Insights into Arcanobacterium haemolyticum: A Narrative Review of an Emerging Pathogen Revisited

TL;DR

This review discusses Arcanobacterium haemolyticum, a bacteria causing infections in young adults, highlighting its symptoms, diagnostic challenges, and treatment.

Contribution

The paper consolidates current knowledge to improve recognition and management of A. haemolyticum infections.

Findings

A. haemolyticum is linked to pharyngitis and severe systemic infections like bacteremia and Lemierre’s syndrome.

Diagnosis is difficult due to slow growth and misidentification as diphtheroids in cultures.

Beta-lactam antibiotics are standard treatment, but resistance patterns require susceptibility testing.

Abstract

Arcanobacterium haemolyticum is a facultative anaerobic, Gram-positive bacillus that has garnered attention due to its role in human infections, particularly among adolescents and young adults. Traditionally associated with pharyngitis, this organism is increasingly recognized for its involvement in systemic infections, including bacteremia, central nervous system abscesses, and Lemierre’s syndrome. The pathogenicity of A. haemolyticum is attributed to its production of hemolysins and neuraminidase, facilitating tissue invasion and immune evasion. Clinically, infections often present with sore throat, fever, and a characteristic scarlatiniform rash, which can lead to their misdiagnosis as streptococcal pharyngitis. Severe manifestations, though rare, have been documented, particularly in immunocompromised individuals. Diagnosis is challenging due to the organism’s slow growth and potential misidentification as diphtheroids in cultures. Accurate identification necessitates specific culture conditions and biochemical testing. Treatment typically involves beta-lactam antibiotics; however, the emergence of resistance patterns necessitate susceptibility testing to guide therapy. This review aims to consolidate current knowledge on A. haemolyticum, emphasizing its clinical presentations, diagnostic challenges, and management strategies, thereby enhancing recognition and treatment of infections caused by this emerging pathogen.

Tables

Table 2. Clinical features of Arcanobacterium haemolyticum infections reported in the literature.

