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Management of Urinary Infections in Infants and Children
Medical Clinics of North America - May, 1939. New York Number
CLINIC OF DR. MEREDITH F. CAMPBELL FROM THE DEPARTMENTS OF UROLOGY AND DISEASES Ol!' CHILDREN, NEW YORK UNIVERSITY COLLEGE OF MEDICINE AND BELLEVUE HOSPITAL MANAGEMENT OF URINARY INFECTIONS IN INFANTS AND CHILDREN
URINARY infection is one of the commonest diseases of childhood despite the relative infrequency with which the condition is detected. Most acute urinary infections are correctly recognized but an enormous number of subacute and chronic infections pass unnoted or are identified only when they have caused serious damage, particularly to the kidneys. Some are chance discoveries when the child is examined because of a nonurologic condition or at the time of a routine physical examination. Pathogenesis and Pathology.-From the standpoint of therapy it is comparatively unimportant whether the kidney has been infected by the hematogenous, lymphohematogenous or urogenous routes. Doubtless hematogenous infection is by far the most frequent, yet observations, in young females especially, suggest ascending infection is probably not unusual. While it is common enough to suggest the eradication of focal infections as part of the therapeutic attack on the urinary disease, this can seldom be satisfactorily accomplished in practice because of inability to detect such foci or to determine suspected foci to be etiologic. Yet such a focal etiologic relationship is undoubted in the massive renal suppurative lesions which so commonly are staphylococcal and metastatic from cutaneous infections (furuncles, boils, infected paronychiae, and other infected wounds). Urinary infections are even today loosely, inadequately, and often incorrectly designated as pyelitis. In speaking of urinary infection here, the important lesion is assumed to be renal 669
MEREDITH F. CAMPBELL
unless otherwise designated. The usual lesion is a suppurative pyelonephritis and for clarity of clinical nomenclature it would seem better to designate these conditions as acute or chronic pyuria until the anatomic diagnosis can properly be made. Often, so-called "pyelitis" is simply a vesical and lower tract infection. Although the important lesion in most non tuberculous urinary infections is an interstitial perivascular suppurative nephritis (Fig. 47), a variable anatomic pyelitis will' exist-in short, a pyelonephritis. The suppurative paren-
A
B
Fig. 47.-A, "Acute pyelitis" in a year-old child. Note the extensive perivascular interstitial suppurative process at upper left and to lesser extent in middle right. Cloudy swelling and hydropic vacuolization of the epithelial cells of the adjacent collecting tubules. By extension, leukocytes from the interstitial process pass between the epithelial cells into the lumen of the collecting tubules and appear in the urine, thus constituting the bulk of the urinary pus found in the usual renal infections. B, "Acute pyelitis" in older child. The hematogenous process is relatively extensive and the suppurative lesion involves destruction of many collecting tubules.
chymal lesion merits chief concern; the infection and inflammation of the kidney pelvis itself can largely be disregarded except as collateral mucosal edema at the pelvic outlet may interfere with urinary drainage. Because of the relatively buried site of the interstitial suppurative parenchymal lesions these bacterial invasions are fairly well protected from chemotherapeutic agents administered orally or intravenously and one can neither effectively nor safely inject antiseptic medication into the renal parenchyma by way of the pelvis. Moreover, when obstruction,
URINARY INFECTIONS IN INFANTS AND CHILDREN
67 1
neuromuscular inertia or inflammatory dilatation of the urinary tract produces urinary stasis (urinary constipation or faulty urinary drainage), chemotherapeutic assault is less likely to be effective than when these channels drain normally. Therefore, combined antiseptic and conservative instrumental attack frequently must be considered and, in a few instances, radical surgical treatment.
Fig. 48.-Extensive hydronephrosis and ureterectasis due to congenital ureterovesical junction stricture in a six months old girl urologically examined because of "chronic pyelitis" since three weeks of age. Culture of the grossly purulent urine showed Bacillus coli (Escherichia) and hemolytic streptococcus. Despite the advanced destructive uropathology and decidedly poor left renal function, the urine was sterilized by sulfanilamide-an utter impossibility with methenamine and other antiseptics which previously enjoyed wide employment. Although renal function has improved slightly following cure of the infection and conservative cystoscopic dilatation of the ureterovesical junction stricture, ureteronephrectomy will doubtless be the ultimate treatment.
