d-Methionine reduces tobramycin-induced ototoxicity without antimicrobial interference in animal models.

BACKGROUND: Tobramycin is a critical cystic fibrosis treatment however it causes ototoxicity. This study tested d-methionine protection from tobramycin-induced ototoxicity and potential antimicrobial interference. METHODS: Auditory brainstem responses (ABRs) and outer hair cell (OHC) quantifications measured protection in guinea pigs treated with tobramycin and a range of d-methionine doses. In vitro antimicrobial interference studies tested inhibition and post antibiotic effect assays. In vivo antimicrobial interference studies tested normal and neutropenic Escherichia coli murine survival and intraperitoneal lavage bacterial counts. RESULTS: d-Methionine conferred significant ABR threshold shift reductions. OHC protection was less robust but significant at 20kHz in the 420mg/kg/day group. In vitro studies did not detect d-methionine-induced antimicrobial interference. In vivo studies did not detect d-methionine-induced interference in normal or neutropenic mice. CONCLUSIONS: d-Methionine protects from tobramycin-induced ototoxicity without antimicrobial interference. The study results suggest d-met as a potential otoprotectant from clinical tobramycin use in cystic fibrosis patients.

Vaccines and vaccine adjuvants as biological response modifiers.

Vaccines have been used successfully for many years to prevent death and morbidity from infectious diseases. In the last two decades major advances in the fields of genetics and immunology have allowed a significant increase in the use of immunomodulatory drugs in a broad range of pathologic conditions. This article reviews several uses of immunomodulating properties of vaccines, both old and new, with a focus on cancer and autoimmune diseases. Special emphasis is placed on the historical aspects and current applications of the bacillus Calmette-Guérin vaccine, the first vaccine to be used in cancer immunotherapy.

Fever of unknown origin in the returning traveler.

The returning traveler with fever presents a diagnostic challenge for the health care provider. When evaluating such a patient, the highest priority should be given to diseases that are potentially fatal or may represent public health threats. A good history is paramount and needs to include destination, time and duration of travel, type of activity, onset of fever in relation to travel, associated comorbidities, and any associated symptoms. Pretravel immunizations and chemoprophylaxis may alter the natural course of disease and should be inquired about specifically. The fever pattern, presence of a rash or eschar, organomegaly, or neurologic findings are helpful physical findings. Laboratory abnormalities are nonspecific but when corroborated with clinical and epidemiologic data may offer a clue to diagnosis.

Pharmacokinetic and pharmacodynamic aspects of antibiotic use in high-risk populations.

The study of pharmacokinetics includes the absorption, distribution, metabolism, and elimination of drugs. The pharmacologic effect that a medication has on the body is known as pharmacodynamics. With antimicrobials, pharmacokinetic and pharmacodynamic parameters become especially important because of the association between host drug concentrations, microorganism eradication, and resistance. This article focuses on the pharmacokinetic changes that can occur with antimicrobials when they are used in patients at high risk of infections and how they influence pharmacodynamic effects. The populations described here include patients with obesity and diabetes mellitus, renal or hepatic failure, chronic lung disease, severe burns, and long-term prosthetic devices and the elderly.