Pyelonephritis and related infections of the urinary tract are among the most frequently encountered, most frequently undiagnosed, and most difficult to manage of all infections. The lack of clear views of the pathogenesis, diagnosis, and treatment of infections of the urinary tract is well recognized.1-3 A few selected data indicate the magnitude of the problem.1. Pyelonephritis is the commonest disease of the kidneys at autopsy. Active pyelonephritis has been found in 10% to 20% of autopsies in several general hospitals,4-6 and healed pyelonephritis occurs about as frequently as does active pyelonephritis.6 2. Pyelonephritis has been implicated, with varying degrees of evidence, in such disorders as hypertension, chronic renal insufficiency, toxemias of pregnancy, various disturbances in electrolyte metabolism, diabetes mellitus, pregnancy, and stone formation.3. Despite the importance of this group of diseases the diagnosis of infection of the urinary tract is made in only about 20% to 30% of those who are found to have active pyelonephritis at autopsy, and the diagnosis is missed about as often in those with massive pyelonephritis as in those with minor and incidental lesions.6That the classic syndrome of fever, flank pain, dysuria, and pyuria may be absent in pyelonephritis is well known, and equally well recognized is the fact that pyelonephri¬ tis frequently occurs as a smoldering chronic infection in which the diagnosis is often overlooked until too late.7"0 It is apparent that there is a large res¬ ervoir of unrecognized infections of the urinary tract and that if the serious conse¬ quences of pyelonephritis are to be averted, early and more precise recognition of the presence of such infections is necessary. The absence of defined clinical symptomatology and the inconstancy of pyuria in chronic active pyelonephritis led to detailed studies of the bactériologie flora of the urine in re¬ lation to the diagnosis of urinary tract in¬ fections.10 Many attempts have been made in the past to distinguish between true bacteriuria, defined as actual residence of bacteria within the urine of the urinary tract, and contamination, defined as the adventitious entry of bacteria into the urine during the collection of the specimen.Most of these attempts have not received widespread acceptance because the criteria for distinguishing between contamination and bacteriuria were usually arbitrary.We have studied the problem in about 2000 persons and advance the following generalizations.(a) Urine is usually an excellent culture medium for the common pathogens of the

The interpretation of bacterial cultures of the urine has been greatly aided by the use of quantitative methods. Analysis of the bacterial colony counts of urines obtained from large numbers of patients has indicated that, except for certain defined clinical circumstances,1 a colony count greater than 100,000 per milliliter of freshly obtained urine generally indicates the presence of true bacteriuria, that is, of actual multiplication of bacteria within the urinary tract. Conversely, bacterial colony counts less than 100,000 usually represent contamination attendant upon the collection of the specimen.2,3The validity of this approach has been amply confirmed,4-6 despite some earlier and relatively minor disagreements that have since been largely resolved.7 The quantitative approach has been of value not only in defining the presence or absence of infection of the urinary tract in the usual clinical setting, but also it has provided a means for determining the presence of asymptomatic infection of the urinary tract.2,3 Per¬ haps equally important, it has provided a dimension which must be taken into account in the study of the natural history and pathogenesis of pyelonephritis.Asymptomatic bacteriuria is found with particular frequency in those population groups that are particularly likely to de¬ velop pyelonephritis (i.e., patients with diabetes mellitus, pregnancy, obstructive uropathy, past histories of instrumentation, etc.). At autopsy, active pyelonephritis is almost always accompanied by bacteriuria, although there are many instances of bac¬ teriuria without morphologic evidence of bacterial invasion of the kidneys or blad¬ der.8The available evidence, therefore, indi¬ cates a strong relationship between bac¬ teriuria and pyelonephritis. It does not, however, offer any clear view of the role of bacteriuria in the pathogenesis of pye¬ lonephritis.It is the purpose of the present report to show that asymptomatic bacteriuria during pregnancy predisposes to the development of pyelonephritis and that, when asympto¬ matic bacteriuria is eliminated by appropri¬ ate treatment, symptomatic infection of the urinary tract is averted. It will be shown further that when persistent bacteriuria is induced in the experimental animal, active pyelonephritis due to ascending infection can be produced regularly in the absence of demonstrable obstruction.The study of asymptomatic bacteriuria in pregnancy was undertaken for several rea¬ sons.Pyelonephritis occurs particularly often in women of childbearing age and is the commonest complication of pregnancy.9Chronic renal failure and hypertension are commoner in women than in men, and ob¬ servant students of the problem have point¬ ed out for years that patients with renal

PLATES 6 AND 7(Received for publication, July 29, 1963) Inhaled bacteria disappear rapidly from the lungs of experimental animals (1-3). This early clearance of bacteria is thought to be an important process in non-specific resistance to infection in the bronchopulmonary tree. Quantitative methods of study have provided a sensitive tool for detecting small as well as large changes in the efficiency of these mechanisms of resistance. A wide variety of chemical, hormonal, and environmental agents depress, :to different degrees, the rate at which inhaled cultivable bacteria disappear from the lungs (4). Such studies support epidemiologic evidence that multiple agents may be involved in the pathogenesis of chronic infections It is not clear to what extent each of the several component defense systems of the bronchopulmonary tree participates in the initial inactivation of inhaled bacteria. Although the mucociliary stream is frequently credited with this cleansing action, indirect evidence suggests that bacterial clearance may be accomplished by alveolar macrophages. In an attempt to answer this question directly, the pathway through the lung followed by inhaled bacteria was first traced by bacterial localization studies using conventional histologic and immunofluorescence methods. The latter method was used to localize bacterial antigen where the structural integrity of the organism had been destroyed. Then, radio-labeled viable bacteria were used to compare the rate at which inhaled bacteria lose their viability with the rate at which they are physically removed from lung tissue. In this way the action of bactericidal mechanisms such as phagocytosis was compared with the action of removal mechanisms such as the mucociliary stream and lymphatic drainage. The results of both studies point to the phagocytic action of macrophages as the major mechanism of early resistance to bacterial infection.

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