The ability to clot blood by producing coagulase distinguishes the virulent pathogen, Staphylococcus aureus, from the less virulent coagulase-negative staphylococcal species. Coagulase-positive S. aureus is among the most ubiquitous and dangerous human pathogens, for both its virulence and its ability to develop antibiotic resistance.
Coagulase-negative species such as S. epidermidis are increasingly associated with hospital-acquired infections; S. saprophyticus causes urinary infections. S. lugdunensis, a coagulase-negative species, can cause invasive disease with virulence similar to that of S. aureus. Unlike most coagulase-negative staphylococcal species, S. lugdunensis often remains sensitive to penicillinase-resistant beta-lactam antibiotics (ie, methicillin-sensitive).
A carrier state is common. Pathogenic staphylococci are ubiquitous. They are carried, usually transiently, in the anterior nares of about 30% of healthy adults and on the skin of about 20%; from these locations, staphylococci can cause infection in the host and others. Carriage rates are higher in hospital patients and personnel. S. aureus infections are more prevalent in carriers than in noncarriers and are usually caused by the colonizing strain.
People who are predisposed to staphylococcal infections include
Neonates and breastfeeding mothers
Patients with influenza, chronic bronchopulmonary disorders (eg, cystic fibrosis, emphysema), leukemia, tumors, chronic skin disorders, or diabetes mellitus
Patients with a transplant, an implanted prosthesis, other foreign bodies, or an indwelling intravascular plastic catheter
Patients receiving adrenal steroids, irradiation, immunosuppressants, or antitumor chemotherapy
Injection drug users
Patients who have chronic kidney disease and are being treated with dialysis
Patients with surgical incisions, open wounds, or burns
Predisposed patients may acquire antibiotic-resistant staphylococci from other patients, health care personnel, or inanimate objects in health care settings. Transmission via the hands of personnel is the most common means of spread, but airborne spread can also occur.
Diseases Caused by Staphylococci
Staphylococci cause disease by
Direct tissue invasion
Sometimes exotoxin production
Direct tissue invasion is the most common mechanism for staphylococcal disease, including the following:
Multiple exotoxins are sometimes produced by staphylococci. Some have local effects; others trigger cytokine release from certain T cells, causing serious systemic effects (eg, skin lesions, shock, organ failure, death). Panton-Valentine leukocidin (PVL) is a toxin produced by strains infected with a certain bacteriophage. PVL is typically present in strains of community-associated methicillin-resistant S. aureus (CA-MRSA) and has been thought to mediate the ability to necrotize; however, this effect has not been verified.
Toxin-mediated staphylococcal diseases include the following:
The diseases listed below are further discussed elsewhere in THE MANUAL.
S. aureus bacteremia Bacteremia Bacteremia is the presence of bacteria in the bloodstream. It can occur spontaneously, during certain tissue infections, with use of indwelling genitourinary or IV catheters, or after dental... read more , which frequently causes metastatic foci of infection, may occur with any localized S. aureus infection but is particularly common with infection related to intravascular catheters or other foreign bodies. It may also occur without any obvious primary site. S. epidermidis and other coagulase-negative staphylococci increasingly cause hospital-acquired bacteremia associated with intravascular catheters and other foreign bodies because they can form biofilms on these materials. Staphylococcal bacteremia is an important cause of morbidity (especially prolongation of hospitalization) and mortality in debilitated patients.
