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Acute bacterial prostatitis in Korea: clinical outcome, including symptoms, management, microbiology and course of disease
International Journal of Antimicrobial Agents 31S (2008) S96–S101
Acute bacterial prostatitis in Korea: clinical outcome, including symptoms, management, microbiology and course of disease U-Syn Ha a , Min Eui Kim b , Chul Sung Kim c , Bong Suk Shim d , Chang Hee Han a , Sang Don Lee e , Yong-Hyun Cho a,∗ a
Department of Urology, The Catholic University of Korea College of Medicine, Seoul, South Korea b Department of Urology, Soonchunhyang University, Bucheon, South Korea c Department of Urology, College of Medicine, Chosun University, Gwangju, South Korea d Department of Urology, College of Medicine, Ewha Womans University, Seoul, South Korea e Department of Urology, College of Medicine, Pusan National University, Busan, South Korea
Abstract The Korean Association of Urogenital Tract Infection and Inflammation (KAUTII) conducted a multicentre, retrospective analysis of acute bacterial prostatitis (ABP) to document clinical features, management, microbiology and the course of disease. The clinical records of 473 cases compatible with a confirmed diagnosis of ABP from 16 urological centres between 2001 and 2005 were reviewed. Susceptibility of the organisms causing ABP, including Escherichia coli, to ciprofloxacin was shown to be very low, fuelling debate as to the efficacy of ciprofloxacin against uropathogens in Korea. When subcategorised according to history of prior manipulation of the lower urinary tract, there were distinct differences between ABP patients with or without a history of prior manipulation with regard to overall clinical and microbiological features. The difference in the distribution of pathogens between the two groups as well as the difference in susceptibility between E. coli and other pathogens should influence empirical antibiotic treatment. In the group with a history of prior manipulation of the lower urinary tract, ciprofloxacin or cephalosporins alone are an inadequate choice and the combination of cephalosporins and amikacin is recommended for empirical therapy. © 2007 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. Keywords: Acute bacterial prostatitis; Microbiology; Susceptibility
1. Introduction Acute bacterial prostatitis (ABP) is characterised by: fever and chills; rectal, low back and perineal pain; and urinary urgency, frequency and dysuria. Prostatic swelling can produce acute urinary retention. Malaise, arthralgia and myalgia are common symptoms. A digital rectal examination reveals a tender, enlarged gland that is irregularly firm and warm. The urine may be cloudy and malodorous due to a concomitant urinary infection; haematuria may also be observed [1–3]. The voided urine shows pyuria, microscopic haematuria and bacteriuria. The causative pathogen may be identified by culturing a urine sample. In the setting of systemic symptoms, most physicians recommend intravenous (i.v.) antibiotics, ∗
Corresponding author. Tel.: +82 2 3779 1024; fax: +82 2 761 1626. E-mail address: [email protected] (Y.-H. Cho).
such as a -lactam agent, aminoglycoside or quinolone, either alone or in combination with supportive measures including i.v. hydration and catheter drainage if the patient cannot void [4]. Early management of ABP focuses on empirical therapy, and accurate and systematic organisation of clinical experience is therefore required. We have noted that the clinical pattern of ABP in patients with prior manipulation of the lower urinary tract, such as prostate biopsy, transurethral surgery or catheterisation, is different from that of spontaneous ABP. The Korean Association of Urogenital Tract Infection and Inflammation (KAUTII) therefore organised a multicentre survey of ABP to classify the clinical features and microbiological characteristics in patients with a history of prior manipulation of the lower urinary tract to provide nationwide information to assist in the selection of empirical antibiotic therapy.
0924-8579/$ – see front matter © 2007 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/j.ijantimicag.2007.07.041
U.-S. Ha et al. / International Journal of Antimicrobial Agents 31S (2008) S96–S101
2. Materials and methods 2.1. Patient selection Sixteen urological centres participated in the study. A retrospective analysis of 526 patients hospitalised at the urological centres between 2001 and 2005 for ABP was performed. None of the patients had a history of prostate cancer at the time of diagnosis or at a mean of 24 months after the infectious episode. ABP was diagnosed in all patients according to clinical features (fever, problems of voiding, painful prostate on digital rectal examination) and laboratory tests (e.g. leukocytosis). Patients with ABP symptoms and a positive urine culture, or those with compatible signs but with a negative urine culture due to a previous course of antibiotics, were selected. Cases in which ABP diagnosis was doubtful were excluded. Patients with other causes of febrile urinary infection (pyelonephritis, orchitis) were also excluded. Finally, 473 cases compatible with a confirmed diagnosis of ABP were enrolled in the study. 2.2. Analysis of clinical variables A detailed history was taken together with physical examination and laboratory/radiological investigations. Treatment parameters and microbiology results were documented. The clinical features considered were: presenting symptoms (fever, pain, dysuria, retention, voiding); laboratory/radiological investigations (urine analysis, prostatespecific antigen (PSA), transrectal ultrasound (TRUS)); treatment parameters (antibiotic treatment, time in hospital, catheterisation); bacteriological results; and the course of disease (abscess formation, recurrence, progression to chronic prostatitis).
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Microbial susceptibility was determined using the agar diffusion method according to the guidelines of the National Committee for Clinical Laboratory Standards. During the follow-up period, if there was possible abscess formation or chronic prostatitis, both TRUS and four-glass tests were carried out. Results were analysed according to two subgroups: (a) those with prior manipulation of the lower urinary tract; and (b) those without prior manipulation of the lower urinary tract. Manipulation of the lower urinary tract included prostate biopsy, catheterisation, urodynamic studies, transurethral surgery and urethral surgery performed within 4 weeks before the onset of ABP. 2.3. Statistical analysis Results (frequency and percentages) were analysed to characterise all variables using Student’s t-test for PSA, TRUS of the prostate and admission period and χ2 test for symptoms, frequency of antibiotic combination treatment, catheterisation, abscess formation, recurrence of infection and progression to chronic prostatitis. A P-value <0.05 was considered statistically significant.