So-called "pyelitis" may be clinically simulated by bacteriuria, infected hydronephrosis, pyonephrosis, hematogenous focal renal suppuration (renal carbuncle), diffuse renal suppur9-tion, perinephritis or perinephric abscess. Excepting bacteriuria, the enumerated conditions usually require special instrumental or urosurgical treatment. Symptoms.-The symptoms of acute urinary infection in children are: abrupt onset with chills, fever, nausea, vomiting,
MEREDITH F. CAMPBELL
enteric disturbances with diarrhea, distention, constipation, neurologic manifestations such as hyperirritability, lethargy, sometimes meningismus or stupor. Loin or renal pain or ten,derness will be identified in a majority of the cases. Symptoms of vesical irritability may be absent. In the chronic forms of urinary infection in the young, gastro-intestinal. disturbances with loss of weight or failure to gain are pronounced in over half. Symptoms directly referable to the urinary tract are strangely lacking in a fourth to a third of patients with chronic pyuria. As a clinical corollary: do not jail to examine the urine oj every child sick jor any cause. In acute urinary infection the clinical course is usually self-limited over a period of seven to ten days with sharp onset and gradual decline, but frequently with transient abrupt recurrences of fever and other disturbing symptoms. When the acute manifestations do not subside in five to seven days, interference with urinary drainage usually exists. Yet massive diffuse renal suppuration-either unilateral or bilateral-may be present and I have seen children with surgical perinephric abscess who had been treated too long under the diagnosis of persistent acute pyelitis. I am aware that under mandelic acid or sulfanilamide therapy many urologic infections which formerly demanded prompt instrumental or surgical relief can now be adequately treated by chemotherapy. We have all observed the miraculous improvement under sulfanilamide therapy of young patients with intense renal infection; the improvement parallels that commonly observed by the otologists in the sulfanilamide treatment of acute mastoiditis. Diagnosis.-The observation of a sick child without demonstrable extra-urinary infection should suggest urinary (renal) infection. The diagnosis is confirmed by urinalysis of a properly collected specimen in which the etiologic bacteria will be found. In most instances the urine will contain pus of variable quantity yet it is notable that bacteriuria may be practically apyuric. The demonstration of pus cysts at once signifies pyelonephritis. A variable number of red cells will also be found in acute urinary infection. At this point let me stress the importance of extreme care in collection of the specimen for examination when urinary infection is the problem. In the female of any age only a cath-
URINARY INFECTIONS IN INFANTS AND CHILDREN
673
eterized specimen is worth the effort of careful examination and certainly no specimen otherwise collected from a female should be subjected to culture. In the male, a satisfactory specimen can usually be obtained in the following manner: the prepuce is kept retracted; the glans and meatus are washed with an antiseptic solution such as mercury oxycyanide 1 :500; the patient then passes a few cubic centimeters of urine to wash out the urethra before he passes still more into a sterile receptacle or, better, into a culture tube. If this procedure cannot be satisfactorily carried out in a male, catheterization should be employed. With gentleness and the use of a soft rubber catheter (which necessitates introduction under visualization) it is inconceivable that catheterization injury should occur in any patient. Prognosis.-The importance and hazard of acute urinary infection in children is suggested by its mortality of 20 to 40 per cent among young infants, and approximately 3 per cent of older children. In children of all ages with chronic urinary infection the prognosis will depend upon the rapidity and degree of renal damage. In this estimation it is essential also to consider existent associated etiologic factors such as obstruction and other urinary stasis producing conditions. Moreover, children debilitated by either acute or chronic urinary infection fall ready prey to grave and often fatal nonurologic complications-notably pneumonia. Treatment.-Acute Urinary Infections.-Too frequently the medicine bottle receives initial consideration. In the very young with acute urinary infection, maintenance of nutrition merits first attention. The acutely ill patient should be kept in bed until the temperature has been normal for at least forty .. eight hours and if fever recurs upon the resumption of activity I the patient should again be confined to bed. There is no special diet in urinary infection. During the acute stage a reasonably high caloric diet can usually be given as milk and glucose. As the patient's condition improves the appetite will return. The administration of large amounts of glucose may be expected materially to assist in the reduction and control of the acidosis which occurs so commonly in all types of acute infection in children and the symptoms of which are apt to predominate during acute renal infection.
