Downregulation of CD28 surface antigen on CD4+ and CD8+ T lymphocytes during HIV-1 infection.

A progressive significant decrease of CD28 surface antigen expression on CD4+ (mean, 90, 86, 79, 68% in stages I, II, III, and IV, respectively, versus 96% in normals), as well as on CD8+ T lymphocytes (mean, 38, 32, 31, and 29% in stages I, II, III, and IV, respectively, versus 47% in normals) was observed during HIV-1 infection. The increase of cytotoxic/suppressor T cells, in both percentage and absolute numbers, that was observed in almost all HIV-1 patients, was associated with an increase of the CD8+ cells lacking the CD28 surface antigen. The loss of CD28 antigen expression was parallel to the increase of CD38, human leukocyte antigen (HLA)-DR, and CD45RO antigen expression on T lymphocytes throughout the disease. Furthermore, a positive significant correlation within the CD4+ but not the CD8+ subset was observed between the percentage of cells lacking the CD28 antigen and the percentage of cells expressing the HLA-DR and CD38 antigens, a finding suggesting that the loss of CD28 antigen expression on CD4+ lymphocytes may be associated with T-lymphocyte activation. Patients treated with zidovudine showed no significant differences in the percentages of either CD4+CD28+ or CD8+CD28+ T-cell subsets when compared to untreated patients. These phenotypic changes may be associated with the functional defects of T lymphocytes in HIV-1 infected individuals.

The treatment of complicated and uncomplicated urinary tract infections with temocillin.

Temocillin was given to 33 patients with urinary tract infection as a once daily dosage regimen of 500mg intramuscularly or Ig intravenously for 7 to 10 days. The lower dose produced a clinical cure in 83% of patients with uncomplicated infection but was ineffective in complicated cases, whereas the higher dose cured 100% of uncomplicated and 70% of complicated cases and there were no side effects or toxicity. In vitro studies with 120 consecutive clinical isolates of Enterobacteriaceae gave an MIC90 of 8 mg/L for Escherichia coli, although some resistant strains were found in other species.

Staphylococcal infections in hospital: the Greek experience.

Resistance rates of various species to many antimicrobials are very high in Greece. Mean resistance rates of Staphylococcus aureus isolated in 12 Athens hospitals in the second half of 1986 were 80% for penicillin, 32% for methicillin, 22% for gentamicin, 27% for erythromycin, 17% for lincomycin and 16% for co-trimoxazole. In a prospective study in the General Hospital of Athens from May to July 1987, 40 coagulase-positive staphylococcal strains were isolated from various materials from inpatients. Of these 78% were resistant to penicillin, 50% to methicillin at 37 degrees C, 62% to methicillin at 30 degrees C, 38% to erythromycin, 32% to tobramycin, 15% to clindamycin, 15% to fusidic acid, 9% to amikacin, 5% to netilmicin and 0% to vancomycin. Ten of these strains (seven methicillin-resistant) were responsible for severe infections and three of the affected patients died (two nosocomial pneumonias, one infected burn, all due to methicillin-resistant strains). Another 11 strains (eight methicillin-resistant) were responsible for mild infections. From 41 coagulase-negative staphylococci isolated from inpatients, seven (five methicillin-resistant) were held responsible for mild infections. Of the 20 patients with infections due to methicillin-resistant strains, nine had previously received a beta- lactam antibiotic. Staphylococci are not responsible, however, for a large proportion of infections in our hospital at the moment. High resistance rates in Greece are due to overuse of antibiotics, a phenomenon attributed to a consumer's society behaviour of doctors and patients.

Cost-minimisation analysis of sequential treatment with ofloxacin or ciprofloxacin in hospitalised patients.

This study evaluated the cost of sequential treatment with once-daily ofloxacin or twice-daily ciprofloxacin in 474 hospitalised patients in different countries. The patients were treated intravenously for at least 3 days, then orally for 7 to 10 days or for 3 days beyond the disappearance of infection-related symptoms. The overall clinical cure rate (86.8% with ofloxacin and 89.6% with ciprofloxacin) and the overall bacteriological response rate (89.9 and 89.0%, respectively) were similar, and a cost-minimisation analysis was conducted. The acquisition costs for ofloxacin and ciprofloxacin in Greece, Israel, Slovenia and Turkey were used and converted to Deutschmarks (DM), and the costs of administration were analysed for each hospital. The different cost categories for oral and intravenous (IV) treatment (e.g. antimicrobial acquisition, drug monitoring, drug delivery costs) were used to identify any differences. The total costs per patient varied between the countries involved, but were higher for ciprofloxacin (ofloxacin: DM239 to DM724; ciprofloxacin: DM540 to DM976). In a sensitivity analysis using identical daily acquisition costs for the 2 fluoroquinolones, the total cost of treatment was higher for ciprofloxacin, as a result of the lower cost of administration of ofloxacin in the once-daily regimen. Continuing IV therapy would be approximately 50% more expensive than switching to oral administration; however, whenever possible, both drugs can be switched from IV to oral treatment.

