meropenem, ampicillin/sulbactam, piperacillin/tazobactam, or ticarcillin/clavulanate. Significant increases in resistance among B. fragilis isolates to cefotetan, ceftizoxime, and clindamycin (p < .01) were noted. Resistance to cefoxitin remained unchanged. Among the non-fragilis species of the B. fragilis group, there was virtually no resistance to imipenem, meropenem, chloramphenicol, or metronidazole. The three beta-lactamase inhibitors had increasing levels of resistance, although 95%-98% of strains were susceptible (p < .05). There was a significant decline in cefoxitin, cefmetazole, and clindamycin activity over time against these strains (p <.01). There was a significant (P < .001) increase in geometric mean minimum inhibitory concentration for most drugs and species tested from 1990 to 1994. Clusters in the eight institutions could not account for this rise in resistance. This survey demonstrates that rates of resistance of B. fragilis and non-fragilis species of B. fragilis group are increasing.
Assuntos
Bacteroides fragilis/efeitos dos fármacos , Resistência Microbiana a Medicamentos , Bacteroides/classificação , Bacteroides/efeitos dos fármacos , Bacteroides/isolamento & purificação , Infecções por Bacteroides/tratamento farmacológico , Infecções por Bacteroides/epidemiologia , Infecções por Bacteroides/microbiologia , Bacteroides fragilis/isolamento & purificação , Coleta de Dados , Humanos , Estudos Prospectivos , Especificidade da Espécie , Fatores de Tempo , Estados Unidos/epidemiologiaRESUMO
A national survey of Bacteroides fragilis group was continued in 1989 for the ninth consecutive year. Seven hundred thirty-nine isolates of B fragilis group from eight centers were tested for susceptibility to 14 antimicrobials. Sulbactam and clavulanic acid, beta-lactamase inhibitors, were tested at a constant concentration of 8 micrograms/ml and 2 micrograms/ml, respectively. Sulbactam was also tested in a fixed ratio of 1:2. Imipenem, ampicillin+sulbactam, and ticarcillin+clavulanic acid had resistance of less than 1% at breakpoints of 8 micrograms/ml, 16 micrograms/ml, and 64 micrograms/ml, respectively. At 32 micrograms/ml, resistance to cefoxitin, cefotetan, ceftizoxime, and ceftriaxone were 4%, 25%, 26%, and 46%, respectively. Clindamycin resistance was 10% at a breakpoint of 4 micrograms/ml. No isolates were resistant to chloramphenicol or metronidazole. Resistance for five B fragilis species to cefoxitin, ceftizoxime, and cefotetan varied greatly among both species and participating institutions. The addition of a beta-lactamase inhibitor increased the potency of the beta-lactam drugs tested as combinations. This finding suggests that beta-lactamase production is the major resistance factor in members of the B fragilis group.
Assuntos
Antibacterianos/farmacologia , Bacteroides fragilis/efeitos dos fármacos , Resistência Microbiana a Medicamentos , Testes de Sensibilidade Microbiana , Estados UnidosRESUMO
PURPOSE: This multicenter study was designed to compare an exclusively oral regimen with "usual care" in patients hospitalized with acute bacterial pneumonia. PATIENTS AND METHODS: One hundred forty-seven patients were enrolled. All patients presented with a clinical picture consistent with pneumonia: (1) clinical symptoms of a lower respiratory tract infection, such as chest pain, cough, and production of purulent sputum; (2) roentgenographic infiltrate compatible with acute infection; and (3) Gram's stain of purulent sputum or other appropriate bronchopulmonary specimen containing gram-negative organisms, staphylococci, or pneumococci. All patients required hospitalization. The design was a parallel-group, open-label study with randomization in blocks of four. Ofloxacin, a new fluoroquinolone antimicrobial agent, was administered orally or by nasogastric tube, 400 mg every 12 hours. This was compared with the individual investigator's best selection of therapy that was administered parenterally, at least initially. RESULTS: One hundred thirty-three patients were evaluable after exclusions for deviation from protocol, early death due to unrelated causes, incorrect diagnosis, or early adverse drug reactions. All 69 patients treated with ofloxacin and 61 of 64 control patients had favorable clinical and microbiologic responses. There were no statistically significant differences between the groups in terms of demographics, therapeutic outcome, and duration of therapy. There were few side effects overall and rates were similar for the two groups. CONCLUSIONS: An exclusively oral regimen, in this case ofloxacin, may be substituted for parenteral therapy in selected patients with pneumonia. This might significantly reduce costs and risks to the patient.
