125 Postgrad Med J: first published as 10.1136/pgmj.35.401.125 on 1 March 1959. Downloaded from

NON-TUBERCULOUS INFECTION OF THE URINARY TRACT RALPH SHACKMAN, M.B., B.S., F.R.C.S. Consultant Surgeon and Urologist, Hammersmith Hospital

The diagnosis of non-tuberculous infection of teriological examination of the urine, the majority the urinary tract is made by microscopic and bac- of patients in their primary attack of acute urinary teriological examinations of the urine: similar infection: the incidence of' honeymoon cystitis' examinations of the urethral discharge are made and coliform cystitis in the female is extremely when is present. Midstream specimens high. It is perfectly reasonable to manage such of urine, after careful cleansing of the prepuce and patients in this way: indeed, urological clinics external urinary meatus by an 0.05 per cent. and pathology services would probably be over- water solution of chlorhexidine in 0.5 per cent. whelmed if such was not the case. Urinalysis, cetrimide, is adequate in males. In females, although always desirable, is thus frequently however, it is traditional to obtain catheter speci- omitted without apparent untoward effects. On mens although it has been suggested recently the other hand, undue persistence or recurrent Protected by copyright. (Boshell and Sandford, 1958) that ' clean' freshly attacks of requires urologi- voided specimens compare favourably, from the cal opinion and full investigation: so also does a bacteriological aspect, with those obtained by frank haematuria. In such cases there may well catheterization. be predisposing causes which require surgical The presence of organisms in the urine in the treatment. absence of a significant number of pus cells, generally speaking, may be disregarded, for the Urological Investigation of Patients with normal commonly contains saprophytic Persistent or Recurrent Urinary Tract bacteria (Harkness, 1950): staphylococci; Str. Infection faecalis, diptheroids, Bact. coli; Str. viridans, and Apart from microscopic and bacteriological bacilli of the Proteus group have all, at times, been examinations of the urine, good-quality X-rays found to be present without evidence of urethritis are required: a straight X-ray of the whole of the (Shackman and Messent, I954). Nevertheless, it urinary tract and, provided there is no sensitivity http://pmj.bmj.com/ is pertinent to point out that 22 per cent. of to iodine and the blood urea is not greater than patients with chronic have bacteria 60 mg. per cent., excretion urograms should be but no pus cells in the urine (Jackson et al., 1958): carried out. In children, when the intravenous quantitative bacterial cultures are recommended route is impracticable, the radio-opaque contrast by these authors and bacterial counts of Ioo,ooo medium, together with hyaluronidase, may be in- per ml. of freshly voided urine are said to be sig- jected subcutaneously at the medial borders of nificant. There is generally a gross excess of the the scapulae. normal 3-4 pus cells per high-power microscopic Cystoscopic examination is usually required but on September 29, 2021 by guest. field when there is acute inflammatory disease in should be avoided in male patients who present the urinary tract but pyuria may be conspicuously with the clinical features of an acute cystitis. absent in cases of renal carbuncle, perinephric Instrumentation, despite extreme care and ex- abscess, or closed pyonephrosis, when the source perience on the part of the operator, is liable to of the infection, temporarily or 'permanently,' produce an exacerbation of the infective process: lacks a direct communication with the urinary when necessary, cystoscopic examination is better passages: it is well, however, to repeat the carried out when the patient is an in-patient and urinalysis whenever the clinical features refute under suitable chemotherapy or antibiotic cover. single negative laboratory observations. The risks of pyelonephritis and epididymitis are There can be little doubt that the family doctor minimal when such precautions are taken. rather than the consultant, sees and successfully Assessment of renal function is seldom indicated treats, without requesting microscopic and bac- in patients who present with acute urinary tract POSTGRADUATE MEDICAL JOURNAL I26 March 1959Postgrad Med J: first published as 10.1136/pgmj.35.401.125 on 1 March 1959. Downloaded from infection: it is better to wait until the acute phase normalities such as hydronephrosis, ureteric of the illness has subsided. Then the total stenosis, ureterocele, ectopia, or urethral valves