Staphylococcal skin infections
Skin infections are the most common form of staphylococcal disease. Superficial infections may be diffuse, with vesicular pustules and crusting (impetigo Impetigo and Ecthyma Impetigo is a superficial skin infection with crusting or bullae caused by streptococci, staphylococci, or both. Ecthyma is an ulcerative form of impetigo. Diagnosis is clinical. Treatment is... read more ) or sometimes cellulitis Cellulitis Cellulitis is acute bacterial infection of the skin and subcutaneous tissue most often caused by streptococci or staphylococci. Symptoms and signs are pain, warmth, rapidly spreading erythema... read more , or focal with nodular abscesses (furuncles and carbuncles Furuncles and Carbuncles Furuncles (boils) are skin abscesses caused by staphylococcal infection, which involve a hair follicle and surrounding tissue. Carbuncles are clusters of furuncles connected subcutaneously,... read more ). Deeper cutaneous abscesses are common. Severe necrotizing skin infections Necrotizing Soft Tissue Infection Necrotizing soft tissue infection is typically caused by a mixture of aerobic and anaerobic organisms that cause necrosis of subcutaneous tissue, usually including the fascia. This infection... read more may occur.
Staphylococci are commonly implicated in wound and burn infections, postoperative incision infections, and mastitis Mastitis Mastitis is painful inflammation of the breast, usually accompanied by infection. Fever later in the puerperium is frequently due to mastitis. Staphylococcal species are the most common causes... read more or breast abscess in breastfeeding mothers.
Staphylococcal neonatal infections
Neonatal infections usually appear within 6 weeks after birth and include
Skin lesions with or without exfoliation
Pneumonia that occurs in a community setting is not common but may develop in patients who
Are receiving corticosteroids or immunosuppressants
Have chronic bronchopulmonary or other high-risk diseases
Staphylococcal pneumonia Community-Acquired Pneumonia Community-acquired pneumonia is defined as pneumonia that is acquired outside the hospital. The most commonly identified pathogens are Streptococcus pneumoniae, Haemophilus influenzae, atypical... read more may be a primary infection or result from hematogenous spread of S. aureus infection elsewhere in the body (eg, IV catheter infection, endocarditis, soft-tissue infection) or from injection drug use. However, S. aureus is a common cause of hospital-acquired pneumonia Hospital-Acquired Pneumonia Hospital-acquired pneumonia (HAP) develops at least 48 hours after hospital admission. The most common pathogens are gram-negative bacilli and Staphylococcus aureus; antibiotic-resistant organisms... read more , including ventilator-associated pneumonia Ventilator-Associated Pneumonia Ventilator-associated pneumonia (VAP) develops at least 48 hours after endotracheal intubation. The most common pathogens are gram-negative bacilli and Staphylococcus aureus; antibiotic-resistant... read more .
Staphylococcal pneumonia is occasionally characterized by formation of lung abscesses followed by rapid development of pneumatoceles and empyema. CA-MRSA often causes severe necrotizing pneumonia.
Endocarditis Infective Endocarditis Infective endocarditis is infection of the endocardium, usually with bacteria (commonly, streptococci or staphylococci) or fungi. It may cause fever, heart murmurs, petechiae, anemia, embolic... read more can develop, particularly in IV drug abusers and patients with prosthetic heart valves. Because intravascular catheter use and implantation of cardiac devices have increased, S. aureus has become a leading cause of bacterial endocarditis.
S. aureus endocarditis is an acute febrile illness often accompanied by visceral abscesses, embolic phenomena, pericarditis, subungual petechiae, subconjunctival hemorrhage, purpuric lesions, heart murmurs, perivalvular abscess, conduction defects, and heart failure secondary to cardiac valve damage.
Osteomyelitis Osteomyelitis Osteomyelitis is inflammation and destruction of bone caused by bacteria, mycobacteria, or fungi. Common symptoms are localized bone pain and tenderness with constitutional symptoms (in acute... read more occurs more commonly in children, causing chills, fever, and pain over the involved bone. Subsequently, the overlying soft tissue becomes red and swollen. Articular infection may occur; it frequently results in effusion, suggesting septic arthritis rather than osteomyelitis. Most infections of the vertebrae and intervertebral disks in adults involve S. aureus.