3. Results 3.1. Initial clinical features Table 1 shows the initial clinical characteristics of the whole population and according to the two subgroups. The mean age of the patients was 55.62 years; 27.5% of the patients had a history of prior manipulation of the lower urinary tract, mostly prostatic biopsy (43.8%; 57/130)
Table 1 Initial characteristics of acute bacterial prostatitis patients in Korea Total (n = 473)
With prior manipulation (n = 130)a
Without prior manipulation (n = 343)
P-value
Age (years)
55.62 ± 14.47
59.74 ± 12.94
54.06 ± 14.73
0.0001
Symptoms Fever Painb Dysuria Retention Obstructive symptoms Storing symptoms Other
68.9% (326) 48.2% (228) 66.2% (313) 19.2% (91) 69.1% (327) 37.0% (175)
79.2% (103) 57.7% (75) 54.6% (71) 35.4% (46) 64.6% (84) 43.8% (57) 16.2% (21)
65.0% (223) 44.6% (153) 70.6% (242) 13.1% (45) 70.8% (243) 34.4% (118) 5.8% (20)
0.0005 0.0109 0.0010 0.0001 0.1904 0.0577
57.1% (270) 75.1% (355) 21.36 ± 24.99 37.44 ± 20.32
71.5% (93) 69.2% (90) 22.08 ± 26.29 43.06 ± 28.16
51.6% (177) 77.3% (265) 21.90 ± 24.54 35.20 ± 15.72
0.0001 0.058 0.7504 0.0109
Initial urinalysis Haematuriac Pyuriad PSA (ng/mL) TRUS (mL)
PSA, prostate-specific antigen; TRUS, transrectal ultrasound. a Prior manipulation includes prostate biopsy, catheterisation, urodynamic study, transurethral surgery, internal urethrotomy and cystoscopy. b Suprapubic pain, arthralgia and myalgia. c >4 Red blood cells/high power field. d >4 White blood cells/high power field.
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U.-S. Ha et al. / International Journal of Antimicrobial Agents 31S (2008) S96–S101
Table 2 Distribution of prescribed antimicrobial agents in acute bacterial prostatitis patients With prior manipulation (n = 130) n (%) Single therapy Penicillin First-generation cephalosporin Second-generation cephalosporin Third-generation cephalosporin First-generation quinolone Second-generation quinolone Third-generation quinolone Aminoglycoside Carbapenem Total Combination antibiotics First-generation cephalosporins + aminoglycoside Second-generation cephalosporins + aminoglycoside Third-generation cephalosporins + aminoglycoside First-generation cephalosporins + quinoloneb Second-generation cephalosporins + quinoloneb Third-generation cephalosporins + quinoloneb Quinolonea + aminoglycoside Othersb Total a b
Without prior manipulation (n = 343) n (%)
1 (1.8) 2 (3.5) 6 (10.5) 13 (22.8) 16 (28.1) 13 (22.8) 3 (5.3) 2 (3.5) 1 (1.8)
3 (3.1) 0 (0) 5 (5.2) 13 (13.5) 15 (15.6) 49 (51.0) 3 (3.1) 5 (5.2) 3 (3.1)
57
96
4 (5.5) 20 (27.4) 36 (49.3) 2 (2.7) 5 (6.8) 3 (4.1) 2 (2.7) 1 (1.4)
62 (25.1) 100 (40.5) 59 (23.9) 0 (0) 5 (2.0) 12 (4.9) 5 (2.0) 4 (1.6)
73
247
Too small number to subdivide according to generations. Others include penicillin + aminoglycoside and penicillin + quinolone.
