Evaluation of the Appropriateness of Antibiotic Use for Treating Hospitalized Uncomplicated Acute Pyelonephritis院內非複雜性腎盂腎炎之抗生素使用合理性評估

San-Ein Tuo 1, Wen-Tao Huang 1, Xiu Zhen Zhan 2, Zhong Wei Cai 2, Yi Chen Chen 2, Yen-Ying Lee 1

庹聖茵 1 ,黃文濤 1 ,詹秀珍 2 ,蔡仲為 2 ,陳怡辰 2 ,黎燕縈 1

Dept. of Pharmacy, Taipei Medical University-Wan Fang Hospital 1, College of Pharmacy, Taipei Medical University2 台北醫學大學‧市立萬芳醫院藥劑部 1,台北醫學大學藥學院 2

BACKGROUND

METHOD

RESULTS

REFERENCES

Urinary Tract Infection (UTI) is a common disease for women. However, the resistance rates of antibiotics commonly used for uncomplicated UTI have been increasing in recent years. Therefore, to determine an appropriate empiric antibiotic for treating hospitalized uncomplicated UTI, such as acute pyelonephritis, is an important issue.

1. Cefazolin is appropriate as a single empiric treatment for inpatients with uncomplicated APN at our hospital.

2. Gentamicin, for the risks of side effects and ineffectiveness compared to cefazolin, combination with cefazolin is not recommended.

CONCLUSION

OBJECTIVE

To evaluate the appropriateness of antibiotic choice for treating hospitalized female patients with acute pyelonephritis (APN) by collecting empiric antibiotics, duration, and urine culture and susceptibility tests.

This was a retrospective observational study. Patients who were diagnosed of uncomplicated APN or UTI and hospitalized at Wanfang medical center in the period of 1 January 2007 to 31 December 2008 were included in the study.

LIMITATIONS

Table 1. Characteristics of Patients Included

Inclusion Criteria A diagnosis of uncomplicated APN or UTI (with

symptoms of APN) Symptoms of flank pain/tenderness or

fever 37.5 or chills.≧ ℃ ≧15 y/o female ≧103CFU/mL and/or urine WBC>5/mm3

No episodes of UTI within the last six months

Diagnosis of uncomplicated APN or UTI (with symptoms of APN)

(n=187)

Diagnosis of uncomplicated APN or UTI (with symptoms of APN)

(n=187)

Analyzed (n=129)Analyzed (n=129)

Exclusion (n=58) Drug allergy (10) Diabetes(19) Cancer (5) Immunosuppressive disease (4) Acute renal failure (5) Pregnancy (3) Recurrence (12)

Exclusion (n=58) Drug allergy (10) Diabetes(19) Cancer (5) Immunosuppressive disease (4) Acute renal failure (5) Pregnancy (3) Recurrence (12)

Primary outcomes:Frequency of correct initial empiric antibiotic

treatments of inpatients with uncomplicated APN According to urine culture & susceptibility results

Summary of urine culture and susceptibility results of inpatients with uncomplicated APN

Empiric Therapy N Culture Susceptibility

S (%) R (%) ND

Cefazolin andGentamicin

115 71 (93.4) 5 (6.6) 39

Cefazolin 3 2 (100) 0 (0) 1

Cefuroxime 1 0 (0) 1 (100) 0

Cefmetazole 8 3 (100) 0 (0) 5

Levofloxacin 1 1 (100) 0 (0) 0

Ceftriaxone 1 0 (0) 0 (0) 1

Total 129

Empiric Therapy

N Treatment

Failure in Vivo (%)

Recurrent Rate (%)

Cefazolin andGentamicin

115 9 (7.9) 3 (2.6)

Cefazolin 3 0 (0) 2 (67)

Cefuroxime 1 0 (0) 0 (0)

Cefmetazole 8 1 (12.5) 0 (0)

Levofloxacin 1 0 (0) 0 (0)

Ceftriaxone 1 0 (0) 0 (0)

Total 129 10 (7.8) 5 (3.9)

Retrospective study

Lack of objective data of bacteria eradication in the urine.

Determination of treatment failure in vivo only depended on clinical responses. The sample size of the study was too small. This study included only inpatients (with symptoms of APN). Therefore, it would not be possible

to extrapolated the results to the whole uncomplicated UTI patient population.

