Prospective endoscopic study of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo.

OBJECTIVE: To compare the frequency of stress erosions and ulcers in critically ill adult patients treated with either sucralfate or placebo. DESIGN: Prospective, randomized study. SETTING: Intensive care unit in a university hospital. PATIENTS: Twenty-six adult patients. All patients were mechanically ventilated and were at risk of developing stress ulceration. INTERVENTIONS: Patients were randomized to receive either sucralfate (2 g every 8 hrs) (group 1) via the nasogastric tube (flushed with 10 mL of sterile water) or 20 mL of sterile water every 8 hrs (group 2) via the nasogastric tube. MEASUREMENTS AND MAIN RESULTS: At the time of intensive care unit admission, the frequency of stress (acute) erosions (as assessed with the endoscope) was 21.7%. No ulcers were detected. By day 3, the frequency had increased to 37.5% in group 1 and 88.9% in group 2. Mucosal deterioration was more likely in the patients treated with placebo (water) (p < .05). In total, seven patients developed acute ulceration in group 2 compared with only one patient in group 1 (p < .05). The frequency of gastric colonization with aerobic Gram-negative bacilli was 25.6% in group 1 and 28.6% in group 2. Only one retrograde nosocomial pneumonia developed (group 1). CONCLUSION: Based on our findings, we strongly recommend the adoption of sucralfate as opposed to no prophylaxis in the prevention of acute upper gastrointestinal ulceration.

A randomized trial of high-dose ciprofloxacin versus azlocillin and netilmicin in the empirical therapy of febrile neutropenic patients.

A prospective, randomized trial comparing monotherapy with high-dose ciprofloxacin versus a standard combination regimen of azlocillin and netilmicin in the empirical treatment of febrile episodes in neutropenic patients was performed. One hundred and forty-six patient episodes were randomized, but ten (seven ciprofloxacin and three azlocillin/netilmicin) were considered unevaluable for efficacy, and three episodes were withdrawn due to incorrect randomization or non-neutropenia. Of the remaining 133 episodes, infections resolved without modification of therapy in 25/66 (38%) versus 28/67 (42%) of ciprofloxacin and azlocillin/netilmicin treated groups respectively (P = 0.72). Considering all randomized episodes, therapy was modified in 46/73 (63%) episodes with ciprofloxacin and 39/70 (56%) with azlocillin/netilmicin (P = 0.40). Of 73 patient episodes randomized to ciprofloxacin, 25 (34%) received oral follow-on therapy after a median of three days of intravenous therapy. Infections were microbiologically documented in 31/73 (42%) ciprofloxacin and 32/70 (46%) azlocillin/netilmicin, of which 8/27 (30%) and 14/31 (45%) of evaluable episodes resolved without modification of therapy respectively (P = 0.28). Gram-positive organisms accounted for 78% of all organisms cultured with 36% coagulase-negative staphylococci. Bacteriological eradication was recorded in 18/24 (75%) and 26/29 (90%) evaluable patient episodes treated with ciprofloxacin and azlocillin/netilmicin respectively (P = 0.27). Superinfections were seen in 14% of episodes in both groups, and subsequent infections in 12% ciprofloxacin and 14% azlocillin/netilmicin treated patients. Two patients (one ciprofloxacin and one azlocillin/netilmicin) died within 48 h of randomization, and a further 13 patients (four ciprofloxacin and nine azlocillin/netilmicin) died before resolution of neutropenia. Adverse events were recorded in 9% and 15% of ciprofloxacin and azlocillin/netilmicin treated patients respectively, with skin rash (five ciprofloxacin and four azlocillin/netilmicin), nephrotoxicity (two azlocillin/netilmicin), abnormal liver function tests (two azlocillin/netilmicin), ototoxicity (one azlocillin/netilmicin) and nausea (one ciprofloxacin) being the major events recorded. It was concluded that monotherapy with ciprofloxacin at this dosage is a safe alternative to combination therapy with azlocillin/netilmicin, and has the advantages of twice daily administration, iv and oral presentations, no cross allergy in beta-lactam-hypersensitive patients, and no nephro- or oto-toxicity.

Imipenem versus netilmicin and vancomycin in the treatment of CAPD peritonitis.

Imipenem/cilastatin is a new thienamycin antibiotic with a broad bactericidal spectrum. We undertook a prospective randomised study to compare the safety and efficacy of intraperitoneal (IP) imipenem/cilastatin (2 gm daily) [group A; 21 patients, mean age 49.2 years] with a combination of IP netilmicin and vancomycin (500 and 60-100 mg daily resp.) [group B; 20 patients, mean age 55.2 years] in CAPD peritonitis. Each patient underwent 4 daily CAPD exchanges with antibiotics in alternate exchanges. The causative organisms were similar in both the groups as was the duration of therapy (gr.A: 6.8 +/- 0.27 days; gr.B: 7.2 +/- 0.51 days; p = NS). Complete cure was marginally better with imipenem/cilastatin (gr.A; 94.1%, gr.B: 83.3%) with less relapses (gr.A: 1 episode; gr.B: 3 episodes). One episode in gr.A (S. aureus) and 2 in gr.B (Yeast & Proteus) failed to resolve and required catheter removal. Two gr. A patients developed generalised convulsions which settled after discontinuation of the drug. Whilst the results show no significant difference in the outcome in the two groups, the use of IP imipenem would offer a possible advantage as a single antibiotic. Larger experience is needed before imipenem can be recommended as a 'blind' first line agent for CAPD peritonitis.

