What is a staph infection

Staphylococcus aureus (staph) is both a commensal bacterium and a human pathogen. Staph is a type of bacteria that about 30% of people carry in their noses ¹. Many healthy people carry these Staph bacteria on their skin and in their noses without getting sick. But when skin is punctured or broken, staph bacteria can enter the wound and cause infections, which can lead to other health problems. Most of the time, staph does not cause any harm; however, sometimes staph causes infections. Staph infection can be minor (such as pimples or boils) or serious (such as blood infections). Some staph infections may even kill you if the Staph bacteria invade deeper into your body, entering your bloodstream, joints, bones, lungs or heart. A growing number of otherwise healthy people are developing life-threatening staph infections. You can help prevent staph infections in your family by encouraging regular hand washing and daily bathing, and by keeping injured skin clean and covered.

Staph infections can range from minor skin problems to endocarditis, a life-threatening infection of the inner lining of your heart (endocardium). As a result, signs and symptoms of staph infections vary widely, depending on the location and severity of the infection.

Skin infections

Skin infections caused by staph bacteria include:

• Boils. The most common type of staph infection is the boil, a pocket of pus that develops in a hair follicle or oil gland. The skin over the infected area usually becomes red and swollen.

If a boil breaks open, it will probably drain pus. Boils occur most often under the arms or around the groin or buttocks.

• Impetigo. This contagious, often painful rash can be caused by staph bacteria. Impetigo usually features large blisters that may ooze fluid and develop a honey-colored crust.
• Cellulitis. Cellulitis — an infection of the deeper layers of skin — causes skin redness and swelling on the surface of your skin. Sores (ulcers) or areas of oozing discharge may develop, too.
  Staphylococcal scalded skin syndrome. Toxins produced as a result of a staph infection may lead to staphylococcal scalded skin syndrome. Affecting mostly babies and children, this condition features fever, a rash and sometimes blisters. When the blisters break, the top layer of skin comes off — leaving a red, raw surface that looks like a burn.

Food poisoning

Staph bacteria are one of the most common causes of food poisoning. Symptoms come on quickly, usually within hours of eating a contaminated food. Symptoms usually disappear quickly, too, often lasting just half a day.

A staph infection in food usually doesn’t cause a fever. Signs and symptoms you can expect with this type of staph infection include:

• Nausea and vomiting
• Diarrhea
• Dehydration
• Low blood pressure

In healthcare settings, these Staph infections can be serious or fatal, including ²:

• Bacteremia or sepsis when bacteria spread to the bloodstream.
• Pneumonia, which predominantly affects people with underlying lung disease including those on mechanical ventilators.
• Endocarditis (infection of the heart valves), which can lead to heart failure or stroke.
• Osteomyelitis (bone infection), which can be caused by staph bacteria traveling in the bloodstream or put there by direct contact such as following trauma (puncture wound of foot or intravenous (IV) drug abuse).

Bacteremia

Also known as blood poisoning, bacteremia occurs when staph bacteria enter a person’s bloodstream. A fever and low blood pressure are signs of bacteremia. The bacteria can travel to locations deep within your body, to produce infections affecting:

• Internal organs, such as your brain, heart or lungs
• Bones and muscles
• Surgically implanted devices, such as artificial joints or cardiac pacemakers

Toxic shock syndrome

This life-threatening condition results from toxins produced by some strains of staph bacteria and has been linked to certain types of tampons, skin wounds and surgery. It usually develops suddenly with:

• A high fever
• Nausea and vomiting
• A rash on your palms and soles that resembles sunburn
• Confusion
• Muscle aches
• Diarrhea
• Abdominal pain

Septic arthritis

Septic arthritis is often caused by a staph infection. The bacteria often target the knees, shoulders, hips, and fingers or toes. Signs and symptoms may include:

• Joint swelling
• Severe pain in the affected joint
• Fever

Staph bacteria can also become resistant to certain antibiotics.

These drug-resistant staph infections include:

• Methicillin-resistant Staphylococcus aureus (MRSA),
• Vancomycin-intermediate Staphylococcus aureus (VISA), and
• Vancomycin-resistant Staphylococcus aureus (VRSA).

When to see a doctor

Go to the doctor if you or your child has:

• An area of red, irritated or painful skin
• Pus-filled blisters
• Fever

You may also want to consult your doctor if:

• Skin infections are being passed from one family member to another
• Two or more family members have skin infections at the same time.

