ORIGINAL CONTRIBUTION pyelonephritis
T r e a t m e n t of Pyelonephritis in an Observation Unit Study objective: To determine the feasibility of managing patients with acute pyelonephritis as outpatients after initial treatment with IV antibiotics in an emergency department observation unit. Design: Prospective and uncontrolled. Setting: ED observation unit. Type of participants: Nonpregnant female patients 14 years old or older without immunocompromise or serious underlying disease and no evidence of septic shock. Interventions: All patients received two IV doses of trimethoprim/sulfam e t h o x a z o l e at a 12-hour dosing i n t e r v a l and p r o m e t h a z i n e and acetaminophen as needed for nausea and fever, respectively Baseline laboratory data, urinalysis, and urine and blood cultures were obtained. Measuremerits and main results: Patients were observed for signs of septic shock, nausea, vomiting, and the ability to tolerate an oral intake. A t the end of the observation period, 43 of 44 patients were discharged on oral trimethoprim/sulfamethoxazole. One additional patient who was doing well clinically was recalled and admitted because of a positive blood culture. Conclusion: Patients with acute pyelonephritis, despite significant fever or nausea and vomiting, can be treated effectively as outpatients after a brief period of observation and IV antibiotics. [Ward G, Jorden RC, Severance HW: Treatment of pyelonephritis in an observation unit. Ann Emerg Med March 1991;20:258-261.]
George Ward, MD Robert C Jorden, MD Harry W Severance, MD Jackson, Mississippi From the Division of Emergency Medicine, University of Mississippi, Jackson. Received for publication October 9, 1989. Revisions received May 9, and October 9, 1990. Accepted for publication October 25, 1990. Presented at the Society for Academic Emergency Medicine Annual Meeting in San Diego, May 1989. Address for reprints: George L H Ward, MD, 1257 Weathervane Lane, Apartment 3-C, Akron, Ohio 44313.
INTRODUCTION Acute pyelonephritis is an upper urinary tract infection that can result in renal damage and sepsis. The diagnosis is frequently made in the emergency department based on clinical findings that include flank pain, irritative voiding symptoms, fever, chills, nausea, and vomiting. Treatment recommendations for acute pyelonephritis vary; some recommend inpatient management for all patients, whereas others prefer outpatient therapy for selected individuals. 1,2 From cost and convenience perspectives, outpatient treatment is desirable provided it can be accomplished safely. To ensure safety, selection criteria for outpatient management have been conservative, including temperature of less than 38.8 C and absence of nausea and vomiting. Applying these conservative criteria, however, may result in the exclusion of many patients who may be appropriate for outpatient management. This study was undertaken to determine the efficacy of combining outpatient management of acute pyelonephritis with an initial course of IV antibiotics administered in the ED observation unit.
METHODS Female patients 14 years old or older who were not allergic to sulfa drugs or trimethoprim were considered for study. Inclusion criteria included flank or costovertebral angle pain or tenderness and a urinalysis demonstrating pyuria of 5 or more WBCs/high power field (hpf) and bacteria seen on an unspun specimen. Because of possible self-administration of antipyretics, temperature elevation was not an inclusion criterion. Irritative voiding symptoms, including frequency, urgency, dysuria, and nocturia,
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and other signs and symptoms, such as abdominal pain, fever, nausea, and vomiting, were documented but not considered criteria for admission into the study. Urine and blood cultures, CBC, electrolytes, blood urea nitrogen, creatinine, and glucose were obtained before treatment was begun. Patients were excluded from the study if they showed signs of sepsis or had a serious underlying disease. A systolic blood pressure of less than 90 m m Hg, a temperature of 40 C or higher, or w i t n e s s e d rigors were equated with bacteremia requiring hospitalization and thus excluded. Similarly, p a t i e n t s w i t h diabetes mellitus, sickle cell disease, cancer, renal disease, an a u t o i m m u n e disease, or any debilitating or immunosuppressive disorder who otherwise met the study criteria were excluded and hospitalized. In addition, pregnancy and advanced age were considered contraindications to outpatient therapy. Exclusion based solely on advanced age, however, was left to the discretion of the treating physician and his interpretation of the physiologic well-being of the patient. Patients meeting the inclusion criteria were admitted to the observation unit after having cultures and laboratory studies obtained. An IV line was started, and all patients received two doses of trimethoprim/ sulfamethoxazole IV at 12-hour dosing intervals. The dosage was based on the t r i m e t h o p r i m c o m p o n e n t ; each dose was approximately 4 mg/ kg. After receiving the two IV doses of trimethoprim/sulfamethoxazole, the patients were discharged from the observation unit and given a tenday course of oral trimethoprim/sulfamethoxazole provided they were tolerating an oral intake and were showing no signs of sepsis. They were advised to increase their fluid intake and to use acetarhinophen as needed for fever or pain. Patients also were instructed to return if they had worsening or persistent pain, persistent fever, or frequent vomiting. A return visit to the ED was scheduled for two weeks after discharge, and telephone follow-up was conducted during the first week of therapy. During the follow-up visit, a CBC, urinalysis, and urine culture were obtained, and the patient was examined by one of the study physicians. If patients became septic (eg, hypotension, rigors with temperature 70/259
of 40 C or higher, disorientation) while in the observation unit, they were eliminated from further study and admitted to the hospital.