glomerular function\nay be indicated by the blood predispose to pyelonephritis and are relatively urea, non-protein nitrogen, or creatinine concen- more common in male children: urinary obstruc- trations, and the total renal tubule function by tion, horseshoe , diabetes, neurogenic ab- measurement of the urine specific gravity after 24 normalities, and instrumentation are other recog- or 36 hours of fluid restriction (the fluid intake nized predisposing causes. should be limited to 500 ml. during this time). In The diagnosis of acute pyelonephritis in children certain cases, for example patients who develop may be difficult: sometimes there is little or no recurrent attacks of pyelonephritis after uretero- reference to the urinary tract and fever, rigors, or intestinal anastomosis, or patients who have had an attack of screaming are the only clinical mani- chronic retention of urine, it is advisable to festations and acute appendicitis may be closely determine the serum electrolyte values: the mimicked. Acute pyelonephritis of pregnancy, a minimal requirements are the serum bicarbonate not uncommon complication, occurs usually about and the serum potassium. In similar circumstances the fourth month and is more common on the the haemoglobin estimation may be of value for an right side. High fever, often with rigors, loin pain otherwise unexplained anaemia may be indicative and local lumbar tenderness, increased urinary of significant chronic renal disease. frequency, and dysuria, suggest the correct diag- The clinical examination of the patient should nosis but the clinical features of acute appendicitis, include the blood pressure, an examination of the torsion of an ovarian cyst, or necrobiosis of a external genitalia (including the penile urethra ureteric fibroid are, at times, all too similar. Acute and the scrotal contents), a rectal examination with pyelonephritis in adult males is usually secondary palpation of the prostate and , and, to a primary abnormality such as calculous, pelvi- when possible, a vaginal examination to exclude ureteric or and obstruction, prostatic obstruction, Protected by copyright. gross gynaecological abnormalities. may progress to a pyonephrosis: the clinical mani- Other urological investigations which are some- festations are seldom obscure but loin tenderness times indicated include ureteric catheterization, may be conspicuously absent despite a severe retrograde pyelography, retrograde cystography, degree of renal parenchymal infection. and aortography, but they are seldom or never Treatment of acute pyelonephritis includes required in the acute phase of urinary tract strict bed rest, a low-protein high-carbohydrate infection. diet, and excess bland fluids: the fluid intake should be enough to produce a daily urine output Pyelitis and Pyelonephritis of at least 3 1. Potassium citrate with hyoscyamus It is doubtful whether pyelitis, nominally in- (National Formulary) should be prescribed and it flammation of the renal pelvis, ever occurs alone is reasonable to give a sulphapreparation(videinfra) without some involvement of the renal paren- while the bacteriology report on the urine is chyma, and it is probably more accurate to use the awaited. The organisms are frequently gram term pyelonephritis if only to emphasize the negative bacilli and, especially in the uncompli- http://pmj.bmj.com/ potential risk of subsequent functional renal cated case, the response to such treatment is damage. The infection is usually haematogenous rapid: in any case, little is lost even when the (Mallory et al., 1940) although ascent of organisms infection subsequently proves to be sulpha-re- along the lumen of the or their migration sistant. Definitive drug therapy is determined through the peri-ureteric lymphatics cannot be only after full bacteriological sensitivity tests and excluded entirely: suppurative pyelonephritis is a complete urological investigation: remedial or recognized serious complication of uretero-colic ablative be

