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Case records from 219 female patients between 1975 and 1992 who were given long-term prophylaxis (1 year) with nitrofurantoin for the prevention of recurrent urinary infections have been reviewed. Patients' age ranged from 9 to 89 years (median 31-35 years, mode 26-30 years); most (61%) were40 years old. The median number of symptomatic episodes in the 12 months immediately before prophylaxis was six (mode 4, mean 6.9). 14.4% of the patients were allergic to an antibiotic, and 23.6% had an imaging abnormality. Three regimens were used: group A (43 patients), 50 mg microcrystalline nitrofurantoin, bd; group B (110 patients), 100 mg macrocrystalline nitrofurantoin (Macrodantin), od; group C (66 patients), 50 mg Macrodantin, od. There were no obvious differences in efficacy between the patient groups (173 assessable patients). The mean incidence of symptomatic episodes decreased 5.4-fold during prophylaxis. Four-fifths of the 43 breakthrough infections (mostly due to Escherichia coli), were caused by nitrofurantoin-sensitive strains. An important finding was that patients with an imaging abnormality responded as well as those with no such abnormalities. In 16% of patients, prophylaxis was not helpful, objectively or subjectively, for no obvious reasons. In most patients where prophylaxis was successful, clinical improvement was maintained for at least 6 months after the end of prophylaxis. Nausea was more common in group A (P0.001), as were 'all adverse events'. Of those in group A 25.6% stopped prematurely as a result of an adverse event of any type, compared with 13% of those taking Macrodantin (P0.01). Older patients (65 years) did not report more adverse events than younger patients. No adverse event was life-threatening. Faecal flora analysis showed neither overgrowth by nitrofurantoin-resistant bacteria nor elimination of sensitive coliforms. Thus, macrocrystalline nitrofurantoin 50 mg at bedtime is appropriate for use in the long-term (12 months) prophylaxis of recurrent urinary infections, in view of its efficacy and favourable safety and tolerability profile. Patients can be managed by their family doctor.

Sir: We have noted with some concern that Schinella and colleagues (1) find that teicoplanin is ineffective in an intermittent intraperitoneal schedule for the treatment of CAPD peritonitis. This is at variance with our experience of more than 2 years' use in such patients. During that time we have reported our pharmacokinetic data (2) in detail, as well as results of a pilot therapeutic study in 12 patients (3) and an interim report of a randomized trial of teicoplanin compared with vancomycin (4). A total of 86 infections have now been treated in the latter trial: bacteriologi cal cure rates were 75% with teicoplanin and 86% with vancomycin (not significantly different). The treatment schedule with teicoplanin was as follows: patients received 400 mg i.v. on entry, and for 1 week 40 mg teicoplanin was added to each 2 L bag ( 4 bags are used every 24 h). Thereafter, the dosage was tapered: during the second week, 40 mg teicoplanin was added to alternate bags, and in the third week 40 mg teicoplanin was added to the overnight dwell bag only. Our success rate using this regime has been very similar to that observed with vancomycin. The majority of the small numbers of therapeutic failures have been due to Staphylacaccus aureu8, where tissue involvement (tunnel infections) has been a clinical feature. We are now exploring the possibility of reducing the total dosage of teicoplanin. Obvious means of doing this are to dispense with the initial i. v. dose, and to shorten the overall treatment period from 21 to 14 days. The consequence of therapeutic failure in this type of patient are potentially serious, as they involve the possible necessity of replacing the peritoneal catheter and the risk of losing the dialysing capacity of the peritoneal membrane. Therefore, we feel it is important to err on the side of overdosing rather than underdosing. In this context we would recommend that teicoplanin be added to every bag during the first week of treatment, rather than to alternate bags as suggested by Schinella et at. (1).