Treatment for Staph Infection

Treatment of a staph infection may include:

• Antibiotics. Your doctor may perform tests to identify of the staph bacteria behind your infection, and to help choose the antibiotic that will work best. Antibiotics commonly prescribed to treat staph infections include certain cephalosporins, nafcillin or related antibiotics, sulfa drugs, or vancomycin.

Vancomycin increasingly is required to treat serious staph infections because so many strains of staph bacteria have become resistant to other traditional medicines. But vancomycin and some other antibiotics have to be given intravenously.

If you’re given an oral antibiotic, be sure to take it as directed, and to finish all of the medication prescribed by your doctor. Ask your doctor what signs and symptoms you should watch for that might indicate your infection is worsening.

• Wound drainage. If you have a skin infection, your doctor will likely make an incision into the sore to drain fluid that has collected there.
• Device removal. If your infection involves a device or prosthetic, prompt removal of the device is needed. For some devices, removal might require surgery.

How do you get a staph infection ?

Anyone can develop a staph infection, although certain groups of people are at greater risk, including people with chronic conditions such as diabetes, cancer, vascular disease, eczema, and lung disease. In a healthcare setting, the risk of more serious staph infection is higher because patients often have weakened immune systems or have undergone procedures such as surgery or have intravenous catheters.

Causes of Staph Infection

Many people carry staph bacteria and never develop staph infections. However, if you develop a staph infection, there’s a good chance that it’s from bacteria you’ve been carrying around for some time.

These bacteria can also be transmitted from person to person. Because staph bacteria are so hardy, they can live on inanimate objects such as pillowcases or towels long enough to transfer to the next person who touches them.

Staph bacteria are able to survive:

• Drying
• Extremes of temperature
• Stomach acid
• High levels of salt

Risk factors for Staph Infection

A variety of factors — including the status of your immune system to the types of sports you play — can increase your risk of developing staph infections.
Underlying health conditions

Certain disorders or the medications used to treat them can make you more susceptible to staph infections.

People who may be more likely to get a staph infection include those with:

• Diabetes who use insulin
• HIV/AIDS
• Kidney failure requiring dialysis
• Weakened immune systems — either from a disease or medications that suppress the immune system
• Cancer, especially those who are undergoing chemotherapy or radiation
• Skin damage from conditions such as eczema, insect bites or minor trauma that opens the skin
• Respiratory illness, such as cystic fibrosis or emphysema

Current or recent hospitalization

Despite vigorous attempts to eradicate them, staph bacteria remain present in hospitals, where they attack the most vulnerable, including people with:

• Weakened immune systems
• Burns
• Surgical wounds

Invasive devices

Staph bacteria can travel along the medical tubing that connects the outside world with your internal organs. Examples include:

• Dialysis tubing
• Urinary catheters
• Feeding tubes
• Breathing tubes
• Intravascular catheters

Contact sports

Staph bacteria can spread easily through cuts, abrasions and skin-to-skin contact. Staph infections may also spread in the locker room through shared razors, towels, uniforms or equipment.

Unsanitary food preparation

Food handlers who don’t properly wash their hands can transfer staph from their skin to the food they’re preparing. Foods that are contaminated with staph look and taste normal.

Prevention of Staph Infection

These commonsense precautions can help lower your risk of developing staph infections:

• Wash your hands. Careful hand-washing is your best defense against germs. Wash your hands briskly for at least 20 seconds, then dry them with a disposable towel and use another towel to turn off the faucet. If your hands aren’t visibly dirty, you can use a hand sanitizer containing at least 60 percent alcohol.
• Keep wounds covered. Keep cuts and abrasions clean and covered with sterile, dry bandages until they heal. The pus from infected sores often contains staph bacteria, and keeping wounds covered will help keep the bacteria from spreading.
• Reduce tampon risks. Toxic shock syndrome is caused by staph bacteria. Since tampons left in for long periods can be a breeding ground for staph bacteria, you can reduce your chances of getting toxic shock syndrome by changing your tampon frequently, at least every four to eight hours. Use the lowest absorbency tampon you can, and try to alternate tampons with sanitary napkins whenever possible.
• Keep personal items personal. Avoid sharing personal items such as towels, sheets, razors, clothing and athletic equipment. Staph infections can spread on objects, as well as from person to person.
• Wash clothing and bedding in hot water. Staph bacteria can survive on clothing and bedding that isn’t properly washed. To get bacteria off clothing and sheets, wash them in hot water whenever possible.
• Also, use bleach on any bleach-safe materials. Drying in the dryer is better than air-drying, but staph bacteria may survive the clothes dryer.
• Take food safety precautions. Wash your hands before handling food. If food will be out for a while, make sure that hot foods stay hot — above 140 F (60 C) — and that cold foods stay at 40 F (4.4 C) or below. Refrigerate leftovers as soon as possible.