RESULTS The study was conducted during the 1 2 - m o n t h p e r i o d of J a n u a r y through December 1988. During that time, 90 patients presented to the ED with a clinical diagnosis of acute py-. elonephritis. Twenty-nine of these patients did not meet study criteria and were admitted for IV antibiotic therapy. The remaining 61 patients were enrolled into the study. In eight of the 61 patients, urine cultures were either lost or not performed; these eight patients were excluded from further analysis. An additional nine patients had negative urine cultures; t h e y also were e l i m i n a t e d from further study based on the assumption that they did not have pyelonephritis. The remaining 44 patients, all of whom had positive urine cultures, constituted the study group. The mean age of these patients was 27.6 years (range, 15 to 55 years). All had flank pain and at least a l0 s colony count on culture; mean oral temperature was 38.2 C. The majority of the patients also had irritative voiding s y m p t o m s or other signs and symptoms as listed (Table). One p a t i e n t developed nausea, vomiting, and a temperature of 39.5 C while in the observation unit. She was hospitalized and treated with IV ampicillin and gentamicin. She had an uneventful hospital course and was discharged on oral ampicillin after five days of inpatient management. Her urine culture grew Esc h e r i c h i a coli, and blood cultures were negative. All except seven of the remaining 43 patients had some form of followup care; 29 returned to the ED, and seven underwent telephone followup (Figure). The patients who returned did so an average of 16 days after discharge; the t i m i n g of the visit ranged from four to 27 days. Mean oral temperature of the returning p a t i e n t s was 36.8 C, and all showed clinical improvement (Table). In 26 of the 28 returning pat i e n t s in w h o m peripheral WBC counts and urine bacteria and leukocyte counts were done, there was uniform improvement. All 26 repeat urine cultures were negative except two that grew organisms resistant to Annals of Emergency Medicine
TABLE. Signs and symptoms of culture positive patients at their initial and follow-up visits
Symptoms
Patients at Initial Visit (N = 44) No. %
Patients Seen in Follow-up (N = 29) No. %
Flank pain 44 100 10 34.5 Fever 39 88.6 0 0 ~,bdominal pain 38 86.4 3 10.3 Frequency 29 65.9 5 17.2 Nausea 27 61.4 0 0 Nocturia 26 59.1 4 13.8 Dysuria 24 54.5 3 10.3 Urgency 22 50.0 0 0 Vomiting 15 34.1 1 3.4 Mean temperature(C) 38.2(SD,0.76) 36.9 (SD, 0.37)
t r i m e t h o p r i m / sulfamethoxazole. Five of the returning patients were seen early, while they were still taking antibiotics. Initial urine cultures in the 43 patients successfully managed in the observation unit grew the following organisms: E coli (39), Proteus mirabilis (two), Klebsiella p n e u m o n i a e (one), and S t a p h y l o c o c c u s epiderm i d i s (one). One patient whose urine culture grew P mirabilis had recurrent infections and u l t i m a t e l y required admission for removal of a staghorn calculus that was not detected during the initial treatment. Two patients had positive blood cultures returned after discharge from the observation unit. One did not return for several days, at which time all her symptoms had resolved, and she was continued on oral trimethoprim/sulfamethoxazole. The other patient also showed signs of improvement but was admitted for a course of IV antibiotic therapy (trimethoprim/sulfamethoxazole). She had an uneventful recovery. No other patients who completed the observation unit treatment developed positive blood cultures. A fourth patient had persistent, s y m p t o m a t i c , culture-negative pyuria (16 to 50 WBCs/ hpf) that resolved after an additional ten-day course of trimethoprim/sulfamethoxazole. The remaining 32 patients who had some form of follow-up, including three with E coli infections resistant to trimethoprim/sul.famethoxa20:3 March 1991
PYELONEPHRITIS Ward, Jorden & Severance
FIGURE. Flowchart of patients diagnosed with acute pyelonephritis.
