Management of gram-negative septic shock.

Gram-negative bacteremias in hospitalized immunocompromised patients can, of course, lead to sepsis and shock. How can such potentially disastrous infections be managed? Among the cornerstones of management that may curb mortality and morbidity are early recognition of infection, invasive monitoring and therapeutic techniques, and careful selection of antibiotics.

Epiglottitis--an increasing problem for adults.

In a 2-year period, 9 adults were admitted to hospital with acute epiglottitis confirmed by direct laryngoscopy or lateral neck radiograph, or both. The mean age was 53 +/- 14 years, with acute epiglottitis occurring in 89% during the months of September to March. Intubation was required in 4 patients. The duration of symptoms was 7.8 +/- 2.4 hours for intubated patients versus 18.8 +/- 8.9 hours for those not intubated. For 6 patients an incorrect diagnosis was made on their first presentation. All 8 patients having laryngoscopy had typical findings, and none had respiratory obstruction precipitated by the procedure. In 5 patients blood cultures were positive, 4 for Hemophilus influenzae type b, and 1 for Streptococcus pneumoniae. In 2 patients the H influenzae was ampicillin-resistant. All patients recovered after receiving parenteral steroid therapy and appropriate antibiotics.

Suppression of recurrent genital herpes by single daily dosages of acyclovir.

Patients with frequent recurrences of genital herpes were treated with oral acyclovir tablets, 800 mg, or placebo once daily for two years. Confirmed recurrences for all patients were treated with acyclovir capsules, 200 mg orally five times per day, for five days. Of 46 patients enrolled, 18 of 22 acyclovir recipients and 14 of 24 placebo recipients completed two years of study. Patients receiving acyclovir experienced a mean of 0.184 recurrences/month compared with a mean of 0.977 recurrences/month for patients receiving placebo (p less than 0.0001). A total of 28 percent of acyclovir recipients and no placebo recipients remained free of recurrences for two years. The low rate of recurrences in the acyclovir group remained consistent throughout the study. No serious clinical or laboratory abnormalities associated with acyclovir were observed. The 800-mg acyclovir tablet given daily was well-tolerated and effective for two years in the management of recurrent genital herpes.

Comparison of cefpimizole with cefotaxime and penicillin G for treatment of uncomplicated gonorrhea.

One hundred sixteen patients (92 men and 24 women) with suspected uncomplicated gonorrhea were randomized in a double-blind manner to receive intramuscular treatment with 1.0 g of cefpimizole, 1.0 g of cefotaxime, or 4.8 x 10(6) units of aqueous procaine penicillin G (APPG) with 1 g of oral probenecid. Seventeen percent were nonassessable (cultures negative, co-existing syphilis, etc.). Infection sites in 96 assessable patients were urethra (78), cervix (17), pharynx (two), and rectum (two). Of 52 patients treated with cefpimizole, 46 (88%) were bacteriologically cured, as compared with 100% (24 of 24) treated with APPG (P = 0.18) and 90% (18 of 20) treated with cefotaxime (P greater than 0.20). On a weight basis the in-vitro activity of cefpimizole against Neisseria gonorrhoeae was similar to that of APPG. Pain at the injection site was reported by 52% of patients treated with cefpimizole as compared with 27% of those given cefotaxime (P = 0.008) and 17% of those given APPG (P = 0.002). No major organ toxicity was found with cefpimizole, cefotaxime, or APPG. Thus, for acute uncomplicated gonorrhea cefpimizole is similar in efficacy to cefotaxime and APPG but has a higher frequency of pain at the injection site.

Prevention, management, and control of influenza. Role of amantadine.

Amantadine, an oral antiviral agent, is effective in the prophylaxis and treatment of all strains of influenza A, preventing 70 to 90 percent of both experimentally induced and natural infections. Although not a substitute for vaccination, prophylactic amantadine can be particularly helpful in high-risk groups, including those with cardiovascular and pulmonary diseases and those in chronic-care settings. Adjunctive administration to previously immunized high-risk persons enhances the vaccine's efficacy. If given to nonimmunized persons who are then vaccinated during an influenza out-break, it will protect them for the two to three weeks needed for vaccine-induced immunity to develop. If given to residents of a chronic-care facility early in an outbreak, it is helpful in controlling the outbreak. Used therapeutically within 48 hours of the onset of symptoms, amantadine will shorten influenza illness by up to 50 percent, reduce fever, and hasten the resumption of normal activities. Amantadine is particularly recommended for high-risk persons in whom influenza-like symptoms develop during a confirmed or suspected outbreak of influenza A.