MEREDITH F. CAMPBELL
It is important that the alimentary tract be thoroughly cleansed. In the very young enemas usually suffice to promote intestinal elimination and reduce abdominal distention. In older children milk of magnesia or my choice-castor oilshould be given in sufficient amount adequately to evacuate the bowels. In older children I have found the employment of colonic irrigations extremely helpful in the detoxication Of the patient. These irrigations are given once or twice daily at first and are reduced as the condition improves. Although we are more interested in the large volume of fluid used than in the fecal return consequent to the colonic irrigation, the physician will usually be utterly amazed at the enormous fecal volume which appears on the third or fourth days of the irrigation treatment. The introduction of mandelic acid and of sulfanilamide therapy has almost caused the abandonment of those so-called "antiseptics" in universal use until three years ago. This relegation includes methenamine, pyridium, caprokol, acriflavine and the empiric rotation of the reaction of the urine from acid to alkaline and vice versa. Yet during the acute stage of renal infection, alkalinization of the urine by the liberal administration of sodium bicarbonate brings about striking symptomatic improvement through successful combat of the acidosis which so regularly exists; the urine, however, shows no improvement. Mandelic acid and sulfanilamide are therapeutically effective against the majority of the usual urinary tract bacterial invaders, yet each medication has its limitations and particular hazards. Many urologists and pediatricians now make sulfanilamide their initial choice but in most instances I employ mandelic acid first and if it fails fall back on sulfanilamide. There is still no urinary antiseptic which may not seriously derange the alimentary tract and for this reason we believe that in the hyperacute stage of urinary infection, medication by mouth is usually best withheld until the child is better stabilized as to alimentation, acidosis, and fluid balance (dehydration) . In most instances I wait until these factors have been controlled before administering any urinary antiseptic. Mandelic Acid.-Although the ammonium salt has been the most popular and is given as a tablet, syrup or elixir, I
URINARY INFECTIONS IN INFANTS AND CHILDREN
675
have found the calcium mandelate tablet (71/z grains, 0.5 Gm.) equally effective and better tolerated, especially by young children. The dosage, titer considenitions and bacteriologic indications for mandelic acid administration are indicated in the Tabulation. To be effective the concentration of mandelic acid in the urine must be greater than 0.5 per cent and the urinary pH 5.5 or less. Best results are obtained with a pH of 5.2 or less and a concentration 0.8 per cent or greater. As a rule the administration of the ammonium or calcium mandelate will render the urine sufficiently acid but if not, the coadministration' of ammonium chloride, ammonium nitrate, calcium chloride or dilute hydrochloric acid will usually produce the requisite acidity. The ammoniogenic proteus bacillus can seldom be eradicated by mandelic acid therapy because of the extreme difficulty in obtaining a highly acid urine. Yet this organism is usually readily vulnerable to sulfanilamide therapy which fortunately is most effective in an alkaline medium. Also, mandelic acid therapy is relatively impotent against Bacillus pyocyaneus-an infrequent urinary tract invader in the youngand which usually may be eradicated by sulfanilamide. On the other hand mandelic acid therapy is usually effective and sulfanilamide is ineffective against the enterococcus (Streptococcus faecalis) which is not uncommonly found in the infected urinary tracts of children. The excretion of mandelic acid will be hampered by serious renal disease and in patients thus afflicted the acid accumulation of the body becomes a factor of grave danger (acidosis). Moreover, mandelic acid in high concentration is likely to produce renal irritation. For these reasons the renal function should be known before SUbjecting a patient of any age to intensive mandelic acid therapy. Moreover, during the period the child is on mandelic acid therapy, alkalis (citrus fruits, sodium bicarbonate, milk of magnesia, and the like) should be prohibited. Sulfanilamide.-The dose, bacteriologic indications and conditions of its administration are indicated in the Tabulation. It is notable that sulfanilamide is most effective in an alkaline medium and for this reason sodium bicarbonate is coadministered. Moreover, the alkali is variably effective in diminish-
MEREDITH F. CAMPBELL TABULATION DATA OF IMPORTANCE IN THE SULFANILAMIDE AND MANDELIC ACID THERAPY OF URINARY INFECTIONS IN THE YOUNG
.
Sulfanilamide, grains.
Dose (in 24 hours). Average dose (per 10 pounds body weight).
Mandelic acid (ammonium or calcium salt), grams.
Under 2 years ....... 5-10 Under 2 years ........ ,2- 4 2--4 years ........... 10-20 2--4 years. . . . . . . . . . .. 4-- 6 5-8 years ........... 15-25 5-8 years ............ 5- 8 9-12 years .......... 20-25 9-12 years ........... 8-12
1.25
5
Gram negative bacilli (B. Gram negative bacilli (B. coli escherichia, B. lactici coli escherichia, B. lactici aerogenes, typhoid). aerogenes, typhoid). Staphylococcus. Bacteriologic indica- Staphylococcus. Streptococcus, hemolytic. Streptococcus, hemolytic and tions. nonhemolytic. Proteus. Enterococcus (Streptococcus faecalis). Pyocyaneus (pseudomonas). Pyocyaneus (pseudomonas). Ineffective against.
Enterococcus (Streptococcus Proteus (unless urine highly fecalis). acid).
Fluid intake.
Restrict only with great caution in children. Preferably alkaline; coad- Must be more acid than pH 5.5. minister sodium bicarbonate, or potassium citrate Mandelic acid concentration greater than 0.5 per cent. q. s.
Urine reaction.*
:ij Ammonium chloride. Calcium chloride. Ammonium nitrate. Dilute hydrochloric acid q. s.
* Best estimated by potentiometer or nitrazine solution or paper.