Author Year Reference	Type of Infection	Underlying Illness and Risk Factors and Medical History	Co-Isolated Bacteria	Treatment	Outcome
Chinello(2025)[28]	Orbital cellulitis and intracerebral abscess	No underlying disease orhistory of interest.	No	Carbapenem, cephalosporin, daptomycin, lincosamide, oxazolidinone, penicillin with β-lactamase inhibitors	Complete resolution of the infection
Faiz(2025)[29]	Appendicitis	No underlying diseaseHistory of cocaine use.	No	Cephalosporin, metronidazole and tetracycline	Complete resolution of the infection
Lovering(2025)[30]	Chronic osteomyelitis and bacteremia	Paraplegia with neurogenic bladder, legs amputation and chronic stage IV ischial decubitus ulcer.	No	Glycopeptide and penicillin with β-lactamase inhibitors	Complete resolution of the infection
Saijo(2025)[31]	Necrotizing fasciitis	Poorly controlled diabetes mellitus.	Streptococcus agalactiae	Lincosamide and penicillin with β-lactamase inhibitors	Resolution of the infection after amputation and more than 30 days of therapy
Bozso(2024)[32]	Bacteraemia with possible meningitis	Myxomatous mitral valve and moderate mitral valve regurgitationand prolapse.	No	Cephalosporin and fluoroquinolone	Complete resolution of the infection
Chang(2024)[33]	Intracerebral abscess	No underlying disease orhistory of interest.	Fusobacterium (blood culture)Streptococcus anginosus (intraoperative samples)	Cephalosporin, glycopeptide, macrolide, metronidazole, penicillin	Complete resolution of the infection
Chin(2024)[34]	Orbital abscess and cerebral ischemia	No underlying disease orhistory of interest.	No	Multiple antibiotic therapy(not specified)	Resolution of the infection (persistence of hemiparesis)
Grusiecki(2024)[35]	Peritonsillar abscess	No underlying disease orhistory of interest.	No	Azole, cephalosporin, lincosamide, metronidazole, penicillin,penicillin with β-lactamase inhibitors	Resolution of the infection after multiple antibiotic therapy
Gu(2024)[36]	Soft-tissue infection	No underlying disease orhistory of interest.	Streptococcus dysgalactiae	Azole, cephalosporinand mupirocin	At the 2-week follow-up, the patient had near-complete resolution of his cutaneous changes.
Lampejo(2024)[37]	Lemierre’s syndrome	NR	No	Cephalosporin, metronidazole and penicillin with β-lactamase inhibitors	NR
Alrwashdeh(2023)[38]	Bacteremia secondary to peritonsillar abscess	History of epilepsy (in treatment with levetiracetam).Remote history of a gunshot wound to his abdomen. Use of marijuana and alcohol consumption.	NR	Cephalosporin, glycopeptide and penicillin with β-lactamase inhibitors	Patient discharged after over a month.Healthy at the follow-up visit after 2 months.
Herai(2023)[39]	Pyothorax	Cerebral infarction and Alzheimer’s disease; diabetes mellitus; foot ulcer.	Staphylococcus aureus	Cephalosporin, lincosamide and penicillin with β-lactamase inhibitors	Complete resolution of the infection
Sahhar(2023)[40]	Intracerebral abscess (subdural empyema) caused by invasive sinusitis	No underlying disease orhistory of interest.	F. necrophorum	Cephalosporin, glycopeptide and metronidazole	Death
Hicks(2022)[41]	Necrotizing fasciitis	Homeless, drug user, history of HCV, malnourishment. No diabetes or HIV.	No	Lincosamide, penicillin, penicillin with β-lactamase inhibitors	Complete resolution of the infection
Thomas(2022)[42]	Necrotic wound on left foot	Diabetes.	No	Fluoroquinolone	NR
	Wound infection	Diabetes and hypertension.	No	Lincosamide and fluoroquinolone	NR
	Wound gangrene infection	Diabetes and Non-ST elevation; myocardial infarction.	No	Glycopeptide and penicillin with β-lactamase inhibitors	NR
	Necrotic wound infection	Diabetes, hypertension, and hypothyroidism.	Β-hemolytic streptococci	Lincosamide and fluoroquinolone	NR
	Wound infection following trauma	No known comorbidities.	S. aureus	Fluoroquinolone and metronidazole	NR
	Ulcer infection following injury	Diabetes.	Proteus penneri	Lincosamide and fluoroquinolone	NR
Adams(2020)[43]	Sinusitis (after pharyngitis) complicated by preseptal cellulitis and cerebral abscess	No underlying disease orhistory of interest.	No	Cephalosporin, glycopeptide and metronidazole	Complete resolution of the infection
Saeb(2021)[44]	Chronic wound infection and osteomyelitis	Type 2 diabetes for 32 years, severe bilateral neuropathy involving both lower extremities and bilateral background retinopathy.	S. aureus	Fluoroquinolone and penicillin	Complete resolution of the infection
Lobo(2020)[45]	Liver abscess	NR	No	Carbapenem and metronidazole	Complete resolution of the infection
Verona(2020)[46]	Bacteraemia	No underlying diseaseor history of interest.	No	Cephalosporin, glycopeptide andpenicillin with β-lactamase inhibitors	Patient discharged after over 19 days.Healthy at the follow-up visit.
Takamura(2019)[3]	Left heel ulcer, osteomyelitis and bacteraemia	Hypertension and left leg deep vein thrombosis.	S. dysgalactiae	Penicillin with β-lactamase inhibitors	Complete resolution of the infection
Poplin(2018)[47]	Brain abscess and subdural empyema	No underlying disease.EBV infection.	No	Cephalosporin, glycopeptide, metronidazole and tetracycline	Complete resolution of the infection
Seki(2019)[48]	Intrathoracic abscess	Uncontrolled diabetes.	No	Penicillin with β-lactamase inhibitors	NR
Cortés-Penfield(2017)[49]	Intracranial abscess and bacteraemia	No underlying diseaseor history of interest.	Blood culture monomicrobial.Intraoperative samples: no growth. PCR 16s rRNA positive also for Bacteroides spp., Anaerococcus tetradius, Dialister micraerophilus, Erysipelotrichaceae spp., and Propionibacterium acnes	Cephalosporin, glycopeptide, metronidazole andpenicillin with β-lactamase inhibitors	Complete resolution of the infection
Smith(2016)[50]	Ulcer and bacteraemia	Uncontrolled diabetes, hypertension, dyslipidemia and osteomyelitis (amputation 1 year previously).	Blood culture monomicrobial.Enterococcus avium(wound swab)	Daptomycin, fluoroquinolone andpenicillin with β-lactamase inhibitors	NR
Miyamoto(2015)[4]	Calf cellulitis	Non-Hodgkin’s malignant lymphoma in the neck.	S. dysgalactiae, Corynebacterium striatum	NR	NR
	Foot, former cellulitis	Brainstem infarction post-treatment for laryngeal cancer.	S. dysgalactiae, C. striatum,S. aureus	NR	NR
	Leg ulcer	Uncontrolled diabetes with gangrene in the foot.	S. dysgalactiae, C. striatum, Peptoniphilus asaccharolyticus	NR	NR
	Femoral ulcer	T2 squamous cell carcinoma in the femur.	Meticillin-resistant S. aureus	NR	NR
	Pressure sore in buttocks	Quadriplegia	S. dysgalactiae, Streptococcusagalactiae, Streptococcus anginosus group, Peptoniphilus anaerobius	NR	NR
	Femoral ulcer	Primary hypertension post-surgery for an Achilles tendon rupture.	S. dysgalactiae, S.agalactiae, S. aureus, S. anginosus group, Anaerococcus prevotii	NR	NR
	Calf cellulitis	Articular rheumatism osteoarthrosis.	C. striatum, Prevotella disiens, Finegoldia magna	NR	NR
Stone(2015)[51]	Orbital necrotizing fasciitis and osteomyelitis	No underlying disease orhistory of interest.	No	Lincosamide,glycopeptide and penicillin with β-lactamase inhibitors	Complete resolution of the infection
