Gram-Positive Bacteria

Etiology

Gram-positive cocci include Staphylococcus (catalase-positive), which forms clusters, and Streptococcus (catalase-negative), which forms chains. The staphylococci are further subdivided into coagulase-positive (S. aureus) and coagulase-negative (S epidermidis and S saprophyticus) species. Streptococcus bacteria are subdivided into S pyogenes (group A), S agalactiae (group B), enterococci (group D), S viridans, and S pneumoniae.

Gram-positive bacilli (rods) are subdivided based on their ability to form spores. Bacillus and Clostridia are spore-forming rods, while Listeria and Corynebacterium are not. Spore-forming rods can survive in environments for many years. Also, the branching filament rods encompass Nocardia and Actinomyces. Gram-positive organisms have a thicker peptidoglycan cell wall than gram-negative bacteria. It is a 20 to 80 nm-thick polymer, whereas the peptidoglycan layer of the gram-negative cell wall is 2-3 nm thick and covered by an outer lipid bilayer membrane.

Epidemiology

Bloodstream infection mortality rates have increased by 78% in just two decades[1]. Gram-positive organisms have highly variable growth and resistance patterns. The SCOPE project (Surveillance and Control of Pathogens of Epidemiologic Importance) found that gram-positive organisms in those with an underlying malignancy accounted for 62% of all bloodstream infections in 1995 and 76% in 2000, while gram-negative organisms accounted for 22% and 14% of infections for these years.[2]

Pathophysiology

Gram-positive Cocci

Staphylococcus aureus is a gram-positive, catalase-positive, coagulase-positive coccus that occurs in clusters. S aureus can cause inflammatory diseases, including skin infections, pneumonia, endocarditis, septic arthritis, osteomyelitis, and abscesses. S aureus can also cause toxic shock syndrome (TSST-1), scalded skin syndrome (exfoliative toxin, and food poisoning (enterotoxin). 

Staphylococcus epidermidis is a gram-positive, catalase-positive, coagulase-negative coccus that occurs in clusters and is novobiocin-sensitive. S epidermidis commonly infects prosthetic devices and IV catheters, producing biofilms. Staphylococcus saprophyticus is novobiocin resistant and is a normal flora of the genital tract and perineum. S saprophyticus accounts for the second most common cause of uncomplicated urinary tract infections (UTI). 

Streptococcus pneumoniae is a gram-positive, encapsulated, lancet-shaped diplococcus that most commonly causes otitis media, pneumonia, sinusitis, and meningitis. Streptococcus viridans consists of S mutans and S mitis, found in the normal flora of the oropharynx, and commonly causes dental caries and subacute bacterial endocarditis (S sanguinis). Streptococcus pyogenes is a gram-positive group A cocci that can cause pyogenic infections (pharyngitis, cellulitis, impetigo, erysipelas), toxigenic infections (scarlet fever, necrotizing fasciitis), and immunologic infections (glomerulonephritis and rheumatic fever). ASO titer detects S pyogenes infections.

Streptococcus agalactiae is a gram-positive group B cocci that colonizes the vagina and is found mainly in babies. Pregnant women need screening for group B strep (GBS) at 35 to 37 weeks of gestation. Enterococci are gram-positive group D cocci found mainly in the colonic flora and can cause biliary tract infections and UTIs. Vancomycin-resistant enterococci (VRE) are an important cause of nosocomial infections. 

Gram-Positive Rods

Clostridia are gram-positive, spore-forming rods, including C tetani, C botulinum, C perfringens, and C difficile. C difficile is often secondary to antibiotic use (clindamycin/ampicillin), PPI use, and recent hospitalization. Treatment involves primarily oral vancomycin. Bacillus anthracis is a gram-positive spore-forming rod that produces anthrax toxin, resulting in an ulcer with a black eschar. Bacillus cereus is a gram-positive rod that can be acquired from spores that survive in undercooked or reheated rice. Symptoms include nausea, vomiting, and watery non-bloody diarrhea. 

Corynebacterium diphtheria is a gram-positive club-shaped rod that can cause pseudomembranous pharyngitis, myocarditis, and arrhythmias. Toxoid vaccines prevent diphtheria. Listeria monocytogenes is a gram-positive rod acquired through ingestion of cold deli meats and unpasteurized dairy products or through vaginal transmission during birth. Listeria can cause neonatal meningitis, meningitis in immunocompromised patients, gastroenteritis, and septicemia. Treatment includes ampicillin. 

History and Physical

It is important to identify patients with sepsis and order necessary blood cultures and labs. 

Physical

• Bullous impetigo
• Draining sinus tracts
• Erythema
• Fever
• Murmur if endocarditis is present
• Petechiae if toxic shock syndrome is present
• Superficial abscesses
• Warmth

Evaluation

Once a gram-positive organism infection is suspected, these laboratory studies are useful:

• Complete blood count
• Electrolytes
• Blood cultures
• Procalcitonin level
• Echocardiogram if endocarditis is suspected
• Joint aspiration if a septic joint is suspected

Treatment / Management

Penicillin, discovered by Alexander Fleming in 1928 and introduced into clinical practice during World War II, was the first widely used antibiotic. Natural penicillins have excellent activity against many streptococcal species, but limited activity against most S aureus strains due to penicillinase production, and they do not reliably cover Enterococcus species. Penicillinase-resistant penicillins, including nafcillin, oxacillin, cloxacillin, and dicloxacillin, are active against methicillin-susceptible S aureus (MSSA) and many streptococcal species. Antipseudomonal penicillins, including piperacillin and ticarcillin, have activity against many gram-positive organisms, gram-negative organisms, Pseudomonas aeruginosa, and, when combined with a β-lactamase inhibitor, many anaerobes. Carbapenems provide broad-spectrum activity against many gram-positive and gram-negative organisms, as well as anaerobes.[3][4][5](B3)

Trimethoprim/sulfamethoxazole, clindamycin, and doxycycline are oral antibiotics used for mild to moderate MRSA infections. It is important to note that trimethoprim/sulfamethoxazole increases warfarin levels, leading to increased INR. Vancomycin, linezolid, daptomycin, and tigecycline cover moderate-to-severe community- and hospital-acquired MRSA. Vancomycin requires renal dosing with trough levels between 15 to 20. Linezolid is an option for patients allergic to vancomycin. A complete blood count should be checked weekly to monitor for bone marrow suppression, neutropenia, thrombocytopenia, and anemia. Linezolid, daptomycin, and tigecycline are options to treat vancomycin-resistant enterococci.[6][7][8]

Differential Diagnosis

The differential diagnosis includes the following:

• Bacteremia
• Bronchiectasis imaging
• Chemical burns
• Diarrhea
• Electrical injuries in emergency medicine
• Emergent management of acute otitis
• Emergent management of thermal burns
• Empyema imaging
• Fever in the infant and toddler
• Fever without a focus
• Henoch-schonlein purpura
• Hospital-acquired infections
• Ingrown nails
• Necrotizing enterocolitis imaging

Prognosis

The prognosis following infection with gram-positive organisms is variable. The highest mortality rates are in elderly persons who tend to have suppressed immune systems and less physiologic reserve.