Antibiotic use in the nursing home. Physician practice patterns.

Antibiotic usage patterns were studied in two nonproprietary nursing homes that included 720 intermediate care and skilled nursing home beds. Medical records of residents receiving antibiotics were reviewed every fourth month for 1 year. Of 181 antibiotic prescriptions written for indications other than prophylaxis, 41% were for presumed urinary tract infections, 35% for respiratory tract infections, and 14% for skin/soft-tissue infections. The majority of antibiotic prescriptions (54%) were made by telephone order. Cultures were obtained in 60% of suspected infections; two thirds of cultures were of the urine. Antibiotics were changed during the course of therapy in only 12% of cases. Eighty-one percent of residents treated with antibiotics improved or were cured, 9.5% were hospitalized or died, and an additional 9.5% failed to improve but remained in the nursing home. Fever was present in 48% of cases prior to treatment, but had no predictive value for patient outcome. We conclude that antibiotic treatment in the nursing home is often initiated in the absence of fever, culture information, or examination of the patient. Empiric prescription of antibiotics in this setting generally is associated with favorable clinical course.

Assessment of antibiotic efficacy in acute bacterial meningitis.

Currently, antibiotic efficacy in acute bacterial meningitis is evaluated in several stages. First, animals are used to assess antibiotic penetration into cerebrospinal fluid (CSF) in the absence and presence of an inflammatory stimulus. Second, concentrations of drug are correlated to in vitro killing studies. Third, clinical evaluations compare the new drugs to currently available antimicrobic--but drug failures nevertheless occur, e.g. the experiences with cephalosporins and aminoglycosides. We propose that brain tissue levels of antibiotics are an additional parameter to be monitored. Drugs that penetrate the brain substance should yield higher ventricular concentrations than drugs that penetrate the choroid plexus alone. A protective benefit may also be afforded to brain tissue per se. Experience with chloramphenicol, which penetrates the blood-brain barrier, supports these concepts; so also, do the failures with cephalosporins and aminoglycosides which, despite high CSF concentrations of these agents, afford evidence that currently monitored parameters are inadequate predictors of therapeutic efficacy.

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.

In vitro activity of sparfloxacin, ciprofloxacin, ofloxacin, and other antibiotics against bloodstream isolates of gram-positive cocci.

The in vitro activity of sparfloxacin was compared with the activities of ciprofloxacin, ofloxacin, and six other antimicrobial agents against 323 bloodstream isolates of staphylococci (both oxacillin susceptible and resistant) enterococci, and pneumococci. Sparfloxacin was more active than both ciprofloxacin and ofloxacin against all the isolates tested. Its activity (MIC for 90% of strains tested < or = 0.10 microgram/ml) against oxacillin-susceptible staphylococci was superior to that of ciprofloxacin and ofloxacin by at least fourfold. Sparfloxacin was also more potent against pneumococci. However, fluoroquinolone resistance was noted among oxacillin-resistant strains of Staphylococcus aureus and coagulase-negative staphylococci.

A comparison of the safety, efficacy, and distribution of ceforanide and cephalothin in coronary artery bypass graft surgery.

Antibiotic prophylaxis in open-heart operations is a widely accepted practice. Introduction of new antibiotics with differences in tissue distribution, spectrum of activity and therapeutic index prompts their evaluation as possible effective prophylactic agents. We compared the distribution, clinical efficacy, and safety of ceforanide with cephalothin as a prophylactic agent in coronary artery bypass graft (CABG) procedures. The results indicated that the intravenous administration of ceforanide at the dose of 1 gm every 12 hours for 2.5 days was equivalent to cephalothin 1 gm every 6 hours for 2.5 days. Serum, muscle, and bone concentrations of ceforanide were significantly greater than those of cephalothin. These concentrations consistently exceeded the minimal inhibitory concentration for Staphylococcus aureus, the major pathogen implicated in wound infections. No toxicty was observed with either antibiotic. Ceforanide merits consideration as a prophylactic antibiotic in CABG operations.

Routine screening for syphilis is justified in patients admitted to psychiatric, alcohol, and drug rehabilitation wards of the Veterans Administration Medical Center.

