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Mid-stream urine specimens from 120 symptom-free males aged between 15 and 60 years were examined for cells and bacteria. Only 3 specimens showed pyuria, all of which yielded fastidious organisms. No specimen yielded a pure growth of an aerobe. Fastidious organisms in pure or mixed growth were isolated from 26% of the specimens, none in a count greater than 10(8)/l and the majority in counts less than 10(7)/l. It was concluded that pure growths of aerobes in any count in patients with symptoms are indicative of infection. Fastidious organisms should be sought in the urine of patients with symptoms or pyuria before more intensive and expensive investigations are pursued.

On my first firm as a student at “Barts” in the early 1950s I was taught so much more than surgery by two eminent surgeons of the day. One small and seemingly insignificant piece of advice was that painful cracks around the mouth should be treated with Ung Hydrarg Ammon Dil . I never forgot this cumbersome name and when, some years later, my family was bothered by such cracks, either beside the mouth or at the tips of the fingers, we had no problem in obtaining the ointment from the local chemist. A minute …

OBJECTIVES--To assess the ease of use of suprapubic aspiration of urine under ultrasound guidance in babies with fever of uncertain cause and to assess the importance of bacterial counts and pyuria in relation to abnormalities of the urinary tract and the importance of pyuria in the absence of bacteriuria. DESIGN--Analysis of urine samples obtained by suprapubic aspiration in babies and children from July 1991 to June 1992. The clinical records of the children with bacteriuria and sterile pyuria were examined retrospectively. SETTING--Neonatal and paediatric wards of a district general hospital. SUBJECTS--508 babies and children who had fever of uncertain cause or were seriously ill. RESULTS--No difficulties arose in the collection of 545 specimens. Bacteria were isolated from the specimens of 44 children, 24 of whom had abnormalities of the urinary tract. The bacterial count was < 10(8)/l in 18 of the children with bacteriuria, 10 of whom had abnormalities. No white cells were seen in 22 of the 46 bacteriuric specimens; nine of the children with no pyuria had vesicoureteric reflux. 439 of the 499 non-bacteriuric specimens showed no white cells. 60 children had pyuria without bacteriuria. CONCLUSIONS--The use of ultrasound guidance simplifies suprapubic aspiration of urine in babies. Low bacterial counts may be associated with abnormalities of the urinary tract. Laboratory techniques capable of detecting such counts reliably should be used. Pyuria is absent in half of babies and very young children with bacteriuria. It rarely occurs without bacteriuria, and if it does an explanation should be sought.

(1990). Effect on Urogenital Flora of Antibiotic Therapy for Urinary Tract Infection. Scandinavian Journal of Infectious Diseases: Vol. 22, No. 5, pp. 631-632.

SUMMARY Clinical details are presented of 16 patients from whom thymine-requiring (thy-) mutants of pathogenic organisms were isolated; all had been treated with co-trimoxazole. The urine of six patients infected with thy- mutants contained levels of a thymine-like compound sufficient to support their growth. This might be the result either of the breakdown of pus cells or of thymine production by living bacteria that persist in stones or scar tissue, a suggestion supported by the observation of mutant growth “in satellitism” in vitro. Since 1975 we have isolated mutants from patients who have had short courses of co-trimoxazole, in contrast to those we reported upon previously, all except one of whom had had long courses. We are now isolating thy- mutants more frequently than hitherto. Secondary mutations to a low thymine requirement may now be occurring more rapidly, thereby allowing more mutant organisms to survive. The clinical significance of infection with thy- mutants is not yet clear, but evidence is accumulating that they are pathogenic. Alternative chemotherapy is suggested for patients from whom such mutants have been isolated.

The reported frequency of coagulase-negative staphylococci in published studies of urinary infections varies widely, and their importance as pathogens is controversial. It is suggested that confusion has arisen as a result of a tendency to dismiss the organisms as contaminants, the use of inappropriate culture methods or inhibitory culture media, and the different age and sex composition of the populations studied. Laboratory data support the view that micrococcus subgroup 3 causes acute infections accompanied by evidence of severe inflammation of the urinary tract, and is virtually confined to women in the sexually active age-group.

Urine samples were cultured for aerobic, fastidious, and anaerobic bacteria in 88 patients (66 F, 22 M) before and after standard urodynamic investigations. 37 of 42 women with detrusor instability, and 14 of 17 women with stress incontinence, had evidence of bacteriuria with aerobic or fastidious bacteria before investigation, as did 6 of 13 men with bladder outflow obstruction. 8 men (36%) acquired bacteriuria with aerobic bacteria after investigation, compared with 10 women (15%). Recalcitrant, irritative urinary symptoms in women may be caused by an underlying infection, the urodynamic changes being secondary. In men who have urodynamic studies, antibiotic prophylaxis should be considered.