Complications of Staph Infections

If staph bacteria invade your bloodstream, you may develop a type of infection that affects your entire body. Called sepsis, this infection can lead to septic shock — a life-threatening episode with extremely low blood pressure. Staph bacteria can also cause toxic shock syndrome.

Skin and Soft Tissue Staph Infection Symptoms

Staph causes a variety of skin and soft tissue infections, ranging from the benign (e.g., impetigo and uncomplicated cellulitis) to the immediately life-threatening. It is the most common pathogen isolated from surgical site infections, cutaneous abscesses, and purulent cellulitis.

While Staph aureus has traditionally been the leading cause of skin and soft tissue infections, its importance has grown exponentially in the past 15 years with the emergence of a worldwide epidemic of community-associated meticillin-resistant Staphylococcus aureus (MRSA) skin and soft tissue infections ³. When community-associated-MRSA was first recognized in the United States in the late 1990s, molecular typing demonstrated that the predominant clone was USA400 ⁴. Since 2000, USA400 has largely been supplanted by a single epidemic clone, USA300, which has been responsible for the rapid shift in epidemiology in the United States. King et al. ⁵ found that the USA300 clone was the cause of most community-onset Staph skin and soft tissue infections. Among 389 patients in a Georgia health system, 72% of all S. aureus Staph skin and soft tissue infections were caused by MRSA, and ∼85% of these were caused by USA300. Similar findings were seen concurrently in cohorts of patients presenting to emergency departments elsewhere in the United States ⁶. Increasing rates of Staph skin and soft tissue infections have also been noted in Australia and the United Kingdom. Notably, the increasing incidence of Staph skin and soft tissue infections in these regions cannot be attributed to USA300, which is an infrequent cause of staphylococcal infections in Europe ⁷ and Australia ⁸.

The primary defense against Staph infection is the neutrophil response. When Staph aureus enters the skin, neutrophils and macrophages migrate to the site of infection. Staph aureus evades this response in a multitude of ways, including blocking chemotaxis of leukocytes, sequestering host antibodies, hiding from detection via polysaccharide capsule or biofilm formation, and resisting destruction after ingestion by phagocytes.

With the rise in the number of Staph skin and soft tissue infections caused by community-associated-MRSA, there has been intense interest in understanding the enhanced pathogenicity of these strains. Multiple virulence factors appear to contribute, including Panton-Valentine leukocidin (PVL), alpha-hemolysin (also called alpha-toxin), phenol-soluble modulins (PSMs), the arginine catabolic mobile element (ACME), and a regulatory locus referred to as agr. Other candidate virulence determinants continue to be discovered. The sasX gene was found in the S. aureus clone most common in Asia. In addition to a putative role in nasal colonization and pleural infection, the presence of this gene was correlated with larger cutaneous abscesses than those in mice infected with sasX mutant strains ⁹.

Figure 1. Staph skin and soft tissue infections

Note: Staphylococcus aureus skin and soft tissue infections. Shown are abscess (top left), cellulitis surrounding a pustule (top right), embolic infarcts complicating infective endocarditis (bottom left), and impetigo complicating scabies infection (bottom right).

Folliculitis and Boils

Folliculitis is an infection of hair follicles, tiny pockets under the skin where hair shafts (strands) grow. In folliculitis, tiny white-headed pimples appear at the base of hair shafts, sometimes with a small red area around each pimple. This infection often happens in areas where there’s been friction or irritation, such as with shaving.

Folliculitis often clears up on its own with good skin care. But sometimes it goes on to become a boil (also called a furuncle). With a boil, the staph infection spreads deeper and wider, often affecting the subcutaneous tissue (deeper tissue under the skin) and oil-producing glands (called sebaceous glands).

In the first stage, which parents and kids often miss, the area of skin either begins to itch or becomes mildly painful. Next, the skin turns red and begins to swell over the infected area. Finally, the skin above the infection becomes very tender and a whitish “head” may appear. The head may break, and the boil may begin to drain pus, blood, or an amber-colored liquid. Boils can occur anywhere on the skin, especially under the arms or on the groin or buttocks in kids.

To help relieve pain from a boil, try warm-water soaks, a heating pad, or a hot-water bottle applied to the skin for about 20 minutes, three or four times a day. Make sure that the washcloths used for the soaks are washed after each use. Boils are occasionally treated with oral antibiotics and in some cases need to be surgically drained.