ing alimentary upsets consequent to the chemotherapy. In my experience a great many children cannot take sulfanilamide without disturbing enteric complications; I have just seen an alarming acute enteritis in an eight-month-old infant who received 6 grains in twenty-four hours and for only three days. The enteritis promptly disappeared following withdrawal of the drug, yet I have also seen this occur with mandelic acid therapy. Serious disturbances of the hemopoietic system do not follow the ingestion of sulfanilamide nearly as often in the young as in adults. On the other hand I have co administered
URINARY INFECTIONS IN INFANTS AND CHILDREN
677
sulfanilamide and direct blood transfusions in two young children whose initial blood study showed a rather marked anemia and in whom mandelic acid therapy had failed. Yet I am constantly anticipating a serious sulfanilamide reaction in some chiid under my care. My profound respect for the toxic properties of this drug has recently been increased by the observation of an adult patient whose normal red cell count was reduced to 1,800,000 and hemoglobin to less than 40 per cent following the administration of only 25 grains of sulfanilamide over a period of thirty-six hours. A pronounced hemolytic crisis accompanied the reaction and even after three copious transfusions, the blood count still remained far below normal. I usually give mandelic acid or sulfanilamide for seven to ten days during which time the· urine is. periodically examined. A rest of three or four days is given at the end of the therapeutic period and a check-up catheterized specimen is then taken for microscopic examination and culture. Unless sufficient time (three to four days) is allowed following discontinuance of medication, the bacteriostatic effect of unexcreted antiseptic may erroneously result in a sterile culture report. If culture reveals no organisms, another catheterized specimen is taken for culture a week or more later. No patient is discharged cured who has not had at least two negative cultures of specimens aseptically collected more than four days after cessation of drug ingestion. If this test of cure is enforced, "recurrences" of so-called "pyelitis" will be relatively few; most "recurrences" are simply exacerbations of uncured infections. If the therapeutic period has been fruitless and the bacteriologic indications are compatible, it is our practice to switch, respectively, to sulfanilamide or mandelic acid. Thus we have several times changed back and forth from the one antiseptic to the other two and three times before achieving success. Yet in such cases the therapeutic difficulty always suggests the existence of conditions causing urinary stasis. These important accessory etiologic agents are usually urographically demonstrable and such patients should be subjected to an excretory urographic study. If this investigation reveals anyabnormality, a comprehensive instrumental urologic examination should follow.
MEREDITH F. CAMPBELL
N eoarsphenamine.-This drug will be found effective in the sterilization of the urinary tract in many cases of staphylococcus infection which do not readily respond to mandelic acid or sulfanilamide. The medication is given intravenously in doses slightly less than used for the treatment of syphilis and at intervals of three or four days. If three doses are ineffective, further administration will probably be fruitless. , It has been my observation that prolonged periods of uninterrupted urinary antisepsis have no special value and may be decidedly deleterious for the child. In successful cases, urinary sterilization is usually accomplished within ten days and frequently within four or five days. Failure to cure the infection by the strenuous administration of mandelic acid or sulfanilamide within a month calls for an excretory urographic series, a determination of vesical residual urine and, if a,ny abnormality is disclosed, a complete urologic examination should be carried out. When the acute urinary infection is uninfluenced by intensive medical therapy as above outlined for a period of five to seven days, comprehensive urologic investigation is indicated. An excretory urographic study should first be made and if this is inconclusive cystoscopy, ureteral catheterization, and, if indicated, retrograde pyelography are employed. Infected hydronephrosis with obstruction at the ureterovesical junction is the usual finding in these cases of so-called "persistent acute pyelitis." Often this condition may be temporarily controlled by the indwelling ureteral catheter; subsequently the accessory etiologic lesion can more effectively be attacked. In cases of· persistent acute infection massive renal suppuration will sometimes be found, perhaps even with perirenal suppuration; here treatment is usually surgical and urgent. Chronic Urinary Infection.-This may be a prolongation of an uncured infection previously acute or may be an asymptomatic condition accidentally discovered. A copious fluid intake, the inauguration of adequate intestinal elimination, and the administration of large doses of mandelic acid or sulfanilamide constitute the initial treatment. If the renal function is considerably depressed and bacteriologic indications warrant, sulfanilamide should be given in preference to mandelic acid.
URINARY INFECTIONS IN INFANTS AND CHILDREN
679
When the renal function is essentially normal I prefer to begin with mandelic acid, giving the medication for a period of not over seven to ten days at a time as previously described under treatment of acute urinary infection. If four weeks of chemotherapy fail, we may assume important uropathology exists. Yet even if the chronic infection can be cured by these powerful antiseptics the child should pe subjected to excretory urography. This study will usually reveal a urinary stasis producing condition which requires special instrumental or urosurgical treatment. Adequate urologic investigation of children with chronic urinary infection has disclosed as accessory etiologic factors or lesions practically every urologic condition known to exist in adults. Only certain of the adult type genital tract malignancies are exempt. In a surprising number of children infravesical obstruction or neuromuscular vesical disease will be demonstrated. Urinary stones are sometimes found and in 1 in approximately every 60 children with chronic pyuria the final diagnosis will be chronic renal tuberculosis. Having established the anatomic diagnosis, treatment will be according to the etiologic indication. It is evident from this brief survey that urinary infection in a child always merits serious consideration. In young infants with acute renal infection the mortality is discouragingly high. In older children with persistent urinary infection, advanced unilateral renal injury frequently demands nephrectomy and bilateral renal injury is often irreparable and fatal. In the chemotherapy of these cases, selection of the medication will rest upon ba.cteriologic indications and the status of the renal function. Recognition of these indications and limitations has materially improved the therapy of renal infections. Yet a regularly satisfactory urinary antiseptic is still lacking. In the management of these cases the accessory etiologic factorspredominantly obstructive-must be accorded therapeutic consideration secondary only to bactericidal chemotherapy. In short, medicinal treatment alone will fail many of these acutely ill patients; the lives of some will be saved only by conservative instrumental aid and a few by radical urosurgery.