Brown(2013)[52]	Soft-tissue infection and sepsis	Hypertension, historyof left-sided Charcot foot.	Blood culture monomicrobial.Group B β-hemolytic streptococci in intraoperative sample	Penicillin with β-lactamase inhibitors	Complete resolution of the infection
Ji(2013)[53]	Lemierre’s syndrome	Smoker.No underlying disease orhistory of interest.	No	Carbapenem, glycopeptide,macrolide, penicillin andpenicillin with β-lactamase inhibitors	Complete resolution of the infection
Ramey(2013)[14]	Orbital cellulitis and bacteraemia	No underlying disease orhistory of interest.Diagnosis of EBV infectious mononucleosis.	Fusobacterium speciesin blood culture.Coagulase-negative staphylococci in abscess culture	Cephalosporin, glycopeptide, macrolide, metronidazole, penicillin and penicillin with β-lactamase inhibitors	Complete resolution of the infection
Alatoom(2012)[54]	Endocarditis	Hypertension, non-insulin-dependent diabetes mellitus, depression, atherosclerotic cardiovascular disease, congenital bicuspid aortic valve, smoker.	No	Macrolide	Death
Hedman(2012)[15]	Septicemia	No underlying disease.Two years before: surgery of the arch of the foot with osteosynthesis to treat pes planus.	S. aureus in wound swab.Blood culture monomicrobial	Cephalosporin and macrolide	Complete resolution of the infection
	Septicemia	No underlying disease orhistory of interest.	F. necrophorum	NR	NR
	Septicemia	Immunocompromised with multiple diseases, including diabetes mellitus, poor dental status and foot wounds.	No	NR	NR
Lee(2012)[55]	Lemierre’s syndrome	No underlying disease orhistory of interest.	No	Aminoglycoside, cephalosporin, glycopeptide and metronidazole	Complete resolution of the infection
Sayyahfar(2012)[56]	Thyroid abscess	No underlying disease orhistory of interest.	No	Cephalosporin and lincosamide	Complete resolution of the infection
Ribakovs(2011)[57]	Spinal infections and severe sepsis	Two weeks before: anal resection of a malignant rectal polyp.	No	Penicillin	NR
Saxena(2011)[58]	Chorioamnionitis	No underlying disease.Primigravida at 32 weeks of gestation.	No	Aminoglycoside and metronidazole	Complete resolution of the infection(patient was induced and a healthy baby was delivered)
Wong(2011)[59]	Endocarditis complicated with cerebral emboli	Congenital heart disease.Surgical repair of pulmonary atresia, quadricuspid aortic valve and a ventricula septal defect.	No	Aminoglycoside, cephalosporin, glycopeptide, metronidazole	Complete resolution of the infection
Lundblom(2010)[60]	Lemierre’s syndrome	No underlying disease orhistory of interest.	F. necrophorum	Aminoglycoside cephalosporin, macrolideand penicillin with β-lactamase inhibitors	Complete resolution of the infection
Fernández-Suárez(2009)[16]	Lemierre’s syndrome	No underlying disease orhistory of interest.	No	Carbapenem, lincosamide, macrolide,Metronidazole, and penicillin with β-lactamase inhibitors	Complete resolution of the infection
Aracil(2008)[61]	Osteomyelitis	No underlying disease.Smoker and onychophagia.	No	Cephalosporin	Resolution of the infection
Lee(2008)[17]	Dog-bite induced necrotizing fasciitis	Uncontrolled diabetes.	F. magna andS. agalactiae	Carbapenem,glycopeptide, lincosamide, penicillin	Complete resolution of the infection
Malini(2008)[62]	Soft-tissue infection	No underlying disease orhistory of interest.	Group G β-hemolytic streptococci	Cephalosporin, macrolide	Complete resolution of the infection
	Soft-tissue infection and osteomyelitis	Diabetes under treatmentfor five years.	Proteus vulgaris	Macrolide and penicillin	NR
	Soft-tissue infection	No underlying disease orhistory of interest.	Group C β-hemolytic streptococci	Fluoroquinolone and penicillin	Complete resolution of the infection
Therriault(2008)[1]	Pneumonia and severe sepsis	Mild asthma.	No	Carbapenem, fluoroquinolone, glycopeptide, macrolide, penicillin, penicillin with β-lactamase inhibitors and trimethoprim–sulfamethoxazole	Complete resolution of the infection
Volante(2008)[18]	Sinusitis	NR	No	Cephalosporin, penicillin	Complete resolution of the infection
	Pharyngitis	NR	No	Cephalosporin and penicillin with β-lactamase inhibitors	Complete resolution of the infection
Schroeder(2007)[63]	Lemierre’s syndrome	No underlying disease.Use of marijuana and tobacco, alcohol consumption.	No	Cephalosporin, metronidazole and penicillin with β-lactamase inhibitors	Complete resolution of the infection
van Loo(2007)[64]	Pelvic abscess	No underlying disease.History of a membranous glomerulopathy in 2004, with complete recovery.	No	Macrolide	Complete resolution of the infection
Ciraj(2006)[65]	Urinary tract infection	NR	No	Penicillin	Complete resolution of the infection
Farmer(2007)[66]	Soft-tissue infection and bacteremia	Bed-bound patient with ulcerated pressure areas and nasogastric feeding regime.History of anemia and recurrent urinary tract infection.	Bacteroides fragilis(blood culture)Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (ulcer culture).	Penicillin with β-lactamase inhibitors	NR
Tan(2006)[67]	Soft-tissue infection and bacteremia	Ischemic heart disease, hypertension and poorly controlled diabetes mellitus.	Blood culture monomicrobial.P. aeruginosa, group G β-hemolytic streptococci and mixed anaerobes(abscess culture).	Fluoroquinolone and penicillin	Clinical improvement after antibiotic therapy
	Soft-tissue infection and bacteremia	Insulin-dependent diabetes mellitus, hypertension, hyperlipidemia and previous metatarsal amputations following infection.	Blood culture monomicrobial.S. aureus and group G β-hemolytic streptococci (abscess culture).	Cephalosporin and metronidazole	NR
	Soft-tissue infection and bacteraemia	Insulin-dependent diabetes mellitus, complicated by hyperlipidemia, peripheral neuropathy, diabetic nephropathy and retinopathy.	No	Penicillin and penicillin with β-lactamase inhibitors	Complete resolution of the infection
	Soft-tissue infection and bacteraemia	Bed-bound patient and nasogastric feeding regime.History of multiple infarct cerebral disease, hypertension and epilepsy.	Blood culture monomicrobial.S. aureus and group G β-hemolytic streptococci(ulcer culture).	Penicillin and penicillin with β-lactamase inhibitors	Complete resolution of the infection
	Spontaneous bacterial peritonitis	No underlying disease orhistory of interest.	No	Macrolide	Complete resolution of the infection
Vargas(2006)[68]	Brain abscess (after dental extraction procedure)	No underlying disease orhistory of interest.Repeated periodontal manipulations.	No	Cephalosporin, metronidazole and penicillin	Complete resolution of the infection
Goyal(2005)[69]	Septic arthritis	No underlying diseaseOsteoarthritis for two last years	No	Aminoglycoside and penicillin with β-lactamase inhibitors	Complete resolution of the infection
Katkar(2005)[70]	Respiratory tract infection	No underlying disease orhistory of interest.	Mycobacterium tuberculosis	Aminoglycoside and penicillin	Complete resolution of the infection
Parija(2005)[71]	Pyothorax	No underlying disease orhistory of interest.	No	Cephalosporin and metronidazole	Complete resolution of the infection
Varma(2005)[72]	Chronic canaliculitis	No underlying disease.Four-month history of painful upper lid swelling and discharge from the left eye.	No	Penicillin	Complete resolution of the infection