Staphylococcal infectious arthritis
Joints typically become infected via hematogenous infection, but infection can also be caused by extension of a bone infection, trauma, or direct infection during joint surgery. Prosthetic joints Prosthetic Joint Infectious Arthritis Prosthetic joints are at risk of acute and chronic infection, which can cause sepsis, morbidity, or mortality. Patients often have a history of a recent fall. Symptoms include joint pain, swelling... read more are particularly prone to infection. Staphylococcal infection of a prosthetic joint in the months after implantation is usually acquired during surgery, whereas infections occurring more than 12 months after surgery are likely due to hematogenous spread. However, infections still may be secondary to organisms that were inadvertently introduced at the time of implantation and remained dormant and then became clinically evident several months later.
Staphylococcal toxic shock syndrome
Staphylococcal toxic shock syndrome Staphylococcal toxic shock Toxic shock syndrome is caused by staphylococcal or streptococcal exotoxins. Manifestations include high fever, hypotension, diffuse erythematous rash, and multiple organ dysfunction, which... read more may result from use of vaginal tampons or complicate any type of S. aureus infection (eg, postoperative wound infection, infection of a burn, skin infection). Although most cases have been due to methicillin-susceptible S. aureus (MSSA), cases due to MRSA are becoming more frequent.
Staphylococcal scalded skin syndrome
Staphylococcal scalded skin syndrome Staphylococcal Scalded Skin Syndrome Staphylococcal scalded skin syndrome is an acute epidermolysis caused by a staphylococcal toxin. Infants and children are most susceptible. Symptoms are widespread bullae with epidermal sloughing... read more , which is caused by several toxins termed exfoliatins, is an exfoliative dermatitis of childhood characterized by large bullae and peeling of the upper layer of skin. Eventually, exfoliation occurs. Scalded skin syndrome most commonly occurs in infants and children < 5 years.
Staphylococcal food poisoning
Staphylococcal food poisoning is caused by ingesting a preformed heat-stable staphylococcal enterotoxin. Food can be contaminated by staphylococcal carriers or people with active skin infections. In food that is incompletely cooked or left at room temperature, staphylococci reproduce and elaborate enterotoxin. Many foods can serve as growth media, and despite contamination, they have a normal taste and odor. Severe nausea and vomiting begin 2 to 8 hours after ingestion, typically followed by abdominal cramps and diarrhea. The attack is brief, often lasting < 12 hours.
Diagnosis of Staphylococcal Infections
Gram stain and culture
Diagnosis of staphylococcal infections is by Gram stain and culture of infected material.
Susceptibility tests should be done because methicillin-resistant organisms are now common and require alternative therapy.
When staphylococcal scalded skin syndrome is suspected, cultures should be obtained from blood, urine, the nasopharynx, the umbilicus, abnormal skin, or any suspected focus of infection; the intact bullae are sterile. Although the diagnosis is usually clinical, a biopsy of the affected skin may help confirm the diagnosis.
Staphylococcal food poisoning is usually suspected because of case clustering (eg, within a family, attendees of a social gathering, or customers of a restaurant). Confirmation (typically by the health department) entails isolating staphylococci from suspect food and sometimes testing for enterotoxins.
In osteomyelitis, x-ray changes may not be apparent for 10 to 14 days, and bone rarefaction and periosteal reaction may not be detected for even longer. Abnormalities in MRI, CT, or radionuclide bone scans are often apparent earlier. Bone biopsy (open or percutaneous) should be done for pathogen identification and susceptibility testing.
Some institutions that have a high incidence of methicillin-resistant S. aureus (MRSA) nosocomial infections routinely screen admitted patients for MRSA (active surveillance) by using rapid laboratory techniques to evaluate nasal swab specimens. Some institutions screen only high-risk patients (eg, those who are admitted to the intensive care unit, who have had previous MRSA infection, or who are about to undergo vascular, orthopedic, or cardiac surgery).
