Thirty-five patients with serious infections and impaired renal function were treated empirically with 2 to 8 g of cefoperazone per day. Infections included sepsis in 14, nonbacteremic urinary infections in nine, pneumonia in five, intra-abdominal infection in five, fasciitis in one, and malignant otitis externa in one. The average age of this group was 64.3 years, 25 had ultimately fatal underlying diseases, and their average serum creatinine level was 5.2 mg/dl. Infections were caused by Enterobacteriaceae in 23 patients, Streptococcus faecalis in five, Pseudomonas aeruginosa in four, Staphylococcus aureus in four, Hemophilus influenzae in three, and Staphylococcus epidermidis, Streptococcus pneumoniae, and Clostridium sordelli in one each. Overall, 32 patients had clinical and microbiologic cures, two had improvement, and one had failure. Hypoprothrombinemia occurred in 18 of 28 patients not given vitamin K for prophylaxis and occurred more often in those with serum albumin concentrations below 3.5 g/dl. Prothrombin times returned to normal within 36 hours of treatment with vitamin K, although two patients experienced mild hematemesis. In anicteric patients with liver function abnormalities, 2 g every 12 hours produced peak and trough serum concentrations that averaged 254 and 125 micrograms/ml, respectively, compared with 179.5 and 19.5 micrograms/ml, respectively, in five with normal liver function test results. In jaundiced patients treated with 1 g every 12 hours, trough concentrations were comparably elevated. Serum concentrations did not correlate with hypoprothrombinemia, but high levels throughout the dosing interval may have contributed to the excellent cure rate in this study.

Acute Kidney Injury↗

PubMed1986

Reduction of oral flora with rifampin in healthy volunteers.

The effect of a short course of rifampin on the oral microflora was evaluated in 17 healthy volunteers. Salivary specimens were collected before and after two 600-mg doses of rifampin administered 6 h apart. Salivary bacteria were identified to species, and total quantitative colony counts were determined for each isolate. For all 17 subjects, treatment with rifampin led to a reduction in total bacterial colony counts; the mean inhibitory activity was 85.8% (range, 48.3 to 99.8%). Both aerobic and anaerobic bacteria were inhibited in every case: 45.5 to 99.8% for aerobic bacteria, mean inhibitory activity of 85.8%; 40.9 to 100% inhibition for anaerobic bacteria, mean inhibitory activity of 87.6%. However, total counts were reduced by greater than or equal to 2 logarithms in only 18% of individuals; for aerobes, in 29%; and for anaerobes, in 41%. All classes of bacteria were inhibited, with mean inhibitory activities ranging from 8.4 to 99.9%. However, only streptococci, Haemophilus spp., Bacteroides spp., and aerobic and anaerobic gram-positive nonsporeforming rods were reduced in counts close to 2 logarithms after treatment with rifampin. Clinical studies are needed to clarify the significance of these in vitro data and to delineate a possible role for rifampin in preoperative prophylaxis of patients undergoing head and neck cancer surgery.

Bacteria, Aerobic↗

PubMed1986

Potential for bleeding with the new beta-lactam antibiotics.

Several new beta-lactam antibiotics impair normal hemostasis. Hypoprothrombinemia has occurred frequently with cephalosporins that possess a methylthiotetrazole substitution (cefamandole, moxalactam, and cefoperazone). The incidence ranges from 4% to 68%, and the risk is greatest in debilitated patients with cancer, intra-abdominal infection, or renal failure. Impaired platelet function caused by perturbation of agonist receptors on the platelet surface has occurred primarily with beta-lactam antibiotics having an alpha-carboxyl substitution (moxalactam, carbenicillin, and ticarcillin). These antibiotics often cause the template bleeding time to be markedly prolonged (greater than 20 minutes). Acylureidopenicillins, which lack the alpha-carboxyl marker, impair platelet function less frequently and only modestly prolong the bleeding time. If serious hemorrhage occurs, hypoprothrombinemia associated with methylthiotetrazole-substituted cephalosporins should be treated with fresh frozen plasma. Likewise, dangerous bleeding due to impaired platelet aggregation requires treatment with platelet concentrates.

Anti-Bacterial Agents↗

PubMed1984

Aztreonam compared with gentamicin for treatment of serious urinary tract infections.

