microorganisms Article Emergence of Staphylococcus lugdunensis as a Cause of Urinary Tract Infection: Results of the Routine Use of MALDI-TOF MS 1, 2, 1 1,3,4, Kelvin H. Y. Chiu y, Rex P. K. Lam y, Elaine Chan , Susanna K. P. Lau * and Patrick C. Y. Woo 1,3,4,* 1 Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; [email protected] (K.H.Y.C.); [email protected] (E.C.) 2 Emergency Medicine Unit, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China; [email protected] 3 State Key Laboratory of Emerging Infectious Diseases, The University of Hong Kong, Hong Kong, China 4 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The University of Hong Kong, Hong Kong, China * Correspondence: [email protected] (S.K.P.L.); [email protected] (P.C.Y.W.); Tel.: +852-2255-2584 (S.K.P.L. & P.C.Y.W.); Fax: +852-2855-1241 (S.K.P.L. & P.C.Y.W.) These authors contributed equally to this work. y Received: 20 February 2020; Accepted: 5 March 2020; Published: 9 March 2020 Abstract: We analyzed the incidence and the clinical and laboratory characteristics of Staphylococcus lugdunensis urinary tract infections (UTIs) during a 10-year period (2009–2018) and compared them with those of Staphylococcus saprophyticus UTIs. A total of 38 and 162 episodes of S. lugdunensis and S. saprophyticus UTIs were observed. The number of S. saprophyticus UTIs was stable throughout the 10 years, whereas there was an obvious surge in the apparent number of S. lugdunensis UTIs since 2014, coinciding with the commencement of a routine use of MALDI-TOF MS. Univariate analysis showed that male sex (p < 0.001), advanced age (p < 0.001), hospital-acquired infections, (p < 0.001), upper UTI (p < 0.005), polymicrobial infections (p < 0.05), hypertension (p < 0.001), solid-organ malignancies (p < 0.001), renal stones (p < 0.001), urinary stricture (p < 0.05), vesicoureteral reflux (p < 0.001), and presence of a urinary catheter (p < 0.001) were significantly associated with S. lugdunensis UTI. Multivariable analysis revealed that S. lugdunensis UTI was associated with male sex (OR = 6.08, p < 0.05), solid-organ malignancies (OR = 12.27, p < 0.01), and urological system abnormalities (OR = 7.44, p < 0.05). There were significant differences in the patient population affected and predisposing factors between S. lugdunensis and S. saprophyticus UTIs. Keywords: Staphylococcus lugdunensis; urinary tract infection; MALDI-TOF MS 1. Introduction Traditionally, staphylococci have been classified phenotypically by the presence or absence of coagulase. This method is also used to identify individual staphylococcus strains such as coagulase-positive Staphylococcus aureus or coagulase-negative staphylococci. Among the coagulase-negative staphylococci, Staphylococcus saprophyticus, identified phenotypically by its resistance to novobiocin, is the second most important cause of community-acquired urinary tract infection (UTI) in sexually active young females [1]. Apart from S. saprophyticus, other coagulase-negative staphylococci isolated from the urinary tract were often not further identified to the species level, and therefore their roles in UTI cannot be ascertained. In recent years, another coagulase-negative staphylococcus, Staphylococcus lugdunensis, has emerged as a cause of invasive bacterial infections, such as infective endocarditis and skin and soft tissue Microorganisms 2020, 8, 381; doi:10.3390/microorganisms8030381 www.mdpi.com/journal/microorganisms Microorganisms 2020, 8, x FOR PEER REVIEW 2 of 9 the species level, and therefore their roles in UTI cannot be ascertained. In recent years, another coagulase-negative staphylococcus, Staphylococcus lugdunensis, has emerged as a cause of invasive bacterial infections, such as infective endocarditis and skin and soft tissue infections [2]. It is of note Microorganisms 2020, 8, 381 2 of 9 that both S. lugdunensis and S. saprophyticus reside around the genitourinary tract, with S. lugdunensis colonizing the pelvic, perineum, and groin region, and S. saprophyticus colonizing the rectum and genitourinaryinfections tract [2]. It [3]. is of Considering note that both theirS. lugdunensissimilar localizationand S. saprophyticus in the humanreside body around as well the genitourinaryas their importanttract, withvirulenceS. lugdunensis properties,colonizing we hypothesize the pelvic,d perineum, that S. lugdunensis and groin is region, a prev andiouslyS. saprophyticus underestimatedcolonizing pathogenthe rectum of the andurinary genitourinary tract. Although tract [3 ].case Considering reports and their small similar case localization series of S. in lugdunensis the human bodyUTI have as well as been theirdescribed important [4– virulence6], there properties,has been weno hypothesized systematic thatanalysisS. lugdunensis of the isclinical a previously and laboratory underestimated characteristicspathogen ofon the this urinary clinical tract. entity. Although case reports and small case series of S. lugdunensis UTI have been Matrixdescribed-assisted [4–6], therelaser hasdesorption been no ionization systematic time analysis-of-flight of the mass clinical spectrometry and laboratory (MALDI characteristics-TOF MS on) this has recentlyclinical entity. emerged as a revolutionary technique for the identification of bacterial pathogens, yielding rapid,Matrix-assisted accurate, and laser highly desorption reproducible ionization results time-of-flight at a lowe massr price spectrometry than any other (MALDI-TOF methods MS) routinelyhas recentlyused in emergedclinical laboratories as a revolutionary [7]. The technique methodology for the is identificationeasy to follow of, requires bacterial only pathogens, a minimalyielding amount rapid, of bacteria accurate, for and the highly analysis, reproducible and provides results results ata within lower minutes. price than Therefore, any other it methodshas now routinelybeen integrated used in into clinical many laboratories clinical laboratories [7]. The methodology and is useful is easyfor the to follow,identification requires of only different a minimal groupsamount of medically of bacteria important for the analysis,bacteria [8 and–10 provides]. Since the results start withinof the routine minutes. use Therefore, of MALDI it- hasTOF now MS been in ourintegrated clinical microbiology into many clinical laboratory laboratories in January and 2014, is useful we have for theobserved identification an unpreced of diffentederent surge groups of of S. medicallylugdunensis important isolates bacteriaidentified [8 –in10 urine]. Since samples the start of of our the patients. routine use In ofthis MALDI-TOF study, we describe MS in our the clinical apparentmicrobiology emergence laboratory and the inclinical January and 2014, laboratory we have characteristics observed an unprecedentedof patients with surge UTIs of causedS. lugdunensis by S. lugdunensisisolates identified in a 10-year in urine period samples and com ofpare our patients. them with In thisthose study, of S. wesaprophyticus describe the in apparentthe same emergencestudy period.and the clinical and laboratory characteristics of patients with UTIs caused by S. lugdunensis in a 10-year period and compare them with those of S. saprophyticus in the same study period. 2. Materials and Methods 2. Materials and Methods 2.1. Ethical Statement 2.1. Ethical Statement This study was approved by the Institutional Review Board of The University of Hong Kong/HospitalThis studyAuthority was (UW16 approved-365, approved by the Institutional 22-07-2016). Review Board of The University of Hong Kong/Hospital Authority (UW16-365, approved 22-07-2016). 2.2. Patients 2.2. Patients All patients whose urine samples were found positive to S. lugdunensis and S. saprophyticus during a All10-year patients period whose (200 urine9–2018) samples in hospitals were found in positiveHong Kong to S. lugdunensisWest Clusterand—includingS. saprophyticus Queenduring Marya 10-yearHospital, period Tung (2009–2018) Wah hospital, in hospitals Grantham in Hong Hospital Kong, Westand Cluster—includingFung Yiu King Hospital Queen Maryof Hong Hospital, KongTung—were Wah included hospital, in Grantham the study. Hospital, The medical and Fungrecords Yiu of King the Hospitalpatients ofwere Hong retrieved Kong—were for analysis. included in Thosethe episodes study. The of illness medical that records met ofthe the definition patients wereof UTI retrieved given below for analysis. were included Those episodes for further of illness analysisthat ( metFigure the 1 definition). of UTI given below were included for further analysis (Figure1). Figure 1. Enrollment flowchart of urinary tract infection (UTI) cases caused by Staphylococcus saprophyticus and Staphylococcus lugdunensis in 2009–2018. Microorganisms 2020, 8, 381 3 of 9 2.3. Microbiological Methods Before January 2014, all staphylococci were first tested with Staphaurex plus latex agglutination test (Thermo Scientific). For all coagulase-negative staphylococci, the novobiocin disk diffusion test was used to identify S. saprophyticus (novobiocin-resistant). All novobiocin-sensitive coagulase-negative staphylococci were discarded, unless the microbiologist had requested their full identification. After January 2014, all staphylococci were preliminarily identified by MALDI-TOF MS. When MALDI-TOF MS results showed the presence of S. lugdunensis, bacterial identity was further confirmed by positive Staphaurex plus latex agglutination test and negative tube