Granulicatella infections: Comprehensive review of an elusive opportunistic pathogen

Table 1 Infective endocarditis

Ref.	Year	Country	Patient(s)	Sex	Age, years	Granulicatella species	Diagnosis	Valves involved	Intervention(s)	Outcome/prognosis
Jones et al[11]	2018	Georgia	1	Male	70	G. adiacens	Prosthetic valve IE	Aortic	Initially, piperacillin/tazobactam 3.375 g IV every 6 hours, levofloxacin 500 mg IV every 24 hours; then modified to vancomycin 15 mg/kg IV every 12 hours, ampicillin 2 g IV every 4 hours; finally, vancomycin continued and ceftriaxone 2 g IV every 12 hours (substituted for ampicillin)	Good prognosis
Tong et al[8]	2017	China	1	Female	42	G. adiacens and Candida albicans	IE with systematic embolization	Aortic	Initially, empirical ampicillin/sulbactam for fever and abdominal pain; meropenem (500 mg IV every 8 hours) after admission; emergency surgery removed a 4 cm fish bone penetrating the left atrium with large vegetation; after the blood cultures, antimicrobial therapy adjusted to meropenem and voriconazole; after two weeks, therapy switched to moxifloxacin and fluconazole	Good prognosis
Podgórska et al[28]	2022	Poland	1	Male	20	G. adiacens	IE	Mitral and aortic	Initially, empirical vancomycin, gentamicin, and rifampicin for suspected IE; cardiac surgery performed for mitral valve replacement and aortic homograft implantation; arterial-venous extracorporeal membrane oxygenation applied due to multi-organ failure; later, G. adiacens was identified and therapy switched to ceftriaxone and gentamicin	Good prognosis
Rosenthal et al[13]	2002	Germany	1	Male	68	G. adiacens	Vertebral osteomyelitis and IE associated with a pacemaker lead	Not specified; vegetation was adjacent to the pacemaker lead	Bed rest, antibiotics (penicillin, rifampin, gentamicin), and discontinuation of gentamicin due to resistance	Good prognosis
Verdecia et al[9]	2019	United States	1	Male	42	G. adiacens Peptostreptococcus species	Tri-valvular IE	Aortic, mitral, tricuspid	IV penicillin G, gentamicin and later vancomycin added	Scheduled follow-up; potential valve replacement surgery
Warren et al[47]	2023	United States	1	Female	74	G. adiacens	Recurrent IE of a bioprosthetic aortic valve	Bio-prosthetic aortic	Initial treatment with IV ceftriaxone for six weeks; later re-operative aortic valve repair with modified nicks root enlargement; subsequent treatment with IV gentamicin and vancomycin for six weeks	Successful clearance of the bacteria after the second course of antibiotics and surgical intervention
Tang et al[10]	2021	China	1	Male	35	G. adiacens	IE with aortic valve vegetation	Aortic	Initially, teicoplanin with ceftriaxone for six weeks, followed by aortic valve replacement surgery	Good prognosis
Maudlin et al[12]	2022	Australia	1	Male	32	G. adiacens	Subacute IE presenting with right sacroilitis	Aortic	Six weeks course of IV ceftriaxone and a two-week course of synergistic gentamicin	Good prognosis
Sim et al[39]	2015	Australia	1	Male	57	G. adiacens	Subacute IE associated with type II mixed cryoglobulinaemia	Aortic (non-coronary cusps)	Six weeks of benzylpenicillin therapy, followed by aortic valve replacement with a biological prosthesis	Good prognosis
Dao et al[21]	2022	United States	1	Male	69	G. adiacens	Subacute IE presenting as diffuse alveolar hemorrhage and infection-related glomerulonephritis	Mitral (severe regurgitation and vegetation on posterior leaflet)	Ceftriaxone (later transitioned to ampicillin and gentamicin); mitral valve replacement and coronary artery bypass graft; continuous renal replacement therapy, mechanical ventilation, and vasopressor support	Mortality due to complications including cardiogenic shock
De Luca et al[16]	2013	Italy	2	Male, female	5, 7	G. adiacens; G. elegans; Granulicatella balaenopterae	IE based on modified Duke criteria; IE involving the pulmonary valve homograft	No vegetation detected on echocardiography; pulmonary valve homograft	Initial treatment with cefotaxime and gentamicin; switched to ciprofloxacin and meropenem; initial treatment with vancomycin and gentamicin; switched to vancomycin plus meropenem; eventual pulmonary valve homograft replacement	Good prognosis
