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1.
Pediatrics ; 103(4 Pt 1): 719-23, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10103292

RESUMO

OBJECTIVE: To predict which patients hospitalized in a pediatric intensive care unit (ICU) are colonized with antibiotic-resistant gram-negative rods on admission. METHODS: Consecutive children admitted to a pediatric ICU over a 6-month period were entered into the study. A questionnaire soliciting information regarding the child's medical history and home environment was completed by the parent or guardian. Nasopharyngeal and rectal cultures were obtained on each of the first 3 days of ICU admission, and organisms resistant to ceftazidime or tobramycin were identified. Only clonally distinct organisms, as confirmed by pulsed field gel electrophoresis, were analyzed. The association between identification of colonization with an antibiotic-resistant gram-negative rod within 3 days of ICU admission and factors included in the questionnaire was tested by chi2 or t test. RESULTS. In 64 (8.8%) of 727 admissions, an antibiotic-resistant gram-negative bacillus was isolated within the first 3 ICU days. More than half were identified on the day of admission. Colonization was associated with two factors related to the patient's medical history, namely, number of past ICU admissions (1.98 vs.87) and administration of intravenous antibiotics within the past 12 months (67.9% vs 28.2%). No association was found between colonization and exposure to oral antibiotics. In addition, factors related to the child's environment were also associated with presumed importation of an antibiotic-resistant gram-negative rod into the ICU. Specifically, residence in a chronic care facility was strongly associated with colonization (28.3% vs 2.6%); exposure to a household contact who had been hospitalized in the past 12 months also predicted colonization (41.7% vs 18.5%). CONCLUSIONS: These data suggest that a profile can be established characterizing children colonized with resistant gram-negative bacilli before admission to a pediatric ICU. Infection control measures may help to contain these potentially dangerous bacteria once they have been introduced into the unit.


Assuntos
Resistência Microbiana a Medicamentos , Bactérias Gram-Negativas/isolamento & purificação , Antibacterianos/uso terapêutico , Criança , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/epidemiologia , Humanos , Unidades de Terapia Intensiva Pediátrica , Testes de Sensibilidade Microbiana , Fatores de Risco
2.
Pediatr Infect Dis J ; 18(4): 357-60, 1999 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-10223690

RESUMO

BACKGROUND: Pulsed field gel electrophoresis (PFGE) is a commercially available technique that can establish clonal relationships among many common hospital-derived organisms with a high degree of accuracy and can yield results in a sufficiently short time to guide interventions during an outbreak investigation. METHODS: The CHEF Genomic Bacterial DNA Plug Kit (Bio-Rad) was applied to an unfolding nursery outbreak of Serratia marcescens infections according to the manufacturer's guidelines. Bacterial genomic DNA was digested with XbaI or SpeI and separated on 1% agarose gels, and the isolates were grouped by restriction endonuclease patterns according to established standards. RESULTS: S. marcescens was isolated from nine patients in an intensive care nursery during an 8-week period. Initial PFGE analysis performed after identification of the first eight patients, when closure of the nursery was imminent, revealed that the epidemic was caused by two groups of four isolates each. In both instances the group was geographically contained, and the nursery remained open. A second PFGE analysis indicated that a ninth S. marcescens isolate, recovered in Week 8, was genetically unrelated to the other two. Surveillance during an additional 6 weeks revealed no new cases, and the epidemic was declared over. No cases of invasive S. marcescens infection were identified during the subsequent 10 months. CONCLUSION: Real-time PFGE determined that an apparent nursery outbreak of S. marcescens infection was, in fact, caused by three genetically distinct strains. This information allowed the nursery to remain open after other appropriate infection control measures had been imposed.


Assuntos
Infecção Hospitalar/diagnóstico , Eletroforese em Gel de Campo Pulsado , Infecções por Serratia/diagnóstico , Serratia marcescens/isolamento & purificação , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , DNA Bacteriano/análise , Humanos , Recém-Nascido , Controle de Infecções , Unidades de Terapia Intensiva Neonatal , Epidemiologia Molecular , Infecções por Serratia/epidemiologia , Infecções por Serratia/prevenção & controle , Serratia marcescens/genética
3.
Infect Control Hosp Epidemiol ; 22(8): 499-504, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11700877