Table 3. Laboratory identification and clinical management of Arcanobacterium haemolyticum infections reported in the literature.

AuthorYearReference	Type of Sample	Method of Identification	Method of Susceptibility Testing	Interpretation Criteria	Antibiotics ResistancePhenotype(MIC mg/L)
Chinello(2025)[28]	Material drained from orbital cellulitis	MALDI-TOF Mass Spectrometry	NR	NR	AMC < 0.016, AZY 2, CLI > 256, DAPTO 4, LZD 0.19, MEM 0.012, MTZ > 256, TZP < 0.016
Faiz(2025)[29]	Intraoperative sample from abscess	MALDI-TOF Mass Spectrometry(Bruker)	Kirby Bauer disk diffusion test	EUCAST 2023breakpoint for Corynebacterium	CLI-, LIN-, RIF-, TET-susceptibleCIP-, MOX-, PEN-, SXT-, VA-resistant
Lovering(2025)[30]	Blood culture	MALDI-TOF Mass Spectrometry	NR	NR	CN, CRO, LZD, MEM, PEN, VA susceptible
Saijo(2025)[31]	Intraoperative sample from debridement	MALDI-TOF Mass Spectrometry	NR	NR	CRO 0.5, FEP 2, CTX 0.5, ERY < 0.12,PEN 0.25, RIF < 1, SXT < 0.5, VA 0.5
Bozso(2024)[32]	Blood culture	NR	NR	NR	CLI ≤ 0.016, PEN ≤ 0.03
Chang(2024)[33]	Blood culture,intraoperative samples from abscess	NR	NR	NR	NR
Chin(2024)[34]	Intraoperative sample from abscess	NR	NR	NR	NR
Grusiecki(2024)[35]	Purulent material from abscess	NR	NR	NR	PEN-susceptibleCIP-, CLI-, MXF-resistant
Gu(2024)[36]	Skin swab	MALDI-TOF Mass Spectrometry(Bruker)	Kirby Bauer disk diffusion test(Etest)	CLSI	PEN-susceptible
Lampejo(2024)[37]	Blood culture	MALDI-TOF Mass Spectrometry	Kirby Bauer disk diffusion test	EUCAST	CLI-, PEN-, VA-susceptible.MTZ-resistant
Alrwashdeh(2023)[38]	Blood culture and BAL	MALDI-TOF Mass Spectrometry		NR	PEN-susceptible
Herai(2023)[39]	Pleural fluid	MALDI-TOF Mass Spectrometry(Bruker)	NR	NR	NR
Sahhar(2023)[40]	Intraoperative sample from abscess	MALDI-TOF Mass Spectrometry(Bruker)	Kirby Bauer diffusion test(Disks and Etest)	NR	CLI-, CRO-, DOX-, LEV-, LZD-, PEN, RIF-, VA-susceptible
Hicks(2022)[41]	Intraoperative sample from abscess	MALDI-TOF Mass Spectrometry	Kirby Bauer diffusion test(Etest)	NR	PEN 0.064
Thomas(2022)[42]	Intraoperative sample from debridement	NR	NR	NR	NR
	Purulent material from wound	NR	NR	NR	NR
	Purulent material from wound	NR	NR	NR	NR
	Intraoperative sample from debridement	NR	NR	NR	NR
	Intraoperative sample from debridement	NR	NR	NR	NR
	Purulent material from ulcer	NR	NR	NR	NR
Adams(2020)[43]	Intraoperative sample from abscess	MALDI-TOF Mass Spectrometry	NR	NR	AMC-, AMP-, CTX-, ERY-, IPM-, LEV, MIN-, VA-susceptibleCLI-resistant
Saeb(2021)[44]	Deep wound swab	16s RNA Sanger sequencing	NR	NR	NR
Lobo(2020)[45]	Purulent material from abscess	Biochemical identification(API Coryne Panel)	NR	NR	Quinolone susceptible
Verona(2020)[46]	Blood culture	Identification based on biochemical tests and MALDI-TOF Mass Spectrometry(Vitek MS)	Kirby–Bauer diffusion test(Etest)	CLSI breakpoint for infrequently isolated or fastidious bacteria (M45 CLSI 2015)	CN 2, PEN 0.023, VA 0.5
Takamura(2019)[3]	Blood culture	Biochemical identification(Walkerway and API Coryne Panel)	NR	CLSI breakpoint for Staphylococci	AMP 0.25, CFZ ≤ 8, CLI ≤ 0.5, CN 2, ERY ≤ 0.25, IPM ≤ 1, LEV ≤ 0.5, PEN 0.12, SAM ≤ 8, VA ≤ 0.5
Poplin(2018)[47]	Blood culture	MALDI-TOF Mass Spectrometry	NR	NR	NR
Seki(2019)[48]	Blood culture and biopsy of the tissue	Biochemical identification(BD Phoenix) and MALDI-TOF Mass Spectrometry	NR	NR	CLI ≤ 0.5, CN ≤ 4, CRO ≤ 0.5, ERY ≤ 0.5,FEP ≤ 0.5, IPM ≤ 0.25, LEV ≤ 2, PEN ≤ 1
Cortés-Penfield(2017)[49]	Blood culture and purulent material from abscess	Biochemical identification (RapID CB Plus Kit) and 16s rRNA sequencing	NR	NR	NR
Smith(2016)[50]	Blood culture and wound swab	Biochemical testing ANC card (VITEK2)	Not performed	Not performed	Not performed
Miyamoto(2015)[4]	Skin secretion	MALDI-TOF Mass Spectrometry(Bruker)	Broth microdilution	CLSI breakpoint (2010) for Corynebacterium	CLA > 32, CLI > 32, CN 2, CRO ≤ 0.25,IPM ≤ 0.25, LEV 0.5, MEM ≤ 0.25, MIN ≤ 0.25, PEN ≤ 0.06, VA 0.5
	Skin secretion				CLA ≤ 0.25, CLI ≤ 0.25, CN 2, CRO ≤ 0.25,IPM ≤ 0.25, LEV 0.5, MEM ≤ 0.25, MIN ≤ 0.25, PEN ≤ 0.06, VA 0.5
	Pus				CLA ≤ 0.25, CLI ≤ 0.25, CN > 32, CRO ≤ 0.25, IPM ≤ 0.25, LEV 0.5, MEM ≤ 0.25, MIN ≤ 0.25, PEN ≤ 0.06, VA 0.5
	Skin secretion				CLA ≤ 0.25, CLI ≤ 0.25, CN > 32, CRO ≤ 0.25, IPM ≤ 0.25, LEV 8, MEM ≤ 0.25, MIN ≤ 0.25, PEN ≤ 0.06, VA 0.5
	Pus				CLA ≤ 0.25, CLI ≤ 0.25, CN 2, CRO ≤ 0.25,IPM ≤ 0.25, LEV 8, MEM ≤ 0.25, MIN ≤ 0.25, PEN ≤ 0.06, VA 0.5
	Pus				CLA ≤ 0.25, CLI ≤ 0.25, CN 2, CRO ≤ 0.25, IPM ≤ 0.25, LEV 0.5, MEM ≤ 0.25, MIN ≤ 0.25, PEN ≤ 0.06, VA 0.5
	Skin secretion				CLA ≤ 0.25, CLI ≤ 0.25, CN 2, CRO ≤ 0.25, IPM ≤ 0.25, LEV 8, MEM ≤ 0.25, MIN ≤ 0.25, PEN ≤ 0.06, VA 0.5
Stone(2015)[51]	Intraoperative sample from debridement	NR	NR	NR	NR
Brown(2013)[52]	Blood culture and intraoperative tissue	Biochemical identification (RapID CB Plus Kit)	NR	NR	NR
Ji(2013)[53]	Blood culture	Biochemical testing(API CORYNE)	NR	NR	NR
Ramey(2013)[14]	Blood cultureOrbital abscess culture	NR	NR	NR	CRO 0.064, ERY 0.032, PEN 0.032
Alatoom(2012)[54]	Postmortem blood culture	Biochemical testing (API CORYNE) and 16s RNA gene sequencing	NR	NR	NR
Hedman(2012)[15]	Wound swab from the footBlood culture	NR	NR	NR	NR
	Blood culture
	Blood culture
Lee(2012)[55]	Blood culture	Biochemical testing (VITEK2) and 16s RNA gene sequencing	Kirby–Bauer disk diffusion test	CLSI breakpoint for Streptococcus spp.	CIP-, CLO-, CN-, VA-susceptible.CLI-, ERY-, PEN-, SXT-, TET-resistant
Sayyahfar(2012)[56]	Intraoperative purulent material from thyroid	NR	NR	NR	CIP-, CLI-, CN-, ERY-, FEP-, IPM-, VA-susceptible
Ribakovs(2011)[57]	Blood culture	NR	NR	NR	PEN-susceptible
Saxena(2011)[58]	Amniotic fluid	Identification based on biochemical tests	NR	NR	AMP-, CFL-, CIP-, CLI-, CN-, ERY-susceptibleSXT-resistant
Wong(2011)[59]	Blood culture	Biochemical testing(API CORYNE) and 16s RNA gene sequencing	Kirby–Bauer disk diffusion test	NR	CIP-, CN-, CRO-, PEN-, RIF-, VA-susceptible
Lundblom(2010)[60]	Blood culture	16s RNA gene sequencing	NR	NR	NR
Fernández-Suárez(2009)[16]	Blood culture	Biochemical testing(API CORYNE)	Kirby–Bauer disk diffusion test	NR	CIP-, CLI-, CTX-, ERY-, OXA-, PEN-, TET-, VA-susceptibleCOL-resistant
Aracil(2008)[61]	Purulent discharge from the finger	Biochemical testing(API CORYNE)	Kirby–Bauer disk diffusion test	CLSI	AMP-, CFZ-, ERY-, LEV-, LIN-, VA-susceptible
Lee(2008)[17]	Wound swab from the left toe	Biochemical testing(API CORYNE)	Kirby–Bauer diffusion test(Etest)	CLSI	CLI 0.06PEN 0.008
Malini(2008)[62]	Case 1Pus sample from the ulcer	Identification based on the hemolytic pattern, catalase reaction and biochemical tests	NR	NR	CIP-, CLI-, CN-, ERY-, PEN-susceptibleSXT-resistant
	Case 2Pus sample from the ulcer				CIP-, CLI-, CN-, ERY-, PEN-susceptibleSXT-resistant
	Case 3Pus sample from the wound				CIP-, CLI-, CN-, ERY-, PEN-susceptibleSXT-resistant
Therriault(2008)[1]	Blood culture, BAL and pus from abscess	16s RNA gene sequencing	Kirby–Bauer diffusion test(Etest)	CLSI breakpoint for Staphylococcus aureus	ERY < 0.016PEN 0.023VA 0.75
Volante(2008)[18]	Case 1Intraoperative sample from abscess	NR	NR	NR	AMP, CRO, ERY, PEN-susceptibleSXT resistant
	Case 2Throat swab	NR	NR	NR	AZM, CIP, CLI, CRO, PEN susceptibleSXT, VA resistant
Schroeder(2007)[63]	Blood culture and intraoperative tissue	NR	NR	NR	NR
van Loo(2007)[64]	Sample drained from abscess	Biochemical testing(API CORYNE)	Kirby–Bauer disk diffusion test	NR	CIP, SXT resistant
Ciraj(2006)[65]	Urine sample	Biochemical reactions	Kirby–Bauer disk diffusion test	NCCLS standards	AMK, AMC, AMP, CIP, CRO, ERY, PEN, VA susceptible
Farmer(2007)[66]	Sample from paracentesis	NR	NR	NR	ERY-susceptible
Tan(2006)[67]	Case 1Blood cultureSample from the ulcer	NR	NR	NR	Four isolates were PEN-susceptible. Susceptibility testing not performed.
	Case 2Blood cultureSample from abscess	NR	NR	NR
	Case 3Blood cultureSample from abscess	NR	NR	NR
	Case 4Blood cultureIntraoperative tissue sample	NR	NR	NR
	Case 5Blood cultureSample from the ulcer	NR	NR	NR
Vargas(2006)[68]	Intraoperative sample from abscess	Identification based on the hemolytic pattern, catalase reaction and biochemical tests	Kirby–Bauer disk diffusion test	NR	CLI-, CN-, CRO-, DOX-, PEN-, VA-susceptibleCIP-, SXT-resistant
Goyal(2005)[69]	Synovial fluid	Identification based on biochemical tests	NR	NR	AMC-, CIP-, CRO-, ERY-, PEN-, VA-susceptible
Katkar(2005)[70]	Sputum	Identification based on the hemolytic pattern, catalase reaction and biochemical tests	NR	NR	NR
Parija(2005)[71]	Pus from thoracentesis	Identification based on the hemolytic pattern, catalase reaction and biochemical tests	Kirby–Bauer disk diffusion test	NR	AMP-, CIP-, CN-, CRO-, ERY-susceptible
Varma(2005)[72]	Purulent intraoperative sample	NR	NR	NR	NR