Shaik et al[22]	2020	United States	1	Male	46	G. albicans	IE and post infectious glomerulonephritis	Mitral (vegetations identified)	IV vancomycin and immunosuppressive therapy; later placed on hemodialysis	Poor prognosis
Patri and Agrawal[43]	2016	United States	1	Male	63	G. elegans	IE with large aortic valve vegetation and associated cervical discitis	Aortic	Initially, vancomycin and ceftriaxone, later switched to ampicillin and ceftriaxone	Mortality due to progressive heart failure
Al-Tawfiq et al[14]	2007	Saudi Arabia	1	Male	47	G. elegans	Native valve IE	Mitral	IV antibiotics (not specified) for 7 days. Mitral valve debridement, repair of perforation, resection of posterior leaflet, and placement of Carpentier-Edwards ring	Good prognosis
Casalta et al[6]	2002	France	1	Male	29	G. elegans	IE	Aortic	Initially, IV amoxicillin and gentamicin, then replacement of aortic valve with bioprosthetic valve	Good prognosis
Vandana et al[25]	2010	India	1	Male	71	G. adiacens	IE with femoral embolism	Mitral	Initially, IV ampicillin (12 g/24 hours) and gentamicin (180 mg/24 hours). Surgical embolectomy (Fogarty’s procedure) for femoral artery thrombus. Antibiotic therapy for a total of five weeks	Good prognosis
Patil et al[41]	2019	United States	1	Female	44	G. adiacens	IE with ruptured chordae tendinae, septic embolization, brain abscess and lumbar spine osteomyelitis	Mitral	IV vancomycin and meropenem. Mitral valve replacement with Hancock type 2 mitral valve tissue. Six-week course of IV vancomycin and ertapenem	Good prognosis
Khan et al[18]	2021	United States	1	Female	73	G. adiacens	IE with severe aortic regurgitation	Aortic	Initially, IV ampicillin (2 g every 6 hours) and ceftriaxone (2 g every 24 hours) for 6 weeks with furosemide	Good prognosis
Adam et al[7]	2015	Brazil	4	Male, male. male, female	31, 64, 75, 59	Not mentioned; G. adiacens; G. adiacens; Not mentioned	IE with complications such as abscess, fistula, embolism, and heart failure	Aortic	Initially, ceftriaxone, oxacillin, and gentamicin; valve replacement surgery; later teicoplanin + gentamicin. Ceftriaxone + oxacillin + gentamicin and valve replacement surgery; later teicoplanin. Penicillin and gentamicin, no surgery. Ceftriaxone + gentamicin; valve replacement surgery; later, vancomycin and gentamicin	Good prognosis; mortality due to complications; mortality due to embolism; good prognosis
Holloway et al[15]	2021	United Kingdom	1	Female	9	G. elegans	IE	Echocardiogram revealed no clear vegetation, but increased stenosis of the right ventricle to pulmonary artery conduit	Initially, benzylpenicillin and cefotaxime, then benzylpenicillin monotherapy for 2 weeks in the hospital followed by 4 weeks of ceftriaxone	Good prognosis
Giuliano et al[32]	2012	Italy	1	Male	40	G. adiacens	IE with vegetation and erosion of aortic valve cusps, periannular abscess, and perivalvular pseudoaneurysm	Aortic	Empirical antibiotic therapy with ampicillin, gentamicin, and vancomycin (vancomycin discontinued after blood culture results). Aortic valve replacement on day 2. Combination therapy with ampicillin (12 g/day) and gentamicin (80 mg every 8 hours) for 4 weeks, followed by an additional 2-week regimen of ampicillin alone	Good prognosis
Paula et al[49]	2017	Brazil	1	Male	67	Granulicatella species	IE of mitral valve in a kidney transplant recipient	Mitral	Initially, ciprofloxacin and metronidazole upon admission. Nitazoxanide (500 mg bid for 7 days) was administered, addressing the cause of diarrhea. The treatment was changed to piperacillin-tazobactam due to persistent fever. Once Granulicatella species was identified in blood cultures, the patient was started on crystalline penicillin G (12000 IU/day, dose adjusted for renal function) and gentamicin (200 mg/day)	Mortality due to septic shock of pulmonary origin