RESUMO

OBJECTIVE: To determine the cause of fever in critically ill children and to identify opportunities for reducing antibiotic use in this population. DESIGN: Prospective case series. SETTING: A tertiary-care medical-surgical pediatric intensive care unit (PICU). PATIENTS: Children admitted to the PICU who experienced fever (axillary temperature >38.3 degrees C). MEASUREMENTS: Consecutive children who were febrile at any point in their PICU stay were investigated over two winter seasons. Etiology of the fever was determined by physical examination and routine microbiology and radiographic tests. Three subgroups were reviewed to approximate the number of antibiotic-days that could have been reduced; namely, those with an indeterminate source, those with a documented viral infection, and those receiving a prolonged course of antibiotics. A set of standards reflecting common antibiotic use then was applied to these three patient groups. RESULTS: Of 211 subjects, the majority (83.3%) had either a definitive or suspected focus for their fever, and nearly all of these patients were judged to have an infectious etiology. The study population received a total of 2,036 antibiotic-days. Despite the high incidence of infectious causes of fever in our subjects, however, approximately 15% of total antibiotic-days could have been reduced by applying common-use standards. CONCLUSIONS: Fever in the PICU was usually of defined focus and infectious in origin. However, among febrile patients in the PICU, substantial opportunity exists for reduction of antibiotic use. Trials determining the safety of antibiotic reduction in this population should be pursued vigorously.


Assuntos
Antibacterianos/uso terapêutico , Revisão de Uso de Medicamentos , Febre/etiologia , Unidades de Terapia Intensiva Pediátrica/normas , Criança , Cuidados Críticos/normas , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Resistência Microbiana a Medicamentos , Febre/tratamento farmacológico , Febre/microbiologia , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva Pediátrica/estatística & dados numéricos , Ohio , Estudos Prospectivos , Fatores de Risco , Resultado do Tratamento
4.
Am J Clin Pathol ; 101(6): 753-5, 1994 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-8209864

RESUMO

Semiquantitative cultures for human immunodeficiency virus type 1 were used to initiate and guide therapy in an asymptomatic, heavily infected premature infant. The cultures were performed on fivefold serial dilutions of peripheral blood mononuclear cells, and viral growth was detected by the appearance of p24 antigen in the supernatant. While the patient was receiving low-dose zidovudine, her titer diminished from 206 infectious units per 10(6) cells to undetectable levels over 20 weeks, and she remained asymptomatic throughout her 1st year of life. This case suggests that semiquantitative HIV-1 culture should be further evaluated for its ability to guide practical therapeutic decisions in patients who do not fulfill currently established criteria for treatment.


Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , HIV-1/isolamento & purificação , Recém-Nascido Prematuro , Técnicas Microbiológicas , Feminino , Humanos , Recém-Nascido , Zidovudina/uso terapêutico
5.
Arch Pediatr Adolesc Med ; 152(6): 554-7, 1998 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-9641708

RESUMO

BACKGROUND: There are few data on the rate of compliance with universal precautions among pediatricians. We hypothesized that compliance in pediatrics would be poor because of the intrinsic difficulties in performing invasive procedures in small subjects. DESIGN: Prospective, observational study. SETTING: Tertiary care children's hospital. STUDY PARTICIPANTS: A convenience sample of pediatric house staff. MAIN OUTCOME MEASURES: Pediatric house staff members were observed while performing invasive procedures. Procedure type, number of attempts required, and patient's age and diagnosis were recorded. Degree of compliance with universal precautions was judged by means of Centers for Disease Control and Prevention guidelines. Comparisons between the compliant and noncompliant groups were analyzed by chi2 and 2-tailed t test. RESULTS: A total of 128 procedures performed by 43 house officers, 4 advanced medical students, and 3 chief residents or fellows were observed. Sixty-nine (53.9%) of the 128 procedures were performed correctly according to universal precaution guidelines. Rate of compliance did not appear to be influenced by small patient size, as judged by the lack of association with the age of the patient (mean+/-SD, 4.8+/-5.7 years among those in whom universal precautions were properly used vs 4.9+/-5.4 years among patients in whom precaution guidelines were breached; P=.96). Moreover, the number of attempts required in compliant procedures (1.31+/-0.53) was almost identical to that in noncompliant procedures (1.28+/-0.49; P=.73). Additionally, compliance did not improve with advanced level of training. CONCLUSIONS: Failure of compliance among pediatricians has no apparent association with procedure difficulty, and compliance rates continue to be poor through the course of pediatric training. These findings underline the need for effective education concerning universal precautions throughout pediatric residency, and they suggest that such efforts will not be precluded by obstacles intrinsic to performing invasive procedures on young subjects.