Full text

1. Introduction

Arcanobacterium haemolyticum, formerly known as Corynebacterium haemolyticum, is a facultative anaerobic, Gram-positive bacterium recognized for its clinical significance as a causative agent of pharyngitis, wound infections, and, less frequently, invasive diseases [1]. This bacterium, belonging to the genus Arcanobacterium, exhibits unique phenotypic and genotypic characteristics that distinguish it from other related species, contributing to its specific pathogenic mechanisms and clinical presentations.

A. haemolyticum is most commonly implicated in infections of the head and neck, particularly acute pharyngitis and sinusitis in children and adolescents. It is also a recognized cause of skin and soft-tissue infections, especially in immunocompromised individuals. Although less frequently encountered, the organism has been documented in a range of invasive infections, including bacteremia, endocarditis, osteomyelitis, severe sepsis, brain abscesses, and pneumonia [2,3,4]. Distinguishing the etiology of acute pharyngitis can be challenging in the absence of microbiological confirmation, as clinical features alone are often insufficient to differentiate bacterial from viral causes. Streptococcus pyogenes remains the most common bacterial pathogen in this context; however, A. haemolyticum is responsible for up to 2.5% of cases [5]. The clinical presentation of these two bacterial infections is often remarkably similar, underscoring the importance of considering A. haemolyticum in the differential diagnosis to ensure accurate identification and timely intervention. The manifestations of A. haemolyticum pharyngitis typically include sore throat, fever, and a pruritic, “sandpaper-like” scarlatiniform rash. This rash may closely resemble the cutaneous findings of scarlet fever caused by S. pyogenes, leading to potential misclassification. Furthermore, the rash may be mistaken for a viral exanthem, adding to the diagnostic complexity [6,7]. Delays in diagnosis are further compounded by laboratory factors: β-hemolysis produced by A. haemolyticum generally becomes evident only after 48–72 h of incubation, in contrast to the more rapid—often within 24 h—hemolytic pattern of S. pyogenes. In addition, A. haemolyticum is inherently more difficult to isolate in culture, creating further obstacles to prompt microbiological confirmation [2]. Early recognition is crucial, as timely initiation of antimicrobial therapy significantly improves outcomes. Effective treatment typically involves penicillins, macrolides, or tetracyclines, administered alongside appropriate supportive care. When diagnosed and managed promptly, patients generally recover fully without long-term sequelae.

Understanding the multifaceted nature of A. haemolyticum requires a comprehensive review of its microbiological properties, pathogenic mechanisms, clinical manifestations, diagnostic approaches, and therapeutic strategies, providing a foundation for improved clinical management and future research directions. The increasing prevalence of antibiotic resistance among bacterial pathogens underscores the importance of understanding the intricacies of bacterial pathogenesis and developing effective strategies for combating infections. Furthermore, insights into the virulence factors and host interactions of A. haemolyticum are crucial for designing targeted therapies and preventive measures. In this review, we aim to synthesize current knowledge regarding A. haemolyticum, offering a holistic perspective on its role in human health and disease.

