Chronic Vulvovaginitis Caused by Antibiotic-Resistant Shigella Flexneri in a Prepubertal Child

A 7-year 8-month-old girl was diagnosed with a prolonged course of vulvovaginitis caused by Shigella flexneri. The child was symptomatic with intermittent vaginal bleeding, dysuria and foul smelling vaginal discharge for a 3-year period. Initial attempts to resolve the infection with successive courses of antibiotic therapy using ampicillin, trimethoprim-sulfamethoxazole, cefixime and amoxicillin/clavulanic acid failed. The child’s infection was finally resolved by a 14-day course of ciprofloxacin. Shigella is an uncommon but known cause of vulvovaginitis in prepubertal girls. 1 We present a case of a 7-year-old girl with a prolonged course of vaginal discharge caused by S higella flexneri exhibiting multi-antimicrobial resistance, in whom the use of a quinolone antibiotic was effective treatment. Patient history. A healthy 7-year 8-month-old girl presented to the outpatient clinic with a 2-day history of intermittent vaginal bleeding, dysuria and persistent foul smelling vaginal discharge. The history was negative for fever, weight loss, abdominal pain, vomiting, diarrhea, constipation, easy bruising or additional sites of bleeding. The child and mother denied any history of trauma, sexual abuse or foreign travel. There was no history of recent antibiotic use. White to yellow vaginal discharge had been noted frequently on the child’s underwear during the previous 3 years. The child had been evaluated by four physicians during the 3-year period. One year prior she had received oral antibiotics and vaginal antifungal creams with no relief of vaginal symptoms. Seven months earlier a diagnosis of nonspecific vaginitis was made, after negative gonococcal and chlamydial vaginal cultures. Reassurance and bathing/hygiene recommendations were made with little change in symptoms. Family history was negative for gynecologic malignancy, bleeding dyscrasias and renal problems. Physical examination revealed a well-appearing girl with normal vital signs and growth measurements. She had Tanner 1 breast and genitalia staging and no pallor or evidence of bleeding. Genitourinary examination in the frog leg and knee-chest position revealed normal external genitalia with no lesions or abrasions, and the hymen was intact. There was mild vulvar erythema and no vaginal discharge. The anus was normal in appearance. A clean catch urine specimen had a specific gravity of 1.025, pH 6.0, 3+ protein, moderate leukocyte esterase, negative nitrites, large blood, with 104 red blood cells, 132 white blood cells and many bacteria on microscopy. A tentative diagnosis of nonspecific vulvovaginitis and hemorrhagic cystitis was made. Urine and vaginal specimens were sent for bacterial culture and the patient was treated with trimethoprim-sulfamethoxazole (TMP-SMX). The urine culture grew >100 000 colonies/ml Escherichia coli resistant to TMP-SMX. The vaginal culture grew Gardnerella vaginalis, rare diphtheroids and Shigella flexneri Group B 2 resistant in vitro to TMP-SMX and ampicillin, but susceptible to cefixime, amoxicillin/clavulanic acid and levofloxacin. TMP-SMX was discontinued and the patient was given a course of cefixime for 10 days. The vaginal bleeding stopped within 48 h of antibiotic therapy and her vaginal discharge improved but had not resolved 1 month after antibiotic treatment. Follow-up vaginal culture remained positive for S. flexneri, and a stool culture was negative for Shigella and other enteric pathogens. A repeat urine culture was negative. The child was given a 14-day course of amoxicillin/clavulanic acid , with no change in vaginal symptoms. One month later the child received ciprofloxacin for 14 days with resolution of the vaginal discharge for the first time in 3 years. Follow-up vaginal culture was negative. She has remained symptom-free for 6 months of follow-up. Discussion. Shigella is an uncommon and often unrecognized cause of vulvovaginitis in prepubertal children. 1–6Shigella vaginitis manifests as a chronic vaginal discharge, present for weeks to months before diagnosis. In one-half of the cases there is associated bloody discharge. 1 Pain, pruritus or dysuria are associated findings in few cases, and few patients have a history of recent diarrhea. 