AUTHOR AND EDITOR INFORMATION

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• Follow-up
• Miscellaneous
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INTRODUCTION

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Background

Most infections caused by staphylococci are due to Staphylococcus aureus. However, the incidence of infections due to Staphylococcus epidermidis and other coagulase-negative staphylococci has been steadily increasing in recent years. This article focuses on S aureus, with occasional comments about the coagulase-negative staphylococci when important differences exist.

Pathophysiology

S aureus is a gram-positive coccus that is catalase positive and coagulase positive. Colonies are golden and strongly hemolytic on blood agar. They produce a range of toxins, including alpha-toxin, beta-toxin, gamma-toxin, delta-toxin, exfoliatin, enterotoxins, Panton-Valentine leukocidin (PVL), and toxic shock syndrome toxin–1 (TSST-1). The enterotoxins and TSST-1 are associated with toxic shock syndrome. PVL is associated with necrotic skin and lung infections. Coagulase-negative staphylococci, particularly S epidermidis, produce an exopolysaccharide (slime) that promotes foreign body adherence and resistance to phagocytosis.

Frequency

United States

As many as 80% of individuals are colonized with S aureus at some point. Most are colonized only intermittently; 20-30% are colonized persistently. Health care workers, persons with diabetes, and patients on dialysis all have higher rates of colonization. The anterior nares are the predominant site of colonization in adults; other potential sites of colonization include the axilla, rectum, and perineum.

International

S aureus occurs with a worldwide distribution. Pyomyositis due to S aureus has an increased prevalence in the tropics.

Mortality/Morbidity

Mortality from staphylococcal infections varies widely. Untreated S aureus bacteremia has a mortality rate exceeding 80%. The mortality rate for staphylococcal toxic shock syndrome is 3-5%. Infections due to coagulase-negative staphylococci usually have a very low mortality rate. Because these infections are commonly associated with prosthetic devices, the most serious complication is the need to remove the involved prosthesis, although prosthetic valve endocarditis might result in significant mortality.

Race

No association is reported with staphylococci infections and race.

Sex

The vaginal carriage rate is approximately 10% in premenopausal women. The rate is even higher during menses.

Age

Many neonates become colonized on the skin, perineum, umbilical stump, and GI tract. The adult colonization rate is approximately 40% at any given time.

CLINICAL

Section 3 of 11  

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• Follow-up
• Miscellaneous
• Multimedia
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History

Common manifestations of staphylococcal infections include the following types of infections. The history obtained usually depends on the type of infection the organism causes.

• Skin infections (Many individuals who present with community-acquired skin infections are initially misdiagnosed with spider bites. These infections are often due to methicillin-resistant S aureus [MRSA].)
• • Folliculitis
  • Furuncles
  • Impetigo (bullous)
  • Wound infections
  • Scalded skin syndrome
• Soft tissue infections (pyomyositis, septic bursitis, septic arthritis)
• Toxic shock syndrome
• Endocarditis
• Osteomyelitis
• Pneumonia
• Food poisoning
• Infections related to prosthetic devices
• • Commonly associated with coagulase-negative staphylococci
  • Includes prosthetic joints and heart valves and vascular shunts, grafts, and catheters
• Urinary tract infection

Physical

• Skin and soft tissue infections
• • Erythema
  • Warmth
  • Draining sinus tracts
  • Superficial abscesses
  • Bullous impetigo
• Toxic shock syndrome
• • Fever greater than 38.9°C
  • Diffuse erythroderma - Deep, red, "sunburned" appearance
  • Hypotension
  • Desquamation - Occurs 7-14 days after onset of illness, most commonly involves palms and soles
• Endocarditis
• • Regurgitant murmur
  • Petechiae or other cutaneous lesions (see Images 1-2)
  • Fever

Causes

Predisposing factors for staphylococcal infections include the following:

