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THE MERCK MANUAL MEDICAL LIBRARY: The Merck Manual of Diagnosis and Therapy
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Staphylococcal Infections

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Staphylococci are gram-positive, aerobic organisms. Staphylococcus aureus is the most pathogenic; it typically causes skin infections and sometimes pneumonia, endocarditis, and osteomyelitis. It commonly leads to abscess formation. Some strains elaborate toxins that cause gastroenteritis, scalded skin syndrome, and toxic shock syndrome. Diagnosis is by Gram stain and culture. Treatment is usually with penicillinase-resistant β-lactams, but because antibiotic resistance is common, vancomycin or other newer antibiotics may be required. Some strains are partially or totally resistant to all but the newest antibiotics, which include linezolid, quinupristin/dalfopristin, daptomycin, telavancin, dalbavancin, and tigecycline.

The ability to clot blood by producing coagulase determines the virulence of the several species of staphylococci. Coagulase-positive Staphylococcus aureus is among the most ubiquitous and dangerous human pathogens, both for 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, has recently been found to 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 β-lactam antibiotics.

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%. Rates are higher in hospital patients and personnel.

Risk factors: Neonates and nursing mothers are predisposed to staphylococcal infections, as are patients with influenza, chronic bronchopulmonary disorders (eg, cystic fibrosis, emphysema), leukemia, tumors, transplants, implanted prostheses or other foreign bodies, burns, chronic skin disorders, surgical incisions, diabetes mellitus, or indwelling intravascular plastic catheters. Patients receiving adrenal steroids, irradiation, immunosuppressants, or antitumor chemotherapy are also at increased risk. Predisposed patients may acquire antibiotic-resistant staphylococci from other patients, health care personnel, and 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

S. aureus bacteremia, which frequently causes metastatic foci of infection, may occur with any localized staphylococcal 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. They are important causes of morbidity (especially prolongation of hospitalization) and mortality in debilitated patients. The diseases listed below are further discussed elsewhere in The Manual.

Direct invasion: Most staphylococcal disease results from direct tissue invasion. Examples are

  • Skin infections
  • Pneumonia
  • Endocarditis
  • Osteomyelitis
  • Septic arthritis

Skin infections are the most common form of staphylococcal disease (see Bacterial Skin Infections: Furuncles and Carbuncles). Superficial infections may be diffuse, with vesicular pustules and crusting (impetigo) or sometimes cellulitis or with focal and nodular abscesses (furuncles and carbuncles). Deeper cutaneous abscesses are common. Severe necrotizing skin infections may occur. Staphylococci are commonly implicated in wound and burn infections, postoperative incision infections, and mastitis or breast abscess in nursing mothers.

Neonatal infections usually appear within 6 wk after birth and include skin lesions with or without exfoliation, bacteremia, meningitis, and pneumonia.

Pneumonia that occurs in a community setting is not common but may develop in patients who have influenza, who are receiving corticosteroids or immunosuppressants, or who have chronic bronchopulmonary or other high-risk diseases. However, S. aureus is a common cause of hospital-acquired pneumonia. Staphylococcal pneumonia is occasionally characterized by formation of lung abscesses followed by rapid development of pneumatoceles and empyema. Community-associated methicillin-resistant S. aureus (CA-MRSA) often causes severe necrotizing pneumonia.

Endocarditis 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, and heart failure secondary to cardiac valve damage.

Osteomyelitis occurs more commonly in children, causing chills, fever, and pain over the involved bone. Redness and swelling subsequently appear. Articular infection may occur; it frequently results in effusion, suggesting septic arthritis rather than osteomyelitis.

Toxin-mediated disease: Staphylococci may produce multiple toxins. 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 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:

  • Toxic shock syndrome
  • Staphylococcal scalded skin syndrome
  • Staphylococcal food poisoning

Toxic shock syndrome (see Gram-Positive Cocci: Toxic Shock Syndrome (TSS)) may result from use of vaginal tampons or occur as a complication of a seemingly minor postoperative 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 (see Bacterial Skin Infections: Staphylococcal Scalded Skin Syndrome), 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 the skin. Eventually, exfoliation occurs.

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 h after ingestion, typically followed by abdominal cramps and diarrhea. The attack is brief, often lasting < 12 h.

Diagnosis

  • Gram stain and culture

Diagnosis 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 to 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.