Exclusion Criteria Diabetes Cancer Acute renal failure Any immunosuppressive disease Pregnancy or breast-feeding Known allergy or contraindication to β-

lactams or TMP-SMX or fluoroquinolones

1. Reasons for patient exclusion showed in figure 1.2. Characteristics of the 129 patients showed in table

1.3. Microbial organisms profile and urine culture and

susceptibility results of the 129 patients were summarized in figure 2 and table 2. E. coli was the most common pathogen.

4. The combination of cefazolin plus gentamicin was the most common empiric choice for antibiotics in the 129 patients reviewed. The empiric antibiotics and the frequency of correct initial empiric antibiotic treatments showed in Table 3.

5. Failure of initial empiric treatments and recurrent rates showed in Table 4.

6. The mean treatment duration was about 14 days. The duration of antibiotic treatment showed in Table 5 .

Figure 2. Microbial Organisms Profile of The 129 Patients

No. of Total Patients 129

Total treatment (day) 13.7±4.4

Length of Stay (day) 5.6±2.4

MBD and OPD order (day) 8.0±4

Temperature when discharged from WFH ( )℃

36.4±0.5

Urine WBC before discharged from WFH (%)

≧5/mm3 16 (30)

<5/mm3 39 (70)

1. Pharmacotherapy 6th ed - J. DiPiro, et al (McGraw-Hill, 2005)2. Foxman B., Barlow R., D'Arcy H., et al: Urinary tract infection: self-reported incidence and associated costs.  Ann Epidemiol 10. 509-515.2000 3. Scholes D., Hooton T.M., Roberts P.L., et al:  Risk factors for recurrent urinary tract infection in young women.  J Infect Dis 182. 1177-1182.2000

follow-up of 179 women.  Clin Infect Dis 22. 91-99.1996; 4. Czaja CA; Scholes D; Hooton TM; Stamm WE: Population-based epidemiologic analysis of acute pyelonephritis. Clin Infect Dis. 2007 Aug

1;45(3):273-80. Epub 2007 Jun 19. 5. Ann Intern Med 2005 Jan 4;142(1):20-7. 6. Risk factors associated with acute pyelonephritis in healthy women. Ann Intern Med 2005 Jan 4;142(1):20-7. 7. Fever in the clinical diagnosis of acute pyelonephritis. Am J Emerg Med 1997; 15:148. 8. Diagnosis and management of acute pyelonephritis in adults. Am Fam Physician 2005;71:933-42.9. Kass EH: Asymptomatic infections of the urinary tract. Trans Assoc Am Physicians 1956;69:56-64.10. Stamm, WE. Measurement of pyuria and its relation to bacteriuria. Am J Med 1983; 75:53.11. Guidelines for Antimicrobial Treatment of Uncomplicated Acute Bacterial Cystitis and Acute Pyelonephritis in Women. Clinical Infectious Diseases

1999;29:745–58

Table 3. Empiric Therapy and Susceptibility Rates

Table 4. Treatment Failure Rate and Recurrent Rate Table 5. Treatment DurationSecondary outcomes:

Failure of initial empiric treatments of uncomplicated APN at our hospital

Treatment failure rateRecurrent rate (within 6 weeks)

Duration of antibiotic treatment

Figure 1. Reasons for Patient Exclusion

DISCUSSIONS The most common pathogen was E. coli, but TMP/SMZ was susceptible to only 47% of the time.

Therefore, empiric use of TMP/SMZ to treat hospitalized uncomplicated acute pyelonephritis is not appropriate in our institution.

The most common empiric antibiotics treated in uncomplicated APN at WFH is Cefazolin plus Gentamicin: 89%

To evaluate the appropriateness of the empiric treatment of cefazolin and gentamicin by the susceptibility results: Cefazolin is susceptible to most pathogens in patients with uncomplicated APN (89%, 77/87)

and is capable as a single empiric treatment. Concomitant treatment with gentamicin provides only a little benefit to the patients with

Cefazolin resistance(3.4%, 3/87).

3.4%

Antimicrobial agent

Susceptibility rate (%)

E. coli K. pneumoniae P. mirabilis

(n=89) (n=5) (n=3)

Ciprofloxacin 97 NA* 100

Cefazolin 90 100 66

Gentamicin 77 100 66

TMP/SMZ 47 100 33

Ampicillin 39 0 33

Table 2. Urine Culture and Susceptibility Results

*NA= Not Available