Safety and effectiveness of ticarcillin plus clavulanate potassium in treatment of lower respiratory tract infections.

The safety and effectiveness of ticarcillin plus clavulanate potassium was evaluated in an open study of 43 patients with community-acquired lower respiratory tract infections. The mean age of the 28 patients in whom bacteriologic evaluations were possible was 55 years; at least two thirds of the patients had a history of alcoholism or chronic obstructive pulmonary disease. A pathogen was isolated from sputum samples in 23 patients; five of these 23 also had documented bacteremia. There were five additional cases of bacteremia associated with clinical signs and symptoms of pneumonia but with no organisms isolated from sputum cultures. Thirty-five pathogens were isolated from the 33 evaluable infection sites, primarily Streptococcus pneumoniae and Hemophilus influenzae. S. pneumoniae was the causative organism in all 10 cases of bacteremia. Ticarcillin plus clavulanate potassium (3 g of ticarcillin and 100 mg of clavulanic acid) was administered intravenously for a mean of six days. All 35 organisms isolated before treatment were eradicated. In one patient a superinfection with Pseudomonas aeruginosa developed after treatment with ticarcillin plus clavulanate potassium. A clinical evaluation was possible for 32 of the 33 infection sites; clinical cure was achieved at 31 sites and improvement was seen at the other site. All 43 patients were monitored for adverse reactions by both clinical observation and laboratory tests. In one patient, reversible thrombocytopenia developed that required discontinuation of ticarcillin plus clavulanate potassium. In another patient, there was a slight decrease in the potassium level during therapy. No systemic adverse reactions occurred, nor was there any instance of local effects associated with the intravenous infusion of the drug.

Pyogenic meningitis manifesting during therapy for Aeromonas hydrophila sepsis.

Pyogenic meningitis became apparent on the third day of ampicillin and gentamicin therapy for Aeromonas hydrophila sepsis in a patient with severe alcoholic hepatitis. The patient responded clinically to therapy with intravenous cefotaxime sodium and gentamicin sulfate. Antibiotic therapy that provides adequate CSF concentrations should be considered in the treatment of patients with Aeromonas sepsis.

Anti-influenza A activity of combinations of amantadine and ribavirin in ferret tracheal ciliated epithelium.

The anti-influenza A activities of amantadine and ribavirin were investigated separately and in combination. Ferret tracheal ciliated epithelium was continuously exposed to the drugs at concentrations (0.25, 0.5, and 1 mg/l) comparable to those found in human serum after oral administration. Each drug alone produced a modest delay in A/Alaska/6/77 (H3N2) induced cytopathic effect. The combination of drugs synergistically delayed cytopathic effect. At 1 mg/l of each, cytopathic effect was prevented in 75% of rings for the 28-day duration of the experiment. This effect was greater than that of 32 mg/l of amantadine or 64 mg/l of ribavirin as single antiviral drugs. Peak virus production was suppressed 4.4 log-fold by the combination of 1 mg/l of each drug. This is in contrast to amantadine alone which suppressed peak virus production by 1 log-fold and ribavirin along which at 1 mg/l suppressed peak virus production by 1.9 log-fold. At lower concentrations, the drugs were at least additive in suppression of virus production.

Anti-influenza A virus activity of amantadine hydrochloride and rimantadine hydrochloride in ferret tracheal ciliated epithelium.

The activities and toxicities of amantadine hydrochloride and rimantadine hydrochloride against influenza A/Alaska/6/77 (H3N2) and A/Bangkok/1/79 (H3N2) viruses were compared in organ cultures and ferret tracheal ciliated epithelium. Pretreatment of cultures with concentrations (0.5 and 1 micrograms/ml) comparable to those found in human serum after oral administration of amantadine revealed that rimantadine produced significantly longer protection than amantadine against virus-induced cytopathic effects. Correspondingly, rimantadine produced a comparable protective effect at four- to eight-fold-lower concentrations than amantadine. Both drugs produced increasing and similar effects at higher concentrations, which were comparable to those reported in nasal washings after aerosol administration of amantadine. At the concentrations tested, amantadine was nontoxic. However, at concentrations of 16 and 32 micrograms/ml, rimantadine was toxic to the ciliated epithelium after 10 to 21 days of continuous exposure. When the drugs were added 24 h or more after infection, protection against cytopathic effects decreased markedly. Both drugs moderately suppressed virus production at concentrations of 0.5 to 16 micrograms/ml. However, no dose response or difference between the drugs was observed. Because of comparable antiviral activity at lower concentrations and greater activity at similar concentrations, rimantadine may be more useful than amantadine for oral prophylaxis and therapy of influenza.