Of 1515 patients admitted to psychiatric, alcohol, and drug rehabilitation services in the Veterans Administration Medical Center, Buffalo, NY, during the year 1987, who were screened by serologic tests for syphilis, 16 (1.05%) had positive rapid plasma reagin and fluorescent treponemal antibody-absorption tests for syphilis. A positive serologic test result was not suspected on clinical grounds in any of these patients. All were detected by routine screening. Of the 16 patients, 15 had charts available for review. Seven patients were treated for primary or late syphilis; four patients had received previous treatment; and four patients had no evaluation of test results and received no treatment. Routine screening of hospitalized patients who are alcohol or drug abusers is justified, but close follow-up is necessary to make screening meaningful.

Ceftriaxone: a beta-lactamase-stable, broad-spectrum cephalosporin with an extended half-life.

Ceftriaxone is an aminothiazolyl-oxyimino cephalosporin. It possesses the typical in vitro activity of a third-generation cephalosporin with excellent activity against many gram-negative aerobic bacilli: Escherichia coli; species of Proteus, Klebsiella, Morganella, Providencia and Citrobacter; and Enterobacter agglomerans. Ceftriaxone also has outstanding bactericidal action against pneumococci, group B streptococci, meningococci, gonococci and Hemophilus influenzae. In healthy volunteers, it has an exceptionally long serum half-life of 5.8-8.7 (mean 6.5) hours. It distributes well throughout all body spaces, including cerebrospinal fluid in the presence of inflammation. Dosage modification is necessary only when there is combined hepatic and renal dysfunction. Adverse reactions characteristic of cephalosporins have been observed with the administration of ceftriaxone. No unique toxicities have been identified, and hypoprothrombinemic bleeding is not part of the adverse reaction profile. Ceftriaxone has been used to treat serious bacterial infections in neonates, infants, children and adults. Bacteriologic and clinical success rates have consistently exceeded 90%. The drug has also been used as single-dose chemoprophylaxis in coronary artery bypass, biliary tract, vaginal hysterectomy and prostatic surgery. Efficacy and safety were similar to multiple-dose cefazolin. Ceftriaxone warrants special consideration because its extended half-life allows for less frequent dosing than other antimicrobials. Significant cost savings can be realized with proper use of this antibiotic.

Pharmacokinetics of methylprednisolone sodium succinate and methylprednisolone in patients undergoing cardiopulmonary bypass.

The pharmacokinetics of methylprednisolone sodium succinate (MPHS) and methylprednisolone (MP) were determined in six patients undergoing open heart surgery with cardiopulmonary bypass. Plasma concentrations of both compounds were measured by high-performance liquid chromatography after doses of MPHS of 1.7-2.4 g. The prodrug ester MPHS yields MP with an average formation rate constant of 0.70 +/- 0.29 hr-1. Peak concentrations of MP occur around 1-2 hours after loading and additional administration of MPHS. The pharmacokinetic values of the two drugs in patients having cardiopulmonary bypass were compared to those in younger, healthy subjects. The volume of distribution of MPHS was lower in the patients, and that of MP was similar to the value in controls. Total clearances of both agents were reduced by about 5 and 2 times. The elimination half-life of MPHS was increased slightly, whereas that of MP increased more than twice in the patients. Significant alterations in clearances occurred in patients, but concentrations of MP were appreciable and prolonged MP due to the extensive formation of MP from MPHS and reduced clearance of MP.

Comparison of ceftriaxone and cefazolin prophylaxis against infection in open heart surgery.

One hundred four patients undergoing elective open heart surgery were enrolled in a prospective, double-blind trial comparing prophylaxis against infection using a single 1 g dose of ceftriaxone and seven doses of cefazolin. Patients in both groups had similar risk factors for infection. The likelihood of achieving a tissue concentration in excess of the minimal inhibitory concentration for Staph. aureus was significantly greater with ceftriaxone in atrial appendage (p less than 0.001), muscle (p less than 0.01), and bone (p less than 0.01) than with cefazolin. The serum half-life of ceftriaxone was approximately 15.7 hours. All 49 serum samples obtained 18 to 24 hours after delivery of ceftriaxone and 26 of 33 samples obtained 40 to 48 hours after delivery had drug concentrations in excess of 3.1 micrograms/ml, the mean minimal inhibitory concentration for isolates of Staph. aureus. Early and late infectious complications were infrequent and occurred at similar rates in both groups. Neither drug was associated with significant toxicity. A single 1 g dose of ceftriaxone was as effective and safe as multiple doses of cefazolin and demonstrated superior tissue penetration.