surgery may required. on September 29, 2021 by guest. anastomosis and following instrumentation in cases Acute pyelonephritis generally undergoes resti- of chronic retention of urine due to prostatic tution and subsequent renal function is ap- obstruction and it is difficult to refute the pos- parently normal: recurrent attacks, however, sibility of ascending infection in such cases. carry a significant risk of permanent renal damage. Acute pyelonephritis may develop in patients At times, the infection persists as a chronic lesion of any age. It is seen in young children, in child- and may be overlooked until renal failure or hyper- bearing women, and in adult or old men. The tension become manifest. Only rarely does death condition is more common in females and the in- follow from sepsis and renal failure early in the fection is thought to arise from the perineum: disease. there is, however, no proof that the bacterial Chronic pyelonephritis frequently differs in spread takes place along the urethra, although the degree in the two kidneys and in different parts of short, straight female urethra would appear to a single kidney: the disease mainly affects the predispose to this possibility. Congenital ab- renal tubules which become dilated, filled with March 1959 SHACKMAN: Non-Tuberculous Infection of the Urinary Tract 127 Postgrad Med J: first published as 10.1136/pgmj.35.401.125 on 1 March 1959. Downloaded from LLOYD-LUKE Practical Problems Obstetric xvi ± 712 pp. (2nd edition) by IAN DONALD 139 illustrations M.B.E., M.D.(Lond.), F.R.F.P.S.(Glas.), F.R.C.O.G. (1959) 55s. net Regius Professor of Midwifery, University of Glasgow Recent Trends in Chronic Bronchitis viii + 200pp. Edited by NEVILLE C. OSWALD 76 illustrations, M.D.(Cantab.), F.R.C.P.(Lond.) 2 colour plates Physician, St. Bartholomew's and Brompton Hospitals, London; (1958) 30s. net Honorary Physician to H.M. The Queen General Pathology xvi+ 932pp. (2nd edition) Edited by SIR HOWARD FLOREY 410 illustrations, M.D., F.R.C.P., F.R.S. 3 colour plates Professor ofPathology, University of Oxford (1958) 84s. net Fluid Balance in Surgical Practice viii 140pp. (2nd edition) by L. P. LE QUESNE 42 illustrations

D.M.(Oxon), F.R.C.S.(Eng.) (1957) 20s. net Protected by copyright. Assistant Director, Department of Surgical Studies, Middlesex Hospital

' 9 Newman Street, London, W. i thyroid-like colloid casts, cystic, or atrophic. losing nephritis' (Enticknap, 1952), dehydration, Glomerular crowding results from disappearance leg cramps, mental confusion, hypotension, and of tubules. Plasma cells and other chronic in- even Addisonian pigmentation (probably the result flammatory cells permeate the renal parenchyma of a compensatory increased production of ACTH) and there is deposition of fibrous scar tissue. Such may develop while an excessive potassium loss pathological changes, if extensive, are associated may give rise to a flaccid paresis similar to that with significant diminution of renal function and produced by an aldosterone tumour of the rise to azotemia and acidosis: abnormal adrenals. give http://pmj.bmj.com/ sodium and potassium loss may also occur. Hypertension may be a sinister sequel to Secondary hyperparathyroidism and renal dwarf- chronic pyelonephritis, not only when the kidney ism may develop. disease is bilateral-and here the treatment is Except during acute exacerbations, loin pain and clearly not surgical-but also when it is limited to tenderness are frequently absent in chronic pyelo- a single kidney. Provided there are no irreversible nephritis and the increased urinary frequency, ac- hypertensive changes in the contralateral kidney, companied by increased thirst, may be a reflection nephrectomy will cure the hypertensive disease. of inability of the renal tubules to conserve water. Unilateral chronic pyelonephritis may be suspected on September 29, 2021 by guest. General malaise and an iron-resistant anaemia may when a kidney, seen on a good-quality straight occur. A low-serum bicarbonate, frequently asso- X-ray, is abnormally small: thinning and irregu- ciated with hyperchloremia, is a biochemical mani- larity of the cortex, demonstrable by excretion festation of functional tubule deficiency: the pro- urography or retrograde pyelography is confirma- duction of ammonia and the exchange of hydrogen tory. A decreased blood flow through such a ions for sodium-important normal functions of kidney may be demonstrated by aortography or the renal tubule epithelium which help to maintain determined by divided renal function tests the body acid/base balance-are impaired and an (Graber and Shackman, 1956). Divided renal abnormal urinary loss ofbase ions occurs. Calcium function tests involve ureteric catheterization and may be excreted in excess and nephro-calcinosis measurements of para-amino hippurate or diodone and multiple calculi may develop. When an ab- clearances and are laborious. Alternative tests normal loss of sodium occurs, the so-called ' salt (Connor et al., 1957), if confirmed, might be 128 POSTGRADUATE MEDICAL JOURNAL March 1959 Postgrad Med J: first published as 10.1136/pgmj.35.401.125 on 1 March 1959. Downloaded from preferable: a unilateral decreased urine flow with lum, calculus, prostatitis, neurogenic