Sera from patients with primary biliary cirrhosis exhibit variable autoantibody reactivity against mitochondria, the commonest antigen (designated M2) including three structures of approximate M.W. 70, 50 and 40 kD. The nature of these antigens has only recently been established; the 70 and 50 kD are the transacetylase E2 and component X, respectively, of the pyruvate dehydrogenase complex and are distinct polypeptides. We have demonstrated, by immunoblotting, elution and rebinding of antibodies, unequivocal cross-reactivity between the major bands of the M2 antigen. In addition, cross-reactivity has been shown between antibodies binding to each of the three M2 bands of mitochondria and two major antigenic bands of both Gram-negative and Gram-positive bacteria. Conversely, antibodies eluted from these two bands of Escherichia coli were found to bind all three M2 bands of mitochondria. These results suggest that the antibodies of primary biliary cirrhosis contain both peptide-specific and cross-reacting antibodies, the latter recognizing a common "M2 epitope" that might include nonprotein components of the peptides. However, direct and competitive enzyme-linked immunosorbent assays failed to implicate the coenzyme of the pyruvate dehydrogenase complex, lipoic acid or its amide, as the common antigenic moiety.

Sixty-two strains of Staphylococcus aureus and coagulase-negative staphylococci, 21 Streptococcus faecalis and 17 other strains of streptococci isolated from cases of endocarditis were tested for sensitivity against rifampicin, teicoplanin, vancomycin, fusidic acid, erythromycin and novobiocin. Only rifampicin, novobiocin and teicoplanin were found to be active against the great majority of these strains. The microbial properties of these antibiotics suggest the necessity of combinations for effective therapy. The combinations rifampicin + novobiocin and rifampicin + teicoplanin were additive and suppressed the emergence of resistant mutants. Thus according to in vitro tests, either of these two combinations would be suitable for prophylactic use in high-risk patients, especially those scheduled to receive prosthetic implants.

Twelve male subjects, aged 19 to 40 years, shown to be healthy by examination and laboratory tests, took 500 mg of ciprofloxacin every 12 h for 7 days. After the first and the last dose, blood and urine samples were taken and drug concentrations were determined by bioassay. There was a significant buildup in mean concentrations in serum from day 1 to day 7; mean peak levels (attained after 1 to 2 h) were 1.9 and 2.8 micrograms/ml, respectively. The terminal half-life was 3.5 to 4 h. About 40% of the drug was excreted into the urine during the 12-h period after dosing; minimum mean concentrations in urine were 105 micrograms/ml on day 1 and 174 micrograms/ml on day 7. Considerable amounts of ciprofloxacin were found in the feces on day 7 (185 to 2,220 micrograms/g). Marked changes in the aerobic part of the fecal flora were observed as a result of taking ciprofloxacin: coliforms were absent on day 7, and concentrations of streptococci and staphylococci were significantly reduced. There was no overgrowth by yeasts. One week later the fecal flora had returned to a state similar to that found before treatment. Anaerobes were little affected quantitatively but acquired resistance to ciprofloxacin. Side effects were mild and transient.

A combination of nitrofurantoin (100 mg) and sulphadiazine (300 mg) given 12-hourly for 7 days was used to treat 51 patients with recurrent urinary infections who were attending an out-patient clinic. Either nitrofurantoin or sulphadiazine was active in vitro against all the organisms isolated. The cure rate 1 week after the end of treatment was 82%; 10 patients relapsed during the following month, giving a cure rate 5 weeks after the end of treatment of 57%. Side effects, although relatively common (37%), were mild. The outcome of treatment with these two long-established drugs is thus as good as that obtained with some newer and more expensive preparations.

The activities of azlocillin and ticarcillin against Pseudomonas aeruginosa were compared by estimating minimum inhibitory and bactericidal concentrations (MIC and MBC) in liquid and solid media, and by constructing killing curves from sequential viable counts. In MIC studies, azlocillin was about three times more active than ticarcillin in solid medium (agar dilution test) and in liquid media (tube and microdilution tests). When the MBC was measured, however, results varied according to the technique used. On agar and in microdilution tests, both azlocillin and ticarcillin were bactericidal, the MBC being 1.3-3 MIC. In the tube test, the MBC for ticarcillin was again about 3 MIC, but azlocillin appeared not to be bactericidal (MBC greater than 1 mg/ml). However, sequential viable counts of four clinical isolates showed that at 4 MIC both antibiotics reduced viable counts by a factor of 10(4) in 8 h. Our results stress the importance of methodology when assessing the antibacterial activity of an antibiotic.