A two-year study of 51 women has shown a highly significant relation between high counts of fastidious organisms in the urine and the presence of symptoms. The patients, even when symptom-free, differed in this respect from a control group who had not had urinary symptoms for 2 years and from a group on long-term low-dose prophylaxis for recurrent urinary infection. The history, physical signs, and natural history of urinary symptoms in these patients were consistent with a diagnosis of urethral or paraurethral infection.

Two observers, unaware of each other's findings and of the diagnosis, examined red cells in the urine of 109 patients by phase-contrast microscopy. All specimens were examined uncentrifuged by inverted microscopy, and 48 of the 109 were also examined under a light microscope after centrifugation. We were unable to confirm with either method the close correlation between red-cell morphology and diagnosis reported in previous studies, and our 2 observers differed in their interpretation on 38% of occasions. Proteinuria associated with the presence of casts in uncentrifuged urine examined by inverted microscopy was a better indication than red-cell morphology of renal parenchymal disease.

73 boys who presented to their general practitioners over the course of one year with symptoms of urinary-tract infection and were found to have bacteriuria were referred to a three-year prospective study. This included clinical and radiological investigations and monitoring of the preputial flora and midstream-urine culture at monthly intervals. 22 (30%) of the boys had radiological abnormalities of the urinary tract; 6 had pyelonephritic changes. Only 2 required urinary-tract surgery. Several findings of the study suggest that the natural history of the disease in boys is different from that in girls. Proteus spp. predominated as the infecting organisms. Culture of swabs from the preputial sac, and comparison with matched controls, suggested that the source of infection in boys is the prepuce or urethra rather than the bowel as in girls. Recurrence of infection, in the absence of radiological abnormality, was rare; 51 boys (70%) had no recurrence throughout the follow-up period. There was evidence that recurrence in boys is related to the persistence of gram-negative organisms in the urethra, revealed by low bacterial counts on midstream culture, and it is suggested that in boys urethral infection may be as important as bladder bacteriuria.

Summary The criterion enunciated by Kass for interpreting the quantitative examination of urine is critically reappraised. The role of organisms other than those of the aerobic bowel flora, especially fastidious organisms, in urinary tract infections is discussed in detail. Clinical microbiologists are urged to pay more attention to the bacteriological examination of urine and to play a greater part in the diagnosis and treatment of infections of the urinary tract and its adjacent structures.

Summary A trial of oral carbenicillin for the treatment of Pseudomonas urinary infections in 8 patients is reported. Pseudomonas was eradicated in 6 patients, but recurred in 1. Treatment had to be curtailed in the remaining 2, who developed rashes. In a pharmacokinetic study of 10 patients with varying degrees of renal insufficiency it was shown that levels of carbenicillin likely to be adequate for the treatment of Pseudomonas urinary infections were attained in patients with creatinine clearances of over 6 ml/min. With clearances below this level there was evidence that absorption was impaired, and adequate urine levels were not achieved. It is suggested that the use of oral carbenicillin should be restricted to the treatment of Pseudomonas and indole-positive Proteus infections confined to the urinary tract.

Daily and weekly bag-changing regimens were compared in 12 elderly catheterised patients with reference to their clinical condition, leakage or blockage of the catheters, and the bacteriological state of the urine. Latex Foley catheters were used for the first 3 months and silastic catheters for the second 3 months of study. All patients had bacteriuria throughout the study, and the average number of bacterial species isolated from each specimen was 3.8. There were no significant clinical or bacteriological differences between the patients on daily and those on weekly bag change. Although significantly more episodes of pyrexia were recorded during latex than during silastic catheterisation there was no correlation between these episodes and the bacteriological state of the urine. Of the 9 courses of antibacterial treatment given during the 6 months, 7 were for indications other than urinary tract infection. There were no episodes of acute pyelonephritis. There were 148 episodes of pyrexia unrelated to any clinical symptoms or signs. Only 2 were treated with antibiotics; the remainder subsided without treatment.

The laboratory diagnosis of 50 consecutive episodes of peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD) was studied. The technique which yielded the highest rate (84%) of positive bacteriological diagnoses was inoculation and subculture of thioglycollate broth. Cloudiness of fluid to the naked eye was an accurate predictor of a raised white cell count. A minimum laboratory protocol for the bacteriological diagnosis of CAPD peritonitis was devised and has been in use satisfactorily since the completion of the study. Antibiotic treatment was given orally in the first instance in 43 episodes and was successful in 34.