2. Materials and Methods

2.1. Search Strategy and Inclusion and Exclusion Criteria

This narrative review aims to summarize all the data on A. haemolyticum infections in humans published in the literature in the last 20 years. Information regarding patients’ demographics, clinical characteristics, site of infection, clinical presentation, and treatment provided were described. There was a particular focus on data regarding microbiological characteristics and methodologies used for identification and antimicrobial susceptibility testing (AST).

By using the PubMed/Medline and Embase database, searches for relevant articles were performed with the following item: “(Arcanobacterium haemolyticum infection)”. Studies providing original data, such as case reports and letters to the editor providing information on A. haemolyticum infections in humans, were included in the review. Searches were limited to articles published in English from 1 January 2005 up to 31 December 2025. Studies regarding infections and/or colonization in animals were excluded from the analysis. Moreover, the reference lists of reports identified by this search strategy were also hand-searched to select further relevant articles.

2.2. Data Extraction

After the initial screening, the following data were extracted from each included study: publication year, age and gender of patients, type of infection, underlying disease and antibiotic therapy. Other relevant microbiological data were collected: type of sample, method of identification, antimicrobial susceptibility testing profile and co-isolated bacteria.

3. Results

3.1. Literature Search and Clinical Information

The literature search yielded a total of 187 records (PubMed, n = 81; Embase, n = 106). After removal of 54 duplicates, 133 articles were screened based on title and abstract, leading to the exclusion of 61 records. Of the remaining 72 full-text articles assessed for eligibility, 21 were excluded for the following reasons: article not published in English (n = 10), review articles or responses to letters (n = 6), and reports describing infections in animals (n = 5). Overall, 51 studies met the inclusion criteria and were included in the qualitative synthesis. These publications comprised case reports, case series, and letters to the editor, describing a total of 73 individual cases of A. haemolyticum infection in humans.

The main demographic and clinical features of A. haemolyticum infections reported in the literature are summarized in Table 1. Among the reported cases, 50 patients were male and 23 were female, resulting in male predominance. Patient age ranged from 2 to 91 years, with a mean age of 44.5 years and an IQR of 21–64 (M: 20.3–61.5; F: 31–66.5). A wide spectrum of clinical manifestations was observed. Bloodstream infections and skin and soft tissue infections were the most frequently reported presentation (n = 19), followed by brain abscess and Lemierre’s syndrome (n = 6). Bone infections (n = 4), intra-abdominal infections (n = 4), and respiratory tract infections (n = 4) were less common. Pyothorax (n = 3), endocarditis (n = 2), and urinary tract infection (n = 1) were rarely reported. When multiple infectious foci were present, classification was based on the most severe infection requiring treatment. Regarding microbiological context, infections were monomicrobial in 38 samples, whereas 32 samples were polymicrobial. In polymicrobial infections, A. haemolyticum was most frequently co-isolated with β-hemolytic streptococci (n = 16), anaerobic bacteria (n = 12), and Staphylococcus aureus (n = 10), supporting a potential synergistic role in mixed infections.

3.2. Phylogenetic of A. haemolyticum

The genus Arcanobacterium was first described by Collins et al. [8] to accommodate the species formerly known as Corynebacterium haemolyticum, initially classified by MacLean et al. (1946) [9]. The delineation of this new genus was based on both morphological features and chemotaxonomic criteria, including the composition of the cell wall peptidoglycan, the presence of specific long-chain fatty acids, and the profile of respiratory quinones. Over time, the genus expanded to include nine validly published species: A. haemolyticum, A. pyogenes, A. bernardiae, A. bialowiezense, A. bonasi, A. abortisuis, A. hippocoleae, A. phocae, and A. pluranimalium. Some of these, including A. pyogenes and A. bernardiae, were transferred from other genera such as Actinomyces and Corynebacterium, reflecting earlier misclassifications. Notably, A. pyogenes originated as ‘Corynebacterium pyogenes’, then ‘Actinomyces pyogenes’, and was eventually assigned to Arcanobacterium by Ramos et al. (1997) [10]. These transfers were based largely on phenotypic similarities and early chemotaxonomic observations. However, emerging evidence began to challenge the coherence of this taxonomic framework. Lehnen et al. (2006) [11] proposed that only A. haemolyticum, A. phocae, A. pluranimalium, and A. hippocoleae should be retained within Arcanobacterium, while A. pyogenes, A. bernardiae, A. bialowiezense, and A. bonsai should be reassigned to a new genus. To test the validity of the proposed subdivision, comprehensive phylogenetic analyses based on 16S rRNA gene sequences were undertaken. These molecular data were systematically compared with extended chemotaxonomic profiles—including fatty acid compositions, polar lipid profiles, cell-wall sugar types, acyl groups of muramic acid residues, peptidoglycan structure, and DNA G + C content—for all nine species within the original Arcanobacterium designation. The integration of these data confirmed a clear dichotomy within the genus, substantiating the earlier hypothesis of polyphyly. Species such as A. haemolyticum, A. hippocoleae, A. phocae, and A. pluranimalium formed a distinct clade consistent with the original definition of Arcanobacterium, while A. pyogenes, A. bernardiae, A. bialowiezense, and A. bonasi were phylogenetically divergent and chemotaxonomically distinct. This comprehensive evidence ultimately justified the establishment of a novel genus, Trueperella, to house the latter group. The reclassification of multiple Arcanobacterium species into the new genus Trueperella represents a necessary refinement in the taxonomy of the family Actinomycetaceae, grounded in molecular phylogenetics and robust chemotaxonomic data. The genus Arcanobacterium, now limited to its core species, is re-affirmed as a coherent phylogenetic unit, while Trueperella accommodates a distinct evolutionary lineage with demonstrably different biochemical and genomic features.

3.3. Etiology and Pathogenesis of A. haemolyticum

A. haemolyticum is a catalase-negative, aerobic, β-hemolytic, non-motile, branching, Gram-positive bacillus that forms part of the normal flora of the skin and nasopharynx. It is notable for its ability to inhibit hemolysis by S. aureus in the Christie–Atkins–Munch–Peterson (CAMP) test, while enhancing hemolysis by Streptococcus agalactiae in the reverse CAMP test [1,2]. A. haemolyticum is primarily transmitted via direct person-to-person contact through respiratory droplets, with detection in the oropharynx of household contacts supporting probable intrafamilial transmission [7]. Two phenotypic biotypes have been described: smooth and rough. Smooth biotypes are more frequently associated with soft-tissue infections and form uniform, β-hemolytic colonies on solid media. They are β-glucuronidase negative and capable of fermenting sucrose and trehalose. In contrast, rough biotypes—commonly linked to pharyngitis—produce uneven, non-hemolytic colonies, are β-glucuronidase positive, and do not ferment sucrose or trehalose [12]. On blood agar, A. haemolyticum produces β-hemolytic colonies composed of Gram-positive bacilli, with optimal growth at 37 °C in an atmosphere containing 5–10% CO_2_. Hemolysis is most prominent on human or horse blood agar; however, growth on sheep blood agar may be slower, with hemolysis becoming evident only after up to 72 h of incubation [13]. This delay may result in false-negative cultures unless extended observation is specifically requested. Definitive identification is achieved through demonstration of catalase negativity and a positive CAMP test. Misidentification can occur in early culture stages, as colony morphology may resemble normal flora or other organisms, including Corynebacterium spp., Streptococcus spp., and A. pyogenes. Differentiation from Corynebacterium spp. is based on β-hemolysis in combination with catalase negativity; from A. pyogenes, based on the inability to ferment xylose and a positive reverse CAMP reaction; and from Streptococcus spp., based on distinct microscopic morphology [2].