or catheterisation (20.8%; 27/130). Overall, the patients complained most frequently of fever (68.9%), obstructive symptoms (69.1%) and dysuria (66.2%). In the group with prior manipulation of the lower urinary tract, the features fever, pain and retention of urine were significantly more frequent and they were older and the prostate volume was larger (P < 0.05) (Table 1). 3.2. Analysis of treatment There was a significant difference in the frequency of antibiotic combinations and catheterisation between the two groups. The frequency of catheterisation, including suprapubic and urethral, was higher in the group with prior manipulation of the lower urinary tract (35.4%; 46/130) than in the group without prior manipulation (12.5%; 43/343) (P < 0.0001, χ2 test). In contrast to catheterisation, the frequency of antibiotic combinations was higher in the group without prior manipulation of the lower urinary tract (72.0%; 247/343) than in the group with prior manipulation (56.2%; 73/130) (P = 0.001, χ2 test), even though combination antibiotic treatment was used more often than single antibiotic treatment in both groups. However, there was a similar duration of hospital admission in the two groups. Table 2 outlines the distribution of prescribed antimicrobial agents in ABP patients. Quinolones were the most commonly prescribed antibiotics. Third-generation cephalosporins were preferred in cases receiving a single antibiotic. Second- and third-generation cephalosporins,
combined with an aminoglycoside, accounted for the large majority of combination therapies, whereas the rate of quinolone administration was low in cases receiving combination antibiotic treatment. 3.3. Microbiological analysis Of the pathogens isolated, the most frequent was E. coli, followed by Pseudomonas spp. and Klebsiella spp. Significant differences were found between the two patient groups regarding the spectrum and distribution of the isolated pathogens. Pseudomonas spp. accounted for a far higher proportion in the group with prior manipulation than in the group without prior manipulation. Mixed infections occurred in 4.3% of cases. The remaining pathogens were so small in number that the ranking and distribution of the difference between the two groups could not be determined (Table 3). Tables 4 and 5 show the susceptibility of the isolated pathogens to antimicrobial agents. Susceptibility to ampicillin, ampicillin/sulbactam, first-generation cephalosporins and trimethoprim/sulfamethoxazole was very low, whereas the second-, third- and fourth-generation cephalosporins as well as aminoglycosides showed relatively high sensitivity rates. Amikacin was the most active aminoglycoside (94.3% susceptibility), followed by tobramycin (85.1%) and gentamicin (82.3%). With regard to ciprofloxacin and tobramycin, ABP developing after manipulation showed relatively lower sensitivities than the ABP group without prior manipulation (Table 4). Of the isolated pathogens, E. coli showed relatively
U.-S. Ha et al. / International Journal of Antimicrobial Agents 31S (2008) S96–S101
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Table 3 Microbial spectrum of patients with acute bacterial prostatitis
Escherichia coli Pseudomonas spp. Klebsiella spp. Enterobacter spp. Streptococcus agalactiae Serratia marcescens CoNS Enterococci Mixed infection Others a
Total (n = 115)
With prior manipulation (n = 39)
Without prior manipulation (n = 76)
P-value
52.2% (60) 15.7% (18) 9.6% (11) 3.5% (4) 3.5% (4) 1.7% (2) 2.6% (3) 2.6% (3) 4.3% (5) 4.3% (5)
46.2% (18) 30.8% (12) 10.3% (4) 2.6% (1) 2.6% (1) 2.6% (1) 2.6% (1) 0% (0) 7.7% (3) 2.6% (1)
55.3% (42) 7.9% (6) 9.2% (7) 3.9% (3) 3.9% (3) 1.3% (1) 2.6% (2) 3.9% (3) 2.6% (2) 5.3% (4)
0.3546 0.0014 0.8567 – – – – – 0.2077 –
CoNS, coagulase-negative staphylococci. a Neisseria gonorrhoeae, Salmonella and Candida. Table 4 Antibiotic susceptibility (%) of pathogens isolated in patients with acute bacterial prostatitis, according to prior manipulation
Ampicillin Ampicillin/sulbactam Piperacillin/tazobactam First-generation cephalosporins Second-generation cephalosporins Third-generation cephalosporins Fourth-generation cephalosporins Ciprofloxacin Ofloxacin Amikacin Gentamicin Tobramycin Imipenem TMP/SMX
Total (n = 115)
With prior manipulation (n = 39)
Without prior manipulation (n = 76)
P-value
29.8 38.9 88.9 60.0 82.0 82.5 84.2 73.8 88.5 94.3 82.3 85.1 99.4 67.4
21.4 45.5 84.6 53.8 75.0 78.6 80.0 53.3 91.5 92.3 66.7 66.8 99.3 54.6
32.6 36.0 90.2 61.9 84.2 83.7 85.7 80.4 85.7 95.0 87.2 91.4 99.5 71.9
0.4292 0.5919 0.5737 0.8965 0.4691 0.6599 0.6706 0.0383 0.3689 0.7152 0.0695 0.0376 0.8985 0.2900
TMP/SMX, trimethoprim/sulfamethoxazole.
higher sensitivity than the other pathogens. The susceptibility of E. coli to cephalosporins and aminoglycosides was ≥90%. However, susceptibility to cephalosporins of the other pathogens was shown to be very low (41.2–58.3%) (Table 5).
Table 5 Antibiotic susceptibility (%) of pathogens isolated in patients with acute bacterial prostatitis sorted by Escherichia coli and other pathogens
Ampicillin Ampicillin/sulbactam Piperacillin/tazobactam First-generation cephalosporins Second-generation cephalosporins Third-generation cephalosporins Fourth-generation cephalosporins Ciprofloxacin Ofloxacin Amikacin Gentamicin Tobramycin Imipenem TMP/SMX
E. coli Other pathogens (n = 60) (n = 55)
P-value
31.9 42.3 95.0 70.4 91.9 95.2 96.2 76.2 94.1 98.3 90.5 91.4 100.0 71.4
0.6822 0.4975 0.0157 0.0293 0.0021 <0.0001 0.0030 0.5229 0.2147 0.0029 0.0141 0.0376 0.7882 0.4459
TMP/SMX, trimethoprim/sulfamethoxazole.
26.3 30.0 71.4 41.2 53.9 46.7 58.3 68.4 77.8 78.6 65.0 66.7 98.2 60.0
3.4. Course of disease The progression of disease was assessed in patients available for follow-up and it was found that the frequency of formation of a prostate abscess was significantly higher in the patient group with prior manipulation of the lower urinary tract before the onset of ABP than in the group without prior manipulation (P < 0.05, χ2 ) (Table 6). However, recurrence of ABP (P = 0.0867, χ2 ) and the frequency of progression to chronic prostatitis (P = 0.3703, χ2 ) were not significantly different between the two groups.
