Empiric antibiotics for an elevated prostate specific: good or evil?
Prostate specific antigen (PSA) is a protein secreted by benign and malignant prostate tissue. Therefore,
an increase in serum PSA is not pathognomonic for cancer but can be attributed to a number of clinical
conditions including inflammation and infection.
To date, several groups have examined the impact of empiric antibiotics on men with an increased PSA.2,3
However, these studies were limited since they lacked a control arm. In the absence of this control population, it is unclear if the observed PSA changes were secondary to natural variation, regression toward the mean or a true antibacterial effect.4
For men with an increasing PSA without clinical evidence of infection, a commonly used strategy
is to empirically prescribe antibiotics and subsequently recheck the PSA.1
The intended goal is to treat a subclinical infection, induce a decrease in PSA and potentially eliminate the
need for a prostate biopsy.
Methods and results
It is a randomized mono institutional trial. 100 men undergoing their first prostate biopsy was recruited and randomized by a computer program of assignment of random number (www.ramdomizer.org) , PSA levels 4.0-10 ng/mL, a negative digital rectal examination and no clinical or laboratory signs of urinary infections. All the specimens were analyzed in our laboratory (using Beckam Coulter access II Immunoassay System PSA). Analysis of data [age, PSA changes, antibiotics therapy, biopsy result (presence of cancer)] was carried out using an SPSS statistical analysis software (IBM SPSS Statistics 21). Kolmogorov-Smirnov test (cutoff at p < 0.01) was used for distributions of continuous variables. Continuous variables were described using mean ± standard deviation. Categorical variables were described using frequency distributions . To compare PSA elevation prior to and following antibiotic therapy we used the Student’s-t-test for independent samples. Multivariate logistic regression analysis was used to model detected prostate cancer. All tests were two-sided and considered significant at p 0.05).
Multivariate analysis revealed no significant difference between the groups (P Value > 0.05 in all categories)
Prostate cancer detection rates were not significantly associated with the change in PSA, regardless of whether levels increased or decreased.
Sepsis after biopsy occurred in 3 patient in the antibiotics group ( 6%) and in 1 of control group (2%)
The results of this study failed to show any advantage for Random floroquinolone antibiotic treatment to avoid biopsy in the setting of PSA levels between 4-10 ng/mL and no signs or symptoms of infection.
In chronic prostatitis, it has been shown that the total PSA and free PSA are all significantly higher in patients with infection. A course of fluoroquinolone therapy in these patients resulted in a median PSA decrease from 8.3 to 5.3ng/ml (10).
For Habermacher et al. (11) the most of cases of asymptomatic prostatitis are not caused by bacteria, eliminating the rationale for antibiotics.
In Kaygisiz et al. study (5), all 48 of their patients were administered antibiotics and underwent biopsies. The PSA levels decreased below 4 ng/mL in 18 (37%) of them and the biopsies of these men were negative for malignancy. The findings for the other 30 men were prostate cancer in 10.8%. The authors suggest a long course of antibiotic treatment at least 3 weeks, regardless of inflammation findings, when PSA levels are mildly high (i.e., 4-10 ng/mL), and by the results they take the decision of whether or not to carry out a biopsy.
Bozeman et al. reported that when serum PSA had normalized with treatment there was no indication for biopsy in almost half of their 95 patients diagnosed with elevated PSA and chronic inflammation, so treatment can decrease the percent of negative biopsies (12).
A recent editorial by Scardino criticized the unjustified use of antibiotics . (8).
Akduman et al demonstrated that patients who received 3 weeks of fluoroquinolones before biopsy had a significantly greater incidence of post-biopsy sepsis (5.4% vs 1.7%) and all sepsis episodes were attributable to quinolone resistant bacteria.(13)
Other studies have similarly shown that prior therapy with quinolones predisposes to rectal flora resistance (14).
Our trial have some limitations. We had few cases with histologic evidence for chronic prostatitis in our study. This may explain why prompt administration of antibacterial therapy was not helpful in our series.
We studied a single antibiotic for 20 day, which we believed reflected common clinical practice. It is possible that a different antibiotic or duration would alter the findings. It is possible that a larger trial would identify a clinical benefit for empiric antibiotics, although we suspect that the lack of any trend toward a clinical benefit makes this unlikely.
It is of paramount importance to use antibiotics responsibly. In patients with an increased PSA antibiotics are appropriate if there is clinical suspicion or evidence of infection.
Any elevation of PSA, be it spurious or true, should be an indication for repeat PSA testing, but we advocate withholding antibiotics until a bacterial cause has been identified.
Empiric use is not of clinical benefit, without clinical or laboratory evidence of infection or inflammation, may paradoxically be harmful , repeating a new PSA test before scheduling a biopsy remains the only sensible approach.
Our data show to be no advantage for antibacterial therapy for decreasing initial PSA levels between 4-10 ng/mL.
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