Assuntos
Internato e Residência/estatística & dados numéricos , Pediatria/educação , Precauções Universais/estatística & dados numéricos , Humanos , Ohio , Estudos Prospectivos
6.
Pediatr Neurol ; 11(4): 308-12, 1994 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-7702691

RESUMO

When a child is admitted to the hospital with presumed encephalitis, the physician must use clinical criteria to gauge the appropriate level of hospital care and to give a preliminary assessment of outcome to the family because the etiology is unknown. This study attempted to determine which clinical factors gathered on hospital admission would be most helpful to the physician. The records of 106 children (ages 1 month to 20 years), admitted to Rainbow Babies and Childrens Hospital between 1978-1989 who had discharge diagnoses of encephalitis, were reviewed. Seventy-five met the case definition of presumed viral encephalitis, with viral etiology established in 23% of patients. Poor short-term outcome was defined as the presence of an abnormal neurologic examination at hospital discharge, and was present in 32% of patients. Focal signs on neurologic examination (odds risk: 16.30, P < .05) and abnormal neuroimaging studies (odds risk: 5.66, P < .05) were the only 2 factors present at admission that predicted a poor short-term outcome. Glasgow coma scale at admission was predictive of an abnormal neurologic examination at discharge only when profoundly depressed (6 or less); otherwise, this scale was not useful as a prognostic tool. Factors that were not correlated with adverse outcomes included age younger than 1 year, any type of seizure occurrence, status epilepticus, diffuse or focal electroencephalographic abnormalities, or abnormal cerebrospinal fluid findings.(ABSTRACT TRUNCATED AT 250 WORDS)


Assuntos
Dano Encefálico Crônico/etiologia , Encefalite/etiologia , Exame Neurológico , Admissão do Paciente , Adolescente , Adulto , Dano Encefálico Crônico/diagnóstico , Criança , Pré-Escolar , Cuidados Críticos , Encefalite/complicações , Encefalite/diagnóstico , Encefalite Viral/complicações , Encefalite Viral/diagnóstico , Encefalite Viral/etiologia , Feminino , Escala de Coma de Glasgow , Humanos , Lactente , Masculino , Prognóstico , Estudos Retrospectivos , Convulsões/etiologia
7.
Pediatr Clin North Am ; 42(3): 687-702, 1995 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-7761147

RESUMO

Gram-negative bacilli that are resistant to commonly used antibiotics are a growing problem in seriously ill, hospitalized patients. Numerous outbreaks involving these organisms have been reported in intensive care nurseries and among critically ill adults. In endemic situations, the major reservoir for these pathogens is the patient; occasionally, transmission from patient to patient occurs through the hands of caregivers. Although the degree of antibiotic use probably plays some role in the emergence of antibiotic-resistant gram-negative bacilli, this relationship has not been uniformly demonstrated, and other factors intrinsic to the organisms themselves and to the critically ill patient may play an important role.


Assuntos
Antibacterianos/farmacologia , Cuidados Críticos , Bactérias Gram-Negativas/efeitos dos fármacos , Adulto , Antibacterianos/uso terapêutico , Infecção Hospitalar , Surtos de Doenças , Resistência Microbiana a Medicamentos/genética , Bactérias Gram-Negativas/genética , Infecções por Bactérias Gram-Negativas , Humanos , Recém-Nascido , Controle de Infecções/métodos
8.
J Perinatol ; 19(7): 483-7, 1999.
Artigo em Inglês | MEDLINE | ID: mdl-10685295

RESUMO

OBJECTIVE: Federal guidelines recommend the provision of human immunodeficiency virus education to all attendees of prenatal clinics. The current study was conducted to assess risk-taking behaviors among urban women voluntarily pursuing prenatal care. DESIGN AND SETTING: African American women attending urban prenatal clinics in Cleveland, Ohio were subjected to an extensive interview before receiving an experimental AIDS education curriculum. The interview sought detailed information regarding demographics, lifetime and recent sexual activity, condom use, and lifetime and recent illicit drug use. RESULTS: A total of 1017 women were interviewed; of those women, approximately 73% were single. The majority had a monthly income of less than $500. A total of 66% had only one partner in the past year, and almost 90% had < or = 1 partner in the past 6 months. A total of 98% identified a main partner. Nearly all subjects were at least fairly certain that this partner did not use intravenous drugs, and 71% were at least fairly certain that he was monogamous. Only 19% used condoms most or all the time. Intravenous drug use among study subjects was very infrequent. CONCLUSION: These data indicate that inner-city Cleveland women seeking prenatal care are largely monogamous around the time of their gestation, and that a history of intravenous drug use is infrequent. They suggest that prenatal counseling in urban clinics will need to address women who largely are engaged in single-partner relationships at the time of the intervention.


