RESUMEN
Vancomycin- and methicillin-resistant gram-positive cocci have emerged as an increasingly problematic cause of hospital-acquired infections. We conducted a literature review of newer antibiotics with activity against vancomycin-resistant and methicillin-resistant gram-positive cocci. Quinupristin/dalfopristin, linezolid, daptomycin, and tigecycline have in vitro activity for methicillin-resistant staphylococci and are superior to vancomycin for vancomycin-resistant isolates. Dalbavancin, telavancin, and oritavancin are new glycopeptides that have superior pharmacodynamic properties compared to vancomycin. We review the antibacterial spectrum, clinical indications and contraindications, pharmacologic properties, and adverse events associated with each of these agents. Daptomycin has rapid bactericidal activity for Staphylococcus aureus and is approved for use in bacteremia and right-sided endocarditis. Linezolid is comparable to vancomycin in patients with methicillin-resistant S. aureus (MRSA) pneumonia and has pharmacoeconomic advantages given its oral formulation. Quinupristin/dalfopristin is the drug of choice for vancomycin-resistant Enterococcus faecium infections but has no activity against Enterococcus faecalis. Tigecycline has activity against both enterococcus species and MRSA; it is also active against Enterobacteriaceae and anaerobes which allows for use in intra-abdominal and diabetic foot infections. A review of numerous in vitro and animal model studies shows that interaction between these newer agents and other antistaphylococcal agents for S. aureus are usually indifferent (additive).
Asunto(s)
Antiinfecciosos/farmacología , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Infecciones por Bacterias Grampositivas/microbiología , Cocos Grampositivos/efectos de los fármacos , Resistencia a la Meticilina , Resistencia a la Vancomicina , Animales , Antiinfecciosos/uso terapéutico , HumanosRESUMEN
The pharmacokinetic profile of oral linezolid makes it an attractive alternative for the treatment of osteomyelitis. Few studies have described the efficacy of linezolid in the treatment of osteomyelitis. A retrospective, observational analysis was conducted at Edward Hines, Jr. VA Hospital. Patients who received oral linezolid from June 2000 to December 2002 were identified from pharmacy records. Forty-two patients who received oral linezolid for osteomyelitis at our institution were identified. Only patients who had received at least six weeks of linezolid therapy were evaluated for clinical effectiveness. Patients were also evaluated for adverse drug reactions due to linezolid. The clinical cure rate was 55% for the 20 patients who received at least six weeks of therapy. Adverse events included gastrointestinal disturbances (15%), thrombocytopenia (10%), anemia (10%), neutropenia (5%) and rash (5%). The authors conclude that oral linezolid is an alterative to intravenous antibiotics for the treatment of osteomyelitis.
Asunto(s)
Acetamidas/uso terapéutico , Antiinfecciosos/uso terapéutico , Osteomielitis/tratamiento farmacológico , Oxazolidinonas/uso terapéutico , Acetamidas/administración & dosificación , Acetamidas/efectos adversos , Administración Oral , Anciano , Anciano de 80 o más Años , Antiinfecciosos/administración & dosificación , Antiinfecciosos/efectos adversos , Hospitales de Veteranos , Humanos , Linezolid , Masculino , Persona de Mediana Edad , Oxazolidinonas/administración & dosificación , Oxazolidinonas/efectos adversos , Estudios RetrospectivosRESUMEN
While filamentous fungi are a rare cause of peritonitis in peritoneal dialysis patients, there is increasing recognition of Paecilomyces species as pathogens in such patients. We herein report a case of fungal peritonitis secondary to the filamentous Paecilomyces variotii species. The patient had a long and ultimately fatal course of illness despite catheter removal, discontinuation of peritoneal dialysis, recurrent intraabdominal abscess drainage, and prolonged courses of antifungal therapy. Our experience with this case and a review of the literature suggests that infection with this fungus can cause substantial morbidity and is probably best treated with prompt catheter removal, aggressive antifungal therapy and vigilant observation for complications.