dysfunc- a low sodium concentration is said to be significant tion, or tumour: cystostomy and, rarely, vesico- when renal arterial obstruction is present while an colic fistula may also be responsible. abnormally high sodium concentration is found Cystoscopy should be avoided, especially in when significant tubule damage exists. Renal male patients, in the acute phase of the disease: biopsy by needle puncture may be advised but the urinalysis and excretion urography are usually patchy nature of the lesion limits the clinical value adequate primary diagnostic measures. The rare of this technique: a negative finding does not condition known as Hunner's ulcer, a localized exclude disease, for the renal parenchyma may be subepithelial and sometimes muscular fibrosis with perfectly normal at the site of the biopsy while chronic inflammatory reaction is an exception to active disease may exist only a centimetre away. this general rule for the instrumentation, particu- Treatment of chronic pyelonephritis is difficult: larly when the bladder is over-distended under mechanical abnormalities associated with urine anaesthesia, preferably extra-dural, seems to offer stasis, for example calculous, hydronephrosis, and some relief and, in any case, cystoscopy is the only bladder neck obstruction, should be treated surgi- way to make the diagnosis: the urine is charac- cally when possible but there can be no guarantee teristically sterile. that pathological changes in the renal parenchyma The symptoms of cystitis are often distressing will regress inevitably as a result of such treatment. and urinary frequency is accompanied by dysuria: Acute exacerbations of the disease should be sleep is disturbed. The degree of inflammation treated by strict bed rest, an adequate fluid intake, varies and may be intense enough to cause frank a low-protein high-carbohydrate diet, and ap- haematuria and mucosal sloughing. propriate chemotherapy or antibiotic cover. Treatment consists of bed rest, adequate bland Alkalis should be given, particularly when acidosis fluids, alkalis and chemotherapy or antibiotic is present, and it is well to anticipate hypokalemia cover, and is combined with a search for an under- which may follow a prolonged diuresis in an lying cause which may require surgical treatment.Protected by copyright. anorexic patient on a low potassium intake. Hypo- When there is alkali incrustation, an indwelling kalemia aggravates the anorexia by producing Foley urethral catheter and repeated bladder mental depression: it also has a direct adverse lavage with a solution of i per cent. Milton is effect on the function of the cells of the renal often beneficial. tubules. Potassium administration, preferably by mouth, should be controlled by the measurement Choice of Drugs of the daily urine potassium output. It is possible The emergence of antibiotic-resistant staphy- that continued dosage of a suitable chemothera- lococci as a result of the universal and often hap- peutic agent, by limiting spread of infection in the hazard administration of antibiotics is now well renal parenchyma, will prove to be of help in recognized: it is a problem of the greatest mag- patients with chronic pyelonephritis: there is, nitude. It is perhaps not so well recognized that a however, no available literature on this aspect of somewhat similar situation has developed in the the problem and personal experience is too small case of infections in the urinary tract. Organisms http://pmj.bmj.com/ to quote. previously sensitive to the sulpha drugs and When overt renal failure supervenes, death streptomycin are now frequently found to be should not be expedited by over-enthusiastic fluid resistant and moreover, as a result of selection, and electrolyte therapy. A strict fluid and there is an increasing incidence of Proteus and electrolyte balance is required and biochemical Ps. pyocyanea infections in our patients: paracolon analysis of the daily urine output is the key to bacilli and Bact. aerogenes are also more common. replacement therapy: treatment should be based Dutton and Ralston (I957) have shown that on sound physiology. patients admitted to hospital with Esch. coli infec- on September 29, 2021 by guest. tions which were sensitive to chemotherapy and Cystitis antibiotic treatment contrasted strongly with those Patients with cystitis who are referred for patients who acquired urological infection in specialist opinion have usually suffered more than hospital. Urinary infections acquired outside the a single attack and it is expedient, therefore, hospital environment are likely to be