• Neutropenia or neutrophil dysfunction
• Diabetes
• Intravenous drug abuse
• Foreign bodies, including intravascular catheters
• Trauma

DIFFERENTIALS

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Other Problems to be Considered

Animal bites
Epidural abscess
Epiglottitis
Osteomyelitis
Septic arthritis

WORKUP

Section 5 of 11  

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Lab Studies

• Obtain cultures (with susceptibilities) as appropriate for the site of infection. Blood culture results may be positive even when results from other cultures are negative. Obtain blood cultures from all patients with serious infections.
• Patients with S aureus bacteremia should have blood cultures repeated after starting appropriate therapy. Patients with persistent bacteremia (after 3 or more days of appropriate therapy) have an increased risk for underlying endocarditis.
• CBC count reveals that most patients have leukocytosis with a left shift (bands). Patients may have thrombocytosis in chronic infection.
• Erythrocyte sedimentation rate and C-reactive protein may be helpful in patients with subacute or chronic infections such as osteomyelitis.
• Teichoic acid antibody titers in patients with continuous S aureus bacteremias suggest a deep-seated (not intravenous line) focus (eg, endocarditis, abscess, osteomyelitis).

Other Tests

• Patients with persistent or high-grade S aureus bacteremia and without a clear source of infection should have transthoracic echocardiography. Some experts recommend transesophageal echocardiography (TEE) in all patients with suspected S aureus endocarditis.
• TEE is recommended for all patients with catheter-related S aureus bacteremia (and no contraindications).

TREATMENT

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Medical Care

Promptly start antimicrobial therapy when S aureus infection is documented or strongly suspected. Temporary intravascular devices should be promptly removed if infection is suspected. Long-term intravascular devices should be removed if infection with S aureus is documented.

Surgical Care

Abscesses must be drained. Usually, infections involving a prosthetic joint require removal of the prosthesis. Other infections involving a prosthetic device, such as a prosthetic heart valve or implanted intravascular device, may or may not require removal of the device.

MEDICATION

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Numerous antibiotics have good activity against S aureus. Historically, isolates resistant to methicillin (methicillin-resistant S aureus [MRSA]) were resistant to most agents other than vancomycin, but these isolates were limited to nosocomial infections. More recently, there have been many reports of community-acquired MRSA infections that have been susceptible to a variety of non–beta-lactam antibiotics. As such, patients with serious staphylococcal infections should be initially started on agents active against MRSA until susceptibility results are available. Many coagulase-negative staphylococci are resistant to all antimicrobials other than vancomycin. The duration of treatment and the use of synergistic combinations depend on the type of infection encountered. Endocarditis due to S aureus may require a prolonged course of antibiotics.

Drug Category: Antibiotics

Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Drug Name	Vancomycin (Vancocin, Vancoled)
Description	Indicated for patients who cannot receive penicillins and cephalosporins or have infections with resistant staphylococci. To lessen the risk for toxicity, assay vancomycin trough levels after third dose drawn 0.5 h prior to next dosing. Use CrCl to adjust dose in patients diagnosed with renal impairment.
Adult Dose	1 g or 15 mg/kg IV q12h
Pediatric Dose	30-40 mg/kg/d IV divided q12h
Contraindications	Documented hypersensitivity
Interactions	Erythema, histaminelike flushing, and anaphylactic reactions may occur when administered with anesthetic agents; taken concurrently with aminoglycosides, risk of nephrotoxicity may increase above that with aminoglycoside monotherapy; effects in neuromuscular blockade may be enhanced when coadministered with nondepolarizing muscle relaxants
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Infuse slowly, rapid infusion may cause hypotension or tingling and flushing (red man syndrome); red man syndrome is caused by IV infusion that is too rapid but rarely happens when dose is administered as 2-h IV administration or with PO or IP administration; red man syndrome is not an allergic reaction; caution in renal failure and neutropenia

