Pyelonephritis‐associated Staphylococcus saprophyticus bacteremia in an immunocompetent host: Case report and review of the literature

Abstract Staphylococcus saprophyticus is one of the coagulase‐negative staphylococcus species. It is the second most frequent causative microorganism in acute uncomplicated urinary tract infections in young women. However, it is potentially capable of causing more invasive infections including bacteremia, particularly secondary to pyelonephritis. We present a young, previously healthy lady who presented with urinary symptoms and hemodynamic instability and was found to have multiple renal and ureteric calculi with pyelonephritis. Later, blood and urine cultures isolated methicillin‐resistant S. saprophyticus. The patient was successfully treated with a course of antibiotics targeting the organism with a favorable outcome. The clinical presentations and management of this rare entity of S. saprophyticus bacteremia‐related pyelonephritis are outlined. In addition, the literature on similar cases was reviewed to raise awareness and avoid devastating consequences.


| INTRODUCTION
Staphylococcus saprophyticus is a gram-positive, novobiocinresistant, coagulase-negative staphylococcus species. 1 It is the second most frequent causative microorganism in acute uncomplicated urinary tract infections in young, sexually active women. 2 However, it can present with a variety of complicated genitourinary tract infections which include prostatitis, pyelonephritis, and epididymitis. 3 Staphylococcus saprophyticus bacteremia rarely complicates the involvement of the urinary tract, particularly in immunocompetent hosts. 4 The clinical presentation and diagnosis are usually undistinguished S. saprophyticus bacteremia secondary to pyelonephritis from typical uropathogens. 5 Typically, S. saprophyticus is sensitive to most antimicrobials used to treat UTIs. However, there is rising resistance of S. saprophyticus to empirically and commonly used antibiotics to treat cystitis, hence, rendering the management more challenging. 6 Herein, we report an unusual highly resistant case of S. saprophyticus pyelonephritis leading to bacteremia in an otherwise healthy young female patient who was successfully treated with a course of vancomycin and daptomycin. In addition, we reviewed the literature for similar cases. capable of causing more invasive infections including bacteremia, particularly secondary to pyelonephritis. We present a young, previously healthy lady who presented with urinary symptoms and hemodynamic instability and was found to have multiple renal and ureteric calculi with pyelonephritis. Later, blood and urine cultures isolated methicillin-resistant S. saprophyticus. The patient was successfully treated with a course of antibiotics targeting the organism with a favorable outcome. The clinical presentations and management of this rare entity of S. saprophyticus bacteremia-related pyelonephritis are outlined. In addition, the literature on similar cases was reviewed to raise awareness and avoid devastating consequences.

K E Y W O R D S
bacteremia, kidney calculi, pyelonephritis, Staphylococcus saprophyticus

| CASE PRESENTATION
A 28-year-old lady, previously well presented to the hospital with a 2 days history of fever, dysuria, and left flank pain. She had no chronic medical condition or previous similar episodes. On examination, vital signs showed a fever of 38.2 with normal BP 115/71 and HR of 87. Abdominal examination revealed suprapubic and costovertebral tenderness. Basic investigation revealed high inflammatory markers with pyuria and acute kidney injury as depicted in the below (Table 1).
Computed tomography scan revealed bilateral renal calyceal and ureteric stones causing hydronephrosis and obstructive uropathy ( Figure 1). The patient was started on meropenem as per local antibiogram for presumptive urosepsis awaiting the results of the cultures. Both blood and urine cultures grew highly resistant staphylococcus saprophyticus that was sensitive only to vancomycin, daptomycin, gentamycin, and linezolid. Hence, the patient's antibiotic was changed to vancomycin. An echocardiogram was done, and it ruled out cardiac vegetations, and repeated blood cultures after 3 days were negative. A bilateral percutaneous nephrostomy was inserted which relieved her urinary obstruction. Subsequently, the patient improved clinically with normalization of her kidney parameters. Following removal of the percutaneous nephrostomy after passing the stones, she was discharged on daptomycin for ease of outpatient administration to complete a total of 14 days of antibiotics. On follow-up visits, she had no recurrence of her urinary symptoms, and normal kidney function was restored. the epithelium of the urogenital tract utilizing hemagglutinin and adhesins that help to anchor the bacteria to the cell wall allowing it to escape the immune system. Furthermore, catalase protects S. saprophyticus from being killed by reactive oxygen species. 7 The existence of a renal tract obstruction would favorably enable S. saprophyticus to ascend more proximally toward the renal pelvis causing pyelonephritis as in our case. 8 Staphylococcus saprophyticus is a well-recognized cause of uncomplicated cystitis after E. coli and has been isolated in 42% of young females with uncomplicated cystitis. 2,9 The usual course of uncomplicated Staphylococcus saprophyticus infection is mild and responds well to antibiotics either orally or intravenously in more severe cases. 3 Nevertheless, complicated genitourinary infections including prostatitis, pyelonephritis, and epididymitis have rarely been reported in certain high-risk patients. 8 Many risk factors have been reported for complicated Staphylococcus saprophyticus UTIs such as immunocompromised hosts, obstructive nephrolithiasis, indwelling urethral catheters, and the presence of renal tract anomalies. 10 However, it rarely causes infection in immunocompetent adults.

| DISCUSSION
Although Staphylococcus saprophyticus is a wellestablished cause of uncomplicated UTIs, it is pathogenic significance, role in complicated UTIs, and clinical significance when isolated from blood culture has not been well defined. 4,10 It has been postulated that S. sapro is of low virulence due to multiple reasons, including the absence of coagulase, unlike other staphylococci. Coagulase degrades fibrin and results in clotting activation, and coats the organism helping to escape phagocytosis. Furthermore, Staphylococcus saprophyticus lacks ATPase; hence, it is difficult to grow in low potassium environments such as the blood, whereas urine is a suitable medium because it is potassium contents. 8 For these reasons, the pathogenicity of S. saprophyticus might be lower in the blood than in urine because of its physiological function and activity. Even though, when bacteremia occurs, the significance is still not well established, and further studies are required to delineate the course. 4 Staphylococcus saprophyticus is generally sensitive to most antibiotics including beta-lactams. However, some strains isolated from complicated UTIs were generally more resistant to broad-spectrum antibiotics than those isolated from uncomplicated infections. 11 This explains the high resistance profile isolated from our patient.
The optimal treatment for bacteremia due to S. saprophyticus is not yet well defined given it is a rarity. In our case, we treated the patient with antibiotics for 2 weeks given the highly resistant nature of the organism and the presence of urinary obstruction. 4 Our search of the literature yielded a total of nine cases of S. saprophyticus bacteremia originating from  (Table 2). Cases ranged between 14 and 53 years of age and were predominantly female. Half of them had underline urolithiasis while no immunosuppressed status was reported. Pyelonephritis is mostly involved in bacteremia rather than uncomplicated UTIs. Of the cases identified, only two cases reported some form of resistant staphylococcus saprophyticus as in our case. The duration of therapy ranged from 7 days to 21 days. All cases achieved complete recovery and clearance of the bacteremia with no complications (Table 2).

| CONCLUSION
Pyelonephritis-associated staphylococcus saprophyticus bacteremia in an immunocompetent host is a rare clinical entity that demonstrates the ability of the organism to manifest as invasive infections. S. saprophyticus is generally sensitive to most antibiotics commonly used to treat uncomplicated community-acquired UTIs; however, resistance strain is raising which necessitating caution when dealing with the invasive infection of this organism. The treatment should be guided by the pattern of antimicrobials sensitivity, and the optimal treatment duration remains unknown.