X-ray changes of osteomyelitis 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.

Screening: Some institutions that have a high incidence of 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 admitted to the intensive care unit or having had previous MRSA infection or about to undergo vascular, orthopedic or cardiac surgeries). Quick identification of MRSA allows carriers to be placed in contact isolation. This practice decreases the spread of MRSA and may decrease the incidence of nosocomial infections with MRSA.

Treatment

  • Local measures (eg, debridement, removal of catheters)
  • Antibiotics selected based on severity of infection and local resistance patterns

Management includes abscess drainage, debridement of necrotic tissue, removal of foreign bodies (including intravascular catheters), and use of antibiotics. Initial choice and dosage of antibiotics depend on infection site, illness severity, and 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-medicated staphylococcal disease (the most serious of which is toxic shock syndrome) involves decontamination of the toxin-producing area (exploration of surgical wounds, irrigation, debridement), intensive support (including vasopressors and respiratory assistance), electrolyte balancing, and antimicrobials. In vitro evidence supports a preference for protein synthesis inhibitors (eg, clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
900 mg IV q 8 h) over other classes of antibiotics. IV immune globulin has been beneficial in severe cases.

Antibiotic resistance: Many staphylococcal strains produce penicillinase, an enzyme that inactivates several β-lactam antibiotics; these strains are resistant to penicillin G Some Trade Names
BICILLIN
WYCILLIN
Click for Drug Monograph
, ampicillin Some Trade Names
OMNIPEN
PRINCIPEN
Click for Drug Monograph
, and antipseudomonal penicillins. Most community-acquired strains are susceptible to penicillinase-resistant penicillins (eg, methicillin, oxacillin Some Trade Names
BACTOCILL
PROSTAPHLIN
Click for Drug Monograph
, nafcillin Some Trade Names
UNIPEN
Click for Drug Monograph
, cloxacillin Some Trade Names
No US trade name
Click for Drug Monograph
, dicloxacillin Some Trade Names
DYCILL
DYNAPEN
PATHOCIL
Click for Drug Monograph
), cephalosporins, carbapenems (eg, imipenem, meropenem Some Trade Names
MERREM
Click for Drug Monograph
, ertapenem Some Trade Names
INVANZ
Click for Drug Monograph
, doripenem), macrolides, fluoroquinolones, trimethoprim/sulfamethoxazole Some Trade Names
BACTRIM
SEPTRA
Click for Drug Monograph
(TMP/SMX), gentamicin Some Trade Names
GARAMYCIN
Click for Drug Monograph
, vancomycin Some Trade Names
VANCOCIN
Click for Drug Monograph
, and teicoplanin.

MRSA isolates have become common, especially in hospitals. In addition, CA-MRSA has emerged over the past several years in many geographic regions. CA-MRSA tends to be less resistant to multiple drugs than hospital-acquired MRSA. These strains, although resistant to most β-lactams, are usually susceptible to TMP/SMX, doxycycline Some Trade Names
PERIOSTAT
VIBRAMYCIN
Click for Drug Monograph
, or minocycline Some Trade Names
MINOCIN
Click for Drug Monograph
and are often susceptible to clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
, but there is the potential for emergence of clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
resistance by strains inducibly resistant to erythromycin Some Trade Names
ERY-TAB
ERYTHROCIN
Click for Drug Monograph
(laboratories may report these strains as D-test positive). Vancomycin Some Trade Names
VANCOCIN
Click for Drug Monograph
is effective against most MRSA, sometimes with the addition of rifampin Some Trade Names
RIFADIN
RIMACTANE
Click for Drug Monograph
and an aminoglycoside for serious infections.

Vancomycin-resistant S. aureus (VRSA) and vancomycin Some Trade Names
VANCOCIN
Click for Drug Monograph
-intermediate-susceptible S. aureus (VISA) strains have appeared in the US. These organisms may require linezolid Some Trade Names
ZYVOX
Click for Drug Monograph
, quinupristin/dalfopristin Some Trade Names
SYNERCID
Click for Drug Monograph
, or daptomycin Some Trade Names
CUBICIN
Click for Drug Monograph
.