Clinical diagnosis of pyelonephritis (90 patients)
\
/
Did not meet study criteria and were admitted to hospital for IV antibiotics (29 patients)
Enrolled into the study (61 patients) /
Urine culture and sensitivity lost or not done (eight patients)
\ Negative urine cultures (nine patients)
Positive urine cultures; constitute study group (44 patients)
S
Becameseptic and was admitted (one patient)
No follow-up (seven patients)
Follow-up (36 patients)
/ Telephonefollow-up only (seven patients)
zole, had symptomatic improvement after treatment. Two of these patients had positive repeat urine cultures. One patient was put on oral norfloxacin, and the other received an additional ten-day course of trimethoprim/sulfamethoxazole. Each patient resolved symptoms and remained asymptomatic for six and ten months, respectively. The third patient did well clinically and had a negative repeat urinalysis and culture. DISCUSSION The management of acute pyelonephritis is controversial. At issue is the antibiotic choice, the length of treatment, and whether hospitalization and IV antibiotics are necessary. Because 25% to 34% of E coli are resistant to sulfonamides, ampicillin, and amoxicillin, recommended oral antimicrobial agents are trimethoprim, t r i m e t h ° p r i m / s u l f a m e t h ° x a zole, and cephalexin. 3 Amoxicillinclavulanic acid and the quinolones
20:3 March 1991
\ Returnedto ED (29 patients)
(norfloxacin and ciprofloxacin) are also occasionally recommended, but they are too expensive for routine use. Sobel and Kaye recommend oral antibiotics in the absence of high fever, shaking chills, or hypotension. 4 T h e y r e c o m m e n d basing e m p i r i c therapy on an initial Gram stain of the urine. For severely ill patients w i t h c o m m u n i t y - a c q u i r e d Gramnegative bacilli, these authors recommend a wide range of antimicrobials, including parenteral trimethoprim/ sulfamethoxazole, aminoglycosides, third-generation cephalosporins, and others. In this study, we reasoned that two doses of IV antibiotics would ensure good initial blood levels and allow several hours of observation to detect symptoms of bacteremia and determine the patient's ability to tolerate an oral intake. We also believed that the same drug should be used for both parenteral and oral antibiotic regimens. Furthermore, because no documentation could be found that Annals of Emergency Medicine
substantiated the benefits of one or two doses of an aminoglycoside in the management of pyelonephritis, none was given. The choice of trim e t h o p r i m / s u l f a m e t h o x a z o l e was based on a previous study documenting antibiotic sensitivities of organisms responsible for acute pyelonephritis. 1 This decision was further supported by the data of Stamm et al, who have shown less bacterial resistance against this drug than against ampicillin in the treatment of acute pyelonephritis, s The most c o m m o n recommendation for treatment is ten to 14 days of oral antibiotics with or without several days of IV antibiotics, depending on the severity of symptoms. Gleckman et al showed no advantage of 21 days compared with ten days of oral therapy after discharge from the hospital. 6 Based on these data and the absence of absolute guidelines, a tenday regimen of oral trimethoprim/ sulfamethoxazole, to begin after observation unit discharge, was chosen for the present study. Although longterm follow-up was not obtained, almost all of the patients seen in follow-up {mean, 16.6 days after treatment) had s y m p t o m a t i c improvem e n t , and o n l y t w o had r e p e a t positive urine cultures because of resistance to trimethoprim/sulfamethoxazole. The issue of hospitalization for IV antibiotic treatment of pyelonephritis has been addressed by several studies.l,2,7, s Existing data suggest that patients with signs and sympt o m s that are variably defined as mild to moderate can be treated as outpatients. Our study was undertaken to verify that hypothesis and broaden the indications for outpatient management. Specifically, patients with a temperature of more than 38.8 C were not excluded from outpatient treatment. In addition, patients w i t h nausea and v o m i t i n g were treated as candidates for outpatient therapy if they were tolerating an oral intake by the end of their observation unit stay. Our results support this approach. Of patients with a temperature of 38.8 C or higher (ten patients, 23%) and those with nausea (27, 61%) or vomiting (15, 37%), only one required hospitalization.