Asunto(s)
Fallo Renal Crónico/terapia , Micosis/etiología , Paecilomyces/patogenicidad , Diálisis Peritoneal Ambulatoria Continua/efectos adversos , Peritonitis/etiología , Humanos , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/microbiología , Masculino , Persona de Mediana Edad , Micosis/diagnóstico , Micosis/microbiología , Paecilomyces/aislamiento & purificación , Peritonitis/diagnóstico , Peritonitis/microbiologíaRESUMEN
To improve vascular access for hemodialysis, a new device (Dialock Hemodialysis Access System, Biolink Corporation, Middleboro, MA) has been developed. Implanted subcutaneously, the device is accessed by percutaneous puncture. Attached to the device are two catheters that are implanted into the superior vena cava or right atrium. Clinical results thus far have been promising. However, use of this device is not free from infectious complications. In the present pilot study, 25 maintenance hemodialysis patients were implanted with 26 Dialock devices. The incidence of bacteremia was 2.9/1,000 catheter days. In 14 episodes of bacteremia in 8 patients the infection was successfully treated with a combination of systemic antibiotic treatment and adjunctive antibiotic/anticoagulant lock therapy. The lock therapy entailed the instillation of both an antibiotic and an anticoagulant into the device. We believe that the antibiotic/anticoagulant lock technique is an effective, adjunctive therapeutic modality in the treatment of infections related to the use of indwelling vascular access devices.
Asunto(s)
Antibacterianos/administración & dosificación , Anticoagulantes/administración & dosificación , Bacteriemia/tratamiento farmacológico , Bacteriemia/etiología , Catéteres de Permanencia/efectos adversos , Diálisis Renal/efectos adversos , Humanos , Proyectos Piloto , Diálisis Renal/instrumentaciónRESUMEN
Urea and creatinine levels in spent hemodialysates showed only small declines in spite of incubation at 37 degrees C for 36 hours. In the determination of dialysate-side solute removal, it would seem prudent to keep spent dialysate cold during collection to retard bacterial breakdown of these waste products.
Asunto(s)
Creatinina/análisis , Soluciones para Hemodiálisis/química , Urea/análisis , Análisis de Varianza , Humanos , Concentración de Iones de Hidrógeno , TemperaturaRESUMEN
BACKGROUND: Bacteremia is commonplace in patients undergoing hemodialysis since the vascular access site is a ready source of infection. Mortality is notably high. However, uncertainties exist with respect to therapy including indications for surgical removal of vascular access site and duration of therapy. We therefore conducted a large-scale collaborative study of bacteremia in hemodialysis patients in six US academic medical centers to define the epidemiology of such infections and to address issues of management. PATIENTS AND METHODS: We conducted a prospective observational study over 2 years. Severity of illness at onset of bacteremia was defined by objective criteria. Patients were followed for 90 days to assess late complications including endocarditis and mortality. Univariate and multivariate analyses were used to assess risk factors for mortality. RESULTS: Patients experiencing 127 consecutive episodes of bacteremia were enrolled. The most common cause of bacteremia was Staphylococcus aureus (31%), followed by aerobic gram-negative bacilli (28%) and coagulase-negative staphylococci (13%). Polymicrobial bacteremia occurred in 6% of patients. The most frequent focus of infection was the access site for hemodialysis, although urinary tract, gastrointestinal tract and lung were also implicated. Aerobic gram-negative bacilli and enterococci usually originated from the urinary tract. S. aureus was significantly more likely to cause infection of the access site than other bacteria (p = 0.0001). S. aureus endocarditis was diagnosed in two patients who were receiving antibiotic therapy for S. aureus bacteremia. Removal of the infected access site (shunt, fistula, catheter) was performed for 86% of the patients (95% of the intravenous catheters and 80% of the arteriovenous fistulas/shunts). Overall mortality was 33% at 90 days and was significantly associated with severity of illness at onset of antibiotic therapy and age >60 years. Mortality was not significantly different in patients undergoing surgical removal of infected access site versus those treated with antibiotics alone. CONCLUSION: When S. aureus was isolated from the blood, the access site was the most frequent source. Surgical removal of the access site did not have a notable impact on mortality. Until a randomized trial proves otherwise, it appears that surgical removal of the access site can be individualized. Selected patients who are less severely ill (based on objective criteria) can maintain their hemodialysis access site and be treated with 2 weeks of antibiotic therapy.