Impetigo

Impetigo is the most common bacterial skin infection of children ¹¹. In general, impetigo presents as bullous or papular lesions that progress to crusted lesions, without accompanying systemic symptoms, on exposed areas of the body (usually the face or extremities). Recent studies of impetiginous lesions found recovery rates of 29 to 90% and 57 to 81% for Streptococcus pyogenes and S. aureus, respectively ¹².

Figure 2. Impetigo

Cutaneous abscess and Nonpurulent cellulitis

While the hallmark of Staph skin and soft tissue infections is generally regarded as the cutaneous abscess ¹³, other manifestations of skin infection are also encountered clinically. Nonpurulent cellulitis may be caused by Staph infection in a minority of cases, although the lack of a diagnostic gold standard and variability introduced by different microbiological methods obscure the true microbiology of this condition ¹⁴. While Staph cellulitis most commonly involves the lower extremities, it may also involve other regions, including the upper extremities, abdominal wall, and face. It vies for primacy with streptococci as a cause of preseptal and orbital cellulitis (321,–323).

Figure 3. Staph cellulitis

Scalded Skin Syndrome

Scalded skin syndrome most often affects newborns and kids under age 5. The illness usually starts with a small staph skin infection, but the staph bacteria make a toxin that affects skin all over the body. The child has a fever, rash, and sometimes blisters. As blisters burst and the rash passes, the top layer of skin sheds and the skin surface becomes red and raw, like a burn.

Scalded skin syndrome is a serious illness that affects the body in the same way as serious burns. It needs to be treated in a hospital. After treatment, most kids make a full recovery.

Necrotizing fasciitis

Necrotizing fasciitis is another cutaneous syndrome caused by Staph infection. Necrotising fasciitis is a very serious bacterial infection of the soft tissue and fascia (a sheath of tissue covering the muscle) ¹⁵. The bacteria multiply and release toxins and enzymes that result in thrombosis (clotting) in the blood vessels. The result is destruction of the soft tissues and fascia. In a review of 843 patients with wound cultures positive for MRSA, 14 isolates were identified as being associated with necrotizing fasciitis or myositis. Coexisting conditions among those patients included injection drug use in 6/14 (43%) patients, previous MRSA infections in 3/14 (21%), diabetes mellitus in 3/14 (21%), and hepatitis C in 3/14 (21%) ¹⁶. In Taiwan, a review of 53 patients with necrotizing fasciitis revealed that 38% of infections were caused by Staph infection, 60% of which were caused by MRSA ¹⁷.

Figure 4. Necrotising fasciitis 

Pyomyositis

Pyomyositis can occur with both MSSA (Methicillin-sensitive Staphylococcus aureus) and MRSA (Methicillin-resistant Staphylococcus aureus). Tropical pyomyositis is a rare condition characterized by primary muscle abscesses arising within large skeletal muscles. It has a tropical predilection, accounting for up to 1 to 4% of hospital admissions in some tropical countries, with Staph being responsible for an estimated 90% of these presentations ¹⁸. It is less common in temperate climates, where it occurs primarily in children and young adults ¹⁹ and has been reported in association with HIV ²⁰.

Surgical site infections

Surgical site infections occur after 2 to 5% of all surgeries ²¹, although there is considerable heterogeneity depending on the type of procedure, population studied, comorbid illnesses, experience of the surgeon, setting, and antimicrobial prophylaxis utilized. According to 2009-2010 U.S. National Healthcare Safety Network data, Staph was the most common cause of surgical site infections overall, accounting for 30% of infections. Of these, 44% of isolates were methicillin resistant ²². In registrational trials of complicated Staph skin and soft tissue infections, even higher proportions of surgical site infections due to Staph have been found; for example, 49% of surgical site infections in ATLAS studies (telavancin versus vancomycin) were due to Staph aureus ²³.

A particularly devastating surgical site infection is mediastinitis complicating median sternotomy for cardiac surgery. Staph aureus is the most common cause of postoperative mediastinitis ²⁴. Fowler et al. ²⁵ demonstrated that the presence of Staph becteremia in the postoperative period was highly predictive of a diagnosis of mediastinitis, with a likelihood ratio of 25, compared to blood cultures positive for other pathogens or negative blood cultures. These findings were subsequently independently validated ²⁶. Thus, the presence of Staph becteremia following sternotomy mandates aggressive investigation to exclude the possibility of postoperative mediastinitis.

Treating Staph Skin Infections

You can treat most small staph skin infections by:

• washing the skin with an antibacterial cleanser
• using warm soaks (to keep the infection from spreading, use a towel only once when you soak or clean an area of infected skin, and then wash it)
• applying antibiotic ointment, if prescribed by your doctor
• covering the skin with a clean dressing or bandage

Your doctor may prescribe an oral antibiotic for your staph skin infection. If so, give the antibiotic on schedule for as many days as the doctor directs.

