Acute pyelonephritis in emergency medicine ward: a four years retrospective review

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1 Hong Kong Journal of Emergency Medicine Acute pyelonephritis in emergency medicine ward: a four years retrospective review TWT Chan, SK Lam, HT Fung Objective: To study the characteristics of patients with acute pyelonephritis (AP) admitted to the emergency medicine ward (EMW) and sensitivity pattern of bacteria cultured from urine as well as to find out which antibiotic should be the best empirical treatment. Methods: This was a retrospective study. All patient diagnosed with AP admitted to the EMW in Tuen Mun Hospital from January 2007 to December 2010 were included in this study. Data on patients' demographics, length of stay, urine culture and antibiotic sensitivity results as well as the types of antibiotics administered to them were collected and analysed. Results: Altogether 308 patients were admitted to the EMW during the study period, accounting for 58% of all hospital admissions with the same diagnosis. There were comparatively more female patients (p<0.001) and fewer patients with diabetes (p<0.001) admitted to the EMW compared with other departments. The mean length of stay in EMW (2.2 days) was significantly shorter than that in other departments (7.1 days) (p<0.001). E. Coli was the commonest cultured bacterium, accounting for 94% of all positive growths. Cefuroxime sodium had high sensitivity (84%) in treating AP, which was significantly higher than that of amoxicillin-clavulanate (75%) (p<0.001). Levofloxacin also had high sensitivity (86%) but the difference between cefuroxime sodium and levofloxacin was not statistically significant (p=0.67). Conclusions: Patients with AP admitted to local EMWs should be given either cefuroxime sodium intravenously or levofloxacin orally (if they can tolerate oral intake) as empirical treatments. Oral levofloxacin can be continued upon discharge. (Hong Kong j.emerg.med. 2011;18: ) % p<0.001 p< p< % Cefuroxime sodium 84% Amoxicillinclavulanate 75% p<0.001 Levofloxacin (86%) Correspondence to: Chan Wai To, Total, MB ChB (CUHK) Tuen Mun Hospital, Accident and Emergency Department, Tsing Chung Koon Road, Tuen Mun, N.T., Hong Kong totalfountain@yahoo.com.hk Lam Shing Kit, MBBS, MRCSEd Fung Hin Tat, MRCP(UK), FRCSEd, FHKAM(Emergency Medicine)

2 Chan et al./acute pyelonephritis in emergency medicine ward 301 Keywords: Antibiotics, observation, pyelonephritis, urinary tract infections Introduction Urinary tract infection is a very common condition encountered in emergency departments in Hong Kong. Acute pyelonephritis (AP) is an infection of the upper urinary tract that progressed from the lower urinary tract. 1 Classically, it is diagnosed by clinical features including fever, loin pain, nausea, vomiting and/or costovertebral angle tenderness. 2 The most common causative organism is E. Coli. 3 Antibiotic is the mainstay of the treatment for acute uncomplicated pyelonephritis. In the past, hospitalisation was the rule for patients with AP. 4 Nowadays, some patients can be discharged from the emergency department while some may need a short-stay admission. 5 For those who need hospitalisation, a lot of them can be admitted to the emergency medicine ward (EMW), which serves as a short stay unit for fluid replacement and parenteral antibiotics. 4,6 Young female patients who have stable vitals and only a low grade fever can even be discharged with a course of oral antibiotics after the urine has been saved for culture. 4,7,8 In our emergency department, most of the stable patients without obvious features of a complicated AP are often admitted to the EMW while those who have features of a complicated AP, unstable vital signs, or serious co-morbidities are usually admitted to other departments. Patients treated in the EMW may be very different from those treated by other specialties. It is therefore necessary to investigate the antibiotic sensitivity patterns of EMW patients, so that we can find evidence to guide us on managing patients with AP in local EMWs. When treating AP, empirical antibiotics with good coverage should be chosen as the urine culture may not come back until after 2 to 3 days. The choices of parenteral and oral antibiotics for our department are cefuroxime sodium (parenteral cefuroxime) and levofloxacin respectively. Admitted patients are given cefuroxime sodium intravenously 750 mg every 8 hours for 1 to 2 days and when the patient clinically