drug-sensitive always to carry out urological investigations to con- and differ from infections acquired within the firm or refute the presence of a predisposing cause. hospital and which are likely to be drug-resistant. In females, acute cystitis is not uncommon as a Sensitivity tests should always be requested in the primary lesion but may be associated with urethral latter case before definitive chemotherapy or anti- narrowing: it may also follow pelvic irradiation. biotic treatment is begun but it might be reason- In males, the condition is almost always secondary able to omit this examination in patients who have to prostatic or bladder neck obstruction, diverticu- not been subjected, immediately or remotely, to March 1959 SHACKMAN: Non-Tuberculous Infection of the Urinary Tract 139 Postgrad Med J: first published as 10.1136/pgmj.35.401.125 on 1 March 1959. Downloaded from instrumentation or operation, or in patients who mandelic acid, methenamine mandelate, and the have not suffered chronic or recurrent attacks. azo-dyes, act only in the urine: and since the blood Garrod et al. (1954) surveyed the efficacy of levels are not great enough to inhibit or kill bac- some chemotherapeutic and antibiotic agents in teria when the organisms are located deep in the patients with urinary tract infections and reported tissues of the urinary tract it follows that a re- immediate cure rates (judged five days after com- currence of urinary infection is liable to develop pletion of the treatment) of 85 per cent., 82 per shortly after completion of a course of treatment cent., and 8I per cent. respectively with trisul- with these particular drugs. phonamide, sulphadimidine, and penicillin. It was noted, however, that these cure rates fell to Cross Infection in Urological Patients 34 per cent. in males and 58 per cent. in females The risk of cross infection in urological patients when there was a demonstrable abnormality- justifies comment. There is little doubt that the apart from the infection-in the urinary tract, and risk is greatest in prostatic and bladder cases that diminished cure rates also occurred when treated by suprapubic, retropubic, or transurethral there was a previous history of urinary infection methods, and when a urethral catheter or supra- without urinary tract abnormalities. pubic tube remains in situ for anylength of time: Trisulphonamide is said to carry a minimal risk in such cases the urine may be sterile on admission of crystalluria but sensitivity may develop after to hospital but the patients are discharged home absorption of any of the soluble sulphonamides with infection in the urine. Although significant and an adequate fluid intake and alkali therapy clinical effects may not be produced by this type should always be maintained throughout the of infection and the urine may become sterile again period of their administration: the development after a few months, the complication must not be of haematuria, loin pain, or oliguria should be disregarded and every attempt should be made to regarded with suspicion. The low-dose, long- prevent it: on occasion, it may lead to serious acting sulphonamide preparations, such as sulpha- secondary haemorrhage, pyelonephritis and septi- Protected by copyright. methoxypyridazine, for use both in adults and caemia (Miller et al., 1958). children, are welcome but, apart from their con- Detailed bacteriological investigation in a male venience, do not differ in their mode of action urological Ward at Hammersmith Hospital by from other sulpha preparations. Dutton and Ralston (i957) has shown that the ward Nitrofuraritoin is valuable as a broad spectrum dust and air are a permanent reservoir of bacterial antibacterial agent and is said to be effective species which infect the urinary tract and that some against many strains of Bact. coli; some have degree of contamination of the nurses' hands is claimed its value in some Proteus and some Str. more or less inevitable. The risks of cross infec- faecalis infections. Its action is inhibited when tion are, therefore, significant during catheteriza- the urine pH is 8.x and optimal when it is 5.4. tion, reconnection of a drainage tube after Mutant bacterial species resistant to nitrofurantoin detachment from a catheter or bottle, or when are, however, now appearing, and organisms such sterilization and handling of the drainage bottles are more as Ps. pyocyanea becoming common: or urinals are imperfect. Bladder irrigations are http://pmj.bmj.com/ parenteral Polymyxin B is the only effective treat- particularly dangerous and it is expedient to avoid ment for Ps. pyocyanea