4. Discussion Of the patients studied, 27.5% had a history of prior manipulation of the lower urinary tract. The pattern of fever and voiding problems in both groups showed a distinct difference. It could be assumed that the difference in fever between the two groups may have been due to invasive procedures such as prostate biopsy, which could cause lymphatic or haematogenous spread of infection. The difference in voiding problems may reflect age differences and the prostate volume. In addition, the frequency of voiding problems, particularly
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U.-S. Ha et al. / International Journal of Antimicrobial Agents 31S (2008) S96–S101
Table 6 Characteristics of course of infection according to prior manipulation in acute bacterial prostatitis
Abscess Recurrencea Progression to chronic prostatitisa a
Total
With prior manipulation
Without prior manipulation
P-value
6.0% (23/384) 9.5% (34/358) 8.1% (24/296)
13.9% (14/101) 14.0% (13/93) 10.5% (8/76)
3.2% (9/283) 7.9% (21/265) 7.3% (16/220)
0.0013 0.0867 0.3703
Only includes patients available to follow-up over 6 months.
urinary retention, was significantly higher in the group that underwent prior manipulation. Consequently, the frequency of suprapubic or urethral catheterisation was relatively high. This study shows different microbiological characteristics between the two groups. The most frequent bacteria causing ABP have been reported to be E. coli [5–7], and in our study E. coli was the most common causative bacterium. In the classification of groups according to the presence or absence of prior manipulation, a distinct difference in the type of pathogens was noted. In the group with prior manipulation, relatively fewer E. coli were detected. Regarding Pseudomonas spp., its isolation was significantly higher in the prior manipulation group compared with the group without manipulation. The susceptibility to ciprofloxacin of E. coli was shown to be very low (Table 5). This is similar to ciprofloxacin susceptibility reported in the survey of antimicrobial susceptibility of uropathogens responsible for female acute uncomplicated cystitis conducted by KAUTII in 2006 [8]. Such a result probably reflects the increase in resistant bacteria owing to the excessive use of ciprofloxacin. The guidelines for the treatment of urinary tract infection of the Infectious Disease Society of America (IDSA) published in 1999 do not recommend a specific antibiotic for empirical treatment when the local level of resistance among E. coli strains exceeds 20%. The IDSA also emphasises that physicians should obtain information about local resistance rates [9]. In a recent guideline for antibiotic treatment of ABP, the administration of cephalosporins or a quinolone alone or in combination with an aminoglycoside has been recommended [10]. In many urology centres in Korea, the management of ABP depends on these guidelines. For single antibiotic administration in Korea, a quinolone is preferred initially followed by a third-generation cephalosporin. Prescription of aminoglycosides was very low in our study. Ciprofloxacin alone is an inadequate choice, especially in patients with prior manipulation of the renal tract. Considering the very low susceptibility to cephalosporins (<60%) in pathogens other than E. coli, and the relative high isolation rates (>40%) of pathogens other than E. coli, cephalosporins as single therapeutic agents may have limited use in this community. Most commonly, antibiotic combination therapy for ABP includes a cephalosporin and an aminoglycoside. The second- and third-generation cephalosporins have been prescribed relatively frequently for this purpose. Administration of an aminoglycoside must be confined to the group of
patients without prior manipulation owing to their susceptibility. In the group of patients with prior manipulation in which pathogens other than E. coli constitute a substantial number of isolates, a combination of a cephalosporin and amikacin should be recommended for empirical therapy. Table 6 may reflect that combination antibiotic administration was performed infrequently in the group with prior manipulation. However, in abscess formation cases in the group with prior manipulation, single antibiotic administration was more frequent (71.4%; 10/14) than combination antibiotic administration. In conclusion, this is the first report recording the clinical and microbiological aspects of ABP in Korea. This survey may help clinicians to select appropriate empirical treatment. In this study, ABP with prior manipulation of the lower urinary tract and spontaneous ABP showed distinct characteristics with regard to clinical and microbiological features. Management of ABP must be tailored to local microbiological sensitivity patterns and with regard to the history of prior manipulation of the lower urinary tract.
Acknowledgments The authors thank the following urologists for contributing case material and for providing patient information: Choong Bum Lee, Sae Woong Kim, Hong Jin Suh, Joon Chul Kim, Su Yeon Cho and Doo Bae Kim (Department of Urology, The Catholic University of Korea College of Medicine, Seoul, South Korea); Dong Deuk Kwon (Department of Urology, Chonnam National University Medical School, Gwangju, South Korea); Sang Eun Lee (Department of Urology, Seoul National University Bundang Hospital, Seongnam, South Korea); Duk Yoon Kim (Department of Urology, College of Medicine, Catholic University of Daegu, Daegu, South Korea); Kyu-Sung Lee (Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea); Sung-Goo Chang (Department of Urology, School of Medicine, Kyung Hee University, Seoul, South Korea); Hyung Jin Kim (Department of Urology, Chonbuk National University Medical School, Jeonju, South Korea); and Luck Hee Sung (Department of Urology, Sanggye Paik Hospital, College of Medicine, Inje University, Seoul, South Korea). We would like to thank Dr Yong Sun Choi and Dr Kang June Cho for data collection and input. Funding: None. Competing interests: None declared.
U.-S. Ha et al. / International Journal of Antimicrobial Agents 31S (2008) S96–S101
Ethical approval: This study was approved by institutional board review in The Catholic University of Korea College of Medicine (approval number SCMC07OT069).
References [1] Krieger JN, Nyberg Jr L, Nickel JC. NIH consensus definition and classification of prostatitis. JAMA 1999;282:236–7. [2] Hua VN, Schaeffer AJ. Acute and chronic prostatitis. Med Clin North Am 2004;88:483–94. [3] Meares Jr EM. Prostatitis. Med Clin North Am 1991;75:405– 24. [4] Schaeffer AJ. Diagnosis and treatment of prostatic infections. Urology 1990;36(5 Suppl.):13–7. [5] Stamey TA. Pathogenesis and treatment of urinary tract infections. Baltimore, MD: Williams & Wilkins; 1980. p. 343–429.
