Short-course quinolones, pivmecillinam on par with standard regimens in uncomplicated cystitis

For women with acute uncomplicated cystitis, treatment regimens that include third- and fourth-generation quinolones and pivmecillinam can be administered in shorter courses, which perform similarly to the currently recommended regimens in terms of achieving symptomatic cure, according to the results of a meta-analysis presented at the 37th Annual European Association of Urology (EAU) Congress.

Pooled data from 61 randomized clinical trials, which comprised a total of 20,780 patients, showed that a 3-day regimen of third- and fourth-generation fluoroquinolones yielded comparable clinical response compared with a single-dose regimen (third gen/3-day vs single dose: risk ratio [RR], 0.994, 95 percent credible interval [CrI], 0.939–1.052; fourth gen/3-day vs single dose: RR, 1.024, 95 percent CrI, 0.974–1.083), with moderate quality of evidence, said lead study author Dr Do Kyung Kim of Soonchunhyang University Seoul Hospital, Seoul, South Korea. [EAU 2022, abstract A0109]

Likewise, for pivmecillinam, clinical responses with the 5- and 7-day regimens were similar to that obtained using the shorter 3-day regimen, with moderate quality of evidence (5- vs 3-day: RR, 1.041, 95 percent CrI, 0.910–1.193; 7- vs 3-day: RR, 1.095, 95 percent CrI, 0.999–1.203).

“Meanwhile, for third-generation cephalosporins and amoxicillin and clavulanate, there was no difference between the single-dose and 3-day regimens, but the quality of evidence supporting this conclusion was low,” Kim noted.  

When it came to second-generation quinolones and co-trimoxazole, a single-dose regimen was found to be less effective than the 3-day regimen, with moderate quality of evidence.

“Evidence from numerous randomized clinical trials suggest that shorter-term antimicrobial therapy is as effective as—and has other advantages over—longer-term antimicrobial regimens at achieving symptomatic cure for acute uncomplicated cystitis. Nevertheless, not all shorter regimens are adopted in clinical guidelines,” Kim pointed out.

The findings of the present meta-analysis suggest that the treatment duration of the third- and fourth-generation quinolones and pivmecillinam could be shortened. “For other antibiotics, shorter duration of regimens could be considered, but further research is needed because of the low quality of supporting evidence,” he added.

Nipping recurrence in the bud

Aside from delivering higher symptomatic and bacteriologic cure rates, appropriate antibiotic therapy also helps to better prevent reinfection in women with uncomplicated cystitis. But with repeated use, antibiotics risk losing their efficacy, with pathogens encouraged to develop immunity. Another downside is the adverse effects of the drugs on the gut and vaginal flora. [J Infect 2009;58:91-102; Nat Rev Urol 2010;7:653-660]

In order to reduce the number of symptomatic episodes and minimize antibiotic use among women with recurrent cystitis, another team of investigators who presented their study at the EAU Congress called for the identification and removal of risk factors, as well as counselling on the natural course of recurrent urinary tract infection.

Such an approach, they said, can change the natural history of the disease and improve antibiotic stewardship.

Led by Dr Tommaso Cai of Santa Chiara Regional Hospital, Trento, Italy, the investigators evaluated the effect of an intervention that involved the treatment or removal of risk factors among 373 women with recurrent cystitis. Those with nonremovable risk factors were included in the control group.

All patients had undergone a systematic and standardized identification of risk factors and were scheduled for follow-up visits every 6 months. Cai and colleagues used the LUTIRE nomogram to stratify the patients into one of the following risk groups: low (total probability of recurrence over 1 year, 0.20–0.45), moderate (0.46–0.70), or high (0.71–0.99).

Risk factors considered as modifiable included diet, sexual activity, vulvovaginal atrophy, urinary incontinence (when removable), and regular treatment of asymptomatic bacteriuria. On the other hand, nonremovable risk factors were congenital diseases of the urological tract, neurological bladder dysfunction, prolapse of the anterior vaginal wall, and increased postvoid residual urine volume (not fit for surgical treatment). 

Of the patients, 196 were allocated to the intervention group and 157 to the control group. Over the 5-year follow-up period, Cai noted that the treatment or removal of risk factors had a favourable effect on the main outcome measures. Compared with the control group, the intervention group had significantly lower symptomatic recurrence rate (0.9 vs 2.6; p<0.001), as well as better quality of life scores (0.88 vs 0.63; p<0.001) and anxiety scores (Spielberger State-Trait Anxiety Inventory-Form Y, 32.7 vs 47.5; p<0.001). [EAU 2022, abstract A0038]

Furthermore, the intervention led to a significantly lower antibiotic use during follow-up (4,410 vs 9,821 used daily dose; p<0.001).

In light of the findings, Cai recommended prompt identification of risk factors related to recurrent urinary tract infection by using a validated and easy-to-use tool and stratification of patients into risk categories in everyday clinical practice for all women with recurrent cystitis. This should be followed by patient counselling and planning of active prophylaxis, which can help increase patients’ adherence to their treatment regimen. [Eur Urol Focus 2020;6:593-604; Clin Infect Dis 2020;71:3128-3135]