The pathogenesis of A. haemolyticum is multifactorial, involving both bacterial virulence factors and host predispositions. Experimental evidence highlights the role of hemolysins and neuraminidase in promoting tissue damage, adherence, and immune evasion, which underlies the scarlatiniform rash and invasive potential observed clinically. Case-based evidence further illustrates that A. haemolyticum infections often arise in otherwise healthy young individuals with pharyngitis and peritonsillar abscesses, but severe manifestations—including intracerebral abscesses, Lemierre’s syndrome, necrotizing fasciitis, endocarditis, and bacteremia—occur more frequently in patients with comorbidities such as diabetes mellitus, cardiac valve disease, or immunosuppression (Table 2) [14,15,16,17,18]. Co-infections with organisms such as S. agalactiae, S. dysgalactiae, S. aureus, Fusobacterium necrophorum, and other anaerobic bacteria are commonly reported and may act synergistically, worsening the clinical course (Table 1 and Table 3). The ability of A. haemolyticum to cause both localized suppurative infections (e.g., soft-tissue abscesses, orbital cellulitis) and disseminated disease (e.g., sepsis, meningitis) reflects its capacity for tissue invasion and survival in blood and deep compartments (Table 2). Limited information is available regarding the virulence factors of A. haemolyticum, and as a result, the mechanisms underlying pharyngeal infection and subsequent spread into deeper tissues remain poorly defined. Early investigations into virulence involved intradermal inoculation of the bacterium into humans, guinea pigs, and rabbits, which produced raised abscesses characterized by necrosis and marked neutrophil infiltration within 24–48 h post-infection. Intravenous administration of A. haemolyticum into rabbits induced hemorrhagic pneumonia [9], indicating that the organism is capable of causing invasive disease once disseminated through the bloodstream. Later, a phospholipase D (PLD) was identified and implicated in the dermonecrotic lesions observed [19]. Although the precise contribution of A. haemolyticum PLD to pathogenesis remains unresolved, its expression during infection has been demonstrated through the detection of serum antibodies in patients with pharyngitis [20,21]. PLDs are widely distributed enzymes that hydrolyze phospholipids such as phosphatidylcholine and sphingomyelin, both of which are abundant in mammalian plasma membranes. Sphingomyelin, together with cholesterol and GPI-anchored proteins, preferentially localizes to lipid rafts—highly ordered membrane microdomains that compartmentalize cellular processes on the outer plasma membrane leaflet [22]. These lipid rafts have also been implicated in microbial invasion of host cells. One molecular mechanism suggested that PLD may be essential for optimal adhesion of the bacterium to host cells through the remodeling of lipid rafts. Moreover, intracellular expression of PLD exerts a direct cytotoxic effect, inducing host cell death via necrosis. In detail, host-derived PLD cleaves sphingomyelin, resulting in the release of ceramide. The accumulation of ceramide within lipid rafts alters their biophysical characteristics, promoting the formation of large, ceramide-enriched membrane platforms [23]. These specialized domains enable the reorganization and clustering of protein receptors and receptor-associated signaling molecules, thereby enhancing the efficiency of signal transduction required for normal physiological functions. A. haemolyticum PLD shares the closest homology with the PLD of Corynebacterium pseudotuberculosis [24]. In C. pseudotuberculosis, PLD is essential for virulence, as mutants lacking the pld gene are unable to disseminate from the initial site of inoculation or persist within lymph nodes [25]. The PLD produced by C. pseudotuberculosis hydrolyzes sphingomyelin in host cell membranes and lysophosphatidylcholine in plasma, resulting in endothelial membrane disruption and cytolysis, which collectively enhance vascular permeability [25]. Additionally, C. pseudotuberculosis PLD has been shown to activate complement [26], induce neutrophil chemotaxis [27], and cause direct dermonecrosis upon intradermal injection.

3.4. Epidemiology of A. haemolyticum Infections

The epidemiology of A. haemolyticum infections reflects its dual role as both a community-associated pathogen in healthy adolescents and young adults, as well as an opportunistic pathogen in older or immunocompromised individuals. As shown in Table 1, cases were reported across a wide age range, with a predominance in adolescents and young adults for pharyngitis-related conditions, including peritonsillar abscesses and Lemierre’s syndrome. In contrast, invasive infections—such as bacteremia, endocarditis, necrotizing fasciitis, osteomyelitis, and intracerebral abscess—were more frequently described in older patients and in those with diabetes mellitus, cardiovascular disease, malignancies, or other chronic conditions. Polymicrobial infections were common, particularly in skin, soft tissue, and deep-seated infections, often involving anaerobes and other Gram-positive cocci. Data from reported cases show a predominance in male patients (Table 2), frequently in the second and third decades of life, particularly in pharyngitis-related conditions such as peritonsillar abscesses and Lemierre’s syndrome. Nonetheless, severe invasive disease—including bacteremia, endocarditis, necrotizing fasciitis, intracerebral abscesses, and osteomyelitis—has been increasingly described among older adults and patients with diabetes mellitus, cardiovascular disease, malignancies, or other chronic conditions. Co-infections are common, with S. agalactiae, S. dysgalactiae, S. aureus and anaerobic bacteria often isolated alongside A. haemolyticum, suggesting synergistic interactions in polymicrobial settings. The geographic distribution of cases indicates global occurrence, with reports spanning Europe, Asia, and North America, though the true burden is likely underestimated due to frequent misidentification as diphtheroids or streptococci in routine laboratories. However, the true burden of A. haemolyticum infections is likely underestimated due to frequent misidentification as diphtheroids or streptococci in routine clinical microbiology laboratories. Overall, these findings underscore the clinical heterogeneity of A. haemolyticum infections and the need for increased awareness of this pathogen in both community and hospital settings.

While pharyngitis remains the classic presentation, the wide spectrum of invasive infections highlights the organism’s capacity to affect diverse populations, with outcomes ranging from complete recovery after prolonged antimicrobial therapy to fatal complications in select cases.

