The terminal quality of life and passive or active euthanasia.

The problems presented by the different categories of dying people are briefly discussed from the point of view of terminal quality of life. Euthanasia is used in its broader meaning, including both passive and active aspects. Passive euthanasia (PE) is exercised by withholding advanced or basic life support measures, the commonest form being do not resuscitate orders (DNR). Some data on its application are presented. Active euthanasia (AE), which has been proposed and being applied to a limited extent lately, is criticized as leading the physician and the Society onto risky ground. A position is being taken against it. Decision making, examples of guidelines, legal, philosophical and spiritual considerations are discussed. Wisdom and loving care should be exercised by the physician to assist people in their terminal phases and to alleviate their suffering. That there is not a single answer to the problem is discussed.

Poor efficacy of teicoplanin in treatment of deep-seated staphylococcal infections.

Teicoplanin in a 400 mg intravenous loading dose followed by 200 mg/day intravenously or intramuscularly was given to 19 patients with deep-seated staphylococcal infections. Only eight patients (44.4%) were considered cured, failure mostly being observed in patients with osteomyelitis, endocarditis and bacteremia. Poor tissue kinetics of teicoplanin and the presence of foreign bodies are probable explanations for the reported failures. Future trials using a higher dose of teicoplanin with or without the addition of rifampicin or gentamicin seem to be justified.

Evaluation of imipenem/cilastatin against nosocomial infections and multiresistant pathogens.

Thirty-five patients suffering from soft tissue infections (12), upper UTIs (6), bronchopneumonia (6), septicaemia (2), chronic osteomyelitis (2), intra-abdominal abscess (2), liver abscess (1), lung abscess (1), acute cholangitis (1), thoracic empyema (1) and chronic prostatitis (1) were given imipenem/cilastatin for 6-21 days. In 22 patients several aggravating factors coexisted, while infection in 16 patients was polymicrobial. The following pathogens were implicated: Pseudomonas aeruginosa (21), Escherichia coli (15), Enterobacter cloacae (6), Proteus spp. (3), Klebsiella pneumoniae(3), Citrobacter freundii (1), Salmonella enteritidis (1), Acinetobacter spp. (4), Haemophilus influenzae (2), Bacteroides fragilis (1) and Peptococcus saccharolyticus (1) with MICs to imipenem ranging between 0.5 and 8 mg/l. A successful clinical response was observed in 91.4% of the patients, while pathogens were eradicated in 75.9%, persisted in 24.2% and recurred, in 9.1% of patients, with development of resistance to imipenem in two Ps. aeruginosa strains. Against 150 multiresistant strains of Ps. aeruginosa, 40% of which were resistant to amikacin, 86.4% and 88.9% were found sensitive to ceftazidime and imipenem respectively. It is concluded that imipenem provides the possibility of treating successfully multiresistant and polymicrobial infections with a single antimicrobial.

Efficacy of sulbactam plus ampicillin in gynecologic infections.

The efficacy of sulbactam plus ampicillin in the treatment of various gynecologic infections was evaluated in 24 women (median age, 35 years). Ten women had pelvic cellulitis plus vaginal cuff abscess; six, pyeloperitonitis; three, vaginal cuff abscess; three, surgical wound sepsis; one, tubo-ovarian abscess; and one, endometritis. Surgical procedures preceding infection included abdominal hysterectomy, ovarian cyst removal, ectopic pregnancy, correction of cystocele, and uterine dilatation and curettage. Twenty patients received 1 g of sulbactam plus 1 g of ampicillin per dose; four received 0.5 g of sulbactam plus 1 g of ampicillin per dose. The combination was given iv every 6 hr for three to four days and then im every 8 hr for three to five days (mean treatment duration, seven days). Pus cultures yielded Enterobacteriaceae (21 cases), enterococci (two), Bacteroides fragilis (12), other Bacteroides species (five), Peptococcus species (nine), Peptostreptococcus species (seven), and other anaerobes (five). Six infections were purely anaerobic; 18 were mixed. All but two infections were cured by both clinical and bacteriologic criteria, with no adverse reactions. Parenteral sulbactam/ampicillin seems safe and effective in the treatment of gynecologic infections of moderate severity.

Evaluation of ciprofloxacin in the treatment of Pseudomonas aeruginosa infections.