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[6] L´opez-Plaza I, Bostwick DG. Prostatitis. In: Bostwick DG, editor. Pathology of the prostate. New York: Churchill Livingstone; 1990. p. 15–30. [7] Dowling KJ, Roberts JA, Kaack MB. P-fimbriated Escherichia coli urinary tract infection: a clinical correlation. South Med J 1987;80:1533–6. [8] Kim ME, Ha US, Cho YH. The prevalence of antimicrobial resistance among uropathogens causing acute uncomplicated cystitis in female outpatients in South Korea: a multicentre study in 2006. Int J Antimicrob Agents [in this Supplement] 2008:p. 15–18. [9] 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. Clin Infect Dis 1999;29:745–58. [10] Naber KG, Bishop MC, Bjerklund-johansen TE, Botto H, Cek M, Grabe B, et al. The management of urinary and male genital tract infections. In: EAU guideline office, editor. European Association of Urology Guidelines. Arnhem, The Netherlands: Drukkerij Gelderland; 2006. p. 1–126.
Acute bacterial prostatitis in Korea: clinical outcome, including symptoms, management, microbiology and course of disease U-Syn Ha a , Min Eui Kim b , Chul Sung Kim c , Bong Suk Shim d , Chang Hee Han a , Sang Don Lee e , Yong-Hyun Cho a,∗ a
Department of Urology, The Catholic University of Korea College of Medicine, Seoul, South Korea b Department of Urology, Soonchunhyang University, Bucheon, South Korea c Department of Urology, College of Medicine, Chosun University, Gwangju, South Korea d Department of Urology, College of Medicine, Ewha Womans University, Seoul, South Korea e Department of Urology, College of Medicine, Pusan National University, Busan, South Korea
Abstract The Korean Association of Urogenital Tract Infection and Inflammation (KAUTII) conducted a multicentre, retrospective analysis of acute bacterial prostatitis (ABP) to document clinical features, management, microbiology and the course of disease. The clinical records of 473 cases compatible with a confirmed diagnosis of ABP from 16 urological centres between 2001 and 2005 were reviewed. Susceptibility of the organisms causing ABP, including Escherichia coli, to ciprofloxacin was shown to be very low, fuelling debate as to the efficacy of ciprofloxacin against uropathogens in Korea. When subcategorised according to history of prior manipulation of the lower urinary tract, there were distinct differences between ABP patients with or without a history of prior manipulation with regard to overall clinical and microbiological features. The difference in the distribution of pathogens between the two groups as well as the difference in susceptibility between E. coli and other pathogens should influence empirical antibiotic treatment. In the group with a history of prior manipulation of the lower urinary tract, ciprofloxacin or cephalosporins alone are an inadequate choice and the combination of cephalosporins and amikacin is recommended for empirical therapy. © 2007 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. Keywords: Acute bacterial prostatitis; Microbiology; Susceptibility
1. Introduction Acute bacterial prostatitis (ABP) is characterised by: fever and chills; rectal, low back and perineal pain; and urinary urgency, frequency and dysuria. Prostatic swelling can produce acute urinary retention. Malaise, arthralgia and myalgia are common symptoms. A digital rectal examination reveals a tender, enlarged gland that is irregularly firm and warm. The urine may be cloudy and malodorous due to a concomitant urinary infection; haematuria may also be observed [1–3]. The voided urine shows pyuria, microscopic haematuria and bacteriuria. The causative pathogen may be identified by culturing a urine sample. In the setting of systemic symptoms, most physicians recommend intravenous (i.v.) antibiotics, ∗
Corresponding author. Tel.: +82 2 3779 1024; fax: +82 2 761 1626. E-mail address: [email protected] (Y.-H. Cho).
such as a -lactam agent, aminoglycoside or quinolone, either alone or in combination with supportive measures including i.v. hydration and catheter drainage if the patient cannot void [4]. Early management of ABP focuses on empirical therapy, and accurate and systematic organisation of clinical experience is therefore required. We have noted that the clinical pattern of ABP in patients with prior manipulation of the lower urinary tract, such as prostate biopsy, transurethral surgery or catheterisation, is different from that of spontaneous ABP. The Korean Association of Urogenital Tract Infection and Inflammation (KAUTII) therefore organised a multicentre survey of ABP to classify the clinical features and microbiological characteristics in patients with a history of prior manipulation of the lower urinary tract to provide nationwide information to assist in the selection of empirical antibiotic therapy.
0924-8579/$ – see front matter © 2007 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. doi:10.1016/j.ijantimicag.2007.07.041
U.-S. Ha et al. / International Journal of Antimicrobial Agents 31S (2008) S96–S101
2. Materials and methods 2.1. Patient selection Sixteen urological centres participated in the study. A retrospective analysis of 526 patients hospitalised at the urological centres between 2001 and 2005 for ABP was performed. None of the patients had a history of prostate cancer at the time of diagnosis or at a mean of 24 months after the infectious episode. ABP was diagnosed in all patients according to clinical features (fever, problems of voiding, painful prostate on digital rectal examination) and laboratory tests (e.g. leukocytosis). Patients with ABP symptoms and a positive urine culture, or those with compatible signs but with a negative urine culture due to a previous course of antibiotics, were selected. Cases in which ABP diagnosis was doubtful were excluded. Patients with other causes of febrile urinary infection (pyelonephritis, orchitis) were also excluded. Finally, 473 cases compatible with a confirmed diagnosis of ABP were enrolled in the study. 2.2. Analysis of clinical variables A detailed history was taken together with physical examination and laboratory/radiological investigations. Treatment parameters and microbiology results were documented. The clinical features considered were: presenting symptoms (fever, pain, dysuria, retention, voiding); laboratory/radiological investigations (urine analysis, prostatespecific antigen (PSA), transrectal ultrasound (TRUS)); treatment parameters (antibiotic treatment, time in hospital, catheterisation); bacteriological results; and the course of disease (abscess formation, recurrence, progression to chronic prostatitis).