52 patients with serious urinary tract infections were randomised to receive either aztreonam (35) or gentamicin (17). In the aztreonam group 23 patients had unqualified cures, 6 cures with relapse, and 6 cures with reinfection; the comparable numbers in the gentamicin group were 9, 1, and 4. There were no failures with aztreonam and 3 with gentamicin. The most important determinant of outcome was the presence or absence of urological abnormalities. 11 further patients, with renal failure or gentamicin-resistant isolates, treated with aztreonam were all cured. Toxic effects were limited to symptomless liver-function-test abnormalities with aztreonam , whereas deterioration in renal function occurred in 4 gentamicin-treated subjects. Urinary colonisation with group D streptococci occurred in 14 of 46 aztreonam -treated patients (1 required treatment) compared with only 1 of 17 gentamicin-treated patients. 97% of 309 consecutive gram-negative urinary isolates tested, including 50 Pseudomonas aeruginosa, were susceptible in vitro to aztreonam and 91% to gentamicin. Aztreonam may prove an effective and safe alternative to the aminoglycosides.

Adolescent↗

PubMed1984

Acyclovir for varicella zoster infection.

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Acyclovir↗

PubMed1984

Another look at trimethoprim-sulfamethoxazole: its role in parenteral therapy.

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Bacteria↗

PubMed1984

Staphylococcus epidermidis bacteremia associated with vascular catheters: an important cause of febrile morbidity in hospitalized patients.

Seventeen episodes of persistent Staphylococcus epidermidis bacteremia (one to nine days) occurred in 16 patients with vascular catheters during a 26-month period. Cases were statistically more likely to have a longer hospitalization (54 v 7.6 days, p less than .0005), longer duration of antibiotic therapy (22 v 2.5 days, p = .002), presence of a central venous pressure (CVP) catheter (14 v 2, p less than 3 X 10(-8), and presence of an arterial catheter (4 v 1, p = 0.037) than randomly selected hospitalized patients matched for age, sex, and date of admission. However, when cases were compared with similarly matched non-bacteremic patients having CVP catheters, these characteristics were not significantly different in the two groups. Furthermore, exposure to total parenteral nutrition (TPN) and duration of TPN were not significantly different between cases and controls. Hence, the presence of a CVP catheter appeared to be the major risk factor for S. epidermidis bacteremia. In 16 episodes, patients had temperature greater than 38.6 degrees C without another identifiable cause, and the average white cell count for the case group was 19,400/mm.3 Seven patients also had diaphoresis, confusion, hypotension, or oliguria. Temperatures returned to normal in 13 within 24 hours after catheter removal, and all patients were afebrile and symptom-free within 72 hours. Thus, vascular catheter-associated S. epidermidis bacteremia was an important case of febrile morbidity in these patients.

Adolescent↗

PubMed1984

Comparison of the effects of mezlocillin, carbenicillin, and placebo on normal hemostasis.

Mezlocillin was compared with carbenicillin and 0.9% NaCl as placebo in a double-blind manner to determine its effect in vivo on hemostasis in normal volunteers. Eighteen subjects were randomized to receive mezlocillin, 4 g every 6 h; carbenicillin, 7.5 g every 6 h; or placebo, 50 ml every 6 h, each given for 20 intravenous doses unless the template bleeding time after 10 doses was greater than 15 min. Template bleeding times were determined before the dose 1 and 1 h after doses 10 and 20. Five of six (83%) subjects receiving carbenicillin developed template bleeding time prolongation to greater than 21 min, and two of six (33%) subjects receiving mezlocillin and one of six (17%) subjects receiving carbenicillin had mild template bleeding time prolongations of less than 13 min. Coagulation studies (prothrombin time, partial thromboplastin time, and thrombin time) were normal in all subjects, and blood salicylate levels were negative. Thus, in standard therapeutic doses, mezlocillin was less likely than carbenicillin to prolong the template bleeding time above normal (P = 0.04) and, when prolongation occurred with mezlocillin, it was mild. These data support the selective use of mezlocillin in patients at increased risk for bleeding and who require therapy with an antipseudomonal penicillin.

Adult↗

PubMed1984

Perirectal infections in acute leukemia. Improved survival after incision and debridement.