CLINIC OF DR. MEREDITH F. CAMPBELL FROM THE DEPARTMENTS OF UROLOGY AND DISEASES Ol!' CHILDREN, NEW YORK UNIVERSITY COLLEGE OF MEDICINE AND BELLEVUE HOSPITAL MANAGEMENT OF URINARY INFECTIONS IN INFANTS AND CHILDREN
URINARY infection is one of the commonest diseases of childhood despite the relative infrequency with which the condition is detected. Most acute urinary infections are correctly recognized but an enormous number of subacute and chronic infections pass unnoted or are identified only when they have caused serious damage, particularly to the kidneys. Some are chance discoveries when the child is examined because of a nonurologic condition or at the time of a routine physical examination. Pathogenesis and Pathology.-From the standpoint of therapy it is comparatively unimportant whether the kidney has been infected by the hematogenous, lymphohematogenous or urogenous routes. Doubtless hematogenous infection is by far the most frequent, yet observations, in young females especially, suggest ascending infection is probably not unusual. While it is common enough to suggest the eradication of focal infections as part of the therapeutic attack on the urinary disease, this can seldom be satisfactorily accomplished in practice because of inability to detect such foci or to determine suspected foci to be etiologic. Yet such a focal etiologic relationship is undoubted in the massive renal suppurative lesions which so commonly are staphylococcal and metastatic from cutaneous infections (furuncles, boils, infected paronychiae, and other infected wounds). Urinary infections are even today loosely, inadequately, and often incorrectly designated as pyelitis. In speaking of urinary infection here, the important lesion is assumed to be renal 669
MEREDITH F. CAMPBELL
unless otherwise designated. The usual lesion is a suppurative pyelonephritis and for clarity of clinical nomenclature it would seem better to designate these conditions as acute or chronic pyuria until the anatomic diagnosis can properly be made. Often, so-called "pyelitis" is simply a vesical and lower tract infection. Although the important lesion in most non tuberculous urinary infections is an interstitial perivascular suppurative nephritis (Fig. 47), a variable anatomic pyelitis will' exist-in short, a pyelonephritis. The suppurative paren-
A
B
Fig. 47.-A, "Acute pyelitis" in a year-old child. Note the extensive perivascular interstitial suppurative process at upper left and to lesser extent in middle right. Cloudy swelling and hydropic vacuolization of the epithelial cells of the adjacent collecting tubules. By extension, leukocytes from the interstitial process pass between the epithelial cells into the lumen of the collecting tubules and appear in the urine, thus constituting the bulk of the urinary pus found in the usual renal infections. B, "Acute pyelitis" in older child. The hematogenous process is relatively extensive and the suppurative lesion involves destruction of many collecting tubules.
chymal lesion merits chief concern; the infection and inflammation of the kidney pelvis itself can largely be disregarded except as collateral mucosal edema at the pelvic outlet may interfere with urinary drainage. Because of the relatively buried site of the interstitial suppurative parenchymal lesions these bacterial invasions are fairly well protected from chemotherapeutic agents administered orally or intravenously and one can neither effectively nor safely inject antiseptic medication into the renal parenchyma by way of the pelvis. Moreover, when obstruction,
URINARY INFECTIONS IN INFANTS AND CHILDREN
67 1
neuromuscular inertia or inflammatory dilatation of the urinary tract produces urinary stasis (urinary constipation or faulty urinary drainage), chemotherapeutic assault is less likely to be effective than when these channels drain normally. Therefore, combined antiseptic and conservative instrumental attack frequently must be considered and, in a few instances, radical surgical treatment.
Fig. 48.-Extensive hydronephrosis and ureterectasis due to congenital ureterovesical junction stricture in a six months old girl urologically examined because of "chronic pyelitis" since three weeks of age. Culture of the grossly purulent urine showed Bacillus coli (Escherichia) and hemolytic streptococcus. Despite the advanced destructive uropathology and decidedly poor left renal function, the urine was sterilized by sulfanilamide-an utter impossibility with methenamine and other antiseptics which previously enjoyed wide employment. Although renal function has improved slightly following cure of the infection and conservative cystoscopic dilatation of the ureterovesical junction stricture, ureteronephrectomy will doubtless be the ultimate treatment.