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A recent retrospective study comparing outpatient with inpatient m a n a g e m e n t of p y e l o n e p h r i t i s lends a d d i t i o n a l s u p p o r t to t h e f e a s i b i l i t y of o u t p a t i e n t m a n a g e m e n t . 9 T h i s s t u d y s h o w e d a 90% success rate for o u t p a t i e n t s m a n a g e d w i t h a ten- to 14-day c o u r s e of a n t i b i o t i c s (most often, trimethoprim/sulfamethoxazole). T h e s e results w e r e c o m p a r a b l e to t h o s e of t h e i n p a t i e n t group. Furthermore, there was no associated m o r b i d i t y or m o r t a l i t y in t h e outpat i e n t group. A p o t e n t i a l s h o r t c o m i n g of o u r s t u d y is t h e r e l a t i v e l y p o o r f o l l o w - u p (67% of p a t i e n t s r e t u r n e d to t h e ED). A n a l y s i s of t h e r e m a i n i n g p a t i e n t s r e v e a l e d n o s i g n i f i c a n t difference in age, s y m p t o m a t o l o g y , or p h y s i c a l findings, m a k i n g a s e l e c t i o n bias unlikely. N e v e r t h e l e s s , it is i m p o r t a n t to e m p h a s i z e t h e i m p o r t a n c e of est a b l i s h i n g close f o l l o w - u p in p a t i e n t s discharged f r o m t h e ED w i t h pyelon e p h r i t i s . R e t u r n v i s i t s s h o u l d be s c h e d u l e d at 48 h o u r s to c h e c k pat i e n t progress and t h e results of cult u r e s a n d s e n s i t i v i t i e s . In a d d i t i o n , f o l l o w - u p in a c l i n i c or w i t h a p r i v a t e p h y s i c i a n a f t e r c o m p l e t i o n of t h e c o u r s e of a n t i b i o t i c s is e s s e n t i a l to e n s u r e e r a d i c a t i o n of t h e i n f e c t i o n . P a t i e n t s w h o are u n l i k e l y to c o m p l y
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w i t h f o l l o w - u p i n s t r u c t i o n s m a y be m o r e o p t i m a l l y m a n a g e d as i n p a tients. Of i n t e r e s t is t h e fact t h a t n i n e patients who were thought to have acute pyelonephritis had negative u r i n e cultures. T h i s d i s t u r b i n g finding illustrates the difficulty in m a k i n g an a c c u r a t e c l i n i c a l diagnosis of this entity. D e s p i t e this s h o r t c o m ing, t h e c l i n i c i a n is left w i t h n o opt i o n e x c e p t to i n i t i a t e t r e a t m e n t based on c l i n i c a l a s s e s s m e n t .
CONCLUSION Forty-four patients with positive urine cultures and flank pain were treated w i t h t w o doses of IV t r i m e t h o p r i m / s u l f a m e t h o x a z o l e f o l l o w e d by a t e n - d a y c o u r s e of o r a l t r i m e t h o "prim/sulfamethoxazole. Forty-three of t h e s e p a t i e n t s did w e l l and w e r e discharged f r o m the h o s p i t a l despite a s i g n i f i c a n t p r e v a l e n c e of fever and nausea. Based on t h e s e data, w e recommend that nonpregnant women w i t h p y e l o n e p h r i t i s w h o are free of serious underlying diseases be treated as o u t p a t i e n t s w i t h t r i m e t h o prim/sulfamethoxazole. P a t i e n t s w i t h s i g n i f i c a n t f e v e r or n a u s e a can be a d m i t t e d to an ED obs e r v a t i o n u n i t for i n i t i a l IV a n t i b i o t i c
Annals of Emergency Medicine
t h e r a p y and v e r i f i c a t i o n of successful oral intake. P r o v i d e d t h e y do w e l l on this r e g i m e n , t h e y can be discharged o n a c o u r s e of oral a n t i b i o t i c s . Pat i e n t s p r e s e n t i n g w i t h l o w - g r a d e or no fever and w i t h o u t n a u s e a can be m a n a g e d s a f e l y as o u t p a t i e n t s f r o m the o u t s e t of therapy, as has b e e n reco m m e n d e d by p r e v i o u s studies.
REFERENCES
1. AbrahamE, BaraffLJ: Oral versus parenteral therapy of pyelonephritis. Curr Therap Res 1982;31:536-542. 2. RonaldAR: Current concepts in the management of urinary tract infections in adults. Med ClJn North A m 1984~68:335-349. 3. GrunBery RN: Antibiotic sensitivities of urinary pathogens, 1971-1982. J Antimicrob Chemotherap 1984;14:17-23. 4. SobeIJD, KayeD: Urinary tract infections,in Mandell GL, Douglas RG, Bennett TE(eds): Principles and Practice of Infectious Diseases, ed 3. New York, John Wiley & Sons, 1990, p 582-611. 5. Stature WE, McKevittM, Counts GW: Acute renal infection in women: Treatmentwith trimethopfim-sulfamethoxazoleor ampicillinfor two or six weeks. Ann Intern Med I987;106:341-345. 6. Gleckman R, Bradley P, Roth R, et al: Therapy of symptomatic pyelonephritis in women. J Urod 1985; 138:176-178. 7. Bailey RR: Intravenous co-trimoxazole("Bactrim") in the treatment of acutepyelonephritis.Chemotherapy 1977;23:7-10. 8. AbrahamE, BrennerED, SimonRR: Cystitisand pyelonephritis. Ann Emerg Med 1983;9~:228-234. 9. SaPrin 8, SiegelD, BlackD: Pyelonephritisin adult women: Inpatient versus outpatient therapy. A m J Med 1988;85:793-798.
