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.

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.

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.

Adverse effects of lidocaine and methylparaben on tracheal ciliary activity.

The effect of standard concentrations of lidocaine HCl and methylparaben (preservative) on the ciliary activity of ferret tracheal rings in organ culture was assessed. Pure lidocaine concentrations as low as 0.5% caused complete ciliostasis which was reversible after removal of the drug. One percent and two percent effects were not completely reversible. Pure methylparaben concentrations as low as 0.06 mg/ml paralyzed cilia; and, at concentrations of 0.5 mg/ml or higher, adverse effects were not completely reversible. When lidocaine and methylparaben were combined at the same ratio used in commercial preparations, their ciliotoxic effects were additive. These data suggest that topical respiratory anesthesia may result in prolonged ciliary paralysis.

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.

Sulfhydryl-mediated depression of ciliary activity: an adverse effect of acetylcysteine.

Although N-acetyl-L-cysteine (Mucomyst) is an effective mycolytic, numerous investigations have failed to demonstrate a consistent improvement in pulmonary mechanics following its use. In order to determine whether its beneficial mucolytic activity might be counterbalanced by a deleterious direct effect on cilia, we studied its effect on the activity of ciliated epithelium in the ferret tracheal organ culture system. N-acetyl-L-cysteine consistently caused progressive time-dependent ciliostasis at concentrations clinically employed, with complete ciliary paralysis within 8 hr. The effect was only partially reversed by the removal of the drug. Control preparations retained full ciliary activity for 3 to 12 weeks. In order to determine the active site on the N-acetyl-L-cysteine molecule, we investigated the ciliostatic effects of five of its chemical analogs. Isomolar N-acetyl-L-alanine was not ciliostatic, indicating the necessity of a sulfhydryl group for activity. Ciliostasis was independent of isomeric structure, acetylation, and chain length, as evidenced by the similar ciliostatic effects of L-cysteine, D-cysteine, 2-mercaptoethylamine, and N-acetyl-L-homocysteine. We conclude that N-acetyl-L-cysteine induces partially reversible ciliostasis of tracheal epithelium via its sulfhydryl group; prolonged use of this drug may impair mucociliary clearance.

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.

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.

An 'in vitro' marker of attenuation for live influenza virus vaccine candidates.

Organ cultures of ferret tracheal rings maintained in tubes for up to two months supported the growth of several strains of influenza A viruses produced by genetic recombination. These strains were developed as possible candidates for live attenuated influenza virus vaccines. By observing the effects on cilia and titrating the growth in eggs it was possible to rank these various influenza strains in order of descending virulence for the respiratory epithelium in organ culture. This rank corresponded in general to the virulence of these viruses for human volunteers. Viruses too virulent to use as vaccine strains in man regularly destroyed the ciliated epithelium of ferret trachea while strains attenuated for man usually did not. Although the ciliated respiratory epithelium of ferret was not as sensitive as that derived from human embryonic trachea, this test did identify all the tested strains too virulent for evaluation in human volunteers.

Local anesthetics and tracheal ring ciliary activity.

The effects of local anesthetics on ciliary activity were studied using ferret tracheal rings maintained in vitro. Ciliary activity was quantitated visually after exposure to varying concentrations of mepivacaine, lidocaine, procaine, chloroprocaine, and bupivacaine. The recovery of ciliary activity was determined after tracheal rings were washed free of the local anesthetic agent. Mepivacaine was the least toxic, with no effect on ciliary activity at a 1.0% concentration. Bupivacaine was the most toxic, with irreversible damage to respiratory epithelium at a concentration of 0.13%. Lower concentrations caused ciliostasis, with some recovery after removal of the anesthetic. Licocaine, procaine, and chloroprocaine also depressed ciliary activity which, in general, was reversible after removal of the anesthetic.

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.

Pulmonary antibacterial defense mechanisms are depressed by halothane.

Pulmonary antibacterial activity was determined by challenging halothane-exposed and control mice to radiolabeled (32P) Staphylococcus aureus produced by an aerosol generator and by determining the relative changes in viable bacterial and radioisotope counts in ground lung immediately after exposure and 4 hours later. Mice that were anesthetized for 4 hours with 1 or 2 MAC halothane and allowed to recover for 1 hour showed higher 4-hour bacterial counts when compared to controls, while radioisotope counts were the same in both groups. These data indicate that 1 and 2 MAC halothane anesthesia is associated with depressed lung bactericidal activity but that physical clearance mechanisms are not depressed.

Impairment of tracheal ring ciliary activity by halothane.

The effects of varying concentrations of halothane on tracheal ciliary activity were studied using a ferret tracheal organ culture technique. Using 1% and 2% halothane produced no impairment of ciliary activity, while 3% halothane caused some ciliostasis; 4% and 5% halothane produced rapid cessation of ciliary activity. Recovery was prompt and complete after exposure to 4% halothane for as long as 3 days, but after 4 days of exposure recovery was incomplete and after a week of exposure death of ciliary cells occurred.