So-called "pyelitis" may be clinically simulated by bacteriuria, infected hydronephrosis, pyonephrosis, hematogenous focal renal suppuration (renal carbuncle), diffuse renal suppur9-tion, perinephritis or perinephric abscess. Excepting bacteriuria, the enumerated conditions usually require special instrumental or urosurgical treatment. Symptoms.-The symptoms of acute urinary infection in children are: abrupt onset with chills, fever, nausea, vomiting,
MEREDITH F. CAMPBELL
enteric disturbances with diarrhea, distention, constipation, neurologic manifestations such as hyperirritability, lethargy, sometimes meningismus or stupor. Loin or renal pain or ten,derness will be identified in a majority of the cases. Symptoms of vesical irritability may be absent. In the chronic forms of urinary infection in the young, gastro-intestinal. disturbances with loss of weight or failure to gain are pronounced in over half. Symptoms directly referable to the urinary tract are strangely lacking in a fourth to a third of patients with chronic pyuria. As a clinical corollary: do not jail to examine the urine oj every child sick jor any cause. In acute urinary infection the clinical course is usually self-limited over a period of seven to ten days with sharp onset and gradual decline, but frequently with transient abrupt recurrences of fever and other disturbing symptoms. When the acute manifestations do not subside in five to seven days, interference with urinary drainage usually exists. Yet massive diffuse renal suppuration-either unilateral or bilateral-may be present and I have seen children with surgical perinephric abscess who had been treated too long under the diagnosis of persistent acute pyelitis. I am aware that under mandelic acid or sulfanilamide therapy many urologic infections which formerly demanded prompt instrumental or surgical relief can now be adequately treated by chemotherapy. We have all observed the miraculous improvement under sulfanilamide therapy of young patients with intense renal infection; the improvement parallels that commonly observed by the otologists in the sulfanilamide treatment of acute mastoiditis. Diagnosis.-The observation of a sick child without demonstrable extra-urinary infection should suggest urinary (renal) infection. The diagnosis is confirmed by urinalysis of a properly collected specimen in which the etiologic bacteria will be found. In most instances the urine will contain pus of variable quantity yet it is notable that bacteriuria may be practically apyuric. The demonstration of pus cysts at once signifies pyelonephritis. A variable number of red cells will also be found in acute urinary infection. At this point let me stress the importance of extreme care in collection of the specimen for examination when urinary infection is the problem. In the female of any age only a cath-
URINARY INFECTIONS IN INFANTS AND CHILDREN
673
eterized specimen is worth the effort of careful examination and certainly no specimen otherwise collected from a female should be subjected to culture. In the male, a satisfactory specimen can usually be obtained in the following manner: the prepuce is kept retracted; the glans and meatus are washed with an antiseptic solution such as mercury oxycyanide 1 :500; the patient then passes a few cubic centimeters of urine to wash out the urethra before he passes still more into a sterile receptacle or, better, into a culture tube. If this procedure cannot be satisfactorily carried out in a male, catheterization should be employed. With gentleness and the use of a soft rubber catheter (which necessitates introduction under visualization) it is inconceivable that catheterization injury should occur in any patient. Prognosis.-The importance and hazard of acute urinary infection in children is suggested by its mortality of 20 to 40 per cent among young infants, and approximately 3 per cent of older children. In children of all ages with chronic urinary infection the prognosis will depend upon the rapidity and degree of renal damage. In this estimation it is essential also to consider existent associated etiologic factors such as obstruction and other urinary stasis producing conditions. Moreover, children debilitated by either acute or chronic urinary infection fall ready prey to grave and often fatal nonurologic complications-notably pneumonia. Treatment.-Acute Urinary Infections.-Too frequently the medicine bottle receives initial consideration. In the very young with acute urinary infection, maintenance of nutrition merits first attention. The acutely ill patient should be kept in bed until the temperature has been normal for at least forty .. eight hours and if fever recurs upon the resumption of activity I the patient should again be confined to bed. There is no special diet in urinary infection. During the acute stage a reasonably high caloric diet can usually be given as milk and glucose. As the patient's condition improves the appetite will return. The administration of large amounts of glucose may be expected materially to assist in the reduction and control of the acidosis which occurs so commonly in all types of acute infection in children and the symptoms of which are apt to predominate during acute renal infection.