improved, treatment will be switched to oral levofloxacin 500 mg daily for 10 to 14 days and the patient will be discharged. This study aims at reviewing the antibiotic sensitivity pattern in patients admitted to EMW over a 4-year period in order to understand whether the antibiotics we are using now are still the appropriate empirical treatments for AP in our locality. The characteristics of patients with AP admitted to EMW as well as the difference from those admitted to other departments were also investigated. Methods A retrospective review was conducted in patients with AP managed in an EMW in a regional hospital (Tuen Mun Hospital) in Hong Kong. The EMW has 34 beds in total and treats up to patients from 2007 to 2010 (around 9300 patients per year). There are 308 subjects, including all age of patients, admitted to our EMW for AP from January 2007 to December This represents 0.83% of all EMW admissions in that period. Urine culture results of these patients were traced and the antibiotic sensitivity pattern was analysed. The primary outcome of this study is to compare the sensitivity of different empirical

3 302 Hong Kong j. emerg. med. Vol. 18(5) Sep 2011 antibiotics commonly used in treating AP in our EMW, including amoxicillin-clavulanate, cefuroxime sodium and levofloxacin. All clinical data was retrieved by hospital electronic record database from the Clinical Data Analysis & Reporting System (CDARS), which is a computerised data retrieval system of the Hospital Authority of Hong Kong. We searched the diagnosis of AP (ICD 9 coding 590.1) under the categories of any diagnoses. All patients admitted between the period January 2007 and December 2010 were included. The Statistical Package for Social Sciences (SPSS) version 19.0 for Windows was used for analysis. Descriptive statistics were used to summarise patient demographics data. The Student's t-test was used to compare continuous variables between the two groups, while the Chi square test was used to compare categorical variables. A p-value of less than 0.05 was considered statistically significant. During the analysis, when the susceptibility is graded as 'intermediate' or 'resistant', it was not regarded as 'sensitive'. The susceptibilities of ESBLpositive bacteria to beta-lactams were not reported by the laboratory, and the beta-lactams to these bacteria were also not regarded as 'sensitive'. Results During the period, 531 patients were admitted to our hospital for AP, 308 (58%) of which were managed in EMW. The demographics of the patients are as shown in Table 1. Most of the admitted patients were females. There were proportionally more female in those admitted to EMW than those admitted to other departments, accounting for 92% and 78% respectively (p<0.001). Patients admitted to EMW had their age ranging from 15 to 87 years (mean=40.8, SD=15.9) and were relatively younger than those admitted to other departments, aged ranging from 9 to 91 years (mean=44.5, SD=19.8) (p=0.018). There were also proportionally more patients with diabetes in those admitted to other departments (15.7%) than in those admitted to the EMW (2.6%) (p<0.001). The mean length of stay in EMW was 2.2 days (SD=1.5) and was significantly shorter than the mean length of stay in other departments, which was 7.1 days (SD=9.5) (p<0.001). The various bacteria cultured from the urine of the studied subjects as well as their susceptibility to different antibiotics were shown in Table 2. Among all Table 1. Characteristics of patients admitted for acute pyelonephritis EMW Other p-value (n=308) departments (n=223) Female gender (%) 283 (91.9) 174 (78.0) <0.001* Mean age (SD) 40.8 (15.9) 44.5 (19.8) Mean length of stay, 2.2 (1.5) 7.1 (9.5) <0.001 days (SD) Diabetes (%) 8 (2.6) 35 (15.7) <0.001* EMW=emergency medicine ward *Chi square test; Student's t-test Table 2. Bacteria cultured and their susceptibility to different antibiotics Total no. Amoxicillin-clavulanate, n(%) Cefuroxime sodium, n(%) Levofloxacin, n(%) E. Coli (76) 155 (86) 157 (87) Klebsiella 5 4 (80) 3 (60) 5 (100) Proteus 4 4 (100) 4 (100) 3 (75) Enterococcus 2 1 (50) 0 (0) 0 (0) Enterobacter 1 0 (0) 0 (0) 1 (100) Staph. areus 1 1 (100) 1 (100) 1 (100) Staph. saprophyticus 1 Unknown* Unknown* Unknown* Non-haemolytic Strep. 1 1 (100) 1 (100) 0 (0) *sensitivity test not done