Assuntos
Infecções por HIV/etiologia , Áreas de Pobreza , Cuidado Pré-Natal , Assunção de Riscos , Adolescente , Adulto , Análise por Conglomerados , Preservativos/estatística & dados numéricos , Coleta de Dados , Feminino , Humanos , Incidência , Entrevistas como Assunto , Pessoa de Meia-Idade , Meio-Oeste dos Estados Unidos , Gravidez , Parceiros Sexuais , Abuso de Substâncias por Via Intravenosa/epidemiologia
9.
Clin Perinatol ; 18(2): 193-208, 1991 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-1879104

RESUMO

Significant progress has been made in the recognition and treatment of herpes simplex disease in the newborn. This review discusses four current issues surrounding this severe and important infection. First, the reasons underlying the failure of antenatal screening programs to identify high-risk pregnancies for herpes simplex are analyzed. Second, typical and atypical clinical manifestations of neonatal herpetic infection are reviewed. Third, determinants of disease, particularly the immune status of the mother and child, and their therapeutic implications are discussed. Finally, controversies surrounding antiviral therapy are examined.


Assuntos
Herpes Simples , Aciclovir/uso terapêutico , Feminino , Herpes Simples/diagnóstico , Herpes Simples/tratamento farmacológico , Herpes Simples/etiologia , Herpes Simples/prevenção & controle , Humanos , Recém-Nascido , Gravidez , Diagnóstico Pré-Natal , Vidarabina/uso terapêutico
10.
Clin Perinatol ; 20(1): 47-60, 1993 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-8458171

RESUMO

Human immunodeficiency virus (HIV) infection has become one of the leading causes of mortality among American women of childbearing age. Many women will experience a pregnancy after they have been infected. Several rationales exist for offering the pregnant infected woman anti-HIV therapy, including interruption of vertical transmission and improvement of her own health and the outcome of her pregnancy. The bases for these rationales are explored, the options (chemotherapy and immunotherapy) are described, and the potential toxicities are examined.


Assuntos
Infecções por HIV/terapia , Imunoterapia , Complicações Infecciosas na Gravidez/terapia , Zidovudina/uso terapêutico , Animais , Feminino , Proteína gp120 do Envelope de HIV/uso terapêutico , Infecções por HIV/prevenção & controle , Infecções por HIV/transmissão , Humanos , Recém-Nascido , Pneumonia por Pneumocystis/prevenção & controle , Gravidez , Resultado da Gravidez , Zidovudina/efeitos adversos
13.
Minerva Pediatr ; 55(5): 385-93, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14608262

RESUMO

Infections with Gram-negative bacilli have affected critically ill newborns throughout the era of modern neonatal intensive care. Selected topics regarding the acquisition of Gram-negative bacteria, particularly those expressing antibiotic resistance, in the neonatal intensive care unit (NICU) are reviewed. Some data suggest that the recent introduction of intrapartum antibiotic prophylaxis programs, through which selected women are administered penicillin or ampicillin during labor to prevent vertically transmitted Group B streptococcal disease, has increased the incidence and resistance of early onset Gram-negative bacillary infection in the newborn over the past 5 years. Additional data suggest that late onset, nosocomially-acquired Gram-negative bacillary infections also are increasing among critically-ill newborns. The seminal event in Gram-negative bacterial infection in the hospitalized infant is colonization of the gastrointestinal tract and nasopharynx. Newborns admitted to the intensive care unit acquire hospital-associated Gram-negative bacterial colonization throughout their NICU stay, presumably transmitted from the environmental flora via the hands of caregivers. Colonization specifically by antibiotic-resistant bacilli follows a similar pattern, suggesting that such bacteria make up part of the modern NICU ecology and are acquired by infants similar to susceptible microorganisms. Althou-gh some clinically-undetected cross-transmission of resistant bacilli occurs during non-outbreak periods, most colonizing antibiotic-resistant bacilli are unique to each infant. The role of antibiotic exposure on the acquisition of antibiotic resistant bacilli in the intensive care nursery is difficult to calculate given the covariance of such exposure to other markers of severe disease. Experience has demonstrated, however, that use of the aminoglycosides is infrequently associated with emergence of resistance in the newborn, whereas the use of higher-generation cephalosporins may be associated with the rapid appearance of bacilli resistant to betha-lactams.


