S.Y. So

Ofloxacin versus co-trimoxazole for prevention of infection in neutropenic patients following cytotoxic chemotherapy.

The efficacy of ofloxacin in preventing infection in neutropenic patients following cytotoxic chemotherapy was evaluated and was compared with that of co-trimoxazole. A total of 102 patients with hematological malignancies were randomly selected to receive either co-trimoxazole or ofloxacin. All patients were monitored for compliance, occurrence of infection, and drug-related side effects. A surveillance culture of a rectal swab was performed regularly. A total of 25 of the 52 patients (48%) who received co-trimoxazole and 11 of the 50 patients (22%) who received ofloxacin developed fever during the study period (P less than 0.025). Gram-negative bacteremia occurred in nine patients in the co-trimoxazole group (17%) but in only one patient (2%) in the ofloxacin group (P less than 0.05). No patient in either group had documented gram-positive bacterial or Pneumocystis carinii infection. Poor performance status was the only identifiable factor associated with an increased incidence of bacteremia. The surveillance study showed that significantly fewer bacterial strains were resistant to ofloxacin than to co-trimoxazole and that acquisition of resistance to co-trimoxazole was more commonly observed than was acquisition of resistance to ofloxacin. Significantly more patients had skin rashes following co-trimoxazole than ofloxacin treatment (P less than 0.05). Ofloxacin was superior to co-trimoxazole in preventing infection in this population of neutropenic patients.

Effect of antibiotics on sputum inflammatory contents in acute exacerbations of bronchiectasis

We studied the changes in sputum neutrophil chemotactic activity (NCA) and elastolytic activity (EA) in acute exacerbations of bronchiectasis before and after treatment with oral antibiotics. Twelve patients who chronically produced sputum were assessed in the stable state, and when they subsequently developed symptoms of acute exacerbations, prior to initiation of antibiotics, during 2 weeks of antibiotics, and at 2 and 6 weeks after stopping antibiotics. NCA was measured using modified Boydens technique with multiwell chemotaxis chamber, and EA with N-succinyl-trialanine-p-nitroanilide as elastase substrate. All 12 patients had NCA (49.3 +/- 8.69% FMLP response) and EA (50.5 +/- 17.1 mU per 100 microliters) in their sputum in the stable state. At acute exacerbation, there was significant increase in NCA (P < 0.001) and EA (P < 0.05). All responded clinically after 1 week of antibiotics, and this was associated with a decrease in NCA and EA back to the levels in stable state. A further week of antibiotics did not result in further decline of NCA or EA. Three patients had another acute exacerbation clinically between 2-6 weeks after stopping antibiotics and their NCA and EA rose again. In the other nine patients, both NCA and EA at 2 and 6 weeks post-treatment were similar to pre-exacerbation levels. Our findings suggest that short course antibiotics effectively control the upsurge in inflammatory activity in acute exacerbations, but has little effect on chronic airway inflammation.(ABSTRACT TRUNCATED AT 250 WORDS)

Analysis of factors associated with bronchial hyperreactivity to methacholine in bronchiectasis

Nonspecific bronchial hyperreactivity (BHR) has been reported to occur in patients with bronchiectasis. To evaluate this further, we studied 77 patients with stable bronchiectasis (noncystic fibrosis) with special reference to the prevalence of BHR to methacholine (MCh), and its relation to lung function, sputum characteristics, concommitant asthma, and atopy. The concentration of MCh required to produce a fall of 20% in forced expiratory volume in 1 s (FEV1), PC20, was determined by Wright’s nebulization tidal breathing method. BHR defined by a PC20 ≤ 8 mg/ml was found in 21 of 47 (45%) subjects who underwent bronchial challenge. Presence of BHR was positively associated with low baseline spirometric values, diagnosis of asthma, long duration of disease, and elevated total IgE on univariant analysis, and was significantly related to FEV1/forced vital capacity (FVC) ratio and asthma on multiple regression analysis. Ten of the 21 hyperreactive subjects did not have clinical asthma, whereas all 11 of 22 subjects with clinical asthma who underwent bronchial challenge were hyperreactive. Among those with BHR, there was a positive correlation between PC20 and baseline FEV1. When patients were further classified into asthmatic and nonasthmatic subjects, a positive correlation between PC20 and FEV1 was seen only in those without asthma. Frequency of infective episodes and inflammatory score of sputum assessed by average daily volume, purulence, and leukocyte count did not differ significantly in the groups with and without BHR. These results suggest that BHR in patients with bronchiectasis is associated with coexistent asthma and worse spriometric values, and not with the severity of bronchial sepsis.