Drug Name	Cefazolin (Ancef, Kefzol)
Description	First-generation semisynthetic cephalosporin that arrests bacterial cell wall synthesis, inhibiting bacterial growth. Primarily active against skin flora, including S aureus (MSSA). Typically used alone for skin and skin-structure coverage. IV and IM dosing regimens are similar.
Adult Dose	1 g IV q8h
Pediatric Dose	50-100 mg/kg/d IV divided q8h
Contraindications	Documented hypersensitivity
Interactions	Probenecid prolongs effect; coadministration with aminoglycosides may increase renal toxicity; may yield false-positive result from urine dip test for glucose
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal impairment; superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy

Drug Name	Clindamycin (Cleocin)
Description	Lincosamide for treatment of serious skin and soft tissue staphylococci infections. Also effective against aerobic and anaerobic streptococci (except enterococcal) (MSSA). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl t-RNA from ribosomes, causing RNA-dependent protein synthesis to arrest.
Adult Dose	150-300 mg PO q8h 300-600 mg IV q8h
Pediatric Dose	25-40 mg/kg/d PO/IV divided tid
Contraindications	Documented hypersensitivity; regional enteritis, ulcerative colitis, or hepatic impairment (use caution)
Interactions	Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects; antidiarrheals may delay absorption; all antimicrobials have been associated with development of pseudomembranous colitis

Drug Name	Dicloxacillin (Dycill, Dynapen)
Description	Binds to one or more penicillin-binding proteins, which, in turn, inhibits synthesis of bacterial cell walls. For treatment of infections caused by penicillinase-producing staphylococci susceptible to methicillin (MSSA). Also active against most nonenterococcal streptococci. May use to initiate therapy when staphylococcal infection is suggested.
Adult Dose	500 mg PO q6h
Pediatric Dose	25 mg/kg/d PO divided q6h
Contraindications	Documented hypersensitivity
Interactions	Decreases efficacy of oral contraceptives; increases effects of anticoagulants; probenecid and disulfiram may increase penicillin levels
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Monitor PT in patients taking anticoagulant medications; toxicity may increase in patients with renal impairment; usefulness limited by need for frequent dosing

Drug Name	Trimethoprim-sulfamethoxazole (Bactrim, Bactrim DS, Septra, Septra DS)
Description	Inhibits bacterial growth by inhibiting synthesis of dihydrofolic acid. Active against most staphylococci (MSSA), including some strains resistant to methicillin (MRSA).
Adult Dose	160/800 mg PO q12h
Pediatric Dose	<2 years: Do not administer >2 years: 6-12 mg of trimethoprim/kg/d PO divided bid
Contraindications	Documented hypersensitivity; megaloblastic anemia due to folate deficiency
Interactions	May increase PT when used with warfarin (perform coagulation tests and adjust dose accordingly); coadministration with dapsone may increase blood levels of both drugs; coadministration of diuretics increases incidence of thrombocytopenia purpura in elderly persons; phenytoin levels may increase with coadministration; may potentiate effects of methotrexate in bone marrow depression; hypoglycemic response to sulfonylureas may increase with coadministration; may increase levels of zidovudine
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Discontinue at first appearance of skin rash or sign of adverse reaction; obtain CBC counts frequently; discontinue therapy if significant hematologic changes occur; goiter, diuresis, and hypoglycemia may occur with sulfonamides; prolonged IV infusions or high doses may cause bone marrow depression (if signs occur, give 5-15 mg/d leucovorin); caution in folate deficiency (eg, chronic alcoholism, elderly, anticonvulsant therapy, malabsorption syndrome); hemolysis may occur in persons with G-6-PD deficiency Persons with AIDS may not tolerate or respond to TMP-SMZ; caution in renal or hepatic impairment (perform urinalyses and renal function tests during therapy); give fluids to prevent crystalluria and stone formation

