streptococcus agalactiae ( s. agalactiae ) is also known as group b streptococcus ( gbs ) , and causes invasive disease in neonates and pregnant women .
however , the incidence of invasive gbs disease among non - pregnant adults has recently increased , especially among elderly persons .
nevertheless , invasive gbs disease is rare among non - pregnant immunocompetent adults , and most patients have a chronic underlying disease , such as diabetes mellitus , neurological disease , renal failure , malignancy , or liver disease , , , .
s. agalactiae is also a rare cause of infective endocarditis ( ie ) , and most cases require early surgery because of serious complications , such as major emboli or heart failure with rapid heart valve destruction , , , .
identification of the causative pathogen is essential for the diagnosis and appropriate treatment of ie , although blood culture - negative endocarditis accounts for 2.531% of all cases of endocarditis .
one of the most common causes of blood culture - negative endocarditis is the administration of antimicrobial agents before performing the blood cultures . in this report
, we describe our experience with a case of rapid progressive culture - negative ie in an immunocompetent man , which was caused by s. agalactiae , based on the results from 16s ribosomal rna ( 16s rrna ) gene sequencing using the resected valve .
a 43-year - old previously healthy japanese man presented with a 3-week history of a high - grade fever (  >  39  c ) , rigor , and lumbago .
he was treated for a common cold using cefditoren pivoxil , although his family physician did not perform blood cultures .
the patient was subsequently referred to our hospital because his symptoms did not resolve . on the first day , chest computed tomography revealed bilateral lower lobe consolidation with pleural effusion .
therefore , we performed two sets of blood cultures and started treatment using ceftriaxone ( 2  g once daily ) , based on a preliminary diagnosis of community - acquired pneumonia .
one week after his first visit , he was admitted to our hospital after he developed dyspnea with or without effort ( body temperature : 36.5  c , heart rate : 117 beats / min , blood pressure : 98/55  mmhg , respiratory rate : 20 breaths / min , and oxygen saturation : 95% in room air ) .
chest radiography revealed a butterfly shadow with cardiomegaly and bilateral pleural effusion , which was consistent with congestive heart failure .
transthoracic echocardiography revealed a 12    10-mm vegetation on the aortic valve and severe aortic regurgitation ( fig .
1 ) . a detailed medical interview revealed that he had undergone dental care without tooth extraction at 1 month before his presentation to our hospital . at the admission , we started treatment using ampicillin / sulbactam ( 12  g daily in four doses ) and gentamicin ( 180  mg daily in three doses ) instead of ceftriaxone for native valve endocarditis , and the patient immediately underwent emergency aortic valve replacement .
the resected aortic valve was bicuspid ( fusion of the right and left coronary cusps ) , and both leaflets of the bicuspid aortic valve ( bav ) were ruptured by the vegetation ( fig .
no organisms were detected from a total of four sets of blood cultures that were performed before the surgery .
. therefore , we performed 16s rrna gene sequencing using the resected valve , which revealed bacterial dna that was 99% identical to the sequence of s. agalactiae .
magnetic resonance imaging on day 8 also revealed spondylodiscitis in the l5 and s1 vertebrae and in the l5s1 disc space ( fig .
3 ) . therefore , we diagnosed the patient as having ie that was caused by s. agalactiae and complicated by lumbar spondylodiscitis . on day 29 , the antimicrobial treatment was changed to ampicillin monotherapy ( 12  g daily in six doses ) . on day 43 after the surgery , the intravenous ampicillin was changed to oral amoxicillin ( 1500  mg daily in three doses ) to treat the spondylodiscitis .
the patient was discharged from our hospital on day 51 , and subsequently completed the 106-day regimen of antimicrobial treatment .
first , s. agalactiae should be considered a potentially causative pathogen in cases of rapid progressive ie , even among non - pregnant immunocompetent adults .
although gbs is a rare cause of ie , gbs endocarditis is associated with a poor prognosis ( a mortality rate of 3556% because of major emboli or heart failure ) , compared to ie that is caused by other streptococci ( e.g. , the viridans group ) ; therefore , early surgery is recommended for gbs endocarditis , , , . in the present case , the man did not exhibit the typical risk factors for gbs disease , although we discovered that he had undiagnosed congenital bav .
similarly , most cases of bav are not detected until the onset of infection or calcification , despite bav being the most common congenital cardiac abnormality ( found in 12% of the population ) .
the second important clinical issue from the present case is that antimicrobial stewardship should be considered , as the administration of antimicrobial agents before performing blood cultures is a major cause of culture - negative ie .
given that blood culture - negative ie accounts for 2.531% of all ie cases , it remains challenging to diagnose and appropriately treat .
up to 61% of culture - negative ie resulted from administration antimicrobial agents before performing blood cultures .
thus , genetic testing ( e.g. , 16s rrna gene sequencing ) can be useful for identifying the causative pathogen in patients with culture - negative ie .
furthermore , 16s rrna gene sequencing using the resected heart valve specimen is an important tool for complementing the diagnosis and therapeutic management of culture - negative ie , .
one reported case of culture - negative ie was caused by s. agalactiae identified using 16s rrna gene sequencing , although the patient died from progressive heart failure despite receiving antimicrobial treatment without surgery . to the best of our knowledge ,
the present case is the first successfully treated case of ie that was caused by s. agalactiae identified using 16s rrna gene sequencing in a non - pregnant immunocompetent adult .
although gbs has been considered completely susceptible to penicillin , an increasing number of japanese isolates exhibit gbs with reduced penicillin susceptibility ( prgbs ) .
the minimum inhibitory concentration ( mic ) of penicillin g for prgbs is 0.251.0  g / ml , . however , the clinical significance of isolated prgbs remains unclear , and most isolates are from elderly individuals respiratory tissue specimens . in the present case , the patient was successfully treated using antimicrobial therapy ( ampicillin / sulbactam and gentamicin ) and surgery . therefore , although we could not perform antimicrobial susceptibility testing , we selected ampicillin to replace the ampicillin / sulbactam as definitive therapy for the ie , after we had identified the s. agalactiae using 16s rrna gene sequencing .
s. agalactiae can causes rapid progressive ie , even among non - pregnant immunocompetent adults .
furthermore , antimicrobial stewardship is important , as the administration of antimicrobial agents before performing blood cultures is a major cause of culture - negative ie .
therefore , although s. agalactiae is a rare cause of rapid progressive ie , it should be considered as a potentially causative pathogen , even among non - pregnant immunocompetent adults .
the increasing incidence of prgbs with elevated -lactam mics may make it increasingly difficult to select an appropriate antimicrobial treatment for gbs endocarditis .
 streptococcus agalactiae ( s. agalactiae ) is a major cause of invasive disease in neonates and pregnant women , but has also recently been observed among non - pregnant adults , especially elderly persons or persons with underlying chronic disease . 
 s. agalactiae is also a rare cause of infective endocarditis , and most cases require early surgery . 
 we report the case of a 43-year - old previously healthy man who experienced rapid progressive culture - negative infective endocarditis with aortic valve vegetation and severe aortic regurgitation , which was complicated by lumbar spondylodiscitis . 
 emergency aortic valve replacement was performed on the day of his admission , which revealed a congenital bicuspid aortic valve was ruptured by the vegetation . 
 the resected aortic valve specimen was submitted for 16s ribosomal rna gene sequencing , which revealed that the pathogen was s. agalactiae . 
 therefore , s. agalactiae should be considered a potentially causative pathogen in cases of rapid progressive infective endocarditis , even if it occurs in a non - pregnant immunocompetent adult . 