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Microbial susceptibility was determined using the agar diffusion method according to the guidelines of the National Committee for Clinical Laboratory Standards. During the follow-up period, if there was possible abscess formation or chronic prostatitis, both TRUS and four-glass tests were carried out. Results were analysed according to two subgroups: (a) those with prior manipulation of the lower urinary tract; and (b) those without prior manipulation of the lower urinary tract. Manipulation of the lower urinary tract included prostate biopsy, catheterisation, urodynamic studies, transurethral surgery and urethral surgery performed within 4 weeks before the onset of ABP. 2.3. Statistical analysis Results (frequency and percentages) were analysed to characterise all variables using Student’s t-test for PSA, TRUS of the prostate and admission period and χ2 test for symptoms, frequency of antibiotic combination treatment, catheterisation, abscess formation, recurrence of infection and progression to chronic prostatitis. A P-value <0.05 was considered statistically significant.
3. Results 3.1. Initial clinical features Table 1 shows the initial clinical characteristics of the whole population and according to the two subgroups. The mean age of the patients was 55.62 years; 27.5% of the patients had a history of prior manipulation of the lower urinary tract, mostly prostatic biopsy (43.8%; 57/130)
Table 1 Initial characteristics of acute bacterial prostatitis patients in Korea Total (n = 473)
With prior manipulation (n = 130)a
Without prior manipulation (n = 343)
P-value
Age (years)
55.62 ± 14.47
59.74 ± 12.94
54.06 ± 14.73
0.0001
Symptoms Fever Painb Dysuria Retention Obstructive symptoms Storing symptoms Other
68.9% (326) 48.2% (228) 66.2% (313) 19.2% (91) 69.1% (327) 37.0% (175)
79.2% (103) 57.7% (75) 54.6% (71) 35.4% (46) 64.6% (84) 43.8% (57) 16.2% (21)
65.0% (223) 44.6% (153) 70.6% (242) 13.1% (45) 70.8% (243) 34.4% (118) 5.8% (20)
0.0005 0.0109 0.0010 0.0001 0.1904 0.0577
57.1% (270) 75.1% (355) 21.36 ± 24.99 37.44 ± 20.32
71.5% (93) 69.2% (90) 22.08 ± 26.29 43.06 ± 28.16
51.6% (177) 77.3% (265) 21.90 ± 24.54 35.20 ± 15.72
0.0001 0.058 0.7504 0.0109
Initial urinalysis Haematuriac Pyuriad PSA (ng/mL) TRUS (mL)
PSA, prostate-specific antigen; TRUS, transrectal ultrasound. a Prior manipulation includes prostate biopsy, catheterisation, urodynamic study, transurethral surgery, internal urethrotomy and cystoscopy. b Suprapubic pain, arthralgia and myalgia. c >4 Red blood cells/high power field. d >4 White blood cells/high power field.
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Table 2 Distribution of prescribed antimicrobial agents in acute bacterial prostatitis patients With prior manipulation (n = 130) n (%) Single therapy Penicillin First-generation cephalosporin Second-generation cephalosporin Third-generation cephalosporin First-generation quinolone Second-generation quinolone Third-generation quinolone Aminoglycoside Carbapenem Total Combination antibiotics First-generation cephalosporins + aminoglycoside Second-generation cephalosporins + aminoglycoside Third-generation cephalosporins + aminoglycoside First-generation cephalosporins + quinoloneb Second-generation cephalosporins + quinoloneb Third-generation cephalosporins + quinoloneb Quinolonea + aminoglycoside Othersb Total a b
Without prior manipulation (n = 343) n (%)
1 (1.8) 2 (3.5) 6 (10.5) 13 (22.8) 16 (28.1) 13 (22.8) 3 (5.3) 2 (3.5) 1 (1.8)
3 (3.1) 0 (0) 5 (5.2) 13 (13.5) 15 (15.6) 49 (51.0) 3 (3.1) 5 (5.2) 3 (3.1)
57
96
4 (5.5) 20 (27.4) 36 (49.3) 2 (2.7) 5 (6.8) 3 (4.1) 2 (2.7) 1 (1.4)
62 (25.1) 100 (40.5) 59 (23.9) 0 (0) 5 (2.0) 12 (4.9) 5 (2.0) 4 (1.6)
73
247
Too small number to subdivide according to generations. Others include penicillin + aminoglycoside and penicillin + quinolone.