Assuntos
Antibacterianos/farmacologia , Infecção Hospitalar/epidemiologia , Surtos de Doenças , Farmacorresistência Bacteriana , Bactérias Gram-Negativas/efeitos dos fármacos , Infecções por Bactérias Gram-Negativas/epidemiologia , Unidades de Terapia Intensiva Neonatal , Aminoglicosídeos/farmacologia , Aminoglicosídeos/uso terapêutico , Cefalosporinas/farmacologia , Cefalosporinas/uso terapêutico , Infecção Hospitalar/tratamento farmacológico , Feminino , Infecções por Bactérias Gram-Negativas/tratamento farmacológico , Humanos , Recém-Nascido , Itália/epidemiologia , Masculino , Gravidez
14.
Adv Pediatr Infect Dis ; 6: 111-36, 1991.
Artigo em Inglês | MEDLINE | ID: mdl-1647166

RESUMO

Nonherpetic encephalitis outside the newborn period is usually a self-limited disease. The majority of patients will recover without significant sequelae, and require only supportive therapy during the acute illness. Though the underlying viral etiology frequently will escape detection, identification of the infecting agent has considerable prognostic value which can complement clinical measures of severity of disease. The most important initial task of the clinician faced with a case of presumptive viral encephalitis is to eliminate the possibility of a treatable illness. Once this has been done, the diagnosis of viral encephalitis can be supported by documenting the characteristic slow-wave background activity on EEG, and a mild lymphocellular pleocytosis in the CSF. Because viral encephalitis can be caused by such a large number of organisms, the search for an etiology can be daunting. Realizing that all the agents described above can, at times, cause encephalitis without any clue to their identity, one nevertheless may use several pieces of historical information to narrow the possibilities. Travel history, animal exposures, immunization history, and seasonality all may help to steer the search in a particular direction and, indeed, may point to a nonvirologic cause as well. In addition, detection of extraneurological signs and symptoms may strongly indicate a specific virologic diagnosis. Finally, knowledge of concurrent community epidemic patterns, and of surveillance data routinely collected by local and state health departments, can help to increase or decrease the likelihood of a given pathogen. The causative viral agent usually can be identified by serological testing and viral culture. Occasionally, single serological determinations are diagnostic: in rabies (when the patient has not received immune prophylaxis), eastern equine encephalitis, and HIV, since seropositivity is strongly associated with symptomatic illness; and in Epstein-Barr virus, if a panel of antibody determinations which can time the infection is available. In addition, high CSF: serum titers for antibody against any neurotropic agent is usually diagnostic, though the absence of a high central nervous system antibody titer does not eliminate any potential viral pathogen. With these few exceptions, a single serological determination for a given pathogen is almost always impossible to interpret; paired sera (one obtained upon diagnosis, and one obtained 10 to 14 days later, either just prior to hospital discharge or at a follow-up visit) are far more helpful. Many viruses that directly infect the central nervous system are difficult to recover from the CSF; therefore, viral isolation from the nasopharynx and stool also should be sought.(ABSTRACT TRUNCATED AT 400 WORDS)


Assuntos
Encefalite/microbiologia , Herpes Simples/microbiologia , Infecções por Adenoviridae/microbiologia , Infecções por Arbovirus/microbiologia , Diagnóstico Diferencial , Vírus da Encefalite Equina do Leste/isolamento & purificação , Encefalomielite Equina/microbiologia , Infecções por Enterovirus/microbiologia , Infecções por HIV/microbiologia , Infecções por Herpesviridae/microbiologia , Humanos , Coriomeningite Linfocítica/microbiologia , Sarampo/microbiologia , Raiva/microbiologia
15.
Curr Opin Infect Dis ; 14(4): 449-53, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11964864