MEREDITH F. CAMPBELL
It is important that the alimentary tract be thoroughly cleansed. In the very young enemas usually suffice to promote intestinal elimination and reduce abdominal distention. In older children milk of magnesia or my choice-castor oilshould be given in sufficient amount adequately to evacuate the bowels. In older children I have found the employment of colonic irrigations extremely helpful in the detoxication Of the patient. These irrigations are given once or twice daily at first and are reduced as the condition improves. Although we are more interested in the large volume of fluid used than in the fecal return consequent to the colonic irrigation, the physician will usually be utterly amazed at the enormous fecal volume which appears on the third or fourth days of the irrigation treatment. The introduction of mandelic acid and of sulfanilamide therapy has almost caused the abandonment of those so-called "antiseptics" in universal use until three years ago. This relegation includes methenamine, pyridium, caprokol, acriflavine and the empiric rotation of the reaction of the urine from acid to alkaline and vice versa. Yet during the acute stage of renal infection, alkalinization of the urine by the liberal administration of sodium bicarbonate brings about striking symptomatic improvement through successful combat of the acidosis which so regularly exists; the urine, however, shows no improvement. Mandelic acid and sulfanilamide are therapeutically effective against the majority of the usual urinary tract bacterial invaders, yet each medication has its limitations and particular hazards. Many urologists and pediatricians now make sulfanilamide their initial choice but in most instances I employ mandelic acid first and if it fails fall back on sulfanilamide. There is still no urinary antiseptic which may not seriously derange the alimentary tract and for this reason we believe that in the hyperacute stage of urinary infection, medication by mouth is usually best withheld until the child is better stabilized as to alimentation, acidosis, and fluid balance (dehydration) . In most instances I wait until these factors have been controlled before administering any urinary antiseptic. Mandelic Acid.-Although the ammonium salt has been the most popular and is given as a tablet, syrup or elixir, I
URINARY INFECTIONS IN INFANTS AND CHILDREN
675
have found the calcium mandelate tablet (71/z grains, 0.5 Gm.) equally effective and better tolerated, especially by young children. The dosage, titer considenitions and bacteriologic indications for mandelic acid administration are indicated in the Tabulation. To be effective the concentration of mandelic acid in the urine must be greater than 0.5 per cent and the urinary pH 5.5 or less. Best results are obtained with a pH of 5.2 or less and a concentration 0.8 per cent or greater. As a rule the administration of the ammonium or calcium mandelate will render the urine sufficiently acid but if not, the coadministration' of ammonium chloride, ammonium nitrate, calcium chloride or dilute hydrochloric acid will usually produce the requisite acidity. The ammoniogenic proteus bacillus can seldom be eradicated by mandelic acid therapy because of the extreme difficulty in obtaining a highly acid urine. Yet this organism is usually readily vulnerable to sulfanilamide therapy which fortunately is most effective in an alkaline medium. Also, mandelic acid therapy is relatively impotent against Bacillus pyocyaneus-an infrequent urinary tract invader in the youngand which usually may be eradicated by sulfanilamide. On the other hand mandelic acid therapy is usually effective and sulfanilamide is ineffective against the enterococcus (Streptococcus faecalis) which is not uncommonly found in the infected urinary tracts of children. The excretion of mandelic acid will be hampered by serious renal disease and in patients thus afflicted the acid accumulation of the body becomes a factor of grave danger (acidosis). Moreover, mandelic acid in high concentration is likely to produce renal irritation. For these reasons the renal function should be known before SUbjecting a patient of any age to intensive mandelic acid therapy. Moreover, during the period the child is on mandelic acid therapy, alkalis (citrus fruits, sodium bicarbonate, milk of magnesia, and the like) should be prohibited. Sulfanilamide.-The dose, bacteriologic indications and conditions of its administration are indicated in the Tabulation. It is notable that sulfanilamide is most effective in an alkaline medium and for this reason sodium bicarbonate is coadministered. Moreover, the alkali is variably effective in diminish-
MEREDITH F. CAMPBELL TABULATION DATA OF IMPORTANCE IN THE SULFANILAMIDE AND MANDELIC ACID THERAPY OF URINARY INFECTIONS IN THE YOUNG
.
Sulfanilamide, grains.
Dose (in 24 hours). Average dose (per 10 pounds body weight).
Mandelic acid (ammonium or calcium salt), grams.
Under 2 years ....... 5-10 Under 2 years ........ ,2- 4 2--4 years ........... 10-20 2--4 years. . . . . . . . . . .. 4-- 6 5-8 years ........... 15-25 5-8 years ............ 5- 8 9-12 years .......... 20-25 9-12 years ........... 8-12
1.25
5
Gram negative bacilli (B. Gram negative bacilli (B. coli escherichia, B. lactici coli escherichia, B. lactici aerogenes, typhoid). aerogenes, typhoid). Staphylococcus. Bacteriologic indica- Staphylococcus. Streptococcus, hemolytic. Streptococcus, hemolytic and tions. nonhemolytic. Proteus. Enterococcus (Streptococcus faecalis). Pyocyaneus (pseudomonas). Pyocyaneus (pseudomonas). Ineffective against.
Enterococcus (Streptococcus Proteus (unless urine highly fecalis). acid).
Fluid intake.
Restrict only with great caution in children. Preferably alkaline; coad- Must be more acid than pH 5.5. minister sodium bicarbonate, or potassium citrate Mandelic acid concentration greater than 0.5 per cent. q. s.
Urine reaction.*
:ij Ammonium chloride. Calcium chloride. Ammonium nitrate. Dilute hydrochloric acid q. s.
* Best estimated by potentiometer or nitrazine solution or paper.