Asunto(s)
Absceso/etiología , Bacteriemia/tratamiento farmacológico , Bacteriemia/etiología , Diálisis Renal/efectos adversos , Infecciones Estafilocócicas/etiología , Staphylococcus aureus/patogenicidad , Absceso/tratamiento farmacológico , Absceso/microbiología , Adulto , Anciano , Catéteres de Permanencia/microbiología , Estudios Epidemiológicos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Planificación de Atención al Paciente , Pronóstico , Estudios Prospectivos , Factores de Riesgo , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/microbiología , Staphylococcus aureus/aislamiento & purificaciónRESUMEN
Exposure to GB virus C (GBV-C) was determined in several U.S. populations by both reverse-transcription-polymerase chain reaction (RT-PCR) and by an enzyme linked immunosorbent assay (ELISA) for antibodies to mammalian cell-expressed GBV-C envelope protein, E2 (GBV-C E2). Most individuals exposed to GBV-C were either RNA positive/ELISA negative or ELISA positive/RNA negative. Exposure, therefore, was measured as the sum of GBV-C RNA positive and GBV-C E2 antibody positive specimens, and was higher in commercial plasmapheresis donors (40.5%) than in volunteer blood donors (5.5%). In intravenous drug users (IVDUs), GBV-C exposure was 89.2%. Serial bleed specimens tested for GBV-C RNA indicate that some patients remain viremic for at least 3 years and fail to produce detectable antibodies to GBV-C E2. In other exposed individuals who tested negative for GBV-C RNA, antibodies to E2 appear to be similarly long-lived (greater than 3 years) with a fairly constant titer (ranging in reciprocal endpoint dilution from 336 to 21,504). Since the detection of GBV-C RNA and GBV-C E2 antibody are mutually exclusive in most exposed individuals, studies pertaining to incidence and prevalence of GBV-C infection require both antibody and nucleic acid detection.
Asunto(s)
Flaviviridae/inmunología , Flaviviridae/aislamiento & purificación , Anticuerpos Antihepatitis/sangre , Hepatitis Viral Humana/virología , ARN Viral/sangre , Enfermedad Aguda , Donantes de Sangre , Transfusión Sanguínea , Hepatitis C/virología , Hepatitis C Crónica/virología , Humanos , Plasma , Abuso de Sustancias por Vía Intravenosa/virologíaRESUMEN
Among the three recently described GB viruses (GBV-A, GBV-B, and GBV-C), only GBV-C has been linked to cryptogenic hepatitis in man. Because of the limited utility of currently available research tests to determine antibody response to GBV-C proteins, the prevalence of GBV-C RNA in human sera was studied using reverse transcription-polymerase chain reaction (RT-PCR). The prevalence of GBV-C is higher among volunteer blood donors with elevated serum alanine aminotransferase (ALT) levels (3.9%) than among volunteer blood donors with normal ALT levels (0.8%). Higher rates were also noted among commercial blood donors (12.9%) and intravenous drug users (16.0%). GBV-C was frequently detected in residents of West Africa, where the prevalence was > 10% in most age groups. Approximately 20% of patients diagnosed with either acute or chronic hepatitis C virus (HCV) were found to be positive for GBV-C RNA. In addition, GBV-C RNA sequences were detected in individuals diagnosed with non-A-E hepatitis, with clinical courses ranging from mild disease to fulminant hepatitis. Fourteen of sixteen subjects with or without clinically apparent hepatitis were positive for GBV-C RNA more than 1 year after the initial positive result.
Asunto(s)
Flaviviridae/aislamiento & purificación , Hepatitis Viral Humana/virología , Reacción en Cadena de la Polimerasa/métodos , ARN Viral/sangre , Flaviviridae/genética , Flaviviridae/fisiología , Hepatitis Viral Humana/sangre , Hepatitis Viral Humana/epidemiología , Humanos , Viremia , Latencia del VirusRESUMEN
A randomized, controlled clinical trial was performed to determine whether individualized dosing by use of Bayesian pharmacokinetic modeling could decrease nephrotoxicity accosted with aminoglycoside therapy. Two hundred forty-three patients receiving aminoglycosides for suspected or proven infection were randomly assigned to one of three groups: usual physician-directed dosing (Group 1), pharmacist-assisted dosing (Group 2), or pharmacist-directed dosing (Group 3). Dosing in Groups 2 and 3 was based on a Bayesian pharmacokinetic dosing program, whereas Group 1 served as the control group. Individualized dosing resulted in higher mean postinfusion (peak) serum aminoglycoside levels, higher ratios of mean peak level to minimum inhibitory concentration (peak/MIC ratios), and a trend toward lower trough serum levels. Milligrams per dose were higher and number of doses per day was lower in the pharmacist-dosed groups. However, the incidence of nephrotoxicity (> or = 100% increase in serum creatinine) was not different among the three groups (16, 27, and 16% in Groups 1, 2, and 3, respectively). Similarly, severity of toxicity was not affected by the dosing intervention. Risk factors for toxicity included duration of therapy, shock, treatment with furosemide, older age, and liver disease. After controlling for these factors, the dosing intervention still had no effect on nephrotoxicity. It was concluded that Bayesian pharmacokinetic dosing did not decrease the risk of nephrotoxicity associated with aminoglycoside therapy.