Wang et al[20]	2015	China	1	Female	32	G. eligans	IE	Tricuspid	Initially, IV levofloxacin (750 mg every 24 hours) for 2 days. Then, IV penicillin (800 U every 12 hours) for 13 days based on antibiotic sensitivity testing	Good prognosis
Chang et al[30]	2008	Taiwan	1	Male	31	G. adiacens	IE with infectious intracranial aneurysms and recurrent hemorrhagic stroke	Mitral	Initially, ampicillin/sulbactam for 14 days, followed by oral amoxicillin/clavulanic acid for 2 weeks. Surgical clipping of infectious intracranial aneurysms. Parenteral oxacillin and gentamicin therapy for recurrent intracranial aneurysms. Mitral valvuloplasty performed 5 months after stabilization of neurological function	Full clinical improvement with no further brain insults over a 5 year follow up period
Morita et al[26]	2017	Japan	1	Female	67	G. adiacens	IE associated with primary Sjogren’s syndrome and chronic periodontitis	Aortic	Initially, ampicillin/oxacillin and gentamicin. Adjusted therapy to ampicillin and gentamicin based on antimicrobial susceptibility findings. Aortic valve replacement. Six weeks of ampicillin and gentamicin therapy	Good prognosis
Shailaja et al[19]	2013	India	1	Male	63	G. adiacens	IE with multiple vegetations on the mitral valve	Mitral	Empirical treatment with high-dose IV ampicillin (2 g every 4 hours) and gentamicin (60 mg every 8 hours) for 28 days	Good prognosis
Granda-Jiménez et al[17]	2023	United States	1	Female	8	G. elegans	IE with vegetation attached to the pulmonary trunk in a child with a history of patent ductus arteriosus	None specified; vegetations on pulmonary trunk	Forty days of IV ceftriaxone, followed by vegetation removal percutaneously. Patent ductus arteriosus closed with Amplatzer duct occluder 8/6	Good prognosis
Lin and Hsu et al[48]	2007	Taiwan	4	Female, male, male, female	18, 61, 30, 21	G. adiacens	IE with rheumatic heart disease and heart failure; IE with heart failure; IE with ruptured mycotic cerebral aneurysm; IE with heart failure and limb embolisation	Aortic; mitral and tricuspid; mitral; mitral and tricuspid	Aortic valve replacement with mechanical valve; penicillin and gentamicin. Mitral and tricuspid valve replacement with bioprosthesis; penicillin and gentamicin. Mitral valve repair; penicillin, gentamicin and ceftriaxone. Mitral and tricuspid valve replacement with bioprosthesis; penicillin, gentamicin and teicoplanin.	Good prognosis with no relapse
Rhodes et al[24]	2016	United States	7	Male, female, male, male, female, male, male	50, 25, 48, 60, 89, 31, 30	Abiotrophia defective; Abiotrophia defectiva; G. adiacens; Abiotrophia defectiva; Abiotrophia defectiva; G. adiacens; G. adiacens	Mitral insufficiency, prior dental infection with IE; mitral valve prolapse, prior dental infection, IE; previous mitral valve repair and IE; severe mitral valve insufficiency and IE; history of rheumatic fever with IE; IE; IE	Mitral; mitral; mitral; mitral; mitral; mitral; mitral	Bioprosthetic mitral valve, dual chamber pacemaker, vancomycin, gentamicin, and cerebral angiography. Ceftriaxone, rifampcin, gentamicin, aneurysmal resection, microvascular bypass, mitral valve repair, plication of the posterior leaflet, insertion of new chordae. Penicillin, gentamicin and mitral valve repair. Penicillin, gentamicin, external ventricular drainage and aneurysm clipped. Penicillin and gentamicin. Ampicillin/sulbactum, oxacillin, gentamicin, right middle cerebral artery clipped, mitral valvuloplasty. Penicillin, ceftriaxone, gentamicin, mitral valve repair	Good prognosis
Padmaja et al[31]	2014	India	1	Female	48	G. adiacens	IE	Mitral	Initially, with IV amikacin (1 mg/kg body weight). Definitive treatment with IV ceftriaxone (1 g) and gentamicin (80 mg) twice daily for four weeks	Good prognosis
Farid et al[33]	2019	United States	1	Male	62	G. elegans	IE	Mitral	Mitral valve replacement surgery, followed by 6 weeks of parenteral therapy with vancomycin and gentamicin	Recovery with trivial prosthetic mitral valve regurgitation