Quick identification of MRSA does the following:
Allows carriers to be placed in contact isolation and, when preoperative antibiotic prophylaxis Prevention of Surgical Infections Most surgical procedures do not require prophylactic or postoperative antibiotics. However, certain patient-related and procedure-related factors alter the risk/benefit ratio in favor of prophylactic... read more against skin organisms is required, to be given vancomycin as part of their drug regimen
Decreases the spread of MRSA
May decrease the incidence of nosocomial infections with MRSA
However, in some studies, decolonization treatments Prevention Staphylococci are gram-positive aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis... read more (eg, giving topical nasal mupirocin) have been proved somewhat effective for reducing MRSA infection in hospitalized patients (eg, patients in intensive care units, those undergoing major surgeries). Furthermore, mupirocin resistance is emerging. However, a recent large study did show a 30% reduction in postdischarge MRSA infection risk over 1 year for patients who were colonized with MRSA and treated with decolonization for 5 days twice monthly for 6 months. Each 5-day decolonization regimen included a 4% chlorhexidine bath or shower daily, 0.12% chlorhexidine mouthwash twice daily, and 2% nasal mupirocin daily (1 Diagnosis reference Staphylococci are gram-positive aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis... read more ).
Treatment of Staphylococcal Infections
Local measures (eg, debridement, removal of catheters)
Antibiotics selected based on severity of infection and local resistance patterns
Initial choice and dosage of antibiotics depend on
Probability that resistant strains are involved
Thus, it is essential to know local resistance patterns for initial therapy (and ultimately, to know actual drug susceptibility).
Treatment of toxin-mediated staphylococcal disease (the most serious of which is toxic shock syndrome Treatment Toxic shock syndrome is caused by staphylococcal or streptococcal exotoxins. Manifestations include high fever, hypotension, diffuse erythematous rash, and multiple organ dysfunction, which... read more ) involves decontamination of the toxin-producing area (exploration of surgical wounds, irrigation, debridement), intensive support (including IV fluids, vasopressors, and respiratory assistance), electrolyte balancing, and antimicrobials. In vitro evidence supports use of a combination of beta-lactamase–resistant, antistaphylococcal antimicrobial agent IV (eg, nafcillin, oxacillin, vancomycin) plus a protein synthesis inhibitor (eg, clindamycin 900 mg IV every 8 hours, linezolid 600 mg IV every 12 hours). IV immune globulin has been beneficial in severe cases.
Many staphylococcal strains produce penicillinase, an enzyme that inactivates several beta-lactam antibiotics; these strains are resistant to penicillin G, ampicillin, amoxicillin, and antipseudomonal penicillins.
Community-acquired strains are often susceptible to penicillinase-resistant penicillins (eg, methicillin, oxacillin, nafcillin, cloxacillin, dicloxacillin), cephalosporins, carbapenems (eg, imipenem, meropenem, ertapenem, doripenem), tetracyclines, macrolides, fluoroquinolones, trimethoprim/sulfamethoxazole (TMP/SMX), gentamicin, vancomycin, and teicoplanin.
MRSA isolates have become common, especially in hospitals. MRSA are resistant to all beta-lactam antibiotics, including cephalosporins and carbapenems; however, they may be susceptible to the newest class of MRSA-active cephalosporins (eg, ceftaroline, ceftobiprole [not available in the US]). Hospital-acquired MRSA are also commonly resistant to many other antibiotics, including erythromycin, clindamycin, and fluoroquinolones. In addition, community-associated MRSA (CA-MRSA) has emerged over the past several years in most geographic regions. CA-MRSA tends to be less resistant to multiple drugs than hospital-acquired MRSA. These strains, although resistant to most beta-lactams, are usually susceptible to TMP/SMX and tetracyclines (minocycline, doxycycline) and are often susceptible to clindamycin, but there is the potential for emergence of clindamycin resistance by strains inducibly resistant to erythromycin (laboratories may report these strains as D-test positive). Vancomycin is effective against most MRSA, sometimes with rifampin and an aminoglycoside added for some serious infections (ie, osteomyelitis, prosthetic joint infections, prosthetic valve endocarditis). An alternative drug (daptomycin, linezolid, tedizolid, dalbavancin, oritavancin, telavancin, tigecycline, omadacycline, lefamulin, eravacycline, delafloxacin, quinupristin/dalfopristin, TMP/SMX, possibly ceftaroline) should be considered when treating MRSA strains with a vancomycin minimum inhibitory concentration (MIC) of ≥ 1.5 mcg/mL.
Vancomycin-resistant S. aureus (VRSA; MIC ≥ 16 mcg/mL) and vancomycin-intermediate-susceptible S. aureus (VISA; MIC 4 to 8 mcg/mL) strains have appeared in the US. These organisms require linezolid, tedizolid, quinupristin/dalfopristin, daptomycin, TMP/SMX, delafloxacin, oritavancin, or ceftaroline. Dalbavancin and telavancin are active against VISA but have little activity against VRSA.
Because incidence of MRSA has increased, initial empiric treatment for serious staphylococcal infections (particularly those that occur in a health care setting) should include a drug with reliable activity against MRSA. Thus, appropriate drugs include the following:
For proven or suspected bloodstream infections, vancomycin or daptomycin
For pneumonia, vancomycin, telavancin, or linezolid (because daptomycin is not reliably active in the lungs)
Table Antibiotic Treatment of Staphylococcal Infections in Adults summarizes treatment options.
Prevention of Staphylococcal Infections
Aseptic precautions (eg, thoroughly washing hands between patient examinations, sterilizing shared equipment) help decrease spread in institutions. Strict isolation procedures should be used for patients harboring resistant microbes until their infections have been cured. An asymptomatic nasal carrier of S. aureus does not need to be isolated unless the strain is MRSA or is the suspected source of an outbreak. The Centers for Disease Control and Prevention recommends placing patients who are colonized or infected with MRSA in private rooms and on contact precautions in inpatient acute care settings and using strict isolation procedures (see Strategies to Prevent Hospital-onset Staphylococcus aureus Bloodstream Infections in Acute Care Facilities.)
The S. aureus organism recurs in up to 50% of carriers and frequently becomes resistant. For certain MRSA carriers (eg, preorthopedic, vascular, and cardiovascular surgical patients), some experts recommend nasal decolonization with mupirocin ointment 2 times a day for 5 to 10 days and topical body decolonization regimens with a skin antiseptic solution (eg, chlorhexidine) or dilute bleach baths (about 5 mL/L) for 5 to 14 days.
In general, oral antimicrobial therapy is recommended only for treatment of active infection.
Multidisciplinary guidelines for antibiotic prophylaxis before certain types of surgery Prevention of Surgical Infections Most surgical procedures do not require prophylactic or postoperative antibiotics. However, certain patient-related and procedure-related factors alter the risk/benefit ratio in favor of prophylactic... read more suggest that most patients can be treated with a single dose of an antibiotic given shortly before surgery (1 Prevention reference Staphylococci are gram-positive aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis... read more ). If colonization recurs despite topical treatments, clinicians should consider using rifampin plus either cloxacillin, dicloxacillin, TMP/SMX, or ciprofloxacin, depending on susceptibility. If MRSA is identified via nasal culture, vancomycin should be used.
Staphylococcal food poisoning can be prevented by appropriate food preparation. Patients with staphylococcal skin infections should not handle food, and food should be consumed immediately or refrigerated and not kept at room temperature.
Staphylococcus aureus is the most dangerous staphylococcal species.
Most staphylococcal diseases involve direct tissue invasion and cause skin and soft-tissue infections, IV catheter infections, pneumonia, endocarditis, or osteomyelitis.
Some strains produce a toxin that can cause toxic shock syndrome, scalded skin syndrome, or food poisoning.
Methicillin-resistant strains are common, and vancomycin resistance is appearing in the US.
Drug choice depends on source and location of infection and community or institutional resistance patterns.