Antibiotic resistance patterns were determined for 106 strains of methicillin-resistant Staphylococcus aureus (MRSA) from 21 countries. Resistance to gentamicin, tobramycin, netilmicin, amikacin, streptomycin, or erthromycin was recorded in more than 90% of strains. Resistance to the other compounds tested was as follows: tetracycline 86%, minocycline 76%, trimethoprim 69%, clindamycin 66%, neomycin 59%, chloramphenicol 39%, rifampicin 26%, fosfomycin 22%, ciprofloxacin 17%, fusidic acid 12%, bacitracin 2%, and novobiocin 1%. All the stains were sensitive to mupirocin, pristinamycin, ramoplanin, teicoplanin, and vancomycin. There were geographical patterns of resistance: MRSA from the UK and Australia were predominantly resistant to trimethoprim, whereas many strains from centres in Europe and the USA were sensitive. MRSA that were resistant to ciprofloxacin were of French and German origin. 15 strains, 12 of which came from France, Turkey, or Brazil, were resistant either to thirteen or to fourteen agents.

of Pseudomonas aeruginosa. Overall, 81% of the strains were sensitive to amikacin and 33% of the strains were sensitive to butirosin, the next most active compound. Results indicated that 54% of the P. aeruginosa strains were sensitive to amikacin and 33% were sensitive to tobramycin. From resistance patterns, enzymes responsible for inactivation of the antibiotics were deduced. The most common enzyme was aminoglycoside nucleotidyltransferase(2"), either alone or combined with either aminoglycoside phosphotransferase(3')-I or aminoglycoside phosphotransferase(3')-II. Aminoglycoside acetyltransferase(2) was identified exclusively in strains of Providencia stuartii. Specific enzymes could not be identified for 30 strains, 21 of which were P. aeruginosa. Several laboratory studies have shown that amikacin, a semisynthetic derivative of kanamycin, not only has a broad spectrum of antibacterial activity but also is active against a significant proportion of bacteria that are resistant to one or more of the aminoglycoside antibiotics. The major reason for this finding seems to be that amikacin is a substrate for only one of the eight known aminoglycoside-inactivating enzymes, namely, aminoglycoside acetyltransferase (6')

24 patients, admitted to hospital with lower respiratory tract infection, were treated with either co-trimoxazole (800 mg sulphamethoxazole + 160 mg trimethoprim) or trimethoprim (200 mg) orally twice daily. All showed a clinical improvement and with one exception respiratory pathogens were eliminated. Pharmacokinetics in blood, sputum and saliva were studied in 11 patients taking trimethoprim and 9 taking co-trimoxazole. No sulphamethoxazole was detected in either the sputum or saliva. Trimethoprim was found in higher concentrations in the sputum than in the blood, although there were wide and significant variations in individual patient's sputum pharmacokinetic profiles. Trimethoprim penetrates into the sputum at therapeutic concentrations in patients with chronic respiratory infections.

Amikacin (250 or 500 mg) was administered intramuscularly twice daily at 12-hr intervals to 34 patients with infections due to various gram-negative bacteria. Usually one or more aggravating factors were present, such as serious underlying pathology or therapy with steroids or immunosuppressants. Clinical isolates from most patients were resistant to gentamicin and other aminoglycosides. The overall response to therapy was excellent in 20 patients; in eight patients clinical response was good, but the organism persisted. Six patients showed some improvement without complete resolution of the infection or eradication of the causative organism. There were no complete clinical or bacteriologic failures. Ototoxicity was not observed in any patient. Levels of blood urea nitrogen and serum creatinine increased in two patients but returned to pretreatment levels within two weeks after therapy. No other adverse reactions were noted. Amikacin may replace gentamicin as initial therapy in serious gram-negative bacillary infections, particularly when resistance to gentamicin is a problem.

Techniques for the microbiological assay of nitrofurans are described. In one the indicator strain is Bacteroides fragilis; use of this system enables concentrations of nifuratel and furazolidone of down to 0.7 micrograms/ml to be estimated. The other system uses a recombination-deficient (recA-uvrA-) mutant of Escherichia coli; with this indicator, concentrations of 0.2 micrograms/ml, or less, of five nitrofurans can be assayed.