More serious staph infections might need to be treated in a hospital, and an abscess (or pocket of pus) that doesn’t respond to home care might need to be drained.

See the doctor whenever you have an area of red, irritated, or painful skin, especially if you see whitish pus-filled areas or you have a fever or feels sick. Also, see your doctor if skin infections seem to be passing from one family member to another or if two or more family members have skin infections at the same time.

Risk factors for Staph Bacteremia

Age is a powerful determinant of Staphylococcus aureus bacteremia incidence, with the highest rates of infection occurring at either extreme of life ²⁷. Studies consistently demonstrate high rates in the first year of life, a low incidence through young adulthood, and a gradual rise in incidence with advancing age. For example, the incidence of Staph bacteremia is >100 per 100,000 person-years among subjects >70 years of age ²⁸ but is only 4.7 per 100,000 person-years in younger, healthier U.S. military personnel ²⁹. Male gender is consistently associated with increased Staph bacteremia incidence ³⁰, with male-to-female ratios of ∼1.5. The basis for this increased risk is not understood.

The incidence of Staph bacteremia is also associated with ethnicity. In the United States, the incidence of invasive Methicillin-resistant Staphylococcus aureus (MRSA) in the black population (66.5 per 100,000 person-years) is over twice that in the white population (27.7 per 100,000 person-years) ³¹. In Australia, the incidence of Staph bacteremia in the indigenous population is 5.8 to 20 times that of nonindigenous Australians ³². Similarly, Maori and Pacific Island people have significantly higher rates of incidence of Staph bacteremia than do those of European ethnicity in New Zealand ³³. Differences in markers of the socioeconomic status of indigenous compared to nonindigenous populations do not fully explain the disparity between these groups ³². The contribution of host genetic susceptibility to these ethnic differences has not yet been investigated.

The HIV-infected population has a significantly increased incidence of Staph bacteremia. Two studies reported incidences of Staph bacteremia in HIV-infected patients of 494 per 100,000 person-years ³⁴ and 1,960 per 100,000 person-years ³⁵, or 24 times that of the non-HIV-infected population ³⁴. Although much of this increase results from high rates of injection drug use in the HIV-infected population, even the non-injection drug-using HIV-infected population exhibits higher rates of Staph bacteremia than those in the non-HIV-infected population ³⁴. Among HIV-infected individuals, a low CD4 count was independently associated with Staph bacteremia. Also, compared to injection drug users, men who have sex with men were likely to have a low CD4 count and to have nosocomial Staph bacteremia ³⁴. Thus, HIV-infected injection drug users tend to acquire community-onset Staph bacteremia as a consequence of injection drug use, whereas men who have sex with men have higher rates of nosocomial Staph bacteremia.

The high risk of Staph bacteremia in the overall injection drug user population can be inferred from a Dutch study that monitored 758 injection drug users for 1,640 person-years and determined that there were 10 confirmed episodes of Staph infective endocarditis ³⁶. Based on these figures, the incidence of Staph bacteremia was at least 610 per 100,000 person-years. In the setting of injection of material into the bloodstream, additional factors contributing to the high incidence of Staph bacteremia include an increased prevalence of Staph colonization compared to that in the general population ³⁷, frequent skin and soft tissue infections ³⁸, and a drug-using environment that facilitates the person-to-person transmission of Staph ³⁹.

Hemodialysis patients are also at a greatly increased risk of Staph bacteremia. The incidences of Staph bacteremia in hemodialysis-dependent patients were 3,064 per 100,000 person-years in Taiwan ⁴⁰, 17,900 per 100,000 person-years in Ireland ⁴¹, and 4,045 to 5,015 per 100,000 person-years in the United States ⁴². The predominant risk factor for these patients is the presence of an intravascular access device and in particular the use of a cuffed, tunneled catheter (e.g., permacath) for dialysis ⁴¹. However, other host factors that result in an impairment of the host immune defense, including neutrophil dysfunction ⁴³, iron overload ⁴⁴, diabetes ⁴⁵, and increased rates of colonization ⁴⁵, may also increase the likelihood of invasive Staph infections. The infrequent vancomycin dosing strategy often used among hemodialysis-dependent patients may not maintain an adequate trough level in high-flux, large-pore-size artificial kidneys ⁴⁶, increasing the risk for relapsing Staph bacteremia.