20:3 March 1991
T r e a t m e n t of Pyelonephritis in an Observation Unit Study objective: To determine the feasibility of managing patients with acute pyelonephritis as outpatients after initial treatment with IV antibiotics in an emergency department observation unit. Design: Prospective and uncontrolled. Setting: ED observation unit. Type of participants: Nonpregnant female patients 14 years old or older without immunocompromise or serious underlying disease and no evidence of septic shock. Interventions: All patients received two IV doses of trimethoprim/sulfam e t h o x a z o l e at a 12-hour dosing i n t e r v a l and p r o m e t h a z i n e and acetaminophen as needed for nausea and fever, respectively Baseline laboratory data, urinalysis, and urine and blood cultures were obtained. Measuremerits and main results: Patients were observed for signs of septic shock, nausea, vomiting, and the ability to tolerate an oral intake. A t the end of the observation period, 43 of 44 patients were discharged on oral trimethoprim/sulfamethoxazole. One additional patient who was doing well clinically was recalled and admitted because of a positive blood culture. Conclusion: Patients with acute pyelonephritis, despite significant fever or nausea and vomiting, can be treated effectively as outpatients after a brief period of observation and IV antibiotics. [Ward G, Jorden RC, Severance HW: Treatment of pyelonephritis in an observation unit. Ann Emerg Med March 1991;20:258-261.]
George Ward, MD Robert C Jorden, MD Harry W Severance, MD Jackson, Mississippi From the Division of Emergency Medicine, University of Mississippi, Jackson. Received for publication October 9, 1989. Revisions received May 9, and October 9, 1990. Accepted for publication October 25, 1990. Presented at the Society for Academic Emergency Medicine Annual Meeting in San Diego, May 1989. Address for reprints: George L H Ward, MD, 1257 Weathervane Lane, Apartment 3-C, Akron, Ohio 44313.
INTRODUCTION Acute pyelonephritis is an upper urinary tract infection that can result in renal damage and sepsis. The diagnosis is frequently made in the emergency department based on clinical findings that include flank pain, irritative voiding symptoms, fever, chills, nausea, and vomiting. Treatment recommendations for acute pyelonephritis vary; some recommend inpatient management for all patients, whereas others prefer outpatient therapy for selected individuals. 1,2 From cost and convenience perspectives, outpatient treatment is desirable provided it can be accomplished safely. To ensure safety, selection criteria for outpatient management have been conservative, including temperature of less than 38.8 C and absence of nausea and vomiting. Applying these conservative criteria, however, may result in the exclusion of many patients who may be appropriate for outpatient management. This study was undertaken to determine the efficacy of combining outpatient management of acute pyelonephritis with an initial course of IV antibiotics administered in the ED observation unit.
METHODS Female patients 14 years old or older who were not allergic to sulfa drugs or trimethoprim were considered for study. Inclusion criteria included flank or costovertebral angle pain or tenderness and a urinalysis demonstrating pyuria of 5 or more WBCs/high power field (hpf) and bacteria seen on an unspun specimen. Because of possible self-administration of antipyretics, temperature elevation was not an inclusion criterion. Irritative voiding symptoms, including frequency, urgency, dysuria, and nocturia,
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and other signs and symptoms, such as abdominal pain, fever, nausea, and vomiting, were documented but not considered criteria for admission into the study. Urine and blood cultures, CBC, electrolytes, blood urea nitrogen, creatinine, and glucose were obtained before treatment was begun. Patients were excluded from the study if they showed signs of sepsis or had a serious underlying disease. A systolic blood pressure of less than 90 m m Hg, a temperature of 40 C or higher, or w i t n e s s e d rigors were equated with bacteremia requiring hospitalization and thus excluded. Similarly, p a t i e n t s w i t h diabetes mellitus, sickle cell disease, cancer, renal disease, an a u t o i m m u n e disease, or any debilitating or immunosuppressive disorder who otherwise met the study criteria were excluded and hospitalized. In addition, pregnancy and advanced age were considered contraindications to outpatient therapy. Exclusion based solely on advanced age, however, was left to the discretion of the treating physician and his interpretation of the physiologic well-being of the patient. Patients meeting the inclusion criteria were admitted to the observation unit after having cultures and laboratory studies obtained. An IV line was started, and all patients received two doses of trimethoprim/ sulfamethoxazole IV at 12-hour dosing intervals. The dosage was based on the t r i m e t h o p r i m c o m p o n e n t ; each dose was approximately 4 mg/ kg. After receiving the two IV doses of trimethoprim/sulfamethoxazole, the patients were discharged from the observation unit and given a tenday course of oral trimethoprim/sulfamethoxazole provided they were tolerating an oral intake and were showing no signs of sepsis. They were advised to increase their fluid intake and to use acetarhinophen as needed for fever or pain. Patients also were instructed to return if they had worsening or persistent pain, persistent fever, or frequent vomiting. A return visit to the ED was scheduled for two weeks after discharge, and telephone follow-up was conducted during the first week of therapy. During the follow-up visit, a CBC, urinalysis, and urine culture were obtained, and the patient was examined by one of the study physicians. If patients became septic (eg, hypotension, rigors with temperature 70/259
of 40 C or higher, disorientation) while in the observation unit, they were eliminated from further study and admitted to the hospital.
RESULTS The study was conducted during the 1 2 - m o n t h p e r i o d of J a n u a r y through December 1988. During that time, 90 patients presented to the ED with a clinical diagnosis of acute py-. elonephritis. Twenty-nine of these patients did not meet study criteria and were admitted for IV antibiotic therapy. The remaining 61 patients were enrolled into the study. In eight of the 61 patients, urine cultures were either lost or not performed; these eight patients were excluded from further analysis. An additional nine patients had negative urine cultures; t h e y also were e l i m i n a t e d from further study based on the assumption that they did not have pyelonephritis. The remaining 44 patients, all of whom had positive urine cultures, constituted the study group. The mean age of these patients was 27.6 years (range, 15 to 55 years). All had flank pain and at least a l0 s colony count on culture; mean oral temperature was 38.2 C. The majority of the patients also had irritative voiding s y m p t o m s or other signs and symptoms as listed (Table). One p a t i e n t developed nausea, vomiting, and a temperature of 39.5 C while in the observation unit. She was hospitalized and treated with IV ampicillin and gentamicin. She had an uneventful hospital course and was discharged on oral ampicillin after five days of inpatient management. Her urine culture grew Esc h e r i c h i a coli, and blood cultures were negative. All except seven of the remaining 43 patients had some form of followup care; 29 returned to the ED, and seven underwent telephone followup (Figure). The patients who returned did so an average of 16 days after discharge; the t i m i n g of the visit ranged from four to 27 days. Mean oral temperature of the returning p a t i e n t s was 36.8 C, and all showed clinical improvement (Table). In 26 of the 28 returning pat i e n t s in w h o m peripheral WBC counts and urine bacteria and leukocyte counts were done, there was uniform improvement. All 26 repeat urine cultures were negative except two that grew organisms resistant to Annals of Emergency Medicine
TABLE. Signs and symptoms of culture positive patients at their initial and follow-up visits
Symptoms
Patients at Initial Visit (N = 44) No. %
Patients Seen in Follow-up (N = 29) No. %
Flank pain 44 100 10 34.5 Fever 39 88.6 0 0 ~,bdominal pain 38 86.4 3 10.3 Frequency 29 65.9 5 17.2 Nausea 27 61.4 0 0 Nocturia 26 59.1 4 13.8 Dysuria 24 54.5 3 10.3 Urgency 22 50.0 0 0 Vomiting 15 34.1 1 3.4 Mean temperature(C) 38.2(SD,0.76) 36.9 (SD, 0.37)
t r i m e t h o p r i m / sulfamethoxazole. Five of the returning patients were seen early, while they were still taking antibiotics. Initial urine cultures in the 43 patients successfully managed in the observation unit grew the following organisms: E coli (39), Proteus mirabilis (two), Klebsiella p n e u m o n i a e (one), and S t a p h y l o c o c c u s epiderm i d i s (one). One patient whose urine culture grew P mirabilis had recurrent infections and u l t i m a t e l y required admission for removal of a staghorn calculus that was not detected during the initial treatment. Two patients had positive blood cultures returned after discharge from the observation unit. One did not return for several days, at which time all her symptoms had resolved, and she was continued on oral trimethoprim/sulfamethoxazole. The other patient also showed signs of improvement but was admitted for a course of IV antibiotic therapy (trimethoprim/sulfamethoxazole). She had an uneventful recovery. No other patients who completed the observation unit treatment developed positive blood cultures. A fourth patient had persistent, s y m p t o m a t i c , culture-negative pyuria (16 to 50 WBCs/ hpf) that resolved after an additional ten-day course of trimethoprim/sulfamethoxazole. The remaining 32 patients who had some form of follow-up, including three with E coli infections resistant to trimethoprim/sul.famethoxa20:3 March 1991
PYELONEPHRITIS Ward, Jorden & Severance
FIGURE. Flowchart of patients diagnosed with acute pyelonephritis.