RESUMO

Important characteristics of hospital infection control are specific to pediatric facilities. For example, colonization and infection with vancomycin-resistant enterococci, which are widely spread in many units housing adult patients, are uncommon in children, especially in the neonatal intensive care unit where vancomycin use is heavy. Characteristics of the neonatal intensive care unit, such as the insulated environment and infrequent treatment with antibiotics with broad anaerobic activity, likely account for this finding. Artificial fingernails have been discovered to promote colonization with potential pathogens; their implication in recent nursery epidemics emphasizes the need to prohibit their use in this environment in particular. Finally, nosocomial viral infections occur with regularity in pediatric hospitals. Programs that successfully and cost-effectively control hospital spread of respiratory syncytial virus, however, demonstrate that rational, multifaceted interventions can nearly eliminate transmission of certain viral pathogens on the pediatric wards.


Assuntos
Infecção Hospitalar/prevenção & controle , Adolescente , Criança , Pré-Escolar , Infecção Hospitalar/transmissão , Enterococcus/efeitos dos fármacos , Infecções por Bactérias Gram-Positivas/prevenção & controle , Mãos/microbiologia , Humanos , Lactente , Recém-Nascido , Unidades de Terapia Intensiva Neonatal , Resistência a Vancomicina , Viroses/transmissão
16.
Annu Rev Med ; 41: 169-76, 1990.
Artigo em Inglês | MEDLINE | ID: mdl-2184721

RESUMO

The majority of central venous line-associated infections are caused by organisms on the skin near the exit site gaining access to the intravascular segment of the catheter. A variety of strategies have been used in an effort to reduce catheter contamination, but one innovation--the semipermeable transparent dressing--may actually increase infection risk. On the other hand, new catheter materials and designs probably reduce the risk. There are only a limited number of well-designed studies of the increasingly popular totally implantable catheter system and the multilumen line, but it appears that the former is associated with a low rate of infection, while the latter may be more hazardous than the single-lumen line.


Assuntos
Infecções Bacterianas/prevenção & controle , Cateterismo Venoso Central/efeitos adversos , Cateteres de Demora/efeitos adversos , Infecções Bacterianas/etiologia , Cateterismo Venoso Central/instrumentação , Cateterismo Venoso Central/métodos , Contaminação de Equipamentos/prevenção & controle , Desenho de Equipamento , Humanos , Próteses e Implantes
17.
Antimicrob Agents Chemother ; 29(6): 1010-6, 1986 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-3015012

RESUMO

Ribavirin at 200 micrograms/ml inhibited vesicular stomatitis virus (VSV) growth in Chinese hamster ovary (CHO) cells by 2.5 logs. To determine the mechanism of this inhibition, viral macromolecular synthesis was examined. VSV primary transcription remained unaffected, but overall VSV RNA synthesis decreased by 40 to 60%. When ribavirin was added 1.5 h after infection, inhibition of progeny production was partially lost, indicating that the antiviral effect was on an early stage after primary transcription. Inhibition of RNA polymerization by premature chain termination was not evident. Viral translation, on the other hand, was reduced by 95% with an inhibition of every protein species. Furthermore, viral RNA synthesized in the presence of ribavirin did not translate well in an in vitro translation system. In contrast, uninfected CHO cells treated with ribavirin showed a greater sensitivity in RNA synthesis than in protein synthesis. This suggests that the cellular translational machinery was not directly affected. Short-term treatment of cells resulted in negligible toxicity, but after 24 h there was marked alteration of cellular integrity. These results, taken together with data on other viruses, suggest that in the presence of ribavirin, dysfunctional VSV mRNA was synthesized, resulting in its failure to be translated. The selective antiviral effects of ribavirin and its relative lack of toxicity for host cells may be predicted on the basis of mRNA turnover and the requirements for de novo functional mRNA.