Summary Evidence is presented that the pathogens causing urinary infection in boys differ significantly from those causing infection in girls and in adult males. Studies of the prepuce flora in boys known to have had urinary infection and in matched controls suggest that the focus of infection is in the preputial sac or urethra, rather than the bowel as in girls. It is suggested that the difference in infecting organisms in boys and in adult males may be related to prostatic secretion.

Summary— During a 1O-week period all mid-stream urine specimens from males aged 15 years and upwards, excluding hospital in-patients, with symptoms suggesting urinary tract infection were examined by techniques capable of detecting aerobes and fastidious organisms. Five hundred and eighty-five such specimens were received; 85% were sent by general practitioners and 182 were from men aged less than 45 years, indicating that urinary symptoms are commoner in young men than is usually believed and that diagnosis and treatment are usually undertaken by general practitioners. One hundred and seventy-nine specimens yielded aerobic pathogens and 140 yielded fastidious organisms; 70% of the former and 33% of the latter showed pyuria. Only 12% of the 196 specimens showing pyuria yielded a negative culture. The possibility of prostatic infection and its relevance to treatment are discussed. Some post-treatment data are presented.

Summary— In a 1-year laboratory-based study the validity of certain findings on microscopy and culture of mid-stream urine specimens as predictive of the presence of structural or functional abnormalities of the urinary tract was tested. During 1986, infection was diagnosed in 12,705 specimens sent to the laboratory by general practitioners; in the light of the findings a comment suggesting the possibility of underlying urinary tract pathology was appended to the reports of specimens from 652 patients. Data were available from the investigation of 233 of these patients. The percentage in whom abnormalities were detected considerably exceeded that reported from studies of bacteriuric children and of adult women with symptoms. It is suggested that the use of these criteria may assist clinicians to select, from the very large number of patients who suffer from urinary tract infection, those who require investigation.

Fifty-eight patients, three male and 55 female, with radiologically apparent renal scarring together with urinary tract infection have been followed for periods from five to 13 years. Control of urinary infection has been attempted by antibacterial treatment and prophylaxis, and radiological appearances, renal function and blood pressure have been monitored. Urinary infection was eliminated in 50 patients (86 per cent), all of whom became symptom-free. Evidence of new renal scarring was not seen, but three patients showed contraction of kidney size and three developed radio-opaque renal calculi. Vesico-ureteric reflux was demonstrated in 20 patients; surgical re-implantation of ureters was carried out in four patients and the indications for this operation are discussed. Of the 12 patients who had a raised serum creatinine at some time during the study only three showed progressive decline in renal function; the serum creatinine returned to normal in seven patients when infection was controlled. Hypertension was more common in patients with bilateral than in those with unilateral scarring, and all patients with evidence of impaired function at any time developed hypertension. We conclude that most patients with scarred kidneys and urinary infection can be rendered symptom-free by control of infection, and that there is some evidence that renal function can be preserved in this way.

Since 1971 thymine-requiring (thy - ) pathogens have been isolated from the urine of 8 patients with renal calculi, and from the sputum of 1 patient with chronic chest infection. The patients had been treated with co-trimoxazole for several months before the isolation of the mutant pathogens. There was persistent pyuria in the patients with renal calculi, and purulent sputum in the patient with chronic chest infection. The mutants were identified by their inability to grow on diagnostic sensitivity test agar (D.S.T., Oxoid) which is deficient in thymine. It was found that wild-type bacteria can produce growth factors for the metabolism of the mutants in vitro, and the urine of the patients contained thymine-like compounds. These findings indicate that thy- mutants may develop in renal calculi during co-trimoxazole therapy. Therapy should be changed to a more suitable antimicrobial as soon as possible after diagnosis of mutant infection.

Twenty-two patients in whom renal calculi and urinary infection were closely associated were studied over two to five years. Four patients had previously had stones surgically removed, and five underwent pyelolithotomy during the course of the study. Urinary infection was treated with an appropriate antibacterial agent, and treatment was followed by long-term prophylaxis, usually with cotrimoxazole. A sterile urine was maintained for long periods in all these patients. In four patients, however, apparent stone growth occurred while the urine was sterile. On entering the study 21 of the 22 patients complained of symptoms. After treatment 19 of the 20 patients who were still attending were symptom-free. Six of the 22 patients entered the study with raised levels of serum creatinine; levels fell in four and remained raised in two. This antibacterial regimen, either alone or after surgery, will usually relieve symptoms and may prevent deterioration of renal function.

