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PubMed1977

Rational antimicrobial therapy.

Rational antimicrobial therapy depends on the identity of the causative organisms, the location of the infection, and the condition of the host. Selection of antimicrobial therapy is often started before identification of the causative organism is complete. Certain cultural and staining procedures must be instigated prior to therapy in order to isolate the causative organism. Knowledge of the host's physiologic state is necessary to minimize toxicities and/or failures of therapy. Knowledge of synergistic and antagonistic actions of some antimicrobial agents is necessary for optimal results.

Anti-Bacterial Agents↗
PubMed1977

The relationship of fever, granulocytopenia and antimicrobial therapy to bacteremia in cancer patients.

The relationship of fever, granulocytopenia, and antimicrobial therapy to bacteremia was studied retrospectively in 53 cancer patients. Severe granulocytopenia was present at the time blood cultures were positive in 27 to 31 episodes of bacteremia. Twenty-five episodes of bacteremia documented before the initiation of antimicrobial therapy in patients who were granulocytopenic and febrile. No bacteremia occurred in the absence of fever. Only two bacteremias occured while patients were receiving parenteral antimicrobials. Antimicrobial therapy was terminated 30 times in the presence of granulocytopenia and fever, and subsequent bacteremia occurred in 14 patients within 4 days. Patients who died with fungal disease did not receive more antibiotics than patients who died without fungal disease. These data suggest a rationale for long-term use of antimicrobial therapy in patients with persistent granulocytopenia and fever.

Adolescent↗
PubMed1977

Laboratory tests used to guide antimicrobial therapy.

Laboratory tests that can be helpful in guiding antimicrobial therapy include antimicrobial susceptibility testing, determination of bacterial beta-lactamase production, assay of serum inhibitory and bactericidal activity, and assay of specific antibiotic levels in serum. Susceptibility studies should be performed on any microorganism that is isolated from normally sterile body fluid (blood, cerebrospinal fluid, pleural fluid, synovial fluid) in the presence of clinical evidence of infection. The standardized disk test provides results that should be comparable from laboratory to laboratory. Dilution methods, however, allow determination of the minimum concentration of an agent which inhibits growth (MIC), and this value can be correlated with blood, urine, and other body fluid levels of the antimicrobial agent. Determination of serum bactericidal activity is, in effect, an assay of the activity of antimicrobial-containing serum; it indirectly measures the combined effects of susceptibility of the test organism and serum concentration of the antimicrobial agent. Accurate measurement of serum concentrations of antimicrobials may be important when treatment includes agents that have a narrow margin between their therapeutic and their toxic levels such as the aminoglycosides (especially gentamicin) or in patients with renal failure, who may accumulate unusually high levels of antimicrobials normally excreted by the kidneys.

Aminoglycosides↗
PubMed1979

[Antimicrobial therapy in granulopenic patients with malignant hematologic diseases (author's transl)].

Rational antimicrobial therapy in neutropenic patients includes early empiric therapy with combinations of antibiotics active in vitro against the causal pathogen. The duration of therapy is to be adapted to the clinical response. In patients who do not respond to antimicrobial therapy, transfusion of granulocytes and empiric use of antifungal drugs should be considered.

Agranulocytosis↗
PubMed1979

Alterations in gastrointestinal microflora during antimicrobial therapy for necrotizing enterocolitis.

Changes in the gastrointestinal microflora were noted in 22 infants during combined topical and parenteral antimicrobial therapy for necrotizing enterocolitis (NEC). Gastric and fecal cultures obtained during therapy showed significantly decreased Gram-negative aerobic organisms, most of which were Enterobacteriaceae, when compared with pretreatment cultures. Members of this bacterial family have been implicated in the pathogenesis of NEC in many reports. The data presented here show that the number of organisms retrieved can be reduced with this method of antimicrobial therapy.

Clindamycin↗
PubMed1977

General principles of antimicrobial therapy.

In the initial therapy of life-threatening infections in which a bacterial cause is suspected, the emphasis should be on broad antibiotic coverage in contrast to definitive therapy, which is dependent on microbial isolation and, when indicated, in vitro susceptibility tests. In severe infections, antimicrobial agents should be given parenterally, at least initially. The need for optimal dosage is emphasized. This is particularly important when aminoglycosides are administered, for there is a tendency to use inadequate dosage because of concern for potential side effects with these agents. The problems leading to recurrence and persistence of fever during antimicrobial therapy include failure to diagnose and drain abscesses, superinfection, drug fever, and clinical or microbiologic errors. Combinations of antibiotics are indicated in severe infections in severe infections due to Pseudomonas aeruginosa, enterococcal group D streptococci, Klebsiella pneumoniae, and Cryptococcus neoformans. Laboratory aid for the selection of antimicrobial therapy can be of great value but need not always be done, because certain microorganisms have stable, predictable susceptibilities, for example, Streptococcus pneumoniae and Streptococcus pyogenes. Cautious conservatism is advocated with regard to the use of new antimicrobial agents.

Aminoglycosides↗
PubMed1979

Diarrhea and colitis associated with antimicrobial therapy in man and animals.

Antimicrobial agent-induced ileocecitis of laboratory animals and colitis of man share common features. The significance of a newly described toxin in these two entities, the apparent source of the toxin (Clostridium difficile) and characteristics of the toxin are reviewed. Methods of toxin detection, isolation and rapid identification of C. difficile, and possible modes of therapy for antimicrobial agent-associated colitis of man are discussed.

Animals↗
PubMed1979

Efficacy of antimicrobial therapy in experimental rat pneumonia: effects of impaired phagocytosis.

The importance of intact host defense mechanisms for successful antimicrobial therapy was investigated in an animal model. Recovery from lobar pneumococcal pneumonia as a result of penicillin therapy was studied in normal rats and in rats treated with cobra venom factor. This factor was used to selectively suppress the phagocytosis of pneumococci as a result of complement depletion. Although complete recovery from the infection occurred in normal rats after appropriate penicillin therapy, this was not the case in cobra venom factor-treated rats. Within the limitations of this study, evidence is presented for loss of antibiotic activity as a consequence of impaired phagocytosis.

Animals↗
PubMed1977

Insuring effective antimicrobial therapy: laboratory evaluation.

Specialized tests for the susceptibility of pathogenic microorganisms are not indicated for most clinical infections. Primary attention should be focused on proper collection of representative culture material and subsequent accurate identification of the offending organism. Specific antimicrobial therapy can then be empirically instituted based upon previously known susceptibility patterns. An overview of the broth dilution, agar dilution, and agar (disk) diffusion techniques is presented. The absolute indications for these tests are as follows: (1) infections with gram-negative bacilli; (2) staphylococcal infections; and (3) enterococcal and other group D beta hemolytic streptococcal infections. The following situations are relative indications for susceptibility testing: (1) infections occurring in immunosuppressed hosts; (2) infections that by their location are more susceptible to certain types of antibiotics; and (3) infections that should be treated with a bactericidal rather than a bacteriostatic drug. The rationale and indications for the serum bactericidal test (SBT or Schlichter test) and antibiotic assay techniques are described. The cases reported illustrate appropriate application of the specialized tests for susceptibility.

Aged↗
PubMed1979

Antimicrobial therapy of septicemia due to Klebsiella pneumoniae in neutropenic rats.

Three different isolates of Klebsiella pneumoniae, highly sensitive to amikacin but varying in susceptibility to cefazolin, were injected intraperitoneally into neutropenic rats. Animals were treated every 8 hr for 72 hr with saline (controls), cefzolin (full dose, 40 mg/kg; one-fourth dose, 10 mg/kg), amikacin (full dose, 8 mg/kg; one-fourth dose, 2 mg/kg), or a combination of both drugs at either full dose or one-fourth dose. All drugs were given intramuscularly. Combination therapy with full doses produced higher mean bactericidal titers in serum and more rapid clearance of bacteria from blood and peritoneal washings. However, cumulative mortality at 72 hr in rats treated with amikacin plus cefazolin in full doses (24%, 23%, and 44%) was not significantly different from mortality in rats treated with amikacin alone (34%, 17%, and 62%). Results with cefazolin alone were not significantly different from the mortality in control animals for two of the three challenge organisms. When the minimal inhibitory concentration of cefazolin was less than or equal to 8 micrograms/ml, in vivo synergy was suggested by the similar survival rate obtained with a combination of a one-fourth dose of each agent and with amikacin alone in a full dose. These results demonstrate the relative ineffectiveness of cefazolin for therapy of klebsiella septicemia and suggest that in vivo antimicrobial synergy occurs in combination therapy against strains of bacteria relatively sensitive to cephalosporins.

Agranulocytosis↗
PubMed1975

Antimicrobial therapy in patients hospitalized in a medical ward. A report from the Boston Collaborative Drug Surveillance Program.

The pattern of use of antimicrobial agents in 1,700 patients hospitalized in a medical ward at the Hadassah University Hospital, Jerusalem, during 1969--72, is analyzed. Penicillins comprised 56%, tetracyclines 11%, streptomycin 9% and cephalosporins 3% of the total antimicrobial exposures. Ampicillin was given to 20% of the patient population. The use of tetracyclines and chloramphenicol fell steadily from 1969 to 1972. Fifty-five percent of the recipients of antimicrobial drugs received only one agent, 19% had concomitant therapy with several agents and the remainder received multiple antimicrobial drugs sequentially. One hundred and ten patients (6.5%) developed adverse reactions; the most common being rash and gastrointestinal reactions. Only two of the reactions were classified as causing major morbidity.

Ampicillin↗
PubMed1978

The need for controlled clinical studies in antimicrobial therapy.

In recent years in-vitro and in-vivo studies have greatly advanced our understanding of the action of antimicrobial agents and have opened new potential avenues for treatment of infectious diseases. Unfortunately, little interest or financial support has been available to test these observations in rigid, controlled clinical studies. New regimens have thus been used without proof of increased efficacy of reduced toxicity over old regimens. Carefully controlled clinical trials are particularly needed to evaluate the efficacy, toxicity, and cost of newly developed regimens in the therapy of chronic bacterial and fungal infections.

Anti-Bacterial Agents↗
PubMed1977

Short-term versus continuous antimicrobial therapy for asymptomatic bacteriuria in pregnancy.

Asymptomatic bacteriuria was identified in 300 pregnant women prior to the 28th week of gestation. In one group of 200 women short-term treatment with either nitrofurantoin or sulfamethizole was given for 14 days, and in another group of 100 women continuous therapy with one of these drugs was given for the remainder of gestation. Weekly urine cultures were obtained from all the women. Of the women treated with short-term therapy, 65% were abacteriuric for the remainder of pregnancy following one course of therapy, 24% became abacteriuric but subsequently relapsed, 2% had reinfection after becoming abacteriuric, and 9% demonstrated no response. Following treatment with a second course of short-term therapy, another 19% of these women were cured for the remainder of their pregnancy, and 3.5% responded to a third course. In the continuous therapy group, 88% of the women became abacteriuric for the remainder of the gestation, 3% demonstrated relapse, 2% developed reinfection, and 7% had no response to the first drug given. These data demonstrate that short-term administration of antimicrobials, when combined with surveillance for recurrent bacteriuria, is effective for the management of the pregnant woman with asymptomatic bacteriuria.

Bacteriuria↗
PubMed1977

Studies of introital colonization in women with recurrent urinary infections. IX. The role of antimicrobial therapy.

To determine if antibiotics used in the treatment of urinary infections alter introital gramnegative carriage after termination of therapy we analyzed 254 cultures obtained between episodes of bacteriuria in 14 women with recurrent urinary infections. Cultures obtained within the first 30 days after termination of therapy were compared to all subsequent cultures. Introital carriage in women with recurrent urinary infections was compared to 416 consecutive introital cultures from 31 control women resistant to bacteriuria. In women with recurrent bacteriuria introital colonization patterns were similar in incidence and density during the immediate post-treatment period compared to later cultures. Four volunteer controls received tetracycline for 10 days. There was no difference in introital carriage of enterobacteria before during or after tetracycline therapy. Consecutive cultures also confirmed a higher incidence and greater density of vaginal carriage of enterobacteria in patients when compared to similar cultures from women who never had a urinary infection.

Anal Canal↗