Leon G. Smith

Beta-lactamase inhibitor combinations

The beta-lactamase inhibitor combinations present a novel approach to the problem of beta-lactamase-induced resistance to antibiotics. These agents are derived from the generally safe beta-lactam class of antibiotics. They are all principally excreted through the kidneys and require dosage adjustment in the face of significant renal insufficiency. They show significantly increased activity against methicillin-sensitive S. aureus, H. influenzae, B. catarrhalis, and B. fragilis. The activity against Enterococcus, Pseudomonas, and most gram-negative bacilli, however, remains limited to that of the respective antibiotic component. Although shown to be clinically useful in a variety of clinical situations, they appear to be most useful for skin and soft tissue infections and lower respiratory tract infections as well as intra-abdominal and gynecologic infections caused by susceptible pathogens.

ORAL ANTIBIOTIC TREATMENT OF INFECTIOUS DISEASES

The use of antimicrobial agents (i.e., penicillins, cephalosporins, macrolides, aminoglycosides, tetracyclines, quinolones) have continued to grow at an astounding rate. Centers for Disease Control and Prevention estimates are of some 150 million prescriptions annually in the United States, amounting to some 50 millions pounds of antibiotics annually being used in the United States with some 15 to 17 million pounds being used in livestock and agriculture alone. These large numbers serve as indicators for caution and concern. Most oral antibiotics are prescribed for respiratory tract infections, more than half of which are probably viral, for which antimicrobials are not necessary. This overprescribing is noted at a time when increasing antimicrobial resistance is being recognized in hospital settings as well as in the community. The dilemma for the practitioner is to be able to use antibiotics efficaciously and prevent overusage and overprescribing.

Bacteriologic studies on electronic hospital thermometers.

Electronic thermometers used in many hospitals require insertion into the mouth of a temperature-sensing probe covered by a pre-packaged probe cover. Handling procedures used by hospital personnel can lead to inadvertent manual contact with the probe cover. We attempted to determine the rate of non-sterility of these probe covers under normal hospital conditions and the extent to which pathogens could be detected on these and other components of the thermometer. Probe covers were removed before entry into the patients mouth and aseptically inoculated into fluid thioglycollate medium. Subcultures were made to appropriate differential media. Over a 13-week period, 180 covers were cultured on two private hospital services. Forty-three percent were found to be non-sterile; control covers from central supply were only 6% non-sterile. Four percent of the probe covers harbored potential pathogens: coagulase positive Staphylococcus aureus, Streptococcus pyogenes, Enterobacter, and Bacteroides. No attempt was made to correlate these findings with infection. These results indicated a potential infection hazard for high-risk patient groups and a need by hospital personnel to consider this as a possible source of contamination.

Noncomparative Trial of Ticarcillin plus Clavulanic Acid in Skin and Soft Tissue Infections

Ticarcillin, a broad-spectrum penicillin [l], is susceptible in inactivation by a number of beta-lactamases. Clavulanic acid, a naturally occurring beta-lactamase inhibitor, has been shown to prevent the enzymatic degradation of beta-lactam antibiotics by a number of bacterial species [2]. In vitro studies have shown that in combination, ticarcillin and clavulanic acid may be synergistic in activity [3,4]. In the current study, we evaluated the clinical efficacy and safety of this combination in hospitalized patients with skin and skin structure infections. PATIENTS AND METHODS Patient Population. This research protocol was approved by the Human Studies Committee at both Hahnemann University Hospital and St. Michael’s Medical Center. The 79 patients in this study were adults hospitalized at either of the just mentioned medical centers, and informed consent was obtained by the investigators from each patient who entered the study. Each patient had either an acute or chronic skin or skin structure infection caused by an organism or organisms known or suspected to be susceptible to the combination of ticarcillin plus clavulanic acid. Patients excluded from the study included: pregnant or lactating women; recipients of an antimicrobial agent within the previous 72 hours to which the pathogen was susceptible; subjects with a known hypersensitivity to penicillin; and patients with known moderate to severe renal or hepatic dysfunction. Laboratory Studies. The following laboratory determinations were made before, during, and after treatment with ticarcillin plus clavulanic acid: complete hemogram, prothrombin time, quantitative platelet count, direct Coombs’ test, alkaline phosphatase, bilirubin, serum glutamic oxalacetic transaminase, serum glutamic pyruvic transaminase, lactic dehydrogenase, serum concentrations of sodium, potassium, chloride, carbon dioxide, blood urea nitrogen, serum creatinine, blood glucose, and urinalysis. Blood, purulent exudates from wounds, pus from abscesses, and excised tissue were obtained before, during, and after antibiotic therapy for aero

Systemic infections treated with amdinocillin in combination with other beta-lactam antibiotics.

Amdinocillin is a semisynthetic derivative of 6-beta-amidinopenicillanic acid, which has bactericidal activity against a broad spectrum of gram-negative bacteria. We report the results of a multicenter study evaluating the safety and efficacy of amdinocillin in combination with other beta-lactam antibiotics in the treatment of 120 serious gram-negative bacterial infections. Amdinocillin was safe and well tolerated and, in combination with other beta-lactam antibiotics, was effective in the treatment of a broad range of gram-negative bacterial infections. Therapy with amdinocillin and other beta-lactam antibiotics was often associated with a demonstrable synergistic effect. Thus, amdinocillin holds promise as an effective antibiotic with synergistic potential when used in combination with penicillins and cephalosporins.

Nosocomial Ultraviolet Keratoconjunctivitis

A series of five successive cases of ultraviolet-induced erythroderma and keratoconjunctivitis, occurring over a one-month period and related to exposure to an improperly installed ultraviolet light are described. Although in this series, as well as others reviewed, the effects appeared self-limited, significant associated morbidity was observed.

Viral hepatitis. The alphabet game.

Differential diagnosis of viral hepatitis begins with a check for darkened urine and bile in the urine. These hallmarks of conjugated hyperbilirubinemia immediately rule out prehepatic liver disease. Next, studies are done for the elevated transaminase levels that are characteristic of hepatitis infection, and a thorough history is taken to rule out drug- and toxin-induced hepatitis that may mimic acute viral hepatitis. Elevated alkaline phosphatase is a good marker of cholestasis. Ultrasonography can clarify this diagnosis. The classic presenting symptoms of viral hepatitis are jaundice, nausea, vomiting, malaise, anorexia, and dull right upper quadrant pain. However, serologic studies are needed to detect the presence of specific viral agents.