During a 6-year period, 16 (7.9%) of 202 patients with acute leukemia of both the lymphocytic and nonlymphocytic types developed perirectal infections. All patients were febrile and severely neutropenic (14 patients had absolute neutrophil counts of less than 100/mm3). Lesions were painful and indurated but lacked fluctuance. Urinary retention, peritoneal signs, and extension of the infection to the genitalia were common. Eleven patients had bacteremia, and an average of 2.1 enteric bacteria were recovered from samples of abscess fluid or blood. Perirectal lesions were operatively incised and debrided (10 patients), unless spontaneous drainage occurred (5 patients). These 15 patients became pain-free in less than 48 hours and afebrile in 2 to 8 days. Drained lesions healed in all. Thirteen of fifteen patients left the hospital, whereas 2 died in the hospital of unrelated causes. The only patient whose lesion was not drained died of continuous bacteremia. Early incision and debridement contributed to our patients' improved survival.

Acute Disease↗

PubMed1983

Efficacy of amdinocillin and lack of nephrotoxicity when combined with a second beta-lactam antibiotic for therapy of serious gram-negative bacillary infections.

Seventy-eight patients with serious gram-negative bacillary infections were assigned at random to receive either amdinocillin or an aminoglycoside. In addition, each patient was also given a broad-spectrum penicillin or cephalosporin antibiotic. The clinical response to treatment was comparable in the two groups. Cures were effected in 35 (92 percent) of 38 patients treated with amdinocillin and a beta-lactam antibiotic, compared with 37 (93 percent) of 40 patients who were treated with an aminoglycoside/beta-lactam combination. For the entire group, only five (7 percent) of the 75 infecting organisms were resistant in vitro to the treatment beta-lactam or amdinocillin combination, and similarly only two (3 percent) organisms were resistant to the treatment aminoglycoside (p = 0.44). Although drug-related toxicity occurred with equal frequency in the two groups, six patients treated with an aminoglycoside experienced nephrotoxicity compared with none of the patients who received amdinocillin (p = 0.034). Thus, amdinocillin plus a broad-spectrum beta-lactam antibiotic may provide suitable empiric therapy for many patients with presumed gram-negative infection and so avoid the risk of aminoglycoside-induced nephrotoxicity.

Adult↗

PubMed1983

Moxalactam. Evaluation of clinical bleeding in patients with abdominal infection.

Previous clinical studies have emphasized that hypoprothrombinemia may occur during treatment with moxalactam disodium, a new broad-spectrum cephalosporin. Usually, this abnormality is corrected by administering vitamin K. Recent case reports have described bleeding complications associated with moxalactam therapy and suggested that platelet function is depressed by this drug. We studied eight patients with abdominal infection who were treated with moxalactam. Six of them had prolonged template bleeding times, and two had clinically significant hemorrhage (epistaxis, hematuria, and rectal bleeding) during treatment with moxalactam. These observations suggest that coagulation studies and template bleeding times should be monitored during moxalactam therapy, especially before major surgery.

Abdomen↗

PubMed1983

Atypical Pneumocystis carinii pneumonia: the potential hazards of empiric treatment.

Pneumocystis carinii pneumonia occurred in two patients with unusual clinical findings. In one case, P carinii infection was diagnosed for the first time in a patient with Crohn's disease. Due to the lack of typical features in both cases an empiric trial of antimicrobial therapy could have delayed diagnosis and initiation of specific treatment for P carinii. Contrariwise, without histologic confirmation, specific therapy for P carinii pneumonia might have been mistakenly discontinued in the second patient. Empiric therapy with trimethoprim-sulfamethoxazole may cause rapid disappearance of P carinii cysts from pulmonary tissues and cause subsequent biopsies to be falsely negative in patients who fail to respond to treatment.

Adult↗

PubMed1983

Penicillin-resistant pneumococcus and meningitis.

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Aged↗

PubMed1983

Intravenous sulfamethoxazole and trimethoprim for serious gram-negative bacillary infection.

Intravenous therapy with sulfamethoxazole and trimethoprim cured seven patients with serious gram-negative infection. Three patients had bacteremia, three had pneumonia, and one each had meningitis, peritonitis, pyogenic liver abscesses, and urinary tract infection. Sulfamethoxazole and trimethoprim was selected in three patients with renal failure to avoid aminoglycoside-induced nephrotoxicity, in three patients because of penicillin allergy, and in two cases because of bacterial resistance to other readily available antibiotics. Adverse drug reactions occurred in three cases and included oral monilia, transient leukopenia, and fluid overload. In contrast to the new broad-spectrum cephalosporin antibiotics, sulfamethoxazole and trimethoprim costs two to 2 1/2 times less and has not been associated with the emergence of bacterial resistance during therapy. This may favor the use of parenteral sulfamethoxazole and trimethoprim for some patients with serious gram-negative infection.

Adult↗