Staph Clinical Syndromes

Epidural Abscess

Epidural abscesses can be intracranial or spinal. Intracranial epidural abscesses are much less common than spinal epidural abscesses and usually follow surgery or trauma. Although a rare infection [∼1 in 20,000 hospitalized patients ⁴⁷], spinal epidural abscess is the second most common infectious cause of medical malpractice in the United States ⁴⁸. The incidence of epidural abscess appears to have increased over the past 30 years (765). This is likely to be in part due to the increasing availability of magnetic resonance imaging (MRI) (which is much more sensitive than previous modalities) and partly due to the increasing use of epidural catheters and electrodes for pain management. Staph aureus is the most common causative agent of spinal epidural abscess, accounting for 60 to 73% of all cases ⁴⁹.

Pathophysiology and clinical manifestations of Staph Epidural Abscess

An epidural abscess may arise by hematogenous seeding from an episode of Staph becteremia, by contiguous spread from an adjacent focus (such as psoas abscess or vertebral osteomyelitis), or due to direct inoculation from trauma, spinal surgery, or the placement of epidural catheters ⁴⁹. Although a spinal epidural abscess may occur anywhere from the cervical to the sacral spine, it is generally more likely to occur where the epidural space is larger. Thus, posterior epidural space involvement is more common than anterior epidural space involvement, and lumbar and lower thoracic epidural abscesses are more common than cervical epidural abscesses ⁵⁰. Because the epidural space is a continuous vertical region, epidural abscesses generally spread over several vertebral levels and rarely may involve the entire spine. The most important potential consequence of spinal epidural abscesses is damage to the spinal cord and nerve roots, which can occur due to direct compression of the cord by an expanding collection of pus ⁵¹ or indirectly through arterial or venous ischemia. The major risk factors for Staph aureus spinal epidural abscess include diabetes mellitus ⁴⁹, injection drug use ⁴⁹, recent spinal surgery or trauma, and recent placement of epidural injections, catheters, or stimulating wires ⁵². Approximately 2.5% of patients with Staph bacteremia have epidural abscesses ⁵³. Thus, any patient with Staph bacteremia who complains of new or changing back pain should undergo spinal imaging, preferably with MRI, to evaluate the possibility of an epidural abscess.

The classic clinical triad for epidural abscess is back pain, fever, and neurological signs; however, the complete triad is present in only a minority of patients at presentation ⁵⁴. For this reason, the diagnosis of spinal epidural abscess is often not initially considered. For example, only 40% of admitting diagnoses included spinal epidural abscess as the suspected diagnosis for one series of 43 patients ultimately found to have epidural abscess ⁴⁷. Darouiche et al. ⁴⁷ described the following clinical staging system, which is useful for determining the timing and nature of management of spinal epidural abscesses: stage 1, back pain at the affected vertebral level; stage 2, nerve root pain radiating from the involved area; stage 3, objective motor and sensory loss and/or bladder and bowel dysfunction; and stage 4, paralysis. This staging system is important because once patients enter stages 2 and 3, their spinal cord is under threat, and urgent surgical decompression is required.

Management of spinal epidural abscess

In general, surgical decompression (laminectomy, debridement of infected or necrotic tissue, and drainage of pus) is required to achieve a successful outcome in cases of Staph aureus spinal epidural abscess. This is in conjunction with a long course of high-dose i.v. antibiotic therapy ⁴⁹. Because of the possibility of permanent paralysis, spinal epidural abscess is a medical and surgical emergency. Once paralysis is established for >24 to 48 h, the damage is likely to be permanent. Thus, the key step is the early recognition of the possibility of spinal epidural abscess and rapid investigation to confirm the diagnosis. Most authors suggest that surgical decompression be performed urgently (within 24 h of diagnosis) in patients with Staph aureus spinal epidural abscess ⁴⁷. However, it is increasingly being recognized that select patients may not require surgical intervention. Such patients include those in whom paralysis has been present for >48 h and those with early (clinical stage 1) infection with small abscesses, where a pathogen has been identified by blood culture or computed tomography (CT)-guided aspiration of the abscess ⁵⁵. MSSA spinal epidural abscesses should be treated with ∼6 weeks of a high-dose i.v. antistaphylococcal β-lactam (e.g., 2 g nafcillin every 4 h [q4h] i.v.). For MRSA, treatment with vancomycin for a similar duration is advised, aiming for plasma levels of 15 to 20 mg/liter.