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, for proven or suspected bloodstream infections, vancomycin Some Trade Names
VANCOCIN
Click for Drug Monograph
or daptomycin Some Trade Names
CUBICIN
Click for Drug Monograph
would be appropriate. For pneumonia, vancomycin Some Trade Names
VANCOCIN
Click for Drug Monograph
or linezolid Some Trade Names
ZYVOX
Click for Drug Monograph
should be used because daptomycin Some Trade Names
CUBICIN
Click for Drug Monograph
is not reliably active in the lungs.

Table 1: Gram-Positive Cocci: Antibiotic Treatment of Staphylococcal Infections in AdultsTables summarizes treatment options.

Table 1

Antibiotic Treatment of Staphylococcal Infections in Adults

Infection

Drugs

Community-acquired cutaneous infections (non-MRSA)

Dicloxacillin Some Trade Names
DYCILL
DYNAPEN
PATHOCIL
Click for Drug Monograph
or cephalexin Some Trade Names
KEFLEX
KEFTAB
Click for Drug Monograph
250–500 mg po q 6 h for 7–10 days

Penicillin-allergic patients

Erythromycin Some Trade Names
ERY-TAB
ERYTHROCIN
Click for Drug Monograph
250–500 mg po q 6 h; clarithromycin Some Trade Names
BIAXIN
Click for Drug Monograph
500 mg po q 12 h; azithromycin Some Trade Names
ZITHROMAX
Click for Drug Monograph
500 mg po on the first day, then 250 mg po q 24 h; or clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
300 mg po q 8 h

Community-acquired cutaneous infections likely to be due to MRSA

Trimethoprim/sulfamethoxazole Some Trade Names
BACTRIM
SEPTRA
Click for Drug Monograph
160/800 mg po q 12 h

Sulfa-allergic patients

Clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
300 mg po q 6 h or doxycycline Some Trade Names
PERIOSTAT
VIBRAMYCIN
Click for Drug Monograph
100 mg po q 12 h

Serious infections unlikely to be due to MRSA

Nafcillin Some Trade Names
UNIPEN
Click for Drug Monograph
or oxacillin Some Trade Names
BACTOCILL
PROSTAPHLIN
Click for Drug Monograph
1–2 g IV q 4–6 h or cefazolin Some Trade Names
ANCEF
KEFZOL
Click for Drug Monograph
1 g IV q 8 h

Penicillin-allergic patients

Clindamycin Some Trade Names
CLEOCIN
Click for Drug Monograph
600 mg IV q 8 h or vancomycin Some Trade Names
VANCOCIN
Click for Drug Monograph
15 mg/kg q 12 h

Serious infection highly likely to be due to MRSA

Vancomycin Some Trade Names
VANCOCIN
Click for Drug Monograph
15 mg/kg IV q 12 h, linezolid Some Trade Names
ZYVOX
Click for Drug Monograph
600 mg IV q 12 h, or daptomycin Some Trade Names
CUBICIN
Click for Drug Monograph
4–6 mg/kg q 24 h

Documented MRSA

By reported sensitivities

Vancomycin Some Trade Names
VANCOCIN
Click for Drug Monograph
-resistant staphylococci*

Linezolid Some Trade Names
ZYVOX
Click for Drug Monograph
600 mg IV q 12 h, quinupristin/dalfopristin Some Trade Names
SYNERCID
Click for Drug Monograph
7.5 mg/kg q 8 h, or daptomycin Some Trade Names
CUBICIN
Click for Drug Monograph
4–6 mg/kg q 24 h

MRSA = methicillin-resistant Staphylococcus aureus.

*No clinical data are available, but listed drugs appear to be active in vitro; doses have not been established.

Prevention

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 need not be isolated unless the strain is MRSA or is the suspected source of an outbreak. Cloxacillin Some Trade Names
No US trade name
Click for Drug Monograph
, dicloxacillin Some Trade Names
DYCILL
DYNAPEN
PATHOCIL
Click for Drug Monograph
, TMP/SMX, ciprofloxacin Some Trade Names
CILOXAN
CIPRO
Click for Drug Monograph
(each of these drugs is often combined with rifampin Some Trade Names
RIFADIN
RIMACTANE
Click for Drug Monograph
), and topical mupirocin Some Trade Names
BACTROBAN
Click for Drug Monograph
have been useful in treating MRSA in carriers, but the organism recurs in up to 50% and frequently becomes resistant.

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.

Last full review/revision December 2009 by Larry M. Bush, MD; Fredy Chaparro-Rojas, MD; Maria T. Perez, MD

Content last modified December 2009

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