infections and this anti- them both before and after operation unless there is biotic has earned a reputation of nephrotoxity. significant bleeding and a risk of clot retention: a Chloramphenicol remains the best antibiotic solution of i per cent. Milton is the only fluid used generally available for the treatment of urinary in- in our service for this purpose. Whenever possible, fections although chloramphenicol-resistant or- open-drainage should be avoided and drainage ganisms may be found and there is a risk of aplasia bottles, after adequate sterilization, should have of bone marrow following its use: the risk is cotton-wool bacterial filters in their air outlets. A on September 29, 2021 by guest. minimal when treatment is limited to seven days. closed-drainage system should be used not only Chloramphenicol should never be given alone: in the prostatic and bladder cases but also, when- it should always be given with tetracyclin, strepto- ever possible, after surgery on the kidney and mycin, or a sulpha drug. In this way there is a ureter. minimal risk of development of resistant strains. Tactful education of the nursing staff and firm The sulphonamides, chloramphenicol, tetra- instruction to the junior medical staff have their cyclin, and streptomycin effect their anti-bacterial place: the ritual of post-operative inspection of activity in the blood stream and in the urine: the wounds should be minimal and conducted only blood levels are great enough to be bacteristatic or with a strict anti-cross infection routine. To turn bactericidal. They are, therefore, particularly down the bed clothes and immediately expose a valuable, in theory at least, in cases of pyeloneph- wound to the air-borne bacteria liberated from the ritis. By contrast, drugs such as nitrofurantoin, bed linen is morally, and possibly legally, wrong. 130 POSTGRADUATE MEDICAL JOURNAL March I959 Postgrad Med J: first published as 10.1136/pgmj.35.401.125 on 1 March 1959. Downloaded from Now that there is an of ENTICKNAP, J. B. (I952), Lancet, ii 458. increasing proportion GARROD, L. P., SHOOTER, R. A., and CURWEN, M. r. hospital strains of bacteria resistant to the anti- (1954), Brit. med. J., i, 1003. biotics it is paradoxical to take maximal care in the GRABER, I. G., and SHACKMAN, R. (x956), Brit. med.J.,,1321 theatre and to the risks in- HARKNESS, A. H. (x950), 'Non-gonococcal Urethritis,' pp. 20, operating disregard I57. curred by imperfections in ward techniques. JACKSON, G. G., GRIEBLE, H. G., and KNUDSEN, K. B. (1958), Y. Amer. med. Ass., x66, 14. BIBLIOGRAPHY MALLORY, G. K., CRANE, A. R., and EDWARDS, J. E. (940o), BOSHELL, B. R., and SANDFORD, J. P. (1958), Ann. intern. Arch. Path. (Chicago), 30, 330. Med., 48, Io40. MILLER, A., GILLESPIE, W. A., LINTON K. B., SLADE, N. CONNOR, T. B., BERTHRONG, M., THOMAS, W. C., and and MITCHELL, J. P. (I958), Lancet, i, 6o8. HOWARD, J. E. (I957), Bull. Johns Hopk. Hosp., zoo, z4I. SHACKMAN, R., and MESSENT, D. (x954), Brit. med. J., ii, DUTION, A. A. C., and RALSTON, M. (I957), Lancet, i, iS. oo009. Anuaema of Pregnaney It has been generally accepted that incidence of megaloblastic anaemia of pregnancy in this country is very low. Reports indicate, however, that this type of anaemia may occur more frequently than has been suspected hitherto, but remains undetected in many cases. These observations suggest that it may be advisable to administer folic acid to all women in the last trimester of pregnancy. Protected by copyright. Marmite yeast extract is a source of all known members of the vitamin B complex and has been used with .conspicuous success in the treatment of nutritional megaloblastic anaemia of pregnancy. Its haemopoietic potency may be associated with the folic or folinic acid fraction. Marmite is readily incorporated in the diet and its pleasant taste ensures easy administration. MARMITE yeast extract

contains RIBOFLAVIN (vitamin B8) 1.5 mg. per oz. NIACIN (nicotinic acid) 16.5 mg. per oz. http://pmj.bmj.com/ MARMITE LIMITED, WALSINGHAM HOUSE, SEETHING LANE, LONDON, E.C.3 5901 on September 29, 2021 by guest. NOTICE OF SPECIAL INTEREST TO SUBSCRIBERS: WHY NU T ,WHY NOT HAVE YOUR COPIES OF THIS * JOURNAL BOUND INTO YEARLY VOLUMES?'HAVE YOUR You can have your twelve monthly issues fully bound in dark green pin head doth. lettered en gilt on spine with name of Journal, Volume Number and year, complete with index at front, for 22s. 6d. post free. A limited number of out of I A Price on application giving deils of issues required to complete back volumes. URNA THE FELLOWSHIP OF POSTGRADUATE MEDICINE BOUND 60 PORTLAND PLACE. LONDON, W.I