4 Chan et al./acute pyelonephritis in emergency medicine ward 303 the patients admitted to EMW, 302 (98%) had urine culture saved of which 191 (62%) had positive growth. Four patients had significant growth of two independent pathogens. E. Coli was the commonest bacteria and accounted for 180 (94%) of all positive cultures. Other bacteria involved, in descending order, included Klebsiella, Proteus, Enterococcus, Enterobacter, Staphlococcus and Streptococcus species. There were 22 (12%) cases with bacteria being ESBL-positive. The sensitivity patterns of commonly used antibiotics including amoxicillin-clavulanate, cefuroxime sodium and levofloxacin to different bacteria are included in Table 2. Most of the bacteria showed high susceptibility to the three drugs. For E. Coli, the commonest pathogen, both cefuroxime sodium and levofloxacin showed high sensitivity. As some subjects had growth of more than one pathogen, the sensitivity patterns of the three antibiotics on all pathogens from urine culture of the same subject were combined for analysis. The antibiotic is regarded as 'sensitive' only if it is 'sensitive' to all the pathogens cultured from the subject. The results are shown in Table 3. The number of subjects with the cultured bacteria being susceptible to amoxicillin-clavulanate, cefuroxime sodium and levofloxacin were 144 (75%), 160 (84%) and 164 (86%) respectively. Cefuroxime sodium had a higher sensitivity than amoxicillin-clavulanate for treating subjects with AP, with a difference of 9% (p<0.001). On the other hand, the sensitivity to cefuroxime sodium and levofloxacin were similar and their difference was not statistically significant (p=0.67). Table 3. No. of patients with cultured bacteria being sensitive to different antibiotics Sensitivity p-value (n=191) (compared with patient (%) cefuroxime sodium) Cefuroxime sodium 160 (84) Amoxicillin-clavulanate 144 (75) p<0.001* Levofloxacin 164 (86) p=0.67* *Chi square test Almost all patients admitted to the EMW for AP during the study period were given cefuroxime sodium followed by oral levofloxacin as the empirical treatment, and the majority showed clinical improvement promptly. In 24 patients, there was a lack of improvement within 1 to 2 days and the empirical antibiotic was switched to ceftriaxone disodium. However, even in most of these cases, the urine culture and sensitivity results ultimately showed that cefuroxime sodium and levofloxacin were sensitive to the bacteria cultured. Finally, all of the patients admitted to the EMW were treated successfully and discharged uneventfully. Discussion AP is a common infection that predominately occurs in women. 1 It is the infection of the renal parenchyma, usually ascending from the lower urinary tract. The most common bacteria involved is E. Coli, being documented as a cause in 82% of women and 73% of men, 9 and in 92% of subjects in our study. AP can be classified as complicated or uncomplicated. A complicated AP is considered if there is suspected functional or anatomic abnormality of the urinary tract. 1 An uncomplicated AP is diagnosed if caused by a typical pathogen in a person who has normal renal anatomy and renal function. 10 Uncomplicated ones account for most cases of AP, and the majority of cases in this study were also uncomplicated infections. In the past, AP required hospitalisation for a long duration of intravenous antibiotics. 4 Nowadays, a lot of patients can be managed on an outpatient basis. A female patient with only low grade fever, stable vitals and without nausea and vomiting can be discharged from the emergency department with a course of oral antibiotics for 2 weeks. If the patient requires parenteral antibiotics, it is recommended that they can be admitted to a hour observation unit. 4 The EMW in this case can offer a good place for monitoring and administration of intravenous antibiotics and patients can be discharged with oral antibiotics when they can tolerate oral intake and when their condition improve. 6 It was shown that this kind of observation unit reduced the number of admissions of AP to other inpatient units. 11