The properties of trimethoprim (TM), reviewed here, show it to be an excellent antimicrobial agent in its own right. However, with very few exceptions, TM has been made available clinically only in combination with a sulphonamide, usually sulphamethoxazole (SMX). We present evidence to suggest that the decision so to restrict the availability of TM was mistaken. Synergy between TM and SMX can be shown clearly in vitro, but there is no evidence from clinical trials that it plays a significant therapeutic role in urinary infections. Also, there is no evidence that combining the two antibiotics suppresses the emergence of resistance. Recently, sulphonamides other than SMX have been proposed as partners for TM, mainly on pharmacokinetic grounds. Compounds other than sulphonamides may also be logical partners for TM: we have made extensive studies on TM + rifampicin, for instance, and have obtained excellent results in certain clearly-defined patient groups. Only clinical trials of these new combinations will reveal whether they are superior to TM/SMX. There is already sufficient evidence to suggest that TM alone will be as effective as, and more acceptable than, TM/SMX. We propose that further large-scale clinical trials with TM alone be carried out, both to treat acute urinary infections and in prophylaxis.

SUMMARYStability of aminoglycoside resistance has been investigated in 20 strains ofStaphylococcus aureusresistant to gentamicin (16 strains were also resistant to methicillin). In view of previous reports that incubation at elevated temperatures can hasten the loss of unstable antibiotic resistance, we passaged strains daily in a liquid medium for 24 days at 43 °C. The nine strains which were resistant to neomycin kept their aminoglycoside resistance virtually intact, whereas most of the other 11 strains (sensitive to neomycin) lost almost all their resistance to gentamicin and kanamycin after 5 days. It thus appears that the stability of aminoglycoside resistances inStaph. aureusis closely linked to the resistance of the strains to neomycin. This finding has important possible consequences in terms of the advisability of the clinical usage of preparations containing neomycin or framycetin for topical application and bowel sterilization.

Mecillinam (MC) was found to be inhibitory at low concentrations to a wide range of Gram-negative bacteria; the sensitivity of such strains could be predicted by using a 10 microgram disk. Resistance to MC did not appear to be associated with beta-lactamase-mediated destruction of the antibiotic. Ampicillin-resistant strains tended to be less sensitive to MC. MC and cephradine acted synergistically against Proteus mirabilis, Pr. vulgaris, Prov. stuartii and Serratia marcescens, and the combination was additive against most Klebsiella aerogenes, Enterobacter spp. and Escherichia coli.

Twenty clinical isolates of Staphylococcus aureus, resistant to both gentamicin and methicillin, were tested in vitro for sensitivity to rifampicin, novobiocin, fusidic acid, vancomycin, teicoplanin and an extended range of aminoglycosides. Rifampicin was the most active compound tested, having an MIC of less than 0.02 mg/l. All the strains were inhibited by 1 mg/l of novobiocin, vancomycin and teicoplanin, and only one strain was resistant to fusidic acid. 50% of the strains were inhibited by less than 1 mg/l of amikacin and netilmicin, but other aminoglycosides were of poor activity. Resistant mutants were selected when strains were grown in the presence of rifampicin, novobiocin or fusidic acid alone, but this did not occur when rifampicin was combined with either novobiocin or vancomycin. Pharmacokinetic and other considerations suggest that a combination of rifampicin and novobiocin deserves further assessment for the treatment of infections caused by this type of organism.

The incidence of primary resistance to rifampicin in Mycobacterium tuberculosis has been analysed in countries where rifampicin is restricted to use for treating tuberculosis and in countries where its use is not restricted. There is no evidence that rifampicin-resistant M tuberculosis strains are more common where the use of the drug is unrestricted. Resistance to rifampicin is less common than is resistance to streptomycin or to isoniazid. We can thus see no danger of producing resistant strains of M tuberculosis if rifampicin therapy is used for short periods for non-tuberculosis infections. The problem of resistance mutants arising in the non-tuberculous species being treated is overcome by combining rifampicin with trimethoprim.

Experimental data, pharmacokinetic results, and clinical trials suggest that trimethoprim (TMP) is effective when used alone and is not associated with the toxicity and adverse effects caused by sulfonamides. Because an analysis of in vitro, pharmacokinetic, and clinical data suggested that the combination of rifampicin and TMP (Rifaprim) would be safe and highly active, an eight-year study of this combination for the treatment of urinary tract infection was done. The results were encouraging. Furthermore, a large multicenter trial of Rifaprim in 800 patients showed Rifaprim to be superior to trimethoprim-sulfamethoxazole for the treatment of chronic infections of the upper urinary tract. In another controlled trial, Rifaprim proved valuable for the treatment of urinary tract infections that resisted eradication and recurred frequently. Evidence suggests that Rifaprim may be useful in the treatment of other disease, such as staphylococcal osteitis (especially that caused by highly resistant organisms). Unlike antibiotics such as gentamicin, the use of which requires hospitalization of the patient and careful monitoring of levels in blood, Rifaprim can be used at home. Thus the danger of nosocomial infection is avoided.

Although rifampicin is active against virtually all pathogenic bacteria, acquisition of resistance means that it cannot be used alone for treating infections. We have shown that, in combination with trimethoprim, this handicap can be overcome. Not only is the emergence of resistance prevented by the presence of trimethoprim, but antibacterial synergy is often observed. By applying certain logical guidelines, we have been able to suggest an appropriate combination of rifampicin and trimethoprim, which is now being tried in the treatment of various injections. There is no evidence that the emergence of resistant tubercle bacilli will be encouraged by the use of rifampicin in this way: on the contrary, this risk seems extremely remote.

366 specimens of serum from children and adults without liver disease were screened for antibody to hepatitis A virus (anti-HAV) by means of radioimmunoassay. 56% were born in London, 26% came to London from various parts of the United Kingdom and the remainder (18%) from various parts of the world. The prevalence of antibody was related to increasing age, ranging from 7% in children under ten years of age to 77% in adults aged 50 years or more. The prevalence of anti-HAV was significantly higher in females, in the lower socio-economic class and in those not indigenous to London. In comparison to other urban populations such as those of the United States and Western Europe, the prevalence of anti-HAV was similar in terms of the overall prevalence and age distribution. By contrast, these findings were entirely different from the countries of Eastern Europe and the Middle East where the overall prevalence was higher but the anti-HAV was equal in all ages. Thus, the findings presented indicate that hepatitis A virus infection is common in London and also shows a clear relationship to advancing age, lower socioeconomic class and the country of origin.

DuP 105 and 721, synthetic antibiotics belonging to a totally novel chemical class (oxazolidinones), have been found to be active in vitro against a wide range of Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus. DuP 721 had geometric mean MICs ranging from 1.1 to 16 mg/l against 167 strains of Staph. aureus, Staph. epidermidis, Staph. saprophyticus, streptococci of Groups A, B and D and diphtheroids. DuP 105 was between 1.5 and eight-fold less active. Bacteroides fragilis strains were also susceptible to the DuP compounds (mean MICs being 8.3 and 14.9 mg/l for DuP 721 and 105, respectively), but other Gram-negative species and yeasts were not inhibited by concentrations in excess of 100 mg/l. Both compounds had a predominantly bacteriostatic action. No primary resistance was found, and the incidence of resistant variants in 105 strains tested was less than 1 per 10(8) bacteria.

Summary A total of 120 patients, including 53 pregnant women with significant bacteriuria, received 163 7-day courses of oral antimicrobial agents allocated in a randomised manner. The cure rates after 6 weeks' follow-up ranged from 73% to 86%, and there was no statistical difference between preparations of ampicillin, carbenicillin indanyl ester, and 2 different formulations of nifuratel. Side-effects occurred in 30% to 40% of the courses of penicillin drugs, but in under 15% of the course of nifuratel. It is concluded that the new oral preparation of carbenicillin is a useful addition to the list of antimicrobial agents which are effective in the treatment of urinary infections in domiciliary patients. Furthermore, nifuratel has been confirmed as a highly active non-toxic drug which is valuable in the treatment of urinary infections.

Five nitrofurans – nitrofurantoin, nifuratel, nitrofurazone, furazolidone and SQ 18,506 – have been tested against 201 microbial strains. Escherichia coli , Streptococcus fa

STAPHYLOCOCCUS AUREUS is one of the most versatile human pathogens. In the late 1930s, sulfonamides offered the first challenge to S. aureus, but they failed because of their poor clinical performa...