Freitas et al[40]	2023	Portugal	1	Male	62	G. adiacens	IE	Aortic	Three weeks of ampicillin and gentamicin followed by aortic valve replacement and interventricular communication repair. Later, extended antibiotics (26 days) for pulmonary valve vegetation due to high surgical risk	Good prognosis
Quiroga et al[23]	2012	Spain	1	Male	86	G. adiacens	IE with associated glomerulopathy	Prosthetic aortic	IV daptomycin (10 mg/kg/48 hours), later switched to ceftriaxone; tooth extraction; no surgical intervention due to age and comorbidities	Patient died after 3 months (Enterococcus species sepsis) due to the permanent catheter
Culleton et al[37]	2016	Ireland	1	Male	35	G. adiacens	IE with embolic stroke and splenic artery aneurysms	Mitral and aortic	Mitral and aortic valve repair surgery, followed by emergency splenectomy	Good prognosis
Rahimi et al[35]	2022	Malaysia	1	Male	19	G. adiacens	IE complicated by left ventricular pseudoaneurysm	Aortic	IV antibiotics prior to collapse and death	Mortality prior to diagnosis
Perkins et al[27]	2003	Spain	1	Male	57	G. adiacens	IE	Aortic and mitral	Ampicillin and gentamicin	Good prognosis
Opperman et al[38]	2020	South Africa	1	Female	29	G. adiacens	IE with stroke and mycotic aneurysm	Mitral	IV penicillin for 4 weeks and gentamycin for 2 weeks	Good prognosis
Prakash et al[46]	2018	India	1	Male	56	G. adiacens	Acute native valve endocarditis	Mitral	IV ceftriaxone 2 g once daily and gentamycin 70 mg once daily for 6 weeks	Good prognosis
Garibyan and Shaw[34]	2013	United States	1	Male	50	G. adiacens	Bivalvular IE	Mitral and aortic	Initial treatment with vancomycin, switched to penicillin and gentamicin based on antibiotic susceptibility; mitral and aortic valve replacement surgery; post-operative IV penicillin for two weeks	Good prognosis
Halford et al[36]	2019	United States	1	Male	82	G. adiacens	IE with paravalvular abscess and complete heart block	Aortic	Tissue aortic valve replacement, pacemaker placement, and antibiotic regimen of ampicillin and ceftriaxone for 6 weeks	Good prognosis
Sendi et al[42]	2019	Switzerland	1	Female	32	G. adiacens	Cardiac implantable electronic devices-related infection and bioprosthesis endocarditis	Bioprosthetic pulmonary valve	Conservative treatment with penicillin G and gentamicin for 2 weeks, followed by ceftriaxone for 4 weeks, and oral amoxicillin for 6 weeks (total 12 weeks of therapy); no device removal or surgical intervention	Good prognosis
Jeng et al[44]	2005	United States	1	Male	18	G. adiacens	Prosthetic valve IE	Prosthetic pulmonary valve	Vancomycin, gentamicin and rifampin for 6 weeks	Good prognosis
Loganathan et al[29]	2020	United States	1	Female	81	G. adiacens	IE and tubulovillous adenoma of the sigmoid colon	Aortic	Started on vancomycin and discharged home on IV vancomycin for 6 weeks for native valve IE	Good prognosis
García-Granja et al[47]	2019	Spain	5	Male, male, male, male, male	43, 53, 57, 65, 50	G. adiacens, Abiotrophia defective; G. adiacens, Abiotrophia defective; G. adiacens, Abiotrophia defective; G. adiacens, Abiotrophia defective; Abiotrophia defectiva	IE with vegetation; IE with vegetation and periannular complications; IE with vegetation; IE with vegetation, renal failure, and septic shock; IE with vegetation	Aortic native valve; aortic native valve; mitral native valve; mitral native valve; aortic native valve	Elective surgery for severe valvular regurgitation, antibiotic therapy with ceftriaxone and gentamicin for 4 weeks. Urgent surgery due to periannular complications, antibiotic therapy with penicillin and gentamicin for 5 weeks. No surgery required, antibiotic therapy with ampicillin and gentamicin for 4 weeks. Urgent surgery due to heart failure, antibiotic therapy with penicillin, ceftriaxone, and gentamicin for 4 weeks. Urgent surgery due to heart failure, antibiotic therapy with penicillin and gentamicin for 4 weeks	Good prognosis; mortality; good prognosis; mortality due to septic shock; good prognosis

G. adiacens: Granulicatella adiacens; G. elegans: Granulicatella elegans; IE: Infective endocarditis; IV: Intravenous.