The efficacy and safety of ciprofloxacin in the treatment of Pseudomonas aeruginosa infections was evaluated in 72 patients suffering from upper urinary tract infection (19 patients), deep soft tissue infection (16), chronic osteomyelitis (12), abscess (7), chronic otitis media (6), otitis externa (3) and bronchopneumonia (9). Forty-eight patients received an oral dose of 500 mg or 750 mg b.i.d. and five patients an i.v. dose of 200 mg b.i.d., while 19 patients were given both oral and parenteral doses. The duration of therapy ranged from seven days to more than four months. The MICs of ciprofloxacin for the Pseudomonas aeruginosa strains isolated were in the range less than 0.06-2 mg/l; 36% of the strains were resistant to all other available antibiotics. At follow-up after a minimum of six months the clinical success rate was 75% and the infecting organism was permanently eradicated in 49% of the patients. In nine patients the organism developed resistance, particularly when the initial MIC was higher than 0.5 mg/l. No significant adverse reactions were observed. Ciprofloxacin is the first antipseudomonal antimicrobial agent which can be administered orally and therefore fulfills a need in chemotherapy.

Clinical experience with aztreonam in four Mediterranean countries.

Aztreonam is a new, synthetic, monobactam beta-lactam antibiotic with activity directed specifically against aerobic gram-negative bacteria. At doses of 1-8 g per day, aztreonam was administered parenterally to patients with serious gram-negative infections of the urinary tract or other sites. A total of 462 organisms were isolated from sites of urinary tract infection; 93% of the isolates obtained within 48 hr before the initiation of aztreonam therapy were eradicated. Forty-three (86%) of 50 strains of Pseudomonas aeruginosa from urinary sites were eradicated. Eighty-six percent of gram-negative organisms isolated before treatment from other sites of infection were eradicated. Whatever the site of infection, the percentage of patients with a complete resolution of signs and symptoms was similar. Aztreonam was well tolerated both locally and systemically.

Postprandial hyperglycemia after ingestion of peeled and non-peeled fruits in type-2 diabetics.

Should diabetics prefer nonpeeled fruits in their diet? To answer this question 27 type-2 diabetics divided into three groups were examined on two different occasions under the same fasting conditions. The first group of patients received 300g of pears with peel and on another day 300g of peeled pears. The second group ate 300g of pears with peel and 230g of peeled pears (the 70g difference represents the weight of the peel). The third group of diabetics consumed 300g of apples with peel and 300g of apples without peel. Blood samples were collected before and 20, 40, 60, 80, 100, 120 and 140 min after fruit ingestion. No significant differences were noted in terms of mean blood glucose, serum insulin and serum triglyceride levels among the two meals (fruits with or without peel). This observation was confirmed in all groups studied. Peeled and nonpeeled fruits appear to produce the same hyperglycemia in type-2 diabetics, in spite of the high fiber content of the peel. Therefore, the suggestion of reducing postprandial hyperglycemia in diabetics by eating nonpeeled fruits does not seem to be justified.

Epidemiological study of Enterobacter cloacae resistant to 3rd generation cephalosporins: a preliminary report.

In 1983 an increase in the resistance rate of cefotaxime against Enterobacter cloacae strains was observed in "Laikos General" hospital, that reached 59.3% in the 2nd half of the same year. All strains resistant to cefotaxime were found resistant to cefamandole, moxalactam and ceftriaxone while 61.8% were also resistant to amikacin. Urine represented the main source of isolation, particularly from the catheterized patient of the Renal Transplantation Unit in whom cefuroxime was mostly over used. Multiresistant strains were virulent since 5 patients died of septicemia. Mechanisms of resistance to cefotaxime are speculated upon because resistance work-up has not yet been completed. SHV, was exclusively isolated in the limited number of strains which have been studied up to now.

Experience with ciprofloxacin in the treatment of various infections caused mainly by Pseudomonas aeruginosa.

Ciprofloxacin, a new quinolone carboxylic acid derivative with an enhanced spectrum of activity including P. aeruginosa, was given to 42 patients, 26 males and 16 females, ranging in age from 12 to 75 years. They were suffering from upper urinary tract infection (15), abscesses (hepatic 1, intra-abdominal 5, retroperitoneal 1, soft tissue, deep soft tissue infection (9), chronic otitis media in exacerbation (3), chronic osteomyelitis in exacerbation (3), bronchopneumonia (3) and otitis externa (1). Pathogens included P. aeruginosa (29), E. cloacae (7), P. mirabilis, E. coli (3) and S. marcescens (1), with MICs for ciprofloxacin ranging from 0.003-2 micrograms/ml. Over half of the isolates were multiresistant, also to amikacin, with almost all the Pseudomonas strains resistant to carbenicillin and the ureidopenicillins. In 21 patients ciprofloxacin was given orally at a dose of 500 mg or 750 mg 12-hourly, in 5 patients i.v. at a dose of 200 mg 12-hourly; while in 16 patients treatment was started i.v. and was continued by the oral route. Seventeen patients were given ciprofloxacin for 7-14 days, 5 for 15-22 days, 4 for 23-28 days, 8 for 29-42 days, and 8 for greater than 42 days. Treatment response was considered clinically as cure in 30 (71.5%) patients, improvement in 8 (19%) and failed in 4 (9.5%). Pathogens were eradicated during treatment in 34 (81%), persisted in 8 (19%) and recurred in 11 (26.2%) patients. Development of resistance was observed in one patient only. Adverse reactions in 12 patients were minimal and self-limited. It was concluded that ciprofloxacin is a very promising new antimicrobial which merits further clinical trials in systemic infections.

Infertility and chronic prostatitis.

Long term treatment of chronic prostatitis with antimicrobials and their influence on semen quality and infertility were studied in 30 men with mean age of 36.7 +/- 6 years. The infection was symptomatic only in 50% of the patients with abnormal prostatic physical findings in 66.7%. Cardinal findings in the spermatogram were leukocytosis in 100% and oligoasthenozoospermia in 66.5% of the patients. E. coli and Staphylococci presented the most commonly isolated bacteria in prostatic secretion cultures. Various treatment schedules, including mostly co-trimoxazole, doxycycline and erythromycin, were given alternatively for 6-8 months. Symptoms were cured or improved in 79.7%, with elimination or improvement of abnormal physical findings in 85%, while the isolated pathogens were eradicated in all. Spermatograms were normalized or improved in 70% of the patients, while among them 9 impregnated their wives and in 2 of them twice. It is concluded that male infertility in the presence of semen leukocytosis and oligoasthenozoospermia should be investigated for underlying chronic prostatitis, while whenever proved, long term treatment with the proper antimicrobials not only cures or improves chronic prostatitis, but subsequently cures or improves male infertility.

Evaluation of aztreonam in difficult-to-treat infections with prolonged posttreatment follow-up.

Aztreonam at doses of 1 or 2 g given intramuscularly or intravenously every 8 h for 7 to 42 days was given to 55 patients, most of them suffering from difficult-to-treat infections either because the isolated pathogens were multiresistant or because of the location of the infection. Infections included: urinary tract (23 cases), deep soft tissue phlegmon (12 cases), chronic osteomyelitis in exacerbation (7 cases), abscesses (7 cases), pneumonia (4 cases), and external otitis (2 cases). In culture specimens, Pseudomonas aeruginosa (24 isolates) and various Enterobacteriaceae species (37 isolates) were isolated with MICs ranging from 0.25 to 16 micrograms/ml. Clinically, at the completion of treatment and after a 6-week posttreatment follow-up, 45 (81.6%) patients were cured, 4 (7.2%) improved, 3 (5.6%) relapsed, and 3 (5.6%) failed to respond to therapy. Bacteriologically, at the end of treatment, the pathogen was eradicated in 50 patients (91%) and persisted in 5 (9%). After a 6-week follow-up, cultures remained sterile in 33 patients (60.0%), 16 (29.1%) relapsed, in 6 (10.9%) bacteria persisted, and superinfection was reported in 4 (7.3%) patients. No appreciable adverse effects or toxicity was observed. From the reported results, it is concluded that aztreonam is a valuable addition to the field of antimicrobial chemotherapy that can be used effectively and safely in the treatment of a variety of gram-negative infections.

Ceftriaxone: therapeutic results in various infections and kinetic studies.

Ceftriaxone (Ro 13-9904, Rocephin) was given to 67 patients suffering from 74 various infections. Patients had infections of the urinary tract (36), soft tissue phlegmon (12), infections of the respiratory tract (13), osteomyelitis (7), abscesses (5) and meningitis (1). Infecting organisms were E. coli (26), Proteus spp. (20), P. aeruginosa (7), H. influenzae (6), Enterobacter spp. (6), K. pneumoniae (3), C. freundii (2), S. marcescens (1), S. aureus (4), S. pneumoniae (2), Peptostreptococcus spp. (4) and Clostridium spp. (1). The organisms were often multiresistant. Dosage ranged from 1-2 g once or twice daily i.m. or i.v. The clinical response was excellent in 56 infections (75.6%) while 13 (17.6%) infections were improved and in 5 (6.8%) treatment failed. The pathogen was eradicated in 63 (85.1%), and relapsed in 3 (4.0%) while bacteria persisted in 11 (14.9%). No appreciable side effects or toxicity were observed. Sputum, bile, cerebrospinal fluid and prostatic fluid kinetics revealed ceftriaxone concentrations several times above the minimal bactericidal concentrations required to kill the enterobacteriaceae, but mostly inadequate to inhibit P. aeruginosa strains. Ceftriaxone was a safe and effective drug for the treatment of various infections. However, with the exception of urinary tract infections it should be given with caution in P. aeruginosa infections.

Experience with ciprofloxacin in vitro and in vivo.

1-Cyclopropyl-6-fluoro-1-dihydro-4-oxo-7-(1-piperazinyl)-1,4-dihydro-3- quinolinecarboxylic acid (ciprofloxacin, Bay-o 9867) a new quinoline carboxylic acid derivative, was tested in vitro against 233 various Gram-negative microorganisms, mostly resistant to nalidixic acid. Minimal inhibitory concentrations (MIC) against the Enterobacteriaceae and P. aeruginosa ranged between less than 0.003 to 1 mg/l and less than 0.003 to 8 mg/l respectively with MIC90 of 2 mg/l. However, when sensitivities were repeated with an acid broth they were increased by greater than or equal to 32 fold. This effect was more prominent when as nutrient pooled human urine was used and particularly for P. aeruginosa strains. Ciprofloxacin at a dose of 250 mg, or 500 mg, 12-hourly for 10 days was randomly given to 40 patients aged 23-76 years, suffering from upper (27) and lower (13) urinary tract infections (UTI) as proved from the "antibody coated bacteria" (ACB) test. Pathogens included E. coli (20), Proteus sp. (13), K. pneumoniae (1), C. freundii (1) and P. aeruginosa (5), with MICs between less than 0.06 to 2 mg/l. During treatment all but one of the patients responded favorably both clinically and bacteriologically, while at a six-week follow-up, nine patients with upper UTIs and underlying chronic pyelonephritis or/and structural abnormalities had relapsed, while only one became reinfected. Treatment schedule did not influence the results. No appreciable side effect or toxicity was observed. It is concluded that ciprofloxacin should have an important role to play in the treatment of UTI as well as in systemic infections whenever multiresistant pathogens are implicated.

A study of cefoxitin, moxalactam, and ceftazidime kinetics in pregnancy.

In 27 women with fetuses affected by beta-thalassemia major, termination of gestation between 19 and 21 weeks was induced by amniocentesis and intrauterine instillation of prostaglandin F2 alpha. Pharmacokinetics in maternal blood and amniotic fluid were studied after at least three doses of one of the following antibiotics and before prostaglandin F2 alpha infusion: (1) cefoxitin, 2 gm, intravenously, 1/2-hour infusion, three times per day; (2) moxalactam, 2 gm, intravenously, 1/2-hour infusion, three times per day; and (3) ceftazidime, 1 gm, intramuscularly, three times per day. Successful amniotic fluid levels effective against various pathogens implicated in maternal-fetal infections appeared at least 3 hours beyond administration of the drug and ranged between 2.3 and 6.7 micrograms/ml, 1.56 and 15 micrograms/ml, and 1.5 and 5 micrograms/ml for cefoxitin, moxalactam, and ceftazidime, respectively. Beyond the third-hour after infusion a percentage ratio of amniotic fluid to simultaneous maternal serum level of almost greater than or equal to 50 was constantly observed for all studied antibiotics. Cefoxitin serum levels were about the same as those in nonpregnant women, while moxalactam and ceftazidime serum levels were 50% lower than the expected level in normal individuals.

Norfloxacin versus cotrimoxazole in the treatment of lower urinary tract infections.

In a randomised prospective study 61 patients with lower urinary tract infection received either 200 mg norfloxacin (33 patients) or 480 mg cotrimoxazole (28 patients) twice daily for ten days. Pathogens included Escherichia coli in 48 patients, Proteus mirabilis in ten patients, and Enterobacter cloacae, Klebsiella pneumoniae, Citrobacter freundii and Staphylococcus saprophyticus in one patient each. The MICs of norfloxacin and cotrimoxazole were less than or equal to 0.03 mg/l and less than or equal to 1 mg/l respectively. On the tenth day of treatment 94% of the patients receiving norfloxacin and 89% of the patients receiving cotrimoxazole were clinically cured, and the pathogens were eradicated in 94% and 96% of the patients respectively. At six week follow-up one patient given cotrimoxazole and two given norfloxacin had a reinfection. No side-effects or toxicity were observed with the exception of a diffuse rash in one patient receiving cotrimoxazole in whom treatment was discontinued. It is concluded that norfloxacin is safe and as effective as cotrimoxazole in the treatment of lower UTI and should have an important role to play whenever multiresistant organisms are implicated.

Hepatitis on high dose isoniazid: reintroduction of the drug in severe tuberculous meningitis.

Hepatitis developed in two patients treated with high doses (1000 mg/day) of isoniazid for severe tuberculous meningitis. Isoniazid was discontinued and later readministered in gradually increasing intrathecal and subsequently oral doses, up to the final dose of 400 mg/day. Transaminases remained normal, during 12 months on this dose, suggesting dose dependence of hepatotoxicity or a metabolic adaptation to the injury. Continued isoniazid treatment can be important in similar cases and it may become possible, if oral or intrathecal doses significantly lower than the initial hepatotoxic ones, are used.

Prospective randomized comparative studies of mezlocillin/cefotaxime vs. gentamicin/cefoxitin.

In 54 patients suffering from a variety of severe systemic infections the combination of mezlocillin (4 g iv 6-hourly) plus cefotaxime (2 g iv 8-hourly) was compared to that of gentamicin (1.5 mg/kg im or iv 8-hourly) plus cefoxitin (2 g iv 6-hourly). In the gentamicin/cefoxitin group metronidazole (500 mg iv 8-hourly) was added for anaerobic infections. Treatment assignment was randomized. The patients' diagnoses were: pyelonephritis (24), pneumonia (14), infected burns (9), osteomyelitis (2), and abdominal infections (5). Pathogens included: Escherichia coli (31), other Enterobacteriaceae (21), Pseudomonas aeruginosa (13), anaerobes (4), and others (2). Treatment with mezlocillin/cefotaxime cured 20 (74%) of 27 patients and caused improvement in 5, while in 19 (70%) patients the pathogens were eradicated. In the gentamicin/cefoxitin group 17 (63%) of 27 patients were cured and 6 improved, while in 15 (56%) pathogens were eradicated. One patient in the first group developed a rash, while in the second group two patients developed thrombophlebitis and another two transient nephrotoxicity. The combination of mezlocillin and cefotaxime can be recommended for the rational and empirical treatment of serious systemic infections.

Rifaprim in urinary tract infection: a comparison with co-trimoxazole.

Two regimes of rifaprim (RPM), a 3.75 to 1 combination of rifampicin (RIF) and trimethoprim (TMP), were compared with co-trimoxazole (CO-T) for the treatment of urinary tract infection in 60 patients. Dosages were: A, 450 mg RIF + 120 mg TMP twice daily; B, 600 mg RIF + 160 mg TMP at bedtime and C, 800 mg sulphamethoxazole (SMZ) + 160 mg TMP twice daily. Clinical results were similar but CO-T treatment was accompanied by a greater number of late bacteriological failures. In none of 40 patients receiving RPM did resistance to any of the components develop, while in three of 20 patients receiving CO-T resistance to TMP or SMZ emerged during treatment. There were no side effects in the patients receiving RPM, but three patients developed transient laboratory abnormalities. One patient receiving CO-T had a rash and one further transient laboratory abnormalities. Satisfactory concentrations of RIF and TMP were measured in urine up to 24 h after a dose of 600 mg RIF + 160 mg TMP. RIF may be a better companion to TMP than the sulphonamides for the treatment of urinary tract infection.