Naloxone hydrochloride, a synthetic N-allyl derivative of oxymorphone, is an effective agent for the reversal of the cardiovascular and respiratory depression associated with narcotic and possibly some non-narcotic overdoses. It is essentially a pure narcotic antagonist, is relatively safe, and is a useful diagnostic and therapeutic agent. Due to naloxone's pharmacokinetic profile, a continuous infusion protocol is recommended when prolonged narcotic antagonist effects are required. The complex pharmacodynamics of naloxone, specifically relating to endorphin receptor sites, focus its potential use in a variety of clinical situations as continuing research illustrates the association of endogenous opioid compounds with various disease states.
Antibiotic combinations are often used in the therapy of infectious diseases to broaden the antibacterial spectrum and to enhance antimicrobial activity. Another potential reason for combination therapy is to reduce or prevent the emergence of resistant organisms during therapy. Antituberculous chemotherapy provides a classic example in which drug combinations have successfully prevented the emergence of drug-resistant organisms and improved clinical outcome. The purpose of this brief report is to review the success of combination therapy in preventing resistance in more common bacterial infections.The emergence of resistance during single-drug therapy is a well-documented clinical phenomenon, especially with the broad-spectrum ß-lactams against gram-negative bacilli. As with Mycobacterium tuberculosis, the resistant organisms are generally thought to be naturally occurring mutants selected by drug exposure. Because mutation frequencies appear to vary from 10-6 to 10-8, it is not surprising that emergence of resistant organisms observed clinically occurs primarily at sites of high organism density, such as the respiratory and urinary tracts.
Antibiotic combinations are often used in the therapy of infectious diseases to broaden the antibacterial spectrum and to enhance antimicrobial activity. Another potential reason for combination therapy is to reduce or prevent the emergence of resistant organisms during therapy. Antituberculous chemotherapy provides a classic example in which drug combinations have successfully prevented the emergence of drug-resistant organisms and improved clinical outcome. The purpose of this brief report is to review the success of combination therapy in preventing resistance in more common bacterial infections.The emergence of resistance during single-drug therapy is a well-documented clinical phenomenon, especially with the broad-spectrum ß-lactams against gram-negative bacilli. As with Mycobacterium tuberculosis, the resistant organisms are generally thought to be naturally occurring mutants selected by drug exposure. Because mutation frequencies appear to vary from 10-6 to 10-8, it is not surprising that emergence of resistant organisms observed clinically occurs primarily at sites of high organism density, such as the respiratory and urinary tracts.
Sulbactam/ampicillin appears to be effective in the treatment of gynecologic and intra-abdominal infections, and infections of skin and skin structures. However, until more data is available from well-controlled, comparative studies, it is difficult to determine the most appropriate place of sulbactam/ampicillin in the therapy of these and other infections. Sulbactam/ampicillin is similar to other agents in the prophylaxis of infectious complications secondary to gastrointestinal and gynecologic surgery, and may have a role in surgical prophylaxis as it is well tolerated by most patients and is cost-effective. Indeed, the discovery of sulbactam provides us with yet another useful compound. Additional study is clearly needed so as to best use sulbactam to its fullest advantage.
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