Rising asthma mortality in young males in Hong Kong, 1976–85

The trend in asthma mortality in Hong Kong was estimated from published statistics for the years 1976-85. To avoid coding errors in death certifications, only asthma deaths in the age group 5-34 years were analysed. Mortality rose annually by an average of 10.5% in male (P less than 0.02), but not female asthmatics. Such an increase was not due to a change in coding as a result of the revision of the International Classification of Diseases in 1979, or an exchange of diagnostic labelling from other respiratory diseases. The exact causes for the increase in asthma mortality have yet to be determined.

Ofloxacin compared with amoxycillin in treating infective exacerbations in bronchiectasis

Forty-one hospitalized adult patients of bronchiectasis (non-cystic fibrotic) with infective exacerbations were entered into a randomized, double-blind, placebo-controlled study comparing ofloxacin (200 mg tid) and amoxycillin (1 g tid) both orally for ten days. In the ofloxacin group (20 patients), improvement in sputum purulence was excellent in 14, and fair in five patients with one failure. In the amoxycillin group (21 patients), improvement in sputum purulence was excellent in eight, fair in five and poor in eight patients. Mean drug levels on day 5 were 4.1 mg l-1 for serum (2 h post-dosage) and 4.0 mg l-1 for sputum for ofloxacin, and 18.4 mg l-1 for serum and 0.3 mg l-1 for sputum for amoxycillin. Ofloxacin thus yielded higher sputum concentration and appeared to be more effective and also better tolerated than amoxycillin in infective episodes of bronchiectasis.

The value of routine bronchial aspirate culture at fibreoptic bronchoscopy for the diagnosis of tuberculosis

We review the results of bronchial aspirate culture for mycobacteria sent routinely in a series of 1734 fibreoptic bronchoscopic procedures. The incidence of tuberculosis in the series was 8.3% (144 cases). Of these cases, a positive bronchial aspirate culture was obtained in 119 (82.6%) cases, and it was the exclusive means of diagnosis in 64 (44.4%). In 66% of these cases tuberculosis was not suspected at the time of bronchoscopy. Our results suggest that in an area with a high prevalence of tuberculosis, routine bronchial aspirate culture is a useful adjunct to diagnosis.

A double-blind randomized study comparing ofloxacin and amoxicillin in treating infective episodes in bronchiectasis

Summary32 hospitalized adult patients with infective episodes of bronchiectasis were enrolled in an ongoing double-blind, placebo-controlled study comparing ofloxacin with amoxicillin. They were randomized to receive either 200 mg ofloxacin or 1 g amoxicillin, both t.i.d.orally for ten days. In the ofloxacin group (15 patients), clinical response was excellent (clinical cure) in 11 and fair (clinical improvement or early reinfection) in three patients with one failure. In the amoxicillin group (17 patients), clinical response was excellent in six, fair in five, and poor (treatment failure) in six patients. Ofloxacin levels at 2 h (day 5) were 2.3 to 8.2 mg/l (mean 3.9 mg/l) for serum and 1.3 to 15 mg/l (mean 4.5 mg/l) for sputum. Sputum: serum ratio was 1.2:1. Amoxicillin levels at 2 h were 10 to 40 mg/l (mean 19.9 mg/l) for serum and 0 to 1.5 mg/l (mean 0.3 mg/l) for sputum, with no amoxicillin detected in sputum in 10 of 17 patients. Sputum: serum ratio was 0.02:1. One patient in the ofloxacin group had nausea. In the amoxicillin group, four patients had nausea and stomach pain, one had vertigo and one had transient peripheral eosinophilia. Ofloxacin thus yielded higher sputum concentration and appeared to be more effective and better tolerated than amoxicillin in infective episodes of bronchiectasis.ZusammenfassungIn einer noch nicht abgeschlossenen Placebo-kontrollierten Doppelblindstudie zum Vergleich von Ofloxacin und Amoxicillin wurden 32 erwachsene stationäre Patienten mit einem infektiösen Schub bei Bronchiektasie behandelt. Zufallsgemäß erhielten sie zehn Tage lang entweder 200 mg Ofloxacin oder 1 g Amoxicillin dreimal täglich oral verabreicht. In der Ofloxacingruppe (15 Patienten) wurde in 11 Fällen ein hervorragendes Therapieergebnis (klinische Heilung), bei drei Patienten ein befriedigendes Therapieergebnis (klinische Besserung oder frühe Reinfektion) und in einem Fall Therapieversagen beobachtet. In der Amoxicillingruppe (17 Patienten) sprachen sechs Patienten ausgezeichnet auf die Therapie an, bei fünf war das Ergebnis befriedigend und bei sechs Patienten schlecht (Therapieversagen). 2 h nach Applikation von Ofloxacin wurden am fünften Therapietag Ofloxacinserumspiegel von 2,3 bis 8,2 mg/l (im Mittel 3,9 mg/l) und Sputumspiegel von 1,3 bis 15 mg/l (im Mittel 4,5 mg/l) gemessen. Der Quotient von Sputum- und Serumkonzentration betrug 1,2:1. Die Amoxicillinserumspiegel 2 h nach Applikation betrugen 10 bis 40 mg/l (im Mittel 19,9 mg/l) und die Sputumkonzentrationen 0 bis 1,5 mg/l (im Mittel 0,3 mg/l). Bei zehn der 17 Patienten war Amoxicillin im Sputum nicht nachzuweisen. Der Quotient von Sputum- und Serumkonzentration betrug 0,02:1. Bei einem Patienten der Ofloxacin-Gruppe trat Übelkeit auf. In der Amoxicillin-Gruppe klagten vier Patienten über Übelkeit und Magenschmerzen, einer über Schwindel, und ein Patient hatte eine vorübergehende Blut-Eosinophilie. Ofloxacin erreichte im Sputum in der Behandlung infektiöser Episoden bei Bronchiektasie höhere Konzentrationen und schien wirksamer und besser verträglich zu sein als Amoxicillin.

Melioidosis: a serological survey in a tuberculosis sanatorium in Hong Kong

A serological survey of 275 Chinese patients with underlying pulmonary diseases in a tuberculosis sanatorium in Hong Kong showed that 39 (14%) had haemagglutinating antibody (HA) against Pseudomonas pseudomallei in a titre of 1: 80 or above. Only 9 of these 39 patients had travelled to endemic areas, suggesting that at least 30 patients (11%) had been exposed to Ps. pseudomallei locally. Females are affected as often as males, and the seropositive rate is the same whether patients are immunosuppressed or not. Because subclinical melioidosis is prevalent and HA may persist for a long time, even at a high titre, after infection, determination of HA alone cannot differentiate between active melioidosis and its masquerade--active tuberculosis.

First report of septicaemic melioidosis in Hong Kong.

Septicaemia due to Pseudomonas pseudomallei was found in five patients; it complicated pneumonia in three. Four patients were old and had diabetes mellitus; the fifth patient, though young, was immunocompromised by steroid therapy. The clinical features were indistinguishable from those of other Gram-negative septicaemia. Four of the patients died. This was the first report of septicaemic melioidosis in Hong Kong where the disease might be endemic. Soil sampling and serological survey gave further supporting evidence. Early treatment using a bactericidal anti-Pseudomonal cephalosporin, such as ceftazidime, was suggested for this life-threatening infection.

Calcium channel blockers and asthma

An increase in cytoplasmic Ca++ concentration can activate not only respiratory smooth muscles, but also mast cells, bronchial mucus glands, and the vagi. Altered control of cytoplasmic Ca++ may also be related to the development of bronchial hyperreactivity. Drugs that block Ca++ influx through specific Ca++ channels in plasma membranes are therefore expected to be effective in the treatment of asthma. Reports so far indicate that such drugs may enhance the action of bronchodilators and may offer partial protection against histamine- or methacholine-induced broncho-constriction; but they neither modify the basal bronchomotor tone of asthmatics nor reverse established bronchoconstriction.Calcium-channel blockers are also weak inhibitors of mediator release from mast cells except at high concentrations, which partly explains their inconsistent blocking activity in allergen-induced asthma. However, they are usually effective in preventing exercise-induced bronchoconstriction.They offer an alternative treatment for patients with chronic airflow obstruction who needβ-adrenergic blockade for coexisting cardiovascular problems. Limited data suggest that long-term use of calcium-channel blockers may benefit patients with chronic asthma.The therapeutic role of currently available Ca++-channel blockers is limited in asthma in view of their low potency; more specific airway Ca++ antagonists need to be developed.