or catheterisation (20.8%; 27/130). Overall, the patients complained most frequently of fever (68.9%), obstructive symptoms (69.1%) and dysuria (66.2%). In the group with prior manipulation of the lower urinary tract, the features fever, pain and retention of urine were significantly more frequent and they were older and the prostate volume was larger (P < 0.05) (Table 1). 3.2. Analysis of treatment There was a significant difference in the frequency of antibiotic combinations and catheterisation between the two groups. The frequency of catheterisation, including suprapubic and urethral, was higher in the group with prior manipulation of the lower urinary tract (35.4%; 46/130) than in the group without prior manipulation (12.5%; 43/343) (P < 0.0001, χ2 test). In contrast to catheterisation, the frequency of antibiotic combinations was higher in the group without prior manipulation of the lower urinary tract (72.0%; 247/343) than in the group with prior manipulation (56.2%; 73/130) (P = 0.001, χ2 test), even though combination antibiotic treatment was used more often than single antibiotic treatment in both groups. However, there was a similar duration of hospital admission in the two groups. Table 2 outlines the distribution of prescribed antimicrobial agents in ABP patients. Quinolones were the most commonly prescribed antibiotics. Third-generation cephalosporins were preferred in cases receiving a single antibiotic. Second- and third-generation cephalosporins,
combined with an aminoglycoside, accounted for the large majority of combination therapies, whereas the rate of quinolone administration was low in cases receiving combination antibiotic treatment. 3.3. Microbiological analysis Of the pathogens isolated, the most frequent was E. coli, followed by Pseudomonas spp. and Klebsiella spp. Significant differences were found between the two patient groups regarding the spectrum and distribution of the isolated pathogens. Pseudomonas spp. accounted for a far higher proportion in the group with prior manipulation than in the group without prior manipulation. Mixed infections occurred in 4.3% of cases. The remaining pathogens were so small in number that the ranking and distribution of the difference between the two groups could not be determined (Table 3). Tables 4 and 5 show the susceptibility of the isolated pathogens to antimicrobial agents. Susceptibility to ampicillin, ampicillin/sulbactam, first-generation cephalosporins and trimethoprim/sulfamethoxazole was very low, whereas the second-, third- and fourth-generation cephalosporins as well as aminoglycosides showed relatively high sensitivity rates. Amikacin was the most active aminoglycoside (94.3% susceptibility), followed by tobramycin (85.1%) and gentamicin (82.3%). With regard to ciprofloxacin and tobramycin, ABP developing after manipulation showed relatively lower sensitivities than the ABP group without prior manipulation (Table 4). Of the isolated pathogens, E. coli showed relatively
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Table 3 Microbial spectrum of patients with acute bacterial prostatitis
Escherichia coli Pseudomonas spp. Klebsiella spp. Enterobacter spp. Streptococcus agalactiae Serratia marcescens CoNS Enterococci Mixed infection Others a
Total (n = 115)
With prior manipulation (n = 39)
Without prior manipulation (n = 76)
P-value
52.2% (60) 15.7% (18) 9.6% (11) 3.5% (4) 3.5% (4) 1.7% (2) 2.6% (3) 2.6% (3) 4.3% (5) 4.3% (5)
46.2% (18) 30.8% (12) 10.3% (4) 2.6% (1) 2.6% (1) 2.6% (1) 2.6% (1) 0% (0) 7.7% (3) 2.6% (1)
55.3% (42) 7.9% (6) 9.2% (7) 3.9% (3) 3.9% (3) 1.3% (1) 2.6% (2) 3.9% (3) 2.6% (2) 5.3% (4)
0.3546 0.0014 0.8567 – – – – – 0.2077 –
CoNS, coagulase-negative staphylococci. a Neisseria gonorrhoeae, Salmonella and Candida. Table 4 Antibiotic susceptibility (%) of pathogens isolated in patients with acute bacterial prostatitis, according to prior manipulation
Ampicillin Ampicillin/sulbactam Piperacillin/tazobactam First-generation cephalosporins Second-generation cephalosporins Third-generation cephalosporins Fourth-generation cephalosporins Ciprofloxacin Ofloxacin Amikacin Gentamicin Tobramycin Imipenem TMP/SMX
Total (n = 115)
With prior manipulation (n = 39)
Without prior manipulation (n = 76)
P-value
29.8 38.9 88.9 60.0 82.0 82.5 84.2 73.8 88.5 94.3 82.3 85.1 99.4 67.4
21.4 45.5 84.6 53.8 75.0 78.6 80.0 53.3 91.5 92.3 66.7 66.8 99.3 54.6
32.6 36.0 90.2 61.9 84.2 83.7 85.7 80.4 85.7 95.0 87.2 91.4 99.5 71.9
0.4292 0.5919 0.5737 0.8965 0.4691 0.6599 0.6706 0.0383 0.3689 0.7152 0.0695 0.0376 0.8985 0.2900
TMP/SMX, trimethoprim/sulfamethoxazole.
higher sensitivity than the other pathogens. The susceptibility of E. coli to cephalosporins and aminoglycosides was ≥90%. However, susceptibility to cephalosporins of the other pathogens was shown to be very low (41.2–58.3%) (Table 5).
Table 5 Antibiotic susceptibility (%) of pathogens isolated in patients with acute bacterial prostatitis sorted by Escherichia coli and other pathogens
Ampicillin Ampicillin/sulbactam Piperacillin/tazobactam First-generation cephalosporins Second-generation cephalosporins Third-generation cephalosporins Fourth-generation cephalosporins Ciprofloxacin Ofloxacin Amikacin Gentamicin Tobramycin Imipenem TMP/SMX
E. coli Other pathogens (n = 60) (n = 55)
P-value
31.9 42.3 95.0 70.4 91.9 95.2 96.2 76.2 94.1 98.3 90.5 91.4 100.0 71.4
0.6822 0.4975 0.0157 0.0293 0.0021 <0.0001 0.0030 0.5229 0.2147 0.0029 0.0141 0.0376 0.7882 0.4459
TMP/SMX, trimethoprim/sulfamethoxazole.
26.3 30.0 71.4 41.2 53.9 46.7 58.3 68.4 77.8 78.6 65.0 66.7 98.2 60.0
3.4. Course of disease The progression of disease was assessed in patients available for follow-up and it was found that the frequency of formation of a prostate abscess was significantly higher in the patient group with prior manipulation of the lower urinary tract before the onset of ABP than in the group without prior manipulation (P < 0.05, χ2 ) (Table 6). However, recurrence of ABP (P = 0.0867, χ2 ) and the frequency of progression to chronic prostatitis (P = 0.3703, χ2 ) were not significantly different between the two groups.