Meningitis

Staph aureus is an uncommon cause of bacterial meningitis, accounting for 4.9 to 6.4% of cases ⁵⁶. Staph aureus meningitis may either arise by hematogenous spread from a non-CNS focus of infection or be secondary to neurosurgical intervention ⁵⁷. Hematogenous Staph aureus meningitis is usually community acquired ⁵⁸ and, compared with postsurgical S. aureus meningitis, typically affects older individuals (mean age of 59 years versus 40 years) ⁵⁹ with severe medical comorbidities such as diabetes or chronic kidney disease ⁵⁸. The initial source of hematogenous Staph aureus meningitis is generally infective endocarditis, pneumonia, or Staph skin and soft tissue infection ⁶⁰. The mortality rate for hematogenous Staph aureus meningitis is higher (43 to 50%) than that occurring postsurgically (14 to 25%) ⁵⁹. Among Staph aureus meningitis cases, methicillin resistance has been increasing in recent years ⁶¹. Specifically, Pintado et al. ⁶² conducted a retrospective, multicenter study examining MRSA meningitis in adults over a 25-year period (1981 to 2005). This group found that nearly half of MRSA meningitis cases arose in the last 5 years of the study. The 30-day mortality rate for these patients was 31%. Most MRSA meningitis cases are nosocomial and postsurgical ⁶².

Clinical manifestations and risk factors for Staph Meningitis

Because meningitis is a rare complication for patients with Staph bacteremia, occurring in 1.7% of 724 prospectively identified patients with Staph bacteremia, clinicians need to be alert to its possibility ⁵³.

Staph aureus meningitis typically presents with one or more of the following signs or symptoms ⁶²:

• persistent fever,
• headache,
• stiff neck, and
• vomiting.

Fever and change in consciousness are the two most common clinical symptoms ⁶³. Patients with hematogenous Staph aureus meningitis typically have a greater degree of CSF leukocytosis than do postsurgical patients ⁵⁹.

The major predisposing factors for postsurgical meningitis are (i) the presence of an intrathecal device or ventriculoperitoneal shunt ⁵⁸, (ii) recent neurosurgery, and (iii) a CSF leak ⁵⁸. Of note, Staph aureus is the second leading cause of bacterial meningitis among patients with a ventriculoperitoneal shunt ⁶⁴. Intravenous drug use is an important risk factor for hematogenous Staph aureus meningitis, being present in 52% of patients in a recent series of 21 cases of hematogenous Staph aureus meningitis from a single center in the United States ⁵⁸ but in only 12.5% of 96 cases from a nationwide Danish study ⁶⁵.

Risk factors for mortality among patients with Staph aureus meningitis include a hematogenous compared with a postsurgical source [e.g., 56% mortality for a hematogenous source versus 18% for a postsurgical source within a national Danish study ⁶⁶], increasing age and number of comorbidities, the presence of septic shock and concurrent infective endocariditis ⁶³.

Management of Staph Meningitis

The IDSA recommends high-dose i.v. nafcillin or oxacillin to treat MSSA (Methicillin-resistant Staphylococcus aureus) meningitis and vancomycin for MRSA (Methicillin-resistant Staphylococcus aureus) meningitis ⁶⁷. Vancomycin has poor penetration into the CSF of ∼1% through uninflamed and 5% through inflamed meninges ⁶³, and in practice, it can be difficult to achieve therapeutic levels within the CSF. This is even more of an issue when the vancomycin MIC (minimum inhibitory concentration) of an MRSA isolate approaches or exceeds 2 μg/ml. In such dire settings, consideration can be given to unproven adjunctive therapies such as the intrathecal administration of vancomycin ⁶⁸ or the addition of antibiotics such as linezolid (CSF penetration, 66%), TMP-SMX (CSF penetration, ∼50%), or daptomycin (CSF penetration, 6%).

Toxic Shock Syndrome

Staph aureus toxic shock syndrome was first described in 1978 by Todd et al. ⁶⁹, who reported the illness in a group of 7 children. Shortly thereafter, Staph aureus toxic shock syndrome became linked with superabsorbent tampons in menstruating women in the 1980s ⁷⁰, reaching an annual infection rate of 13.7 per 100,000 menstruating women ⁷¹. After the removal of highly absorbent tampons from the market, the annual incidences of S. aureus TSS declined to 1 per 100,000 menstruating women and 0.3 per nonmenstruating persons ⁷². The incidence of Staph aureus toxic shock syndrome has remained stable since that time, with the current annual incidences reported to be 0.69 per 100,000 menstruating women and 0.32 per 100,000 total population ⁷³. Currently, the numbers of menstrual and nonmenstrual cases of staphylococcal toxic shock syndrome are similar, and the most common foci of infection in nonmenstrual cases are Staph skin and soft tissue infections ⁷³. Nonmenstrual cases have been associated with a higher mortality rate than menstrual cases ⁷⁴.