Asunto(s)
Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Riñón/efectos de los fármacos , Anciano , Aminoglicósidos , Antibacterianos/sangre , Antibacterianos/farmacocinética , Teorema de Bayes , Relación Dosis-Respuesta a Droga , Humanos , Infecciones/tratamiento farmacológico , Persona de Mediana Edad , Estudios Prospectivos , Resultado del TratamientoRESUMEN
The synergistic activity of levofloxacin and oxacillin against levofloxacin-resistant isolates of methicillin-resistant Staphylococcus aureus was tested by the time-kill method. The combination of levofloxacin at 1/4 the MIC for the isolate plus oxacillin at 8 micrograms/ml (< 1/4 the MIC) was synergistic against seven of nine isolates at 8 h, although no significant synergy was demonstrated at 24 h. This combination may prove to be effective against multidrug-resistant methicillin-resistant S. aureus, and further studies are warranted.
Asunto(s)
Antiinfecciosos/farmacología , Levofloxacino , Ofloxacino/farmacología , Oxacilina/farmacología , Staphylococcus aureus/efectos de los fármacos , Farmacorresistencia Microbiana , Sinergismo Farmacológico , Cinética , Resistencia a la Meticilina , Pruebas de Sensibilidad MicrobianaRESUMEN
Fleroxacin, a new quinolone antimicrobial agent, was evaluated as part of a multicenter, comparative, open-label, randomized trial with ceftazidime in the treatment of lower respiratory tract infections and skin and soft-tissue infections. After written informed consent was obtained, 20 patients were entered at our center. Twelve patients were assigned to the fleroxacin group; 6 in each infection category. Of these 12 patients, 2 with pneumonia and 3 with skin and soft-tissue infection were not clinically evaluable. The mean duration of therapy was 5.7 +/- 3.0 days in the fleroxacin group versus 7.9 +/- 2.0 days in the ceftazidime group. The gram-positive organisms responsible for those infections not evaluable were methicillin-resistant Staphylococcus aureus, Streptococcus pneumoniae, and group F streptococcus, all of which were resistant to fleroxacin. In total, 6 gram-positive isolates were resistant to fleroxacin. All but 2 S aureus isolates were susceptible to ceftazidime. Adverse reactions in both groups were negligible. Fleroxacin was found to be as effective as ceftazidime against a variety of gram-negative pathogens, but local susceptibility patterns for quinolones should be checked before empiric use of fleroxacin against gram-positive pathogens such as streptococci.
Asunto(s)
Infecciones Bacterianas/tratamiento farmacológico , Ceftazidima/uso terapéutico , Enfermedades del Tejido Conjuntivo/tratamiento farmacológico , Fleroxacino/uso terapéutico , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Enfermedades Cutáneas Infecciosas/tratamiento farmacológico , Adulto , Anciano , Anciano de 80 o más Años , Infecciones Bacterianas/microbiología , Ceftazidima/efectos adversos , Enfermedades del Tejido Conjuntivo/microbiología , Fleroxacino/administración & dosificación , Fleroxacino/efectos adversos , Humanos , Infusiones Intravenosas , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Estudios Prospectivos , Infecciones del Sistema Respiratorio/microbiología , Enfermedades Cutáneas Infecciosas/microbiología , Resultado del TratamientoRESUMEN
We surveyed for serologic evidence of either HIV-1 or HTLV-I/II infection in 387 male veterans who entered into an inpatient drug treatment center. Serum was obtained after receiving written informed consent. Serum specimens were tested by enzyme-linked immunosorbent assay for antibody to HIV-1 and for antibody to HTLV-I/II; sera that were repeatedly reactive were then tested by Western blot (HIV-1/HTLV-I/II) and radioimmunoprecipitation assay (HTLV-I/II). Sixty-five of 387 (16.79%) patients were tested and confirmed as positive for HTLV-I/II only antibodies and 30 of the 387 (7.75%) were positive for HIV-1 only antibodies. An additional nine patients (2.32%) were seropositive for antibodies to both viruses. A statistically significant difference in the CD4/CD8 lymphocyte ratio was associated with HIV-1 seropositivity. HTLV-I/II seropositivity was strongly associated with black race, age, and duration of i.v. drug use, but not with sexual intercourse as determined by lifetime history of number of sexual partners, incidence of sexually transmitted diseases, type of drug used, or needle-sharing practices.