Assuntos
Ribavirina/farmacologia , Ribonucleosídeos/farmacologia , Vírus da Estomatite Vesicular Indiana/efeitos dos fármacos , Animais , Células Cultivadas , Cricetinae , Cricetulus , Dactinomicina/farmacologia , Interações Medicamentosas , Feminino , Ovário , RNA Mensageiro/biossíntese , RNA Viral/biossíntese , Transcrição Gênica/efeitos dos fármacos , Vírus da Estomatite Vesicular Indiana/metabolismo , Proteínas Virais/biossíntese
18.
J Infect Dis ; 169(5): 1100-2, 1994 May.
Artigo em Inglês | MEDLINE | ID: mdl-8169400

RESUMO

Previous experiments have indicated that zidovudine is cytotoxic to early murine embryos both in vivo and in vitro. Newer nucleoside analogs (ddI, ddC, and d4T) with antiretroviral activity were tested to determine whether they had similar toxicity. Exposure of two-cell embryos to each of these three drugs inhibited blastocyst formation only at concentrations > or = to 100 microM. Sublethal preblastocyst exposure to d4T resulted in failure to develop beyond the blastocyst stage at 10 microM; no effect was seen with ddC or ddI at concentrations up to 100 microM. In each instance, however, cytotoxicity of all three drugs was significantly less than with zidovudine at equivalent concentration. These experiments suggest that newer antiretroviral nucleosides may be safer to use in early pregnancy than zidovudine.


Assuntos
Antivirais/toxicidade , Embrião de Mamíferos/efeitos dos fármacos , Nucleosídeos/toxicidade , Animais , Técnicas de Cultura , Didanosina/toxicidade , HIV/efeitos dos fármacos , Camundongos , Nucleosídeos/uso terapêutico , Estavudina/toxicidade , Zalcitabina/toxicidade , Zidovudina/toxicidade
19.
New Horiz ; 4(3): 353-60, 1996 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8856753

RESUMO

Antibiotic resistance in the neonatal and pediatric intensive care environments has not been rigorously investigated. There is reason to believe that the epidemiology of antibiotic resistance in these settings may be different from that in other hospital settings because the patients' preadmission health status, the maturity of their immune systems, and their outpatient exposure to antibiotics are different from those seen in adults. At the present time, the areas of greatest concern are the outbreaks of infection caused by methicillin-resistant Staphylococcus aureus in the neonatal ICUs and the emergence of antibiotic-resistant Gram-negative bacteria in pediatric intensive care units (PICU). In the former, colonization and transmission by nursery personnel remains one of the great challenges in infection control. In the latter, new information is emerging which challenges the notion that antibiotic-restriction policies might be an effective means for modulating the emergence of antibiotic-resistant Gram-negative pathogens in the pediatric intensive care environment. It appears that these organisms are largely imported into the ICU from the community and are not a result of antibiotic practices within the unit itself. This observation requires that strategies to control these organisms in the PICU be reassessed.


Assuntos
Cuidados Críticos , Resistência Microbiana a Medicamentos , Pediatria , Enterococcus/efeitos dos fármacos , Enterococcus/fisiologia , Bactérias Gram-Negativas/fisiologia , Humanos , Unidades de Terapia Intensiva Neonatal , Meticilina/uso terapêutico , Resistência às Penicilinas , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus aureus/fisiologia , Vancomicina/uso terapêutico
20.
Antimicrob Agents Chemother ; 37(8): 1610-3, 1993 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-8215271

RESUMO

It previously has been demonstrated that zidovudine (AZT) is lethal to early murine embryos. The effect of the drug on pre- and postimplantation embryos was examined to delineate the timing of this toxicity and to investigate its possible mechanisms. Embryos exposed in the whole mouse during preblastocyst development were unable to proceed beyond the blastocyst stage. Similarly, when two-cell embryos harvested from unexposed females were exposed to low-concentration (1 microM) AZT in vitro over 24 h, development beyond the blastocyst stage was inhibited. In contrast, drug exposure during in vitro blastocyst and postblastocyst development resulted in little or no morphologic toxicity. Further investigation revealed that preblastocyst AZT exposure resulted in the development of blastocysts with significantly lower cell numbers than control embryos. While embryonic exposure to AZT at the blastocyst and postblastocyst stages also resulted in retarded cell division, the effects were milder than those recorded after preblastocyst exposure. These data demonstrate that the critical period of AZT toxicity toward murine embryos is between ovulation and implantation and indicate that AZT directly suppresses cell division in the preimplantation embryo.


Assuntos
Blastocisto/efeitos dos fármacos , Implantação do Embrião/efeitos dos fármacos , Zidovudina/toxicidade , Animais , Blastocisto/fisiologia , Divisão Celular/efeitos dos fármacos , Implantação do Embrião/fisiologia , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/fisiologia , Feminino , Camundongos , Oócitos/efeitos dos fármacos , Oócitos/fisiologia , Gravidez , Fatores de Tempo
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