3.5. Diagnosis of A. haemolyticum

Accurate diagnosis of A. haemolyticum remains challenging due to its slow growth, morphological similarity to coryneform bacteria, and frequent misidentification as diphtheroids or streptococci in routine laboratories. Early suspicion is crucial, particularly in patients with pharyngitis and scarlatiniform rash or invasive infections not explained by more common pathogens. Advances in diagnostic methods have improved detection, but awareness among clinicians and microbiologists is still limited.

3.5.1. Identification of A. haemolyticum

Data regarding microbiological identification methods and antimicrobial susceptibility testing (AST) are summarized in Table 2. Traditional identification relies on colony morphology, β-hemolysis on human or horse blood agar, catalase negativity, and a positive reverse CAMP test. However, hemolysis may take up to 72 h to become apparent, leading to under-recognition in standard cultures. Recent case series demonstrate the increasing use of MALDI-TOF mass spectrometry (Maldi Biotyper (Bruker, Billerica, MA, USA), Vitek MS (bioMérieux, Marcy, l’Étoile, France), and other platforms) as a rapid and reliable method for species-level identification. In some cases, confirmatory testing with biochemical panels (API Coryne (bioMérieux, Marcy, l’Étoile, France), RapID CB Plus (Thermo Fisher Scientific, Waltham, MA, USA), BD Phoenix (Becton Dickinson and Company, Franklin Lakes, NJ, USA)) or molecular methods such as 16S rRNA sequencing has been necessary, particularly when cultures yielded mixed flora or atypical results. Despite these advances, the absence of standardized diagnostic algorithms contributes to variable recognition rates, and misclassification in polymicrobial infections remains a concern.

3.5.2. Antimicrobial Susceptibility of A. haemolyticum

Antimicrobial susceptibility testing (AST) of A. haemolyticum is complicated by the lack of species-specific breakpoints, with laboratories commonly applying EUCAST or CLSI criteria for Corynebacterium or other fastidious Gram-positive organisms. AST was most commonly performed using the Kirby–Bauer disk diffusion method. Data from published cases show that most isolates remain susceptible to penicillin, ampicillin-sulbactam, and vancomycin, which form the mainstay of therapy. However, resistance has been variably reported to macrolides (erythromycin, clarithromycin), clindamycin, fluoroquinolones, trimethoprim–sulfamethoxazole, and, occasionally, rifampicin. Multidrug-resistant phenotypes, although rare, have been documented, including isolates resistant to penicillin and vancomycin. Co-infections with Fusobacterium necrophorum, Streptococcus agalactiae, or Staphylococcus aureus may further complicate susceptibility interpretation and therapeutic decision-making. These findings emphasize the importance of performing AST on all clinical isolates to guide therapy and highlight the emerging variability in resistance patterns among strains.

In Table 4, we suggest a laboratory approach for identification and AST of A. haemolyticum isolate.

4. Discussion, Treatment, and Outcomes of A. haemolyticum Infections

This narrative review provides an updated overview of the clinical spectrum, epidemiology, and microbiological characteristics of A. haemolyticum infections in humans, highlighting the persistent under-recognition of this pathogen in routine clinical practice. Although traditionally associated with pharyngitis in adolescents and young adults, the analysis of published cases demonstrates that A. haemolyticum is capable of causing a wide range of invasive and potentially life-threatening infections.

As shown in Table 1, skin and soft-tissue infections and bloodstream infections represented the most frequently reported clinical manifestations, followed by Lemierre’s syndrome and central nervous system involvement. These findings confirm that A. haemolyticum should no longer be regarded as a pathogen limited to benign upper respiratory tract infections. Instead, it should be considered a clinically relevant organism with the ability to invade deep tissues and cause systemic disease, particularly in the presence of predisposing factors such as diabetes mellitus, malignancy, or other chronic conditions. A notable finding of this review is the high proportion of polymicrobial infections. A. haemolyticum was frequently isolated alongside β-hemolytic streptococci, anaerobic bacteria, and Staphylococcus aureus, suggesting that it may act synergistically with other pathogens, especially in skin, soft tissue, and deep-seated infections. This observation aligns with previous hypotheses proposing that toxin production—most notably phospholipase D—may facilitate tissue invasion and enhance the pathogenicity of co-infecting organisms. The frequent involvement of anaerobes further underscores the importance of considering broad-spectrum antimicrobial coverage in severe infections until microbiological results become available.

From a diagnostic perspective, this review highlights substantial heterogeneity in laboratory identification methods over time. Earlier studies relied predominantly on phenotypic characteristics, which are often insufficient to reliably distinguish A. haemolyticum from other Gram-positive bacilli or β-hemolytic streptococci. The increasing adoption of MALDI-TOF mass spectrometry, as reported in more recent cases (Table 2), represents a major advance in diagnostic accuracy and is likely to contribute to improved detection rates. Nevertheless, misidentification remains a concern, particularly in laboratories without access to advanced diagnostic tools. Antimicrobial susceptibility data revealed considerable variability. While most isolates remained susceptible to β-lactam antibiotics, resistance to macrolides, clindamycin, fluoroquinolones, and trimethoprim–sulfamethoxazole was documented, and sporadic resistance to vancomycin was also reported. These findings are clinically relevant, as macrolides are frequently used for empirical treatment of pharyngitis and skin infections. The lack of standardized AST breakpoints specific for Arcanobacterium spp. further complicates therapeutic decision-making and underscores the need for susceptibility testing whenever feasible. The global distribution of reported cases suggests that A. haemolyticum infections occur worldwide. However, the true incidence is likely underestimated due to diagnostic challenges and limited awareness among clinicians and microbiologists. Increased recognition of this pathogen, combined with improved laboratory identification, may reveal a higher burden of disease than currently appreciated. This review has several limitations. The analysis is based primarily on case reports and small case series, which are subject to publication bias and incomplete reporting. In addition, heterogeneity in diagnostic methods and antimicrobial susceptibility testing limits the ability to draw firm conclusions regarding resistance patterns. Despite these limitations, the collected data provide valuable insights into the evolving clinical relevance of A. haemolyticum.

5. Conclusions

Arcanobacterium haemolyticum is an underdiagnosed but clinically significant pathogen capable of causing a broad spectrum of infections, ranging from mild pharyngitis to severe invasive disease. The findings of this review emphasize its frequent involvement in polymicrobial infections, its association with both immunocompetent and immunocompromised hosts, and the growing relevance of antimicrobial resistance. Improved awareness, accurate laboratory identification—particularly through MALDI-TOF mass spectrometry—and routine antimicrobial susceptibility testing are essential to optimizing patient management. Given the absence of standardized AST guidelines for this organism, further studies are needed to better define susceptibility patterns and inform evidence-based therapeutic strategies. Overall, A. haemolyticum should be systematically considered in the differential diagnosis of invasive and polymicrobial infections to reduce the risk of delayed or inappropriate treatment.