Patients with primary biliary cirrhosis have an abnormally high incidence of urinary tract infection (35%). Susceptibility to urinary infection and other infectious diseases has been linked with certain blood group antigens and secretor status. We have therefore studied these characteristics in patients with primary biliary cirrhosis. We were unable to show any abnormal distribution in blood groups or secretor status in patients with primary biliary cirrhosis (compared with a normal population) which might reflect their predisposition to urinary infection. The distribution of blood groups and secretor status in patients with primary biliary cirrhosis with a history of urinary infections was not significantly different from patients without such a history. Escherichia coli strains isolated from patients with primary biliary cirrhosis did not bind in any greater numbers to the uroepithelial cells of primary biliary cirrhosis patients than to the cells of a normal healthy control. We therefore conclude that blood group distribution, abnormal secretor status, and epithelial cell type are not important factors in the predisposition of primary biliary cirrhosis patients to urinary infections.

Over an 18-month period (October 1973 to April 1975), 133 strains of gram-negative bacteria with acquired resistance to trimethoprim (TM) were isolated from infected urines cultured at the Royal Free Hospital. The overall frequency of resistance was 3.2%. A disproportionately high number of resistant strains (63.1%) were Kebsiella aerogenes. Resistance to TM mediated by R plasmids occurs infrequently (9% of all resistant strains); the majority of TMR plasmids isolated belonged to one incompatability group (W). Chromosomally mediated resistance to TM in most Escherichia coli and K. aerogenes strains appears to be due mainly to production of a dihydrofolate reductase with a reduced susceptibility to TM. In some strains, increased activity of the DHFR was also a contributing factor. Increase in enzyme level alone was only great enough to account for the level of resistance to TM in a small number of cases.

Summary The historical development of antibiotics has been summarized. Three distinct phases are discernible. The first (from historical times to about 1900) involved mostly folk remedies. The second (1900-c. 1940) was ushered in by Paul Ehrlich’s development of the concept of ‘selective toxicity’ and saw the establishment of arsenicals and sulphonamides. The third, lasting to the present day, started with the exploitation of the pioneering studies of Fleming, Dubos and Waksman on antibiotic production by soil fungi. This latest phase has continued with the improvement of natural products by the skills of the medicinal chemist. The properties and evolution of three major groups of antibiotics, penicillins, cephalosporins and aminoglycosides are fully described. Finally, pathways of possible future evolution of antibiotics are outlined.

Cefoxitin, a semisynthetic cephamycin, has been compared with the widely used parenteral cephalosporin, cephalothin, in terms of antibacterial activity, human pharmacokinetics, and toxicity. For both compounds, minimal inhibitory concentrations were within the therapeutic range against the 156 gram-positive cocci tested (except group D streptococci), but cephalothin was 8 to 20 times more active. Regarding the 313 gram-negative organisms tested, both antibiotics were of approximately equal activity against cephalothin-susceptible strains, but cefoxitin was outstandingly superior against Providencia spp. and indole-producing Proteus spp., and markedly better against Serratia marcescens and Bacteroides fragilis . Against these organisms, cefoxitin but not cephalothin would be expected to be therapeutically valuable. Antibiotic activity levels in the serum and urine of 18 human volunteers after parenteral administration were higher and more prolonged in the case of cefoxitin, which had an average terminal serum half-life of about 45 min and a urinary recovery of about 90%. Cefoxitin was entirely nontoxic and, given intramuscularly, slightly less painful then cephalothin. These preliminary results suggest that cephamycins may prove to be a significant chemotherapeutic advance.

The cephamycins are a group with great potential. The first member of the group intended for therapeutic use offers the following advantages over existing cephalosporins: 1. Stability to various beta-lactamases; in an environment increasingly threatened by R-factors, this property may be of increasing value as time passes. 2. Possible lack of cross-allergenicity with other beta-lactam antibiotics. 3. Activity against anaerobic strains. Cefoxitin is only the first semi-synthetic derivative; presumably there are other compounds awaiting assessment which have even more favourable properties.

The incidence of resistance to trimethoprim among urinary isolates between October 1978 and November 1979 was 11.5%, more than double the figure found April 1973 and October 1975. Of the resistant strains, 60% had a minimum inhibitory concentration in excess of 1 mg/ml. Escherichia coli and Proteus mirabilis showed the greatest increase in resistance since the previous study. Rather wide fluctuations occurred in the incidence of resistance for various species when the figures were analysed over two-month periods, hence studies of short duration must be interpreted with caution. There are not yet enough data from this or other studies for the cause of the increased incidence of resistance to trimethoprim to be determined.