Drug Name	Minocycline (Minocin)
Description	Inhibits protein synthesis and thus bacterial growth by binding to 30S and possibly 50S ribosomal subunits of susceptible bacteria. Active against MSSA/MRSA. Less active against coagulase-negative staphylococci. Doxycycline (Vibramycin) may be used in place of minocycline
Adult Dose	100 mg PO/IV q12-24h
Pediatric Dose	2-4 mg/kg/d PO divided bid
Contraindications	Documented hypersensitivity
Interactions	Bioavailability decreases slightly with antacids containing aluminum, calcium, magnesium, iron, or bismuth subsalicylate; tetracyclines can increase hypoprothrombinemic effects of anticoagulants; tetracyclines can decrease effects of oral contraceptives, causing breakthrough bleeding and increased risk of pregnancy
Pregnancy	D - Unsafe in pregnancy
Precautions	Tetracycline use during tooth development (last half of pregnancy through 8 y) can cause permanent discoloration of teeth

Drug Name	Linezolid (Zyvox)
Description	Prevents formation of functional 70S initiation complex, which is essential for bacterial translation process. Bacteriostatic against staphylococci (MSSA/MRSA).
Adult Dose	400-600 mg PO/IV q12h
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May cause hypertension when used concomitantly with adrenergic agents, including pseudoepinephrine, sympathomimetic agents, vasopressors, or dopaminergic agents (reduce dose of dopamine or epinephrine if concurrent use required); serotonin syndrome may occur if used concomitantly with serotonergic agents, including TCAs, meperidine, dextromethorphan, trazodone, venlafaxine, and selective serotonin reuptake inhibitors
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Has mild MAOI properties and has potential to have same interactions as other MAOIs; caution in uncontrolled hypertension, pheochromocytoma, carcinoid syndrome, or untreated hyperthyroidism and in and patients who are at increased risk for bleeding, have preexisting thrombocytopenia, receive concomitant medications that may decrease platelet count or function, or who may require > 2 wk of therapy (monitor platelet counts); unnecessary use may lead to development of resistance to drug

Drug Name	Quinupristin/dalfopristin (Synercid)
Description	Belongs to the streptogramin group of antibiotics. Mechanism of action is similar to macrolides/lincosamides. Inhibits protein synthesis and is usually bacteriostatic. Also an option for methicillin-resistant staphylococcal (MRSA) infections.
Adult Dose	7.5 mg/kg IV q8h
Pediatric Dose	Not established
Contraindications	Documented hypersensitivity
Interactions	May decrease elimination and increase toxicity of cyclosporine A, midazolam, nifedipine, terfenadine astemizole, cisapride, alfentanil, alosetron, alprazolam, carbamazepine, delavirdine, diazepam, diltiazem, disopyramide, dofetilide, donepezil, erythromycin, ethinyl estradiol, felodipine, fexofenadine, indinavir, lidocaine, lovastatin, methylprednisolone, nevirapine, norethindrone, quinidine, ritonavir, saquinavir, simvastatin, tacrolimus, triazolam, trimetrexate, verapamil, vinblastine, and, possibly, other drugs
Pregnancy	C - Safety for use during pregnancy has not been established.
Precautions	Arthralgias and myalgias are common and may be severe; venous irritation common when administered through a peripheral line; administration through central venous line recommended; asymptomatic elevation of unconjugated bilirubin level may occur