Clinical diagnosis of pyelonephritis (90 patients)
\
/
Did not meet study criteria and were admitted to hospital for IV antibiotics (29 patients)
Enrolled into the study (61 patients) /
Urine culture and sensitivity lost or not done (eight patients)
\ Negative urine cultures (nine patients)
Positive urine cultures; constitute study group (44 patients)
S
Becameseptic and was admitted (one patient)
No follow-up (seven patients)
Follow-up (36 patients)
/ Telephonefollow-up only (seven patients)
zole, had symptomatic improvement after treatment. Two of these patients had positive repeat urine cultures. One patient was put on oral norfloxacin, and the other received an additional ten-day course of trimethoprim/sulfamethoxazole. Each patient resolved symptoms and remained asymptomatic for six and ten months, respectively. The third patient did well clinically and had a negative repeat urinalysis and culture. DISCUSSION The management of acute pyelonephritis is controversial. At issue is the antibiotic choice, the length of treatment, and whether hospitalization and IV antibiotics are necessary. Because 25% to 34% of E coli are resistant to sulfonamides, ampicillin, and amoxicillin, recommended oral antimicrobial agents are trimethoprim, t r i m e t h ° p r i m / s u l f a m e t h ° x a zole, and cephalexin. 3 Amoxicillinclavulanic acid and the quinolones
20:3 March 1991
\ Returnedto ED (29 patients)
(norfloxacin and ciprofloxacin) are also occasionally recommended, but they are too expensive for routine use. Sobel and Kaye recommend oral antibiotics in the absence of high fever, shaking chills, or hypotension. 4 T h e y r e c o m m e n d basing e m p i r i c therapy on an initial Gram stain of the urine. For severely ill patients w i t h c o m m u n i t y - a c q u i r e d Gramnegative bacilli, these authors recommend a wide range of antimicrobials, including parenteral trimethoprim/ sulfamethoxazole, aminoglycosides, third-generation cephalosporins, and others. In this study, we reasoned that two doses of IV antibiotics would ensure good initial blood levels and allow several hours of observation to detect symptoms of bacteremia and determine the patient's ability to tolerate an oral intake. We also believed that the same drug should be used for both parenteral and oral antibiotic regimens. Furthermore, because no documentation could be found that Annals of Emergency Medicine
substantiated the benefits of one or two doses of an aminoglycoside in the management of pyelonephritis, none was given. The choice of trim e t h o p r i m / s u l f a m e t h o x a z o l e was based on a previous study documenting antibiotic sensitivities of organisms responsible for acute pyelonephritis. 1 This decision was further supported by the data of Stamm et al, who have shown less bacterial resistance against this drug than against ampicillin in the treatment of acute pyelonephritis, s The most c o m m o n recommendation for treatment is ten to 14 days of oral antibiotics with or without several days of IV antibiotics, depending on the severity of symptoms. Gleckman et al showed no advantage of 21 days compared with ten days of oral therapy after discharge from the hospital. 6 Based on these data and the absence of absolute guidelines, a tenday regimen of oral trimethoprim/ sulfamethoxazole, to begin after observation unit discharge, was chosen for the present study. Although longterm follow-up was not obtained, almost all of the patients seen in follow-up {mean, 16.6 days after treatment) had s y m p t o m a t i c improvem e n t , and o n l y t w o had r e p e a t positive urine cultures because of resistance to trimethoprim/sulfamethoxazole. The issue of hospitalization for IV antibiotic treatment of pyelonephritis has been addressed by several studies.l,2,7, s Existing data suggest that patients with signs and sympt o m s that are variably defined as mild to moderate can be treated as outpatients. Our study was undertaken to verify that hypothesis and broaden the indications for outpatient management. Specifically, patients with a temperature of more than 38.8 C were not excluded from outpatient treatment. In addition, patients w i t h nausea and v o m i t i n g were treated as candidates for outpatient therapy if they were tolerating an oral intake by the end of their observation unit stay. Our results support this approach. Of patients with a temperature of 38.8 C or higher (ten patients, 23%) and those with nausea (27, 61%) or vomiting (15, 37%), only one required hospitalization.