5 304 Hong Kong j. emerg. med. Vol. 18(5) Sep 2011 In this study, more than half of patients with AP were admitted to the EMW. Patients were admitted to EMW if they had stable vitals, did not have other comorbidities and did not have features suggesting a complicated AP. The disposition was based on clinical decisions individually. From our data, there was a tendency that more male patients were admitted to other departments other than the EMW. This is as expected because male sex would increase the clinicians' suspicion of a complicated AP. There were also more diabetic patients being admitted to other departments than to the EMW. This was probably because diabetic patients were considered to be immunocompromised. Moreover, some of them might have been admitted to other departments for poor glycemic control or other co-morbidities. Concerning local data on antibiotic sensitivity in treating urinary tract infection, there was a recent study by Ho et al on simple cystitis, 12 but there was no published data on AP. According to this study, E. Coli was also the commonest cultured bacteria and accounted for 77% of the pathogens. The sensitivity of amoxicillin-clavulanate, cefuroxime sodium and cipofloxacin to E. Coli were 84.9%, 88.2% and 87.1% respectively. There was no data on levofloxacin. The overall sensitivity of different antibiotics in that study was a bit higher than that of our study, but similarly cefuroxime sodium had a higher sensitivity than amoxicillin-clavulanate. According to the IDSA guidelines, 4 fluroquinolones were recommended as the oral empirical antibiotic of choice. For intravenous antibiotics, recommended choices included fluoroquinolones, extended-spectrum cephalosporins or aminoglycosides. However, local guideline (IMPACT) 13 recommended either amoxicillin-clavulanate, ampicillin-sulbactam or fluroquinolones as the initial therapies. According to our study, cefuroxime sodium seems to be a better empirical antibiotic when compared with amoxicillinclavulanate, as it has a significant higher sensitivity. Moreover, the majority of patient in the EMW received cefuroxime sodium as the empirical treatment and most of them showed prompt improvement and were discharged in a short period uneventfully. Although cefuroxime sodium is effective in treating AP, oral cefuroxine (cefuroxine axetil) is not commonly used as a treatment for AP as it has low oral-bioavailability. 14 In contrast, levofloxacin is not only an effective agent, but it also has high oral-bioavailability. An ideal empirical antibiotic should not only have a high sensitivity to pathogens but should also be costeffective. Treatment costs of the patients could be determined by referring to the latest drug formulary of our hospital. The cost of intravenous cefuroxine sodium 750 mg is $4.99. For amoxicillin-clavulanate, 1.2 g of the inraveous form costs $13.3 and 375 mg of the oral form costs $0.94. For levofloxacin, 500 mg of the intravenous form costs $ while the same dose of the oral form costs only $ The total treatment costs can be compared by classifying the treatment into 3 different regimes. Regime A is that a patient is given intravenous cefuroxime sodium 750 mg 3 times daily for 2 days and then prescribed oral levofloxacin 500 mg daily for 14 days. Regime B is that a patient is given intravenous amoxicillinclavulanate 1.2 g 3 times daily for 2 days followed by oral amoxicillin-clavulanate 375 mg 3 times daily for 14 days. Regime C is that the patient is only given levofloxacin 500 mg daily for 14 days. The total costs of treatment regime A, B and C are $96.3, $ and $66.36 respectively. Therefore, if the patient is stable and can tolerate oral intake, oral levofloxacin is the cheapest empirical antibiotic to prescribe. If an intravenous antibiotic is needed as an initial therapy, the regime of cefuroxime sodium followed by oral levofloxacin is more cost effective than intravenous amoxicillin-clavulanate followed by its oral form. Although intravenous levofloxacin can be an effective treatment as well, it is usually not chosen as it is not more effective than cefuroxime sodium but is much more expensive. Undoubtedly, safety of the drugs and their potential of producing resistant strains should also be considered. Adverse reactions to cefuroxime sodium are generally mild and transient. For levofloxacin, although adverse effects may occur, clinically significant ones are relatively rare. 16 Levofloxacin belongs to the fluoroquinolone group. It is also known that frequent