48 non-pregnant domiciliary patients referred by general practitioners and 50 pregnant women were treated for bacteriuria with either 500 mg cephradine or 400 mg pivmecillinam every 6 h for 7 days. In the pregnant women, cure rates were over 90% after 2 weeks for both compounds, and after 6 weeks were 86% for cephradine and 78% for pivmecillinam. Cure rates in the non-pregnant were 83% for cephradine and 95% for pivmecillinam at 6 weeks. Seven patients (3 given cephradine, 4 given pivmecillinam) stopped treatment due to side-effects. Overall, side-effects (many of which were trivial) were more common in patients treated with cephradine (51%) than in those receiving pivmecillinam (33%). It is concluded that both drugs are highly effective in these two common types of urinary infection.

Mid-stream specimens (MSU) of urine were collected from 142 healthy women (pregnant and non-pregnant) and cultured for lactobacilli and other fastidious bacteria. The latter either require CO2 or are obligate anaerobes. Lactobacilli were present in counts of 10(4)/ml or more in 34.8% of the women, and in counts of 10(5)/ml or more in 20.2%. Besides lactobacilli, which were the bacteria most frequently isolated, anaerobic gram-positive cocci (peptococci and peptostreptococci) were often found. This flora is typical of that of the lower vagina, and none of these women had either symptoms of urinary infection of pyuria. Therefore, the bacteria isolated were commensals or contaminants. Cultures of MSUs taken from 26 women with symptoms of dysuria and/or frequency, but without significant numbers of conventional pathogens such as Escherichia coli, contained commensals and contaminants of the same variety and in similar numbers. Urine samples from 50% of these patients contained at least 10(4) lactobacilli/ml and 27% had 10(5) or more/ml. Lactobacilli were absent from the suprapubic urine specimens cultured from a further 44 women. There was no significant difference between the isolation rate of lactobacilli in urine cultures from healthy women and the rate in women with dysuria and frequency.

Rifampicin (rif) and trimethoprim (tm) are familiar broad-spectrum oral antimicrobial agents. Both drugs owe their antibacterial activity primarily to their effect on the biosynthesis of nucleic acids. Their target sites may thus be regarded as occurring on the same metabolic pathway; sequential blockade of a metabolic pathway has been shown to result in a potentially synergistic situation. Consequently, we tested rif and tm in combination, to investigate possible antibacterial interactions.

Twelve cases of peritonitis caused by Gram-positive bacteria in 11 dialysis patients were treated with teicoplanin. Treatment, which was continued for three weeks, consisted of the addition of teicoplanin to the dialysis fluid. Six patients who were febrile on admission were also given a single intravenous dose of 400 mg teicoplanin. For patients on continuous ambulatory peritoneal dialysis 20 mg teicoplanin per litre was added to each dialysis bag during the first week of treatment, to alternate bags during the second week, and only to the overnight dwell bag in the third week. For patients on intermittent peritoneal dialysis, 20 mg/l teicoplanin was added at each dialysis session. Resolution of peritonitis occurred in all patients within one to five days (mean 2.2); nine were discharged within this period and the patients continued to treat themselves at home. The other two patients were kept in hospital for reasons unconnected with the peritonitis. Nine patients have remained well at follow-up 2-13 months (mean 6.3) later. Two patients, both of whom had Staphylococcus aureus peritonitis, relapsed three months after the end of treatment. Mean serum teicoplanin concentrations were less than 10 mg/l, except in one patient who was re-treated when he relapsed. No adverse effects were recorded; one patient who developed a conductive hearing loss was found to have otitis media and obstruction due to wax. We conclude that teicoplanin is safe and effective in treating peritonitis in patients on peritoneal dialysis.

Thirteen patients with a mean age of 67 years admitted to hospital with signs and symptoms of lower respiratory infections were treated with ‘Augmentin’ (500 mg amoxycillin + 250 mg clavulanic acid) given orally every 8 hours, for 7 days. The clinical response was ‘good’ in ten cases and one ‘failed’. Two patients could not be assessed. Side-effects were not serious: only one patient had to stop treatment (due to diarrhoea). The pharmacokinetic results show that peak levels of amoxycillin and of clavulanic acid in the blood and in sputum are achieved at a later time in the patients studied than occurs in healthy volunteers.