A comparison of the frequency of stress ulceration and secondary pneumonia in sucralfate- or ranitidine-treated intensive care unit patients.

OBJECTIVE: To compare the frequency of acute stress ulceration and secondary pneumonia caused by aerobic Gram-negative bacilli in ICU patients treated with either sucralfate or ranitidine. DESIGN: Prospective, randomized study. SETTING: ICU, university hospital. PATIENTS: Sixty adult patients who were mechanically ventilated and at risk of developing stress ulceration. INTERVENTION: The patients were randomized to receive either sucralfate (1 g every 6 hrs) via the nasogastric tube or iv ranitidine (50 mg every 6 hrs). If the gastric pH was less than 3.5 in the latter group, 30 mL of 0.3M sodium citrate was given via the nasogastric tube. MEASUREMENTS AND MAIN RESULTS: On admission, the frequency rate of erosion/ulceration (assessed with the endoscope) was 13.5%. After 4 days, this rate had increased to 18% in sucralfate-treated patients and 36% in ranitidine-treated patients (NS). Mean gastric pH was more alkaline in the ranitidine-treated patients (5.50) compared with the sucralfate-treated patients (4.26) (p less than .01). This pH permitted a higher occurrence rate of gastric colonization by aerobic Gram-negative bacilli in ranitidine-treated patients (64.3%) compared with sucralfate-treated patients (23.8%) (p less than .01). Retrograde bacterial colonization from the stomach to oropharynx and trachea occurred more frequently in ranitidine-treated patients compared with sucralfate-treated patients. Ultimately, the occurrence rate of pneumonia was greater in the ranitidine-treated (35.7%) than in the sucralfate-treated patients (10.3%) (p less than .05). CONCLUSION: Based on our findings, we recommend the adoption of sucralfate for routine prophylaxis against stress ulceration.

Ofloxacin in the treatment of uncomplicated gonorrhea and chlamydial genital infection.

The subjects were 149 patients (96 men, 53 women) with gonorrhea only (n = 66), chlamydial infection only (n = 48), or both gonorrhea and chlamydial infection (n = 35). All patients with gonorrhea were culture positive; all isolates cultured before treatment were sensitive to ofloxacin. Chlamydial infection was diagnosed by culture, inclusions being identified by indirect immunofluorescence. The patients with gonorrhea received a single dose of 400 mg of ofloxacin. Clinical and microbiologic cure was evident in 86 of 88 patients evaluated at seven days after treatment and in 71 of 72 patients at 14 days. Three patients developed postgonococcal urethritis; the cause was chlamydial in two. The patients with chlamydial infection received 200 mg of ofloxacin twice daily for seven days. Clinical and microbiologic cure was evident in all 78 patients evaluated one day after treatment and in 73 of 74 patients at 14 days. Side effects were reported by 11 patients. It is concluded that ofloxacin is a safe and effective treatment for uncomplicated gonorrhea in patients with and without concurrent chlamydial infections.

High dose intravenous ciprofloxacin in febrile neutropenic patients.

We have evaluated the use of high-dose intravenous ciprofloxacin as monotherapy in the empirical therapy of febrile episodes in neutropenic patients during the course of a randomized trial comparing ciprofloxacin with a standard combination regimen. Sixty-four episodes of fever were studied in a high risk population of 42 patients mostly undergoing intensive chemotherapy for leukaemia. Ciprofloxacin achieved clinical responses as follows: completely successful in 39%, partially successful in 20%, and unsuccessful in 41%. Infections were microbiologically documented in 37 (58%), with Gram-positive bacteria (of which 37% were coagulase negative staphylococci and 34% were streptococci) accounting for 81% of all organisms cultured. Responses in documented infections were as follows; completely successful in 32%, partially successful in 27%, and unsuccessful in 41%. One infection-related death occurred 30 h after starting ciprofloxacin, and a further three patients died before the resolution of neutropenia. The early death was caused by fulminant infection with a ciprofloxacin-resistant Pseudomonas aeruginosa. No other ciprofloxacin resistance was seen amongst eight Gram-negative isolates. There was no evidence of emerging ciprofloxacin resistance during the course of the study. Ciprofloxacin was associated with a low incidence of adverse events with skin rash (five cases) and nausea (one case) being reported as possibly or probably related to ciprofloxacin. We conclude that high-dose intravenous ciprofloxacin may be safely employed as monotherapy in the empirical treatment of febrile episodes in neutropenic patients. It has the additional advantages of twice daily administration, the availability of intravenous and oral presentations, and absence of cross-allergy in beta-lactam antibiotic hypersensitive patients.