In a study of the diagnosis and treatment of Corynebacterium vaginale (Hœmophilus vaginalis) vaginitis in 30 patients, clinical and microscopical findings were compared with laboratory cultures. The study also included a double-blind randomised trial of treatment regimens including placebo therapy. Laboratory cultures of C. vaginale corresponded well with clinical findings, and we suggest that C. vaginale vaginitis can be reliably diagnosed with clinical and microscopical findings. Tetracycline was effective in half the patients treated, whereas all but 1 of the 17 patients eventually treated with metronidazole were cured. The apparent discrepancy between in-vitro sensitivity and in-vitro efficacy of metronidazole in this condition is discussed.

A study was made of 20 patients fulfilling the criteria customarily used for the diagnosis of interstitial cystitis. A possible infective aetiology was sought by culture of bladder tissue, catheter and midstream specimens of urine, and urethral swabs by methods capable of detecting fastidious bacteria as well as aerobic pathogens. All bladder biopsies showed the histological appearances usually associated with interstitial cystitis, and bacteria were isolated from the catheter specimens and/or bladder biopsies of 12 patients. Eight of these isolates were fastidious bacteria, Gardnerella vaginalis (6) and Lactobacillus sp. (2). Fastidious bacteria were isolated from the midstream specimen of urine (MSU) and/or urethral swab of 6 other patients. The correlation of the histological and bacteriological findings supports the hypothesis of an infective aetiology and suggests that the so-called urethral syndrome and interstitial cystitis may be the earlier and later stages of the same disease process. The importance of early diagnosis of infection in these patients is emphasised.

82 strains of slow-growing, CO2-dependent, gram-positive organisms have been isolated from the urine of 9 male and 73 female patients. 100% of the men and 93% of the women had urinary symptoms at the time of isolation, and 66% of the specimens showed pyuria. These organisms might account for the urinary symptoms of some patients previously diagnosed as having "urethral syndrome". Preliminary data show that, if appropriate antibacterial treatment is given, most of these patients become symptom-free, and the organism can no longer be isolated from the urine.

A controlled trial of the use and interpretation of dip-inoculation slides for the diagnosis of urinary infection in four general practices is reported. Two slides were inoculated from each specimen, one being incubated and read in the surgery by the practitioner, the other being sent to the laboratory for incubation and interpretation. It is shown that the presence or absence of bacteriuria can be detected with a high degree of accuracy by a surgery procedure. The implications for the laboratory, the patient, and the practitioner are discussed. It is suggested that the financial saving on laboratory time and unnecessary treatment would far outweigh the outlay on apparatus and materials, and that many patients would benefit from the accurate diagnosis of urinary infection which, for a variety of reasons, is at present denied them.

Out of 87 patients who underwent micturating cystourethrography (M.C.U.) 14 had infection at the time of the procedure, and infection later developed in 18 patients. The occurrence of post-M.C.U. infection was significantly influenced by whether the patient was on antibacterial treatment at the time of the procedure, but not by the sex of the patient, difficulty of catheterisation, or radiological abnormality. Hence, antibacterial prophylaxis should be given, and subsequent urine culture is mandatory.

To the Editor. —The interesting article onHemophilus influenzaein urine by Gabre-Kidan et al1uncovers the tip of a fairly large iceberg. We also have isolated this organism from urine during the past five years: from three men with prostatitis and from three children with chronic pyelonephritis. These figures compare with several thousand isolations of other organisms that are not detected by overnight aerobic culture. The majority of these isolations have been from women with urethral syndrome; we have demonstrated the relevance of these organisms to this syndrome2and a search for them is now included in our routine protocol for urine culture from adult women with symptoms (see below). In addition, in a recent study of urine culture from adult men with symptoms3we isolated fastidious organisms from 140 (24%) of 585 specimens received; 179 specimens (31%) yielded conventional aerobic pathogens. We suspect that the

In a 2-month prospective study of streptococci isolated from urine specimens in the laboratory, 242 strains of catalase-negative gram-positive cocci or coccobacilli were isolated in substantial numbers from 11 725 specimens. These comprised 10% of the important isolates. Species identification of all isolates was undertaken. 74 (30%) of the isolates were of species other than Streptococcus faecalis and S agalactiae. 79 (33%) were not detected on cysteine-lactose-electrolyte-deficient agar after overnight incubation in a carbon dioxide incubator. 20 of the 24 isolates of coccobacilli were Gardnerella vaginalis. Many of the isolates of fastidious species were accompanied by pyuria. An isolation protocol practicable in busy laboratories is proposed.