Drug Name	Daptomycin (Cubicin)
Description	Indicated to treat complicated skin and skin structure infections caused by S aureus (including methicillin-resistant strains), Streptococcus pyogenes, Streptococcus agalactiae, Streptococcus dysgalactiae, and Enterococcus faecalis. Also indicated for right-sided endocarditis due to S aureus. First of new antibiotic class called cyclic lipopeptides. Binds to bacterial membranes and causes rapid membrane potential depolarization, thereby inhibiting protein, DNA, and RNA synthesis and ultimately causing cell death.
Adult Dose	CrCl >30 mL/min: 4 mg/kg IV q24h infused over 30 min CrCl <30 mL/min: 4 mg/kg IV q48h (including hemodialysis or CAPD)
Pediatric Dose	<18 years: Not established >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Coadministration with tobramycin slightly increases daptomycin Cmax and AUC and decreases tobramycin Cmax and AUC; may experience additive effects with other drugs (eg, HMG-CoA reductase inhibitors), causing myopathy
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Decrease dose with renal function <30 mL/min; pseudomembranous colitis may occur; may cause muscle pain or weakness; monitor CK levels and discontinue daptomycin with elevated CK and unexplained myopathy or marked CK elevation (10-times upper limits of reference range); not indicated for pneumonia (higher death rate in daptomycin-treated patients during phase III trials); not compatible with dextrose-containing solutions

Drug Name	Tigecycline (Tygacil)
Description	A glycylcycline antibiotic that is structurally similar to tetracycline antibiotics. Inhibits bacterial protein translation by binding to 30S ribosomal subunit, and blocks entry of amino-acyl tRNA molecules in ribosome A site. Indicated for complicated skin and skin structure infections and complicated intra-abdominal infections. Active against S aureus (including MRSA), as well as most streptococci, enterococci (including VRE), and gram-negative organisms (including anaerobes).
Adult Dose	Infuse each dose over 30-60 min 100 mg IV once, then 50 mg IV q12h Severe hepatic impairment (ie, Child Pugh class C): 100 mg IV once, then 25 mg IV q12h
Pediatric Dose	<18 years: Not established >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	Coadministration decreases warfarin clearance and increases warfarin Cmax and AUC (monitor aPTT and INR); coadministration of antibiotics with oral contraceptives may decrease contraceptive effect
Pregnancy	D - Unsafe in pregnancy
Precautions	Caution in severe hepatic impairment (reduce dose); may adversely effect tooth development; may permit clostridia overgrowth, resulting in antibiotic-associated colitis.

FOLLOW-UP

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Complications

• Complications of S aureus bacteremia include septic arthritis, osteomyelitis, pyomyositis, endocarditis, and pneumonia.

Prognosis

• Prognosis varies widely with the site of infection and the underlying condition. Overall, prognosis is good, with full recovery in most patients who receive appropriate therapy.

Patient Education

• For excellent patient education resources, visit eMedicine's Women's Health Center. Also, see eMedicine's patient education article Toxic Shock Syndrome.

MISCELLANEOUS

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Medical/Legal Pitfalls

• Prompt surgical debridement is important for abscesses.
• S aureus bacteremia must be treated with at least 2 weeks of antibiotic therapy; osteomyelitis, endocarditis, and pneumonia require 3-6 weeks of antibiotic therapy. The duration of treatment for central catheter infections with staphylococci is debatable. Most recommend 2 weeks of treatment if the catheter is removed and longer (at least 3 wk) if the catheter is maintained.

MULTIMEDIA

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Media file 1:  Embolic lesions in patient with Staphylococcus aureus endocarditis.
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Media type:  Photo

Media file 2:  Close-up view of embolic lesions in patient with Staphylococcus aureus endocarditis.
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Media type:  Photo

Media file 3:  Fifty-six-year-old man with erythema, edema, and drainage from below his right eye.
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Media type:  Photo

Media file 4:  Gram stain in a 70-year-old woman with rheumatoid arthritis.
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Media type:  Histology

REFERENCES

Section 11 of 11

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• Moran GJ, Krishnadasan A, Gorwitz RJ, Fosheim GE, McDougal LK, Carey RB. Methicillin-resistant S. aureus infections among patients in the emergency department. N Engl J Med. Aug 17 2006;355(7):666-74. [Medline].
• Naimi TS, LeDell KH, Como-Sabetti K, et al. Comparison of community- and health care-associated methicillin-resistant Staphylococcus aureus infection. JAMA. Dec 10 2003;290(22):2976-84. [Medline].
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Article Last Updated: May 8, 2007