Cryptococcosis complicating continuous ambulatory peritoneal dialysis.

We report a case of invasive cryptococcosis complicating continuous ambulatory peritoneal dialysis and its successful treatment. This form of infection has not been previously described.

The efficacy of ofloxacin against infection caused by Neisseria gonorrhoeae and Chlamydia trachomatis.

Ofloxacin was used to treat patients with gonorrhoea and/or Chlamydia trachomatis infection. Gonorrhoea was treated with a single 400 mg dose and chlamydial infection with a seven day course (200 mg bd). Fifty of 84 patients with gonorrhoea (60 men and 24 women) returned for two follow-up examinations 7 and 14 days after treatment, 17 patients returned for only one follow-up examination and 17 defaulted. Neisseria gonorrhoeae was re-isolated from three patients who had probably become re-infected. Treatment was successful in 64 patients, 58 of whom were assessed after a single 400 mg dose of ofloxacin. Chlamydial infection was identified in 30 patients with gonorrhoea (13 men and 17 women) and in 35 other patients (17 men and 18 women). C. trachomatis was not recovered from any of the 49 patients who returned for two follow-up examinations, or from the ten patients who attended for one follow-up visit only. Sixteen patients did not return for follow-up examination. Our results suggest a seven day course of ofloxacin would eradicate N. gonorrhoeae and C. trachomatis in patients infected with both organisms. Such treatment may be advisable in patients with gonorrhoea if microbiological tests for C. trachomatis are not available.

Systemic infection with Aureobasidium pullulans in a leukaemic patient.

Aureobasidium pullulans, a conidial fungus widely distributed in the environment, was repeatedly isolated from the blood of a 28-year-old man with acute myeloid leukaemia. Amphotericin B failed to eliminate the organism.

Immunotherapy alone vs no maintenance treatment in acute myelogenous leukaemia.

Forty-one adult patients with acute myelogenous leukaemia entered remission induced by daunorubicin and cytosine arabinoside, and subsequently received 6 weeks' consolidation therapy with cyclophosphamide plus 6-thioguanine. They were then randomized to either immunotherapy consisting of intradermal BCG plus allogeneic cells or to "no maintenance". Patients receiving immunotherapy had significantly longer remission (P = 0.039) and survival from remission (P = 0.044) as assessed by the log-rank test. The median duration of first remission for 21 patients receiving immunotherapy was 35.14 weeks, compared with 19.71 weeks for 20 patients on no maintenance, and the median survival from remission was doubled in patients receiving immunotherapy. The value of adequate consolidation chemotherapy is confirmed by the comparatively long first remissions in both groups compared with our previous trials, whilst avoidance of maintenance chemotherapy possibly allowed frequent second remissions and similar post-relapse survival in patients from both treatment arms.

Active immunotherapy in acute myelogenous leukaemia and the induction of second and subsequent remissions.

One hundred and ninety-one adults with acute myelogenous leukaemia were treated with combination chemotherapy consisting of daunorubicin and cytosine arabinoside (Barts III). Sixty-three patients achieved remission and were admitted to one of 3 trials of active immunotherapy: immunotherapy alone, immunotherapy and maintenance chemotherapy or neither of these. All patients had weekly clinical and blood examination and monthly marrow examination. Reinduction chemotherapy was given as soon as relapse was diagnosed in the marrow. The most striking observation was that immunotherapy was associated with easy and repeated reinduction of remission and marked prolongation of survival after first relapse when compared with immunotherapy plus chemotherapy. The possible reasons for this and the value of immunotherapy are discussed in relation to the third trial still in progress which includes 2 maintenance arms, immunotherapy alone and surveillance only.

Prescribing aids for gentamicin.

1 A nomogram and a digital computer program have been developed to calculate dosage schedules of gentamicin for individual patients. The minimum input data consist of the patients' age, sex, body weight and serum creatinine concentration. 2 These prescribing aids have been evaluated in 36 patients with severe Gram negative infections. Renal function ranged from normal to complete anuria. Nomogram dosage schedules gave serum concentrations of gentamicin within the chosen therapeutic limits. Physician dosage schedules gave serum concentrations which sometimes exceeded and sometimes fell below these limits. The validity of the computer program was demonstrated by its ability to predict serum concentrations of gentamicin whatever the dosage schedule. 3 Half the patients recovered from the bacterial infection but seven remained infected and eleven died. Pseudomonas aeruginosa was the most difficult organism to eradicate. 4 Four of the patients who survived developed ataxia and two developed hearing loss at high frequencies. The risk of ototoxicity was a function of mean trough serum gentamicin concentration and duration of treatment. Ototoxicity was only detected in patients with serum creatinine concentrations above 3 mg/100 ml who tended to have higher trough concentrations. When treatment was prolonged beyond 8-10 days the risk of ototoxicity was increased without evidence of further substantial therapeutic benefit.