Clinical manifestations and diagnosis of toxic shock syndrome

Staph aureus toxic shock syndrome is a superantigen-mediated process. Some strains of Staph aureus secrete an exotoxin called toxic shock syndrome toxin 1 (TSST-1) ⁷⁵. TSST-1 cross-links the T-cell receptor with major histocompatibility complex class II (MHC-II) on antigen-presenting cells, triggering large-scale T-cell activation and massive cytokine release ⁷⁶. This leads to an overwhelming systemic inflammatory response syndrome and is manifested by septic shock with organ failure. The CDC reported diagnostic criteria for staphylococcal toxic shock syndrome ⁷⁷.

A confirmed case must meet all of the following criteria:

• (i) a fever of >38.9°C,
• (ii) shock (systolic blood pressure of <90 mm Hg despite adequate fluid resuscitation),
• (iii) a diffuse macular erythematous rash (typically followed 1 to 2 weeks later by desquamation), and
• (iv) specific abnormalities involving at least three organ systems:
  • The organ system involvements that can be included are as follows:
    • (i) gastrointestinal, with vomiting or diarrhea;
    • (ii) musculoskeletal, with severe myalgia or creatinine kinase levels >2 times the upper limit of normal;
    • (iii) renal, with serum creatinine levels >2 times the upper limit of normal;
    • (iv) hepatic, with bilirubin or transaminase levels >2 times the upper limit of normal;
    • (v) hematologic, with platelet counts of <100,000 platelets/μl; and
    • (vi) CNS, with delirium without focal signs.

Management of toxic shock syndrome

The key aspects of treatment of Staph aureus toxic shock syndrome include identifying and removing the source of Staph aureus toxin production (e.g., tampon or surgical wound) and supportive care ⁷⁸. In the setting of postoperative Staph aureus toxic shock syndrome, the involved surgical wound often appears normal ⁷⁴. However, this benign appearance in no way reduces the need for surgical debridement in patients with wound-associated Staph aureus toxic shock syndrome. Antibiotics, in contrast, play a secondary role in the management of toxic shock syndrome. Because it can block the production of exotoxins by the bacterial ribosome, clindamycin or linezolid is often added to standard antibiotic therapy ⁷⁹. Intravenous immunoglobulin may also be effective, although clinical evidence of benefit is not well established, and there is less evidence supporting the use of i.v. immunoglobulin to treat staphylococcal toxic shock syndrome than for streptococcal toxic shock syndrome. Nonetheless, it is recommended that i.v. immunoglobulin be considered for patients who have had no clinical response to aggressive supportive therapy within 6 h ⁸⁰.

Osteoarticular Infections

Staph aureus is the most common pathogen in all three major classes of osteoarticular infection, namely, osteomyelitis ⁸¹, native joint septic arthritis ⁸², and prosthetic joint infection ⁸³. As staphylococcal osteoarticular infections in children are common and have distinctive clinical and management issues compared to those in adults, we include an in-depth discussion of this important subpopulation.

Osteomyelitis

Osteomyelitis is an infection of bone resulting in its inflammatory destruction, bone necrosis, and new bone formation. The Waldvogel classification system ⁸⁴ describes three types of osteomyelitis: hematogenous osteomyelitis, contiguous-focus osteomyelitis (from adjacent structures such as joint spaces or soft tissues or from trauma or surgery with direct implantation of organisms), and osteomyelitis with vascular insufficiency (most commonly in patients with diabetes or peripheral vascular disease and generally involving the foot). Staph aureus is the predominant cause of osteomyelitis in all of these categories and is identified in 30 to 60% of cases. Hematogenous osteomyelitis generally involves the ends of long bones in children and adolescents and the axial skeleton in older adults (408), partly due to the blood supply to vertebrae in adults being more extensive than that to the long bones. This section principally focuses on hematogenous osteomyelitis that most commonly manifests as vertebral osteomyelitis in adults and long bone osteomyelitis in children, where Staph aureus is typically the key pathogen.

Clinical manifestations and outcomes of Osteomyelitis

Vertebral osteomyelitis generally involves the endplates of two adjacent vertebrae and the intervening disc space. The most common route of spread is hematogenous seeding to the vertebral endplates, and from here, the infection spreads directly into the disc space. Hence, the term “discitis” is a misnomer, since disc space infection is secondary. The exception is where infection has been directly introduced to the disc space (e.g., following a surgical microdiscectomy). