Fever duration in hospitalized acute pyelonephritis patients

Fever Duration in Hospitalized Pyelonephritis Patients

Acute

Marcel A. Behr, MD, MSc, Robert Drummond, MD, CM, Michael D. Libman, MD, CM, J. Scott Delaney, MD, CM, Joseph S. Dylewski, MD, CM, Montreal, Quebec, Canada

PURPOSE: To study persistence of fever in treated pyelonephritis with respect to guidelines recommending investigation and modification of therapy after 2 to 3 days of fever. PATIENTS AND METHODS: A retrospective chart review was made of 70 patients hospitalized for febrile pyelonephritis at a community hospital in Canada. RESULTS: Median duration of fever was 34 hours; persistence of fever at 48 and 72 hours was 26% and 13%, respectively. No patients had complications such as intrarenal or perirenal abscess. Prolonged fever was independently associated with increasing baseline creatinine (P = O.OOOl), younger age (P = 0.027), and increasing total leukocyte count (P = 0.026). Results of ultrasonography and intravenous urograms were not predictors

describe the frequency of prolonged fever, and whether there was an association with complications (eg, stones, abscess).

METHODS AND MATERIALS

St. Mary’s Hospital is a 400-bed, university-affiliated, community hospital serving an urban population of mixed socioeconomic status. Charts were obtained from medical records where the discharge diagnosis listed urinary tract infection as either the principle or a secondary diagnosis. All 234 charts meeting this criterion from August 1991 to July 1994 were retrospectively reviewed. The criteria for pyelonephritis were fever (temperature ~38.0”C oral), a positive urine culture (210” colony-forming units/L (cfu/L) organisms, pure growth), and the absence of another possible source of infection on chart review. of fever duration. Clinical data on admission and during hospitalizaCONCLUSION: Fever in treated pyelonephritis can tion were obtained from the chart. Data at presentation included past medical and surgical history, take 4 days to resolve, and routine urologic investigation after 2 to 3 days of fever may be such as previous urinary tract infections, pregnancy, unwarranted. Am J Med. 1996; 101:277-280. bladder catheterization, and nosocomial acquisition. Laboratory data from specimens collected within 12 cute pyelonephritis is a common medical illness hours of presentation included blood leukocyte that may require hospitalization. Approximately count (WBC) , renal function as assessedby blood 250,000 cases per year are treated in the United creatinine and urea nitrogen (BUN), and organism States and fever is present in at least 70%.*The pres- cultured. Information on duration of illness prior to admission, presence of flank pain, and urinalysis ence of fever is used both for diagnosis and to follow up treatment response. Several infectious disease were not routinely available and therefore were not textbooks3-” recommend that after 2 to 3 days of included. Data on antibiotic therapy were collected, continued fever, testing should be done to exclude although there were often several changes in the first obstruction or abscess formation (Table I). It is day between choices and doses by emergency and also common clinical practice to consider modifying ward physicians. therapy if fever persists after 72 hours of antibiotics.” Duration of fever was defined as the interval from The objective of this study was to determine the initial evaluation until the beginning of the first 12clinical course and the predictors of fever duration hour period with a maximum temperature 37.5”C in febrile patients admitted for a confirmed diagnosis (oral). Reports of radiologic investigations, such as of acute pyelonephritis. By describing the clinical abdominal x-rays, ultrasound (US), and intravenous outcome in these patients, we hoped to be able to urograms (IVP) were also recorded.

A

Data Analysis From the Departments of Medicine (MAB, MDL. JSD) and Family Medlclne (RD. JSD). St. Marv’s Hosoital. Montreal, Ouebec. Canada. Requests for reprints>should be addressed to Joseph S. Dylewski, MD, Department of MIcrobiology. St. Mary’s Hospital, 3830 Lacombe, Montreal, Quebec, H3T 1M5 tinada. Manuscript submltted December 15, 1995 and accepted in revised form May 28, 1996. I

I

‘cl996 by Excerpta All rights reserved.

Medica,

Data analysis was performed using Statistical Applications Software (SAS) . Simple univariate analysis was applied to determine descriptive statistics of the variables; for reasons of precision, fever is rounded to the nearest whole number. Bivariate analysis was employed to explore correlations be-

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277

FEVER

IN PYELONEPHRITIS

TABLE

PATlENTS/BEHR

ET AL

I Recommendations

for Investigating

Pyelonephritis

Recommendation

Mandell

Reese4

Gorbach’

X-ray Ultrasound IVP Other

On admission: all patients On admission: all patients Positive blood culture or fever CT or MRI for fever >3 days

No mention Fever >48 hours Pending ultrasound

On admission: all patients Failure to improve in 3 days Pending ultrasound

IVP = intravenous

pyelogram;

CT = computerized

tomography;

>3 days

MRI = magnetic resonance imaging.

tween two variables, and multivariate analysis was used to study the independent. contributions of variables when controlling for such correlations.

RESULTS A total of 234 charts were reviewed, and 70 patients fit the inclusion criteria. Complete data were obtained for 69 patients, with 1 subject missing creatinine and blood urea nitrogen data. The reasons for exclusion were another evident possible diagnosis on chart review (n = 13, including gastroenteritis 4, acute prostatitis 4, cellulitis 2, pneumonia 2, and pelvic inflammatory disease l), absence of fever (n = 40)) absence of positive urine culture with pure growth of > lOa cfu/L (n = 51), treatment with antibiotics prior to presentation (n = 15)) and diagnosis made at necropsy (n = 2). Twenty-one records had no record of a urinary tract infection, and were likely miscoded by medical records. A total of 22 charts had either incomplete fever charts or other elements of the medical record missing. Patient characteristics are given in Table II. Duration of fever had a mea.n time of 39 hours and a median of 34 hours. The frequency of different fever durations is shown in the Figure. After 48 hours, 18 of 70 (26%) patients were still febrile, and at 72 hours, 9 of 70 (13%) had not yet defervesced. The 95th percentile for fever duration was 92 hours. One patient, a 25-year-old catheterized male, was febrile for 225 hours with Enterococcus faecalis in his urine, and had a normal IVP but an ultrasolmd that reported “medical-renal disease.” No diagnosis other than pyelonephritis could be determined on further chart review. However, because of the effect this duration of fever would have had on further analysis (all attributes of this patient became significant, such as normal NP) , his results were then excluded from further statistical analysis. He was the only patient in the study with a permanent urinary catheter. Radiologic studies were performed in 43 patients. Results of US and IVP studies with respect to fever duration are given in Table III. For the 7 patients (16%) with obstructive urinary tract abnormality, median duration of fever was not prolonged (38 hours). No cases of intrarenal or perinephric abscess were found. 278

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TABLE

II

Clinical

and Laboratory

Variables

(n = 70 Subjects)

Variable

Value

Duration of fever (in hours) mean (SD) Age, mean (SD) Female:male Previous UTI (%I Hospital acquired (%) Catheter associated (%) Known previous renal calculi (%I Diabetes (%) Pregnant (%) WBC (x lO”/L), mean (SD) Creatinine (pMol/L), mean (SD) BUN (mMol/L), mean (SD) Organism Escherichia co/i (%) Antibiotic changed because organism resistant (%) Positive blood culture (%I Ultrasound done (%) IVP done (%I’

39 (33) 53.6 (23.3) 52:18 30/70 (42.9%) 4/:70 (5.7%) l/I70

(1.4%)

5/‘70 (7.1%) 8170

(11.4%)

3/‘70 13.7 94..2 5.3 56/70

(4.3%) (4.9) (24.7) (2.86) (80%)

8/70 24/69 42/70 6/70

134.8%) (60%) (8.6%)

(11.4%)

* Five subjects also had ultrasound. UTI = urinary tract infection; WBC = white blood cell count; BUN = blood urea nitrogen; IVP = intravenous pyelogram.

Fever Duration (h) Figure. rounded

Distribution of fever duration. to the nearest hour.

Durations

are in hours and are

Table IV shows variables significantly associated with fever duration. Bivariate associations were found with creatinine, WBC, and organism being 101

FEVER IN PYELONEPHRITIS PATIENTS/BEHR TABLE

ET AL

Ill Fever Duration and Radiologic

Radiologic Finding Overall sample US normal IVP normal US Parenchymal disease Radiologic obstruction

Findings Median Duration 34 (n 36 (n 41 (n 225 (n

Radiologic Abnormality

US hydronephrosis US and IVP renal calculi plus hydronephrosis US pyelocaliectasis IVP calculi US calculi Any obstructive abnormality US = ultrasound:

IVP = intravenous

Creatinine White blood cell count Organism Escherichia coli Gender

0.0007* 0.82 0.0085* 0.054 0.13

* P <0.05. T Becomes

from model.

significant

if E cob removed

42 (n = 30 (n = 21 In = 42 (n = 9(n= 38 (n =

2) 2) 1) 1) 1) 7)

pyelogram.

female gender (P = 0.03) or isolation of I? coli (P = 0.008) were associated with prolonged fever, but because they were closely associated (P = 0.002), when both were entered into the model, the R’ only increased by 0.02, and both became borderline for statistical significance.

TABLE IV Association of Dependent Variables with Fever Duration Bivariate Multivariate Variable P Value P Value

Age

Fever (Hours) = 70) = 35) = 3) = 1)

0.0001* 0.027* 0.026’ 0.038* 0.16+

DISCUSSION

coli. Variables of interest not; associated with fever duration included female gender, age, previous infections, previously known calculi, diabetes, pregnancy, BUN, and use or results of IVP and US. Positive blood cultures were also not associated with increased fever duration, and no patient with positive blood cultures was noted clinically to have a site of metastatic infection (0 of 24). The effect of antibiotic therapy was difficult to determine because there was no patient who received antimicrobials with no in-vitro activity. Resistance to one of the two antibiotics (usually ampicillin resistance in a patient treated with ampicillin and an aminoglycoside) occurred in only 8 patients (not significantly associated with prolonged temperature, mean increase in fever duration of only 9 hours, P = 0.27). Multivariate analysis found five variables (increased creatinine, increased WBC, decreased age, isolation of E coti, female gender) independently associated with fever duration, with an R2 for the model of 0.37 (P = 0.0001). Age, which was not associated on bivariate analysis, was negatively associated with fever duration, with a P value of 0.027, The lack of bivariate association was likely because age and creatinine were associated (R” = 0.46, P = O.OOOl), masking the effect of age on fever duration. Finally, either

Escherichia

September

In this series of 70 patients with pyelonephritis, fever usually resolved in 48 hours, but persisted as long as 4 days. Although the majority of cases had uncomplicated pyelonephritis, fever was not prolonged in the 7 cases where radiologic changes of obstruction were present. Our frequency of complicated cases is no different from three published series of radiologic findings in pyelonephritis, where obstruction occurred in 0% to 4%, and abscessin 0% to 11%of cases.‘,‘,* While radiologic studies were not performed on every patient, all cases did resolve without clinically evident complications. Complications requiring intervention appear to be infrequent events that may not warrant a routine radiologic search, although if clinical suspicion arouses concern, appropriate investigations should be performed. Only two other series in part addressed the question of fever duration. Grover et al’ assessedthe accuracy of diagnosis of pyelonephritis and diagnostic utility of certain clinical and laboratory markers. They found that of febrile patients admitted for suspected pyelonephritis, a temperature of 101°F (38.3”C) persisted in 10 of 130 (8%) after 72 hours, and the temperature remained above 100°F (37.8”C) in 21 of 130 (16%). In these 21 patients, 8 patients had uncomplicated pyelonephritis, 5 patient.s had an unstated diagnosis other than pyelonephritis, 4 were previously known to have stones or anatomic abnormalities, and in 4 patients a new diagnosis of calculi or other genitourinary abnormality was made. 1996

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There were no patients with abscesses. Thorley et al” described a series of 9 cases of perinephric abscessesand contrasted these with 37 undefined historical pyelonephritis controls. Patients with perinephric abscesshad a longer duration of illness prior to admission and much longer duration of fever (up to 10 days) after institution of therapy whereas none of the 37 patients with pyelonephritis had fever longer than 4 days. The factors associated with longer fever in the current study were creatinine, total leukocyte count, age (inversely), and isolation of E cdi or female gender. None of these associations has previously been described, and should be verified by others prior to being interpreted as having clinical relevance. Factors not associated with prolonged fever included positive blood cultures, resistance to one of the two initial antibiotics, and the results of radiologic investigations. Many other variables of interest were present too infrequently (eg, pregnancy, n = 3; diabetes, n = 8) to permit reliable analysis. The strongest positive association of fever was with initial creatinine level, but not blood urea nitrogen. In this study, the maximum value of creatinine (180 /*Mel/L, normal range 44 to 123 pMol/L) was well below the range of uremia. We postulate that higher creatinine may reflect relatively lower renal concentration of antibiotics and/or slower clearance of bacterial pyrogens. A tendency for less fever in the elderly has been previously described, lo and could explain t,he inverse relation of fever and age. The final association with fever duration was female gender or the organism being E coEi. In this study the relative effects of gender and E coti could not be untangled, because women were most likely to be infected with E coli. Possible explanations include either E coli being more virulent than other organisms and predisposing to severe infection, or a referral bias whereby males with milder infections were hospitalized but females were not. Also the fact that the 18 men in this study had a favorable outcome does not obviate the concern that urinary tract infection in men requires special attention and may require further elective investigation, especially on relapse.“,4

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The limitations of this study include the retrospective nature and the patient population. The relatively benign course and low rates of complications may not reflect the experience at centers servicing specialized populations, where the prevalence of stones, anatomic abnormalities, or neurologic defects may be higher. Nonetheless, this series does represent the largest description of the natural history of treated pyelonephritis. In summary, fever can persist up to 4 dayisin treated pyelonephritis, and routine urologic investigation and change of therapy after 2 to 3 days of fever may not be warranted. Prolonged fever may represent a normal response to appropriate therapy rather than a complicated course. With the current trend toward outpatient oral treatment of pyelonephritis, one might. expect fevers to last at least as long as with intravenous therapy. Further study with a larger number of patients (including more patients with a priori risk factlors such as pregnancy and diabetes) should describe fever duration in outpatient pyelonephritis, and address the associations found with creatinine, age, female gender, and E coli infection.

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