1 Our case is noteworthy for the very prolonged clinical course of 3 years because the longest duration of symptoms previously reported is 8 months. 1 Recognition of Shigella vaginitis is a diagnostic challenge because it can present similarly to a urinary tract infection with urinary complaints of dysuria, bleeding without diarrheal or dysenteric symptoms. In our case it is likely that the exacerbation of the vaginal infection and the genital inflammation were predisposing factors for the development of the urinary infection. The urinary infection was caused by a strain of E. coli responsive to antibiotic therapy. Vulvovaginitis is a common pediatric gynecologic disease usually associated with mixed growth of fecal organisms and less often with specific bacterial, fungal or parasitic infection, irritation, allergy, foreign bodies or sexual abuse. 7 Gonorrhea can manifest as vaginitis in prepubertal girls and therefore is included in the differential diagnosis of vulvovaginitis; however, gonorrhea is not associated with bloody discharge. There is one report of a child with documented sexual abuse and Shigella vulvovaginitis. 5 Although all types of Shigella have the potential of causing vaginal infections, most reported cases are caused by S. flexneri, even though this species is not the predominant cause of shigellosis in most counties. Murphy and Nelson 1 reported that 87% of 38 cases of Shigella vaginitis were caused by S. flexneri while during the same period at their institution S. flexneri and S. sonnei were equally common isolates from all other sites of infection. In Chicago and all of the United States, Shigella sonnei is the predominant species associated with shigellosis. In 1999, 76% of Shigella serogroups reported to the Centers for Disease Control and Prevention were S. sonnei, whereas only 16% were S. flexneri.8 Many treatment modalities have been used to treat Shigella vaginitis. Systemic antibiotic therapy has been more effective than topical antimicrobials or estrogen therapy. 1 Until a few years ago ampicillin and TMP-SMX were acceptable empiric therapy for shigellosis in developed countries. There are an increasing number of resistant strains especially in infections associated with foreign travel. In 1999 a CDC national survey showed that 75% of Shigella isolates were resistant to ampicillin and 34% were resistant to TMP-SMX. No isolates were resistant to ciprofloxacin. 9 The authors concluded that when antibiotics are indicated, a quinolone or cefixime should be used as empiric therapy. In our patient the S. flexneri isolate was susceptible in vitro to amoxicillin/clavulanic acid and cefixime, but treatment with these antibiotics was not successful. Negative stool cultures ruled out an intestinal source of reinfection. A failure of cefotaxime has been reported in a child with shigellosis in which the organism was ampicillin-resistant but susceptible to cefotaxime. 10 The mechanism for treatment failure is unknown. In our case a 14-day course of ciprofloxacin successfully eradicated the infection. This positive result is supported by a study documenting excellent penetration of oral ciprofloxacin into gynecologic tissues. 11 The use of fluoroquinolones in children has been limited because of the potential cartilage damage that occurred in young laboratory animals. However, several reports of ciprofloxacin use in hundreds of children for severe infections, such as Pseudomonas infections in cystic fibrosis, febrile neutropenia and bone and joint infections, have shown minimal adverse reactions and no evidence of arthropathy. 12, 13 Also three randomized, controlled trials of ciprofloxacin in shigellosis have demonstrated its efficacy and safety in children 14, 15 and adults. 16 In conclusion this case is unique because of the prolonged duration of the child’s symptoms and the therapeutic challenge posed by this multi-drug-resistant organism. Although much of the United States, including Chicago, is not endemic for Shigella, clinicians should consider Shigella as a potential cause of vulvovaginitis. Finally our case also exemplifies the efficacy and lack of adverse reaction in short course therapy with ciprofloxacin for an extraintestinal manifestation of shigellosis in pediatric patients.