Assuntos
Infecções Bacterianas/tratamento farmacológico , Ofloxacino/administração & dosagem , Pneumonia/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Infecções Bacterianas/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ofloxacino/efeitos adversos , Ofloxacino/sangue , Pneumonia/sangue , Pneumonia/microbiologia , Projetos de Pesquisa , Escarro/microbiologiaRESUMO
A nationwide survey to monitor the susceptibility of the Bacteroides fragilis group, which began in 1981, was continued during 1987. In addition to the eleven drugs evaluated in 1986, sulbactam, a potent beta-lactamase inhibitor, was tested alone and in combination with ampicillin and cefoperazone. Imipenem, ampicillin/sulbactam, cefoperazone/sulbactam, and ticarcillin/clavulanic acid were the most active newer drugs tested, with less than 1% resistance rates. Chloramphenicol, metronidazole and clindamycin also had excellent activity with resistance rates of 0%, 0%, and 3% respectively. Resistance rates to cefoxitin remained stable at 8%. Ceftizoxime and cefotetan had resistance rates of 26% and 29%, respectively. Rates of resistance varied among different institutions and between the various species.
Assuntos
Antibacterianos/farmacologia , Bacteroides fragilis/efeitos dos fármacos , Bacteroides/efeitos dos fármacos , Combinação de Medicamentos , Resistência Microbiana a Medicamentos , Humanos , Lactamas , Testes de Sensibilidade Microbiana , Estados UnidosRESUMO
A nationwide susceptibility survey of 557 isolates of the Bacteroides fragilis group was continued in 1986. The most active beta-lactam drugs were imipenem and ticarcillin-clavulanic acid, which had 0.2 and 1.7% resistance, respectively. The rank order of activity of beta-lactam drugs was imipenem, ticarcillin-clavulanic acid, cefoxitin, piperacillin, moxalactam, ceftizoxime, cefotetan, cefotaxime, cefoperazone, and ceftazadime.
Assuntos
Antibacterianos/farmacologia , Bacteroides fragilis/efeitos dos fármacos , Resistência Microbiana a Medicamentos , Testes de Sensibilidade Microbiana , beta-LactamasRESUMO
One hundred thirty-one patients of urologists and infectious disease specialists were entered into an open trial of norfloxacin in the therapy of urinary tract infections (UTIs). All patients were evaluable for tolerability and 98 were evaluable for efficacy. The patient population in this study was older (mean age 53 years) and had more underlying urogenital disorders (30%) or recent invasive urologic procedures (20%) than the typical patient population with UTIs. Over 50% of the patients had infections due to organisms other than Escherichia coli, including Pseudomonas aeruginosa (14), Klebsiella pneumoniae (5), Enterobacter spp (3) and Group D streptococcus (6). Clinical and bacteriologic cure rates were 90 and 91%, respectively. Side effects occurred in 5 patients and were generally mild.
Assuntos
Norfloxacino/uso terapêutico , Infecções Urinárias/tratamento farmacológico , Administração Oral , Adulto , Idoso , Resistência Microbiana a Medicamentos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Norfloxacino/efeitos adversos , Infecções Urinárias/microbiologiaRESUMO
Cytomegalovirus pneumonia, Pneumocystis carinii pneumonia, and pulmonary and disseminated aspergillosis occurred simultaneously in a 66-year-old white man with oat cell carcinoma and ectopic corticotropin production. Hypokalemia, a recent normal chest roentgenogram, and a large left adrenal mass on a computed tomographic scan confused the initial clinical evaluation. The aspergillosis proved fulminant and lethal.