6 Chan et al./acute pyelonephritis in emergency medicine ward 305 use of fluoroquinolones can aggravate the development of resistance easily because of the stepwise mutation of antibiotic target site. 12 However, the emergence of resistance can be reduced by limiting the use of fluoroquinolones to upper tract infections only. There is no reason to withhold levofloxacin in treating AP, as it is more effective than other oral antibiotics. Although there are guidelines on management of AP in our locality, there has been no much published local data on antibiotic sensitivity results of AP. There was also no previous data on AP being managed in our local EMWs. This study may therefore help us in choosing the appropriate empirical antibiotics in patients with AP being admitted to the EMW. Limitations Our study is not without limitations. Firstly, it is a retrospective study only and some cases of AP can be missed if the diagnostic code was not correctly entered. This can also happen if some patients (especially elderly) were admitted to other departments for fever which resolves after receiving empirical antibiotics before the diagnosis of AP was made. For this reason, some cases of AP may be missed. Secondly, we found that urine culture was not saved for a few subjects admitted to the EMW, thus giving rise to incomplete data. However, the number of such subjects was small and the effect should be minimal. Finally, our study only showed the in-vitro sensitivity results, which may not reflect the clinical efficacy of different antibiotics in practice. Some antibiotics with 'intermediate' sensitivity results may still be able to control the infection provided that the dose of antibiotic is high enough and that the organ infected remains wellperfused. 17 However, as there has been no previous data regarding the clinical response of different antibiotics on AP in our locality, we have to rely on in-vitro sensitivity results for our choice of empirical treatments. Conclusion Patients with uncomplicated AP requiring hospitalisation can be managed successfully in the EMW. Compared with amoxicillin-clavulanate, cefuroxime sodium and levofloxacin are more effective empirical antibiotics. If a parenteral empirical antibiotic is required, cefuroxime sodium remains the best option in our locality. If the patient can tolerate oral treatments, levofloxacin is the appropriate antibiotic of choice. References 1. Stamm WE, Hooton TM, Johnson JR, Johnson C, Stapleton A, Roberts PL, et al. Urinary tract infections: from pathogenesis to treatment. J Infect Dis 1989;159 (3): Ramakrishnan K, Scheid DC. Diagnosis and management of acute pyelonephritis in adults. Am Fam Physician 2005;71(5): Stamm WE, Hooton TM. Management of urinary tract infections in adults. N Engl J Med 1993;329(18): Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer AJ, Stamm WE. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women. Infectious Diseases Society of America (IDSA). Clin Infect Dis 1999;29(4): Fung HT, Tsui KL, Kam CW. An overview of an emergency department short stay ward in Hong Kong. Hong Kong J Emerg Med 2007;14(3): Israel RS, Lowenstein SR, Marx JA, Koziol-McLain J, Svoboda L, Ranniger S. Management of acute pyelonephritis in an emergency department observation unit. Ann Emerg Med 1991;20(3): van Nieuwkoop C, van't Wout JW, Spelt IC, Becker M, Kuijper EJ, Blom JW, et al. Prospective cohort study of acute pyelonephritis in adults: safety of triage towards home based oral antimicrobial treatment. J Infect 2010; 60(2): Pinson AG, Philbrick JT, Lindbeck GH, Schorling JB. ED management of acute pyelonephritis in women: a cohort study. Am J Emerg Med 1994;12(3): Czaja CA, Scholes D, Hooton TM, Stamm WE. Population-based epidemiologic analysis of acute pyelonephritis. Clin Infect Dis 2007;45(3): Bergeron MG. Treatment of pyelonephritis in adults. Med Clin North Am 1995;79(3):

7 306 Hong Kong j. emerg. med. Vol. 18(5) Sep Schrock JW, Reznikova S, Weller S. The effect of an observation unit on the rate of ED admission and discharge for pyelonephritis. Am J Emerg Med 2010;28(6): Ho PL, Yip KS, Chow KH, Lo JY, Que TL, Yuen KY. Antimicrobial resistance among uropathogens that cause acute uncomplicated cystitis in women in Hong Kong: a prospective multicenter study in 2006 to Diagn Microbiol Infect Dis 2010;66(1): Ho PL, Wong SSY, editors. Reducing bacterial resistance with IMPACT (Interhospital Multidisciplinary Programme on Antimicrobial ChemoTherapy), 3rd ed Chapter 4; p Williams PE, Harding SM. The absolute bioavailability of oral cefuroxime axetil in male and female volunteers after fasting and after food. J Antimicrob Chemother 1984;13(2): Tuen Mun Hospital Drug Formulary. Hong Kong: Tuen Mun Hospital; Leong WF, editors. MIMS Annual Hong Kong. 21st ed. Hong Kong: UBM Medica Pacific Ltd; 2010/ Rodloff A, Bauer T, Ewig S, Kujath P, Muller E. Susceptible, intermediate, and resistant - the intensity of antibiotic action. Dtsch Arztebl Int 2008;105(39):

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