Participants in HIV clinical trials in Europe.

In recent years an increasing number of antiretrovirals have become available. In order to define the optimal treatment regimens an increasing number of clinical trials are needed. Our objective was to study the profile of participants in HIV clinical trials in Europe and learn from their experience and views. Between August 1996 and September 1997, self-administered anonymous questionnaires were distributed to people with HIV infection at inpatient and outpatient clinics in 11 European countries. One thousand three hundred and sixty-six people completed the questionnaire (50% response rate). Four hundred and twenty (31%) of the respondents reported that they had previously participated in at least one HIV clinical trial. The percentage of people who had taken part in a clinical trial varied widely between the different centres, from 12% in Athens to 61% in Antwerp and Brussels. A significantly higher participation rate was observed in the northern and central part of Europe compared with the south (respectively 40% vs 18%) and also among people with a higher income. Most people (92%) stated that they were 'well' or 'very well' informed prior to enrolment in the trial. However, 4% reported that they had not given written approval and 22% felt that they were pushed into participating. Only 21% stated that they were informed about the outcome of the study on its completion. The most important reason for non-participation (37% of the non-participants) was because a clinical trial had never been proposed. In conclusion, a majority of people with HIV infection in European HIV treatment reference centres were willing to participate in clinical trials. HIV clinical trials in Europe should adhere more strictly to universal ethical standards.

Asymptomatic bacteriuria of pregnancy: do obstetricians bother?

In view of the potentially serious consequences of asymptomatic bacteriuria of pregnancy (ASB), we surveyed the attitudes of Greek obstetricians towards this entity. A total of 108 obstetricians practicing in the area of Athens completed a questionnaire concerning ASB. Only 73 of the 108 stated that they screen their clients for ASB (51 of them when pyuria is present and only 22 in all pregnant women). Of special interest is the finding that a larger percentage of younger obstetricians (practicing for up to 9 years) habitually screen their patients, compared to older ones (83% vs 60%). Concerning treatment of ASB, only 45 out of 73 doctors screening for ASB give any treatment when ASB is present. Most obstetricians (87%) prefer a beta-lactam antibiotic. In almost all cases 7-10 days are considered the appropriate duration of treatment. Better education of obstetricians, especially the older ones, concerning detection and management of ASB is needed.

Acute prostatitis: which antibiotic to use first.

Six antimicrobial agents were administered to 48 patients (divided in 6 groups) who underwent prostatectomy. Half of the patients received the antibiotic in a single dose one hour before the operation and the rest in divided doses 24 hours before the operation. The concentration levels in serum and in prostatic tissue were measured for each of the antibiotics and for each mode of administration. The obtained ratios of prostatic tissue to serum concentrations and the relative antimicrobial activity to local pathogens of each agent indicate that the agent of choice for prostatic disease is netilmicin followed by aztreonam, cefuroxime and the ticarcillin-clavulanic acid combination.

Management of surgical infections.

Results of treatment of 151 surgical infections with a variety of antimicrobial regimes were retrospectively compared. Diagnoses included diffuse peritonitis (43), severe soft tissue infections (11), septicaemia accompanying abdominal infections (29), intra-abdominal abscesses (36), local peritonitis (27) and other localized infections (5). A total of 211 anaerobic and 130 aerobic strains were isolated. A cure rate of 92% was achieved with metronidazole or ornidazole used alone and 89% with these nitroimidazoles plus an aminoglycoside. Results were equally satisfactory regardless of whether a surgical procedure, such as drainage was performed. Clindamycin and the aminoglycosides had satisfactory results in combination, but not when used alone. Good controlled trials are now justified to define the need for an aminoglycoside and/or surgery in addition to a nitroimidazole.

Ticarcillin and clavulanic acid in serious infections.

In an open, non-comparative study 40 patients with severe, often life-threatening infections, were treated with Timentin 5.2 g (5 g ticarcillin plus 200 mg potassium clavulanate) by iv infusion every 6 or 8 h. They were suffering from septicaemia (9), obstructed UTI (8), non-obstructed urinary tract infection (10), respiratory tract infection (6), infected burns (4) or malignant otitis externa (3). Many patients had important aggravating factors such as renal transplantation, peritoneal or haemodialysis, leukaemia, extensive burns, renal stones, tracheostomy and diabetes. Pathogens included Pseudomonas aeruginosa (21), Escherichia coli (7), and other Enterobacteriaceae (6). Twenty-four pathogens (13 P. aeruginosa) were ticarcillin-resistant. Thirty-six patients were clinically cured including all cases of malignant otitis externa, infected burns and non-obstructed urinary tract infection. Three patients improved and one patient with obstructed urinary tract infection failed. In 32 patients the pathogen was eradicated, in one patient it persisted and in seven it reappeared. In particular, 11 of 13 patients with infections due to ticarcillin-resistant P. aeruginosa were cured and two improved. There was, however, bacteriological relapse in five. There were no side-effects or evidence of toxicity in any of the patients. In an in-vitro study a synergistic effect between ticarcillin and clavulanate was noted against Enterobacteriaceae but only a slight synergistic effect against P. aeruginosa. Studies in patients with normal liver and kidney function showed pharmacokinetic compatibility of the two agents. Timentin can be recommended for the initial treatment of serious infections.

A double-blind study of once-daily temafloxacin in the treatment of bacterial lower respiratory tract infections.

The safety and efficacy of a seven to 14 day course of temafloxacin 600 mg once daily were compared to ciprofloxacin 500 mg bd in adult patients with bacterial infections of the lower respiratory tract in a multicentre, double-blind, randomized clinical trial. Patients were enrolled if they had symptoms and signs of infection consistent with acute exacerbation of chronic bronchitis or uncomplicated pneumonia, confirmed by X-ray. Clinical and bacteriological evaluations were performed within 48 h before enrollment, during treatment (study day 2 to 5), 1-3 days post-treatment, and 5-9 days post-treatment. Interim results are reported. Temafloxacin produced a similar clinical success to ciprofloxacin, 98% (114 of 116) and 97% (117 of 121) of patients respectively; all treated patients with pneumococcal infection except one who received ciprofloxacin were clinical successes. Temafloxacin resulted in earlier bacteriological response, especially apparent after the second and third day of therapy and among smokers and the elderly (greater than or equal to 65 years old). Five to nine days after stopping treatment 98% of pretreatment pathogens were eradicated: 124/126 and 132/135 in the temafloxacin and ciprofloxacin groups respectively. Adverse reactions occurred among 8.6% (12 of 140) of temafloxacin treated patients compared to 5.8% (8 of 138) of ciprofloxacin treated patients. All adverse events reported were of mild to moderate severity and no patients withdrew from the study prematurely due to these events. The preliminary results from this study suggest that once daily temafloxacin gives high rates of clinical and bacteriological success, similar to twice daily ciprofloxacin, in the management of bacterial infections in the lower respiratory tract.

The use of new beta-lactam antibiotics in urinary tract infections.

Results of treatment of urinary tract infection in 110 patients using new beta-lactam antibiotics are presented in summary. While in the uncomplicated infections a cure rate approaching 100% was observed even with very small dosages, complicated cases required higher dosages to achieve satisfactory clinical cure rates and especially to achieve acceptable bacteriological cure rates. The continuous need for new, more potent antibiotics is becoming apparent due to the increasing resistance rates of pathogens to the existing agents. The group of beta-lactam antibiotics offers much hope due to the continuous development of numerous new compounds with better antibacterial and kinetic properties, offering at the same time a very high degree of safety, compared to aminoglycosides and most other antibiotic groups.

Emergence of resistant bacterial strains during treatment of infections in the respiratory tract.

In order to investigate the frequency of the emergence of resistance during treatment, 1,403 episodes of lower respiratory infection were studied in a General Hospital with three departments of Chest Medicine in a period of four years. In 650 episodes the pathogen was isolated and in 82 of those failure of therapy was accompanied by emergence of resistance to the agent used. Factors associated with this phenomenon were: intensive care, tracheostomy, involvement of Pseudomonas aeruginosa, Enterobacter spp., Serratia marcescens, Staphylococcus aureus or Acinetobacter calcoaceticus, use of antipseudomonas penicillins, cefotaxime (especially when used in P. aeruginosa infections) and co-trimoxazole and monotherapy as opposed to appropriate combination therapy in patients with nosocomial pneumonia.

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.

In-vitro studies with ceftazidime.

MIC determinations for 275 multiply-resistant nosocomial isolates of enterobacteria showed that ceftazidime was more effective than cefotaxime, cefoxitin or cephalothin. Enterobacter species were the most resistant with 12% isolates resistant to more than 8 mg/l of ceftazidime, but this was still the most active agent. Of 150 isolates of Pseudomonas aeruginosa (55% of which were resistant to gentamicin), only 9% were resistant to 8 mg/l of ceftazidime and 2% to cefsulodin, both of which were more active than cefotaxime, ceftriaxone, cefoperazone or moxalactam. Ceftazidime was less active than cefoxitin against Bacteroides fragilis, with 30% of strains resistant to 8 mg/l of ceftazidime, but it was more active than cefotaxime or cephalothin.