Definitions of Complicated Urinary Tract Infection and Pyelonephritis

To the Editor—I have concerns regarding some of the definitions Wagenlehner et al [1] used in their trial of ceftazidime-avibactam vs doripenem for urinary tract infections (UTIs) because of the possible adverse impact on interpretation of trial results and on readers’ understanding of how to rationally classify UTIs. First, the title and second sentence of the article indicate that pyelonephritis per se constitutes complicated UTI [1]. Although this is a common misunderstanding among nonspecialists, to specialists “complicated UTI” means UTI occurring in a host with predisposing conditions, regardless of the presenting syndrome (eg, cystitis vs pyelonephritis) or severity of illness. Ironically, the references that Wagenlehner et al cite to support pyelonephritis as representing complicated UTI instead contradict this notion. For example, Foxman writes, “UTIs are classified as either lower (confined to the bladder) or upper (pyelonephritis), and as either uncomplicated or complicated. An uncomplicated UTI is one occurring in a normal host who has no structural or functional abnormalities, is not pregnant, or who has not been instrumented (for example, with a catheter). All other UTIs are considered complicated” [2]. Johansen et al (including Dr Wagenlehner) likewise clearly distinguish between (1) clinical presentation (eg, lower vs upper UTI) and (2) risk factors for UTI, the latter being what qualify a UTI as complicated, regardless of clinical presentation [3]. Second, the study’s definition of pyelonephritis did not require fever [1]. This is curious, as most authorities include fever as a necessary criterion for pyelonephritis. Here, although 72% of subjects ostensibly had pyelonephritis, only 38% had fever. Even if all 38% were in the pyelonephritis group, this would mean that more than half of subjects with (supposed) pyelonephritis were afebrile. This either represents very mild pyelonephritis or something else entirely—for example, cystitis, plus other symptoms (nausea/vomiting or flank pain/tenderness) of a different cause. Third, complicating factors were present in only 38% of subjects overall, including 28% without pyelonephritis and 10% with (supposed) pyelonephritis. The remaining 62% had no complicating factors, and had either mild pyelonephritis or an undefined UTI syndrome—hardly a suitable study population for a treatment trial of either complicated UTI or pyelonephritis. In view of these definitional issues, the applicability of the study’s findings to patients with true complicated UTI, or classic (febrile) pyelonephritis, is unknown. Potential conflicts of interest. J. R. J. reports personal fees from Crucell/Janssen and grants from Actavis/Forest, Merck, and Tetraphase, outside the submitted work; he also has patents pending (“High-Resolution Two-Locus Clonal Typing of Extraintestinal Pathogenic Escherichia coli,” provisional 61/749,144, and “Primers, Assays and Methods for Detecting an E. coli subtype,” provisional 61/667,402).