ing alimentary upsets consequent to the chemotherapy. In my experience a great many children cannot take sulfanilamide without disturbing enteric complications; I have just seen an alarming acute enteritis in an eight-month-old infant who received 6 grains in twenty-four hours and for only three days. The enteritis promptly disappeared following withdrawal of the drug, yet I have also seen this occur with mandelic acid therapy. Serious disturbances of the hemopoietic system do not follow the ingestion of sulfanilamide nearly as often in the young as in adults. On the other hand I have co administered
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sulfanilamide and direct blood transfusions in two young children whose initial blood study showed a rather marked anemia and in whom mandelic acid therapy had failed. Yet I am constantly anticipating a serious sulfanilamide reaction in some chiid under my care. My profound respect for the toxic properties of this drug has recently been increased by the observation of an adult patient whose normal red cell count was reduced to 1,800,000 and hemoglobin to less than 40 per cent following the administration of only 25 grains of sulfanilamide over a period of thirty-six hours. A pronounced hemolytic crisis accompanied the reaction and even after three copious transfusions, the blood count still remained far below normal. I usually give mandelic acid or sulfanilamide for seven to ten days during which time the· urine is. periodically examined. A rest of three or four days is given at the end of the therapeutic period and a check-up catheterized specimen is then taken for microscopic examination and culture. Unless sufficient time (three to four days) is allowed following discontinuance of medication, the bacteriostatic effect of unexcreted antiseptic may erroneously result in a sterile culture report. If culture reveals no organisms, another catheterized specimen is taken for culture a week or more later. No patient is discharged cured who has not had at least two negative cultures of specimens aseptically collected more than four days after cessation of drug ingestion. If this test of cure is enforced, "recurrences" of so-called "pyelitis" will be relatively few; most "recurrences" are simply exacerbations of uncured infections. If the therapeutic period has been fruitless and the bacteriologic indications are compatible, it is our practice to switch, respectively, to sulfanilamide or mandelic acid. Thus we have several times changed back and forth from the one antiseptic to the other two and three times before achieving success. Yet in such cases the therapeutic difficulty always suggests the existence of conditions causing urinary stasis. These important accessory etiologic agents are usually urographically demonstrable and such patients should be subjected to an excretory urographic study. If this investigation reveals anyabnormality, a comprehensive instrumental urologic examination should follow.
MEREDITH F. CAMPBELL
N eoarsphenamine.-This drug will be found effective in the sterilization of the urinary tract in many cases of staphylococcus infection which do not readily respond to mandelic acid or sulfanilamide. The medication is given intravenously in doses slightly less than used for the treatment of syphilis and at intervals of three or four days. If three doses are ineffective, further administration will probably be fruitless. , It has been my observation that prolonged periods of uninterrupted urinary antisepsis have no special value and may be decidedly deleterious for the child. In successful cases, urinary sterilization is usually accomplished within ten days and frequently within four or five days. Failure to cure the infection by the strenuous administration of mandelic acid or sulfanilamide within a month calls for an excretory urographic series, a determination of vesical residual urine and, if a,ny abnormality is disclosed, a complete urologic examination should be carried out. When the acute urinary infection is uninfluenced by intensive medical therapy as above outlined for a period of five to seven days, comprehensive urologic investigation is indicated. An excretory urographic study should first be made and if this is inconclusive cystoscopy, ureteral catheterization, and, if indicated, retrograde pyelography are employed. Infected hydronephrosis with obstruction at the ureterovesical junction is the usual finding in these cases of so-called "persistent acute pyelitis." Often this condition may be temporarily controlled by the indwelling ureteral catheter; subsequently the accessory etiologic lesion can more effectively be attacked. In cases of· persistent acute infection massive renal suppuration will sometimes be found, perhaps even with perirenal suppuration; here treatment is usually surgical and urgent. Chronic Urinary Infection.-This may be a prolongation of an uncured infection previously acute or may be an asymptomatic condition accidentally discovered. A copious fluid intake, the inauguration of adequate intestinal elimination, and the administration of large doses of mandelic acid or sulfanilamide constitute the initial treatment. If the renal function is considerably depressed and bacteriologic indications warrant, sulfanilamide should be given in preference to mandelic acid.
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679
When the renal function is essentially normal I prefer to begin with mandelic acid, giving the medication for a period of not over seven to ten days at a time as previously described under treatment of acute urinary infection. If four weeks of chemotherapy fail, we may assume important uropathology exists. Yet even if the chronic infection can be cured by these powerful antiseptics the child should pe subjected to excretory urography. This study will usually reveal a urinary stasis producing condition which requires special instrumental or urosurgical treatment. Adequate urologic investigation of children with chronic urinary infection has disclosed as accessory etiologic factors or lesions practically every urologic condition known to exist in adults. Only certain of the adult type genital tract malignancies are exempt. In a surprising number of children infravesical obstruction or neuromuscular vesical disease will be demonstrated. Urinary stones are sometimes found and in 1 in approximately every 60 children with chronic pyuria the final diagnosis will be chronic renal tuberculosis. Having established the anatomic diagnosis, treatment will be according to the etiologic indication. It is evident from this brief survey that urinary infection in a child always merits serious consideration. In young infants with acute renal infection the mortality is discouragingly high. In older children with persistent urinary infection, advanced unilateral renal injury frequently demands nephrectomy and bilateral renal injury is often irreparable and fatal. In the chemotherapy of these cases, selection of the medication will rest upon ba.cteriologic indications and the status of the renal function. Recognition of these indications and limitations has materially improved the therapy of renal infections. Yet a regularly satisfactory urinary antiseptic is still lacking. In the management of these cases the accessory etiologic factorspredominantly obstructive-must be accorded therapeutic consideration secondary only to bactericidal chemotherapy. In short, medicinal treatment alone will fail many of these acutely ill patients; the lives of some will be saved only by conservative instrumental aid and a few by radical urosurgery.