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PYELONEPHRITIS Ward, Jorden & Severance
A recent retrospective study comparing outpatient with inpatient m a n a g e m e n t of p y e l o n e p h r i t i s lends a d d i t i o n a l s u p p o r t to t h e f e a s i b i l i t y of o u t p a t i e n t m a n a g e m e n t . 9 T h i s s t u d y s h o w e d a 90% success rate for o u t p a t i e n t s m a n a g e d w i t h a ten- to 14-day c o u r s e of a n t i b i o t i c s (most often, trimethoprim/sulfamethoxazole). T h e s e results w e r e c o m p a r a b l e to t h o s e of t h e i n p a t i e n t group. Furthermore, there was no associated m o r b i d i t y or m o r t a l i t y in t h e outpat i e n t group. A p o t e n t i a l s h o r t c o m i n g of o u r s t u d y is t h e r e l a t i v e l y p o o r f o l l o w - u p (67% of p a t i e n t s r e t u r n e d to t h e ED). A n a l y s i s of t h e r e m a i n i n g p a t i e n t s r e v e a l e d n o s i g n i f i c a n t difference in age, s y m p t o m a t o l o g y , or p h y s i c a l findings, m a k i n g a s e l e c t i o n bias unlikely. N e v e r t h e l e s s , it is i m p o r t a n t to e m p h a s i z e t h e i m p o r t a n c e of est a b l i s h i n g close f o l l o w - u p in p a t i e n t s discharged f r o m t h e ED w i t h pyelon e p h r i t i s . R e t u r n v i s i t s s h o u l d be s c h e d u l e d at 48 h o u r s to c h e c k pat i e n t progress and t h e results of cult u r e s a n d s e n s i t i v i t i e s . In a d d i t i o n , f o l l o w - u p in a c l i n i c or w i t h a p r i v a t e p h y s i c i a n a f t e r c o m p l e t i o n of t h e c o u r s e of a n t i b i o t i c s is e s s e n t i a l to e n s u r e e r a d i c a t i o n of t h e i n f e c t i o n . P a t i e n t s w h o are u n l i k e l y to c o m p l y
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w i t h f o l l o w - u p i n s t r u c t i o n s m a y be m o r e o p t i m a l l y m a n a g e d as i n p a tients. Of i n t e r e s t is t h e fact t h a t n i n e patients who were thought to have acute pyelonephritis had negative u r i n e cultures. T h i s d i s t u r b i n g finding illustrates the difficulty in m a k i n g an a c c u r a t e c l i n i c a l diagnosis of this entity. D e s p i t e this s h o r t c o m ing, t h e c l i n i c i a n is left w i t h n o opt i o n e x c e p t to i n i t i a t e t r e a t m e n t based on c l i n i c a l a s s e s s m e n t .
CONCLUSION Forty-four patients with positive urine cultures and flank pain were treated w i t h t w o doses of IV t r i m e t h o p r i m / s u l f a m e t h o x a z o l e f o l l o w e d by a t e n - d a y c o u r s e of o r a l t r i m e t h o "prim/sulfamethoxazole. Forty-three of t h e s e p a t i e n t s did w e l l and w e r e discharged f r o m the h o s p i t a l despite a s i g n i f i c a n t p r e v a l e n c e of fever and nausea. Based on t h e s e data, w e recommend that nonpregnant women w i t h p y e l o n e p h r i t i s w h o are free of serious underlying diseases be treated as o u t p a t i e n t s w i t h t r i m e t h o prim/sulfamethoxazole. P a t i e n t s w i t h s i g n i f i c a n t f e v e r or n a u s e a can be a d m i t t e d to an ED obs e r v a t i o n u n i t for i n i t i a l IV a n t i b i o t i c
Annals of Emergency Medicine
t h e r a p y and v e r i f i c a t i o n of successful oral intake. P r o v i d e d t h e y do w e l l on this r e g i m e n , t h e y can be discharged o n a c o u r s e of oral a n t i b i o t i c s . Pat i e n t s p r e s e n t i n g w i t h l o w - g r a d e or no fever and w i t h o u t n a u s e a can be m a n a g e d s a f e l y as o u t p a t i e n t s f r o m the o u t s e t of therapy, as has b e e n reco m m e n d e d by p r e v i o u s studies.
REFERENCES
1. AbrahamE, BaraffLJ: Oral versus parenteral therapy of pyelonephritis. Curr Therap Res 1982;31:536-542. 2. RonaldAR: Current concepts in the management of urinary tract infections in adults. Med ClJn North A m 1984~68:335-349. 3. GrunBery RN: Antibiotic sensitivities of urinary pathogens, 1971-1982. J Antimicrob Chemotherap 1984;14:17-23. 4. SobeIJD, KayeD: Urinary tract infections,in Mandell GL, Douglas RG, Bennett TE(eds): Principles and Practice of Infectious Diseases, ed 3. New York, John Wiley & Sons, 1990, p 582-611. 5. Stature WE, McKevittM, Counts GW: Acute renal infection in women: Treatmentwith trimethopfim-sulfamethoxazoleor ampicillinfor two or six weeks. Ann Intern Med I987;106:341-345. 6. Gleckman R, Bradley P, Roth R, et al: Therapy of symptomatic pyelonephritis in women. J Urod 1985; 138:176-178. 7. Bailey RR: Intravenous co-trimoxazole("Bactrim") in the treatment of acutepyelonephritis.Chemotherapy 1977;23:7-10. 8. AbrahamE, BrennerED, SimonRR: Cystitisand pyelonephritis. Ann Emerg Med 1983;9~:228-234. 9. SaPrin 8, SiegelD, BlackD: Pyelonephritisin adult women: Inpatient versus outpatient therapy. A m J Med 1988;85:793-798.
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