Asunto(s)
Síndrome de Inmunodeficiencia Adquirida/epidemiología , VIH-1 , Infecciones por HTLV-I/epidemiología , Infecciones por HTLV-II/epidemiología , Trastornos Relacionados con Sustancias , Síndrome de Inmunodeficiencia Adquirida/transmisión , Adulto , Western Blotting , Chicago , Demografía , Anticuerpos Anti-VIH/análisis , Anticuerpos Anti-HTLV-I/análisis , Infecciones por HTLV-I/transmisión , Anticuerpos Anti-HTLV-II/análisis , Infecciones por HTLV-II/transmisión , Humanos , MasculinoRESUMEN
We evaluated the safety and efficacy of ofloxacin administered both by the intravenous route and orally in 26 men with serious skin and soft tissue infection. Twenty-one patients completed antimicrobial therapy and were fully evaluable. Of these, 18 were judged to be cured, while 3 failed therapy either during or within 2 weeks after completion of therapy. Overall, Staphylococcus aureus was the most commonly isolated pathogen and was found to be susceptible to ofloxacin in 12 of 14 patients. Two patients, 1 with a tolerant isolate of S. aureus, the other patient with a resistant isolate of S. aureus, responded clinically to ofloxacin therapy; a third patient with an initially ofloxacin-sensitive isolate failed therapy, and on subsequent culture an ofloxacin-resistant S. aureus was isolated. Ofloxacin was well tolerated and efficacious in the treatment of skin and soft tissue infections including those caused by staphylococci and streptococci.
Asunto(s)
Celulitis (Flemón)/tratamiento farmacológico , Ofloxacino/uso terapéutico , Enfermedades Cutáneas Infecciosas/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Celulitis (Flemón)/microbiología , Humanos , Infusiones Intravenosas , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Ofloxacino/administración & dosificación , Ofloxacino/efectos adversos , Inducción de Remisión , Enfermedades Cutáneas Infecciosas/microbiologíaRESUMEN
We compared the activity of daptomycin, vancomycin and fluoroquinolones against 46 blood isolates of Staphylococcus epidermidis. Daptomycin was more rapidly bactericidal than vancomycin and demonstrated less of an inoculum effect than the quinolones. Time-kill kinetic studies demonstrated no significant differences in survival in broth as compared to 50% human serum-supplemented broth. Daptomycin and the quinolones are suitable for study in clinical trials of efficacy as therapeutic alternatives to vancomycin for S. epidermidis infections.
Asunto(s)
Antibacterianos/farmacología , Antiinfecciosos , Ciprofloxacina/análogos & derivados , Ciprofloxacina/farmacología , Fluoroquinolonas , Staphylococcus epidermidis/efectos de los fármacos , Vancomicina/farmacología , Daptomicina , Cinética , Pruebas de Sensibilidad Microbiana , Péptidos/farmacologíaRESUMEN
An outbreak of influenza A/Philippines H3N2 at a 1156-bed Veterans Administration Hospital involved 118 hospital personnel and 49 patients. Prospective surveillance methods that had been established within the hospital were not useful in identifying the number of involved individuals. Community indicators of influenza, which were reviewed retrospectively, would not have identified circulating influenza in this population. Control of the outbreak was accomplished using a creative approach that immunized over a third of the physician and nursing staff. This immunization program was successfully used in subsequent years to increase personnel compliance with the Immunization Practices Advisory Committee recommendations to annually immunize hospital personnel.
Asunto(s)
Infección Hospitalaria/prevención & control , Brotes de Enfermedades/prevención & control , Vacunas contra la Influenza/uso terapéutico , Gripe Humana/prevención & control , Infección Hospitalaria/epidemiología , Humanos , Virus de la Influenza A/aislamiento & purificación , Gripe Humana/epidemiología , Estudios Prospectivos , Estudios RetrospectivosRESUMEN
Methicillin and gentamicin resistant strains of Staphylococcus aureus (MRSA) remains a cause of significant morbidity and mortality. Vancomycin is usually effective against these strains, but toxicity and expense are significant drawbacks. Resistance to the new quinolones has been demonstrated in vitro and during clinical therapeutic trials. Trimethoprim-sulphamethoxazole has proved to be effective in vitro against staphylococcal strains that are resistant to gentamicin, methicillin, and quinolones. As determined by time-kill kinetic studies, trimethoprim-sulphamethoxazole was rapidly bactericidal. Clinical evaluation of trimethoprim-sulphamethoxazole against MRSA in patients with osteomyelitis is under study. We believe that our data support the use of trimethoprim-sulphamethoxazole as a potentially economical and effective alternative for the treatment of infections caused by MRSA.