4. Discussion Of the patients studied, 27.5% had a history of prior manipulation of the lower urinary tract. The pattern of fever and voiding problems in both groups showed a distinct difference. It could be assumed that the difference in fever between the two groups may have been due to invasive procedures such as prostate biopsy, which could cause lymphatic or haematogenous spread of infection. The difference in voiding problems may reflect age differences and the prostate volume. In addition, the frequency of voiding problems, particularly
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Table 6 Characteristics of course of infection according to prior manipulation in acute bacterial prostatitis
Abscess Recurrencea Progression to chronic prostatitisa a
Total
With prior manipulation
Without prior manipulation
P-value
6.0% (23/384) 9.5% (34/358) 8.1% (24/296)
13.9% (14/101) 14.0% (13/93) 10.5% (8/76)
3.2% (9/283) 7.9% (21/265) 7.3% (16/220)
0.0013 0.0867 0.3703
Only includes patients available to follow-up over 6 months.
urinary retention, was significantly higher in the group that underwent prior manipulation. Consequently, the frequency of suprapubic or urethral catheterisation was relatively high. This study shows different microbiological characteristics between the two groups. The most frequent bacteria causing ABP have been reported to be E. coli [5–7], and in our study E. coli was the most common causative bacterium. In the classification of groups according to the presence or absence of prior manipulation, a distinct difference in the type of pathogens was noted. In the group with prior manipulation, relatively fewer E. coli were detected. Regarding Pseudomonas spp., its isolation was significantly higher in the prior manipulation group compared with the group without manipulation. The susceptibility to ciprofloxacin of E. coli was shown to be very low (Table 5). This is similar to ciprofloxacin susceptibility reported in the survey of antimicrobial susceptibility of uropathogens responsible for female acute uncomplicated cystitis conducted by KAUTII in 2006 [8]. Such a result probably reflects the increase in resistant bacteria owing to the excessive use of ciprofloxacin. The guidelines for the treatment of urinary tract infection of the Infectious Disease Society of America (IDSA) published in 1999 do not recommend a specific antibiotic for empirical treatment when the local level of resistance among E. coli strains exceeds 20%. The IDSA also emphasises that physicians should obtain information about local resistance rates [9]. In a recent guideline for antibiotic treatment of ABP, the administration of cephalosporins or a quinolone alone or in combination with an aminoglycoside has been recommended [10]. In many urology centres in Korea, the management of ABP depends on these guidelines. For single antibiotic administration in Korea, a quinolone is preferred initially followed by a third-generation cephalosporin. Prescription of aminoglycosides was very low in our study. Ciprofloxacin alone is an inadequate choice, especially in patients with prior manipulation of the renal tract. Considering the very low susceptibility to cephalosporins (<60%) in pathogens other than E. coli, and the relative high isolation rates (>40%) of pathogens other than E. coli, cephalosporins as single therapeutic agents may have limited use in this community. Most commonly, antibiotic combination therapy for ABP includes a cephalosporin and an aminoglycoside. The second- and third-generation cephalosporins have been prescribed relatively frequently for this purpose. Administration of an aminoglycoside must be confined to the group of
patients without prior manipulation owing to their susceptibility. In the group of patients with prior manipulation in which pathogens other than E. coli constitute a substantial number of isolates, a combination of a cephalosporin and amikacin should be recommended for empirical therapy. Table 6 may reflect that combination antibiotic administration was performed infrequently in the group with prior manipulation. However, in abscess formation cases in the group with prior manipulation, single antibiotic administration was more frequent (71.4%; 10/14) than combination antibiotic administration. In conclusion, this is the first report recording the clinical and microbiological aspects of ABP in Korea. This survey may help clinicians to select appropriate empirical treatment. In this study, ABP with prior manipulation of the lower urinary tract and spontaneous ABP showed distinct characteristics with regard to clinical and microbiological features. Management of ABP must be tailored to local microbiological sensitivity patterns and with regard to the history of prior manipulation of the lower urinary tract.
Acknowledgments The authors thank the following urologists for contributing case material and for providing patient information: Choong Bum Lee, Sae Woong Kim, Hong Jin Suh, Joon Chul Kim, Su Yeon Cho and Doo Bae Kim (Department of Urology, The Catholic University of Korea College of Medicine, Seoul, South Korea); Dong Deuk Kwon (Department of Urology, Chonnam National University Medical School, Gwangju, South Korea); Sang Eun Lee (Department of Urology, Seoul National University Bundang Hospital, Seongnam, South Korea); Duk Yoon Kim (Department of Urology, College of Medicine, Catholic University of Daegu, Daegu, South Korea); Kyu-Sung Lee (Department of Urology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea); Sung-Goo Chang (Department of Urology, School of Medicine, Kyung Hee University, Seoul, South Korea); Hyung Jin Kim (Department of Urology, Chonbuk National University Medical School, Jeonju, South Korea); and Luck Hee Sung (Department of Urology, Sanggye Paik Hospital, College of Medicine, Inje University, Seoul, South Korea). We would like to thank Dr Yong Sun Choi and Dr Kang June Cho for data collection and input. Funding: None. Competing interests: None declared.
U.-S. Ha et al. / International Journal of Antimicrobial Agents 31S (2008) S96–S101
Ethical approval: This study was approved by institutional board review in The Catholic University of Korea College of Medicine (approval number SCMC07OT069).
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