Routine culturing for Legionella in the hospital environment may be a good idea: a three-hospital prospective study.

The source for nosocomial Legionnaires' disease is the water distribution system. However, the implications for legionella contamination in a hospital without known Legionnaires' disease is unclear. Therefore, culturing for Legionella pneumophila in the environment has not been routinely recommended. The authors conducted a prospective pneumonia study in three hospitals, none of which was known to have a major problem with endemic legionellosis. The water system of Hospital 1 was colonized with L. pneumophila, serogroup 1; Hospital 2 was colonized by L. pneumophila, serogroup 5 (which is rarely associated with disease); Hospital 3 was essentially free of L. pneumophila. Sputum culture on selective legionella media, direct fluorescent antibody testing, and serology were performed for all nosocomial pneumonias regardless of clinical impression. At the end of the study the incidence of nosocomial legionnaires' disease was found to be 9%, 0%, and 0% in Hospitals 1, 2, and found to be 9%, 0%, and 0% in Hospitals 1, 2, and 3, respectively. In Hospital 1, monoclonal antibody subtyping confirmed that the patient isolates were identical to the environmental isolates. The authors conclude that environmental culturing, despite the absence of known Legionnaires' disease, is useful. Positive cultures from the hospital water supply would mandate the introduction of legionella testing into the laboratory and stimulate physicians to consider Legionnaires' disease when encountering nosocomial pneumonias.

Prevention, diagnosis, and treatment of common infections in geriatric patients.

Prevention of infection in the elderly is far preferable to treatment of the disease, and can be promoted through precautionary measures when undertaking invasive procedures in older patients as well as through the administration of available vaccines. Difficulties in diagnosing bacterial pneumonia, influenza, tuberculosis, diphtheria, tetanus, and urinary tract infections in the elderly, and schedules for treating these diseases, are discussed.

Anti-infective drugs in the prevention and treatment of sepsis syndrome.

Anti-infective drugs may be used to prevent or treat infectious diseases. Preventing serious infections using aerosolized drugs, selective decontamination of the intestinal tract, or devices impregnated with anti-infective materials generally has been unsuccessful. Treatment of serious infections arising from the community or hospital setting requires knowledge of the most likely pathogens responsible for the illness, the antimicrobial susceptibility of those organisms, and the proper dosing of antimicrobial therapy.

Quinolone therapy in intensive care unit settings.

Three fluoroquinolone antimicrobials (norfloxacin, ciprofloxacin, and ofloxacin) could be used to prevent or treat infections in intensive care unit patients. All of these fluoroquinolones are particularly active against Gram-negative, aerobic bacteria. However, the pharmacokinetic properties of each fluoroquinolone are unique. Furthermore, only ciprofloxacin and ofloxacin are available for intravenous administration. Based on current, available information: a) fluoroquinolones are not endorsed for inclusion in selective decontamination protocols; b) fluoroquinolones are endorsed for empiric therapy of suspected Gram-negative bacterial infections based on local microorganism susceptibility patterns; and c) fluoroquinolones are endorsed for treatment of microbiologically documented infections based on their distribution properties, low rate of toxicity, and rapid bactericidal effect.

Preventing infection in open heart surgery.

The risks for infection following open heart surgery may be divided into three components: the environment, operating room personnel, and the patient. Critical appraisal of the available literature yields the following conclusions. First, the environment may result in fungal or bacterial contamination of the surgical wound or mucosal surfaces. However, it is infrequently possible to prove that such contamination causes infections. Second, personnel may contaminate the patients, but rarely do so. Third, the patient's endogenous flora is most often the source of infecting bacteria. Proper preoperative preparation and judicious use of prophylactic antibiotics minimize the risk of infection.

New concepts of pathogens, and pathogenesis.

Recent changes in thinking about the host-parasite relationship are reviewed. New agents have been identified as respiratory and urinary tract pathogens. Agents previously considered benign, eg., Staphylococcus epidermidis, have become increasingly important causes of disease. Finally, studies on patients with the acquired immune deficiency syndrome have yielded important new information about both host defenses and pathogens. Continued investigation should provide important data which expand the understanding of what causes an infection and the factors responsible for disease.

Recent developments in antimicrobial therapy with beta-lactam antibiotics.

There are three new penicillin and three new cephalosporin compounds available in the United States. All have been developed via biochemical manipulation of the beta-lactam ring and its adjacent chemical groups. The antibacterial spectrum of activity has been greatly expanded. Each of the six new agents has a unique antimicrobial profile which mandates independent evaluation. Therapeutic use of these drugs, particularly in treatment of gram-negative meningitis, has yielded success rates not previously witnessed. Application of these antibiotics as prophylactic agents for surgical procedures remains controversial. Guidelines are offered to distinguish one agent from another based on antimicrobial, pharmacokinetic and toxicologic properties.

Sequestration of staphylococci at an inaccessible focus.

The persistence of staphylococcal arthritis in a patient treated with nafcillin was attributed to intracellular sequestration of staphylococci. These intraphagocytic organisms were protected against bactericidal activity. The infection was cleared by rifampin--an agent which can penetrate leucocyte membranes. When clinical infections do not respond to seemingly adequate antimicrobial treatment, intracellular persistence of bacteria should be considered.

Patterns of infection in untreated acute leukemia: impact of initial hospitalization.

Several previous authors have examined the association between infection and acute leukemia, especially at the time of death, but none has assessed this problem at the time of diagnosis and initial hospitalization. We have undertaken a retrospective review of cases of acute leukemia diagnosed at the affiliated hospitals of the State University of New York at Buffalo. Results suggest that bacteriologic findings in this population initially resemble those in the general outpatient population. Gram-negative bacilli, especially Pseudomonas aeruginosa, appear as important pathogens after the first week of hospitalization. A statistically significant association with prolonged granulocytopenia and use of antibiotics develops during this course. As a consequence of these data, we recommend careful culture and clinical delineation of the early infection, choosing the narrowest spectrum of antibiotic coverage appropriate to the infection present as data evolve.

Comparison of cefamandole, cephalothin, ampicillin, and chloramphenicol in experimental Escherichia coli meningitis.

The activities of cefamandole, cephalothin, ampicillin, and chloramphenicol were compared in fulminant and temperate Escherichia coli meningitis in rabbits. Intensive dosing schedules were employed to achieve maximal therapeutic benefits with short-term treatment. In an 8-h schedule chloramphenicol was significantly more effective in sterilizing the cerebrospinal fluid and curing both fulminant and temperate infections than cefamandole or ampicillin. Cephalothin was without effect in fulminant meningitis. Cefamandole and ampicillin were equivalent in activity in this and longer (12- and 24-hr) treatment schedules. The therapeutic benefits of chloramphenicol were purchased via use of doses above those generally regarded as safe for human use. The mean serum, cerebrospinal fluid, and brain concentrations of chloramphenicol, cefamandole, and ampicillin were significantly greater in rabbits with fulminant meningitis than in those with temperate meningitis. The difference was of such magnitude as to support the need to monitor drug concentrations.

Therapy of nosocomial infections: past, present and future trends.

There has been a significant increase in the number of bacteremias sustained by hospitalized patients over the past 45 years. Responsible bacterial flora has shifted from streptococcal to staphylococcal to gram-negative. Simultaneously, the patient population has become significantly older. Two types of nosocomial infection are reviewed in this clinical setting. Pneumococcal disease still accounts for 10% of nosocomial pneumonias and 5-10% of nosocomial bacteremias. Antimicrobial therapy, although effective, has not eliminated mortality, particularly among older patients with one or more underlying diseases. Vaccination with pneumonococcal polysaccharide vaccine may reduce the morbidity and mortality associated with this infectious process. Several Pseudomonas vaccines have been evaluated, but none has proven both efficacious and non-toxic. Further development of a gram-negative vaccine, preferably one which protects against several types of bacteria, is required.