Prolonged Antibiotics Cut Risk of Recurrence in Polycystic Kidney Disease

Pam Harrison

June 11, 2021

A prolonged course of antibiotic therapy dramatically reduces the risk of recurrence in patients with renal cyst infections in the context of autosomal dominant polycystic kidney disease (ADPKD), a new study indicates.

However, lipid-soluble antibiotics are not more effective than water-soluble antibiotics as suggested in earlier studies, the same analysis shows.

"Cyst infections affect around 17% of ADPKD patients, mostly before the age of 45, and are associated with a high rate of recurrence even though we still don't understand either the risk factors for [the development of] cyst infections or the risk factors for treatment failure," Julien Dang, MD, said during a presentation at the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) 2021 annual meeting.

A renal cyst infection is considered a major complication of ADPKD, he added, and is associated with frequent hospitalization, worsening kidney function, and significant mortality. Data regarding treatment are scarce and recommendations are only expert-based, with a low level of evidence.

"We too found that cyst infections recur frequently, at around 14%, during the first year of follow-up, that the risk is higher in kidney transplant recipients, but that recurrence can be effectively prevented by prolonged antibiotic treatment of at least 28 days," added Dang, of Necker-Enfants Malades Hospital, Paris, France.

Asked by Medscape Medical News to comment on the findings, Neera Dahl, MD, PhD, noted that the teaching has always been that the antibiotics important for the treatment of infected cysts are those that allow for good cyst penetration. "Some cysts do not have good communication with the urinary tract — they are isolated within the tissue — so they may not have a good connection to a blood vessel," she explained.

"So, the current recommendations are to use either a fluoroquinolone or a third-generation cephalosporin," said Dahl, who is associate professor of medicine, Yale University School of Medicine, New Haven, Connecticut.

She also noted that with ADPKD, "cyst infections are rare so you have to have a pretty high threshold [of suspicion] to think about them because ADPKD patients often have pain and sensitivity anyway, and it can be challenging to think whether this is something that requires an antibiotic or not in patients who are not very sick."

Single-Center Retrospective Review

Dang and colleagues reviewed a total of 377 episodes of kidney cyst infections diagnosed at the Necker-Enfants Malades Hospital between 2000 and 2018. Out of these episodes, 11 infections in 10 patients were "definite" (microbiologically proven), 74 infections in 48 patients were "probable", and 54 episodes in 44 patients were "possible" cyst infections. In total, 149 episodes in 90 patients were included in the review.

Fever occurred as a presenting symptom in all patients in all three groups. Median age of the group was 53 years and almost one third of patients were kidney transplant recipients. The most common bacterial cause of infections was Escherichia coli, identified in 84% of all episodes.

The rate of initial antibiotic treatment failure was 16% overall, Dang reported. Antibiotic treatment failure was defined as either a need to change or adapt the initial antibiotic, or need for cyst drainage or nephrectomy. Persistent infection after 72 hours or more following a change in antibiotic therapy was also defined as initial treatment failure.

"Three risk factors were associated with first-line antibiotic treatment failure," Dang observed. These were male sex, at an odds ratio (OR) of 9.6 (P = .008), higher C-reactive protein (CRP) levels (210 vs 145 mg/L; P = .005), and cyst wall thickening (OR, 8.6; P = .008).

Independent risk factors for recurrent cyst infections during the first year of follow-up included kidney transplantation, which increased the risk of recurrence by almost fourfold, at a hazard ratio (HR) of 3.76 (P = .041).

Prolonged antibiotic therapy given for at least 28 days, in contrast, reduced the risk of recurrent infection by 98% at an HR of 0.02 (P < .001), Dang emphasized.

There were, however, no significant differences in efficacy either in the way in which antibiotic therapy was delivered or between lipid-soluble and water-soluble antibiotics.

It had been previously suggested that lipid-soluble antibiotics such as ciprofloxacin might penetrate the cyst wall more easily and therefore prove to be more effective than water-soluble antibiotics, but this observation was not confirmed in the current analysis.

"We conclude that physicians should follow treatment guidelines," Dang said. "More importantly, we saw no benefit of lipid-soluble antibiotics in kidney cyst patients as was suggested by previous cases series."

Dahl said what physicians need to find out first is whether an ADPKD patient has fever, or an elevated white cell blood count, or any other sign of infection.

If they do, then the standard would be to start them empirically on a recommended antibiotic, but if they are not getting better, "you would do something like a PET/CT scan to make sure that you have the correct diagnosis in order to be able to better treat that patient," she concluded.

Dang has reported no relevant financial relationships. Dahl has reported receiving consultancy fees from Otsuka, Natera, and Vertex.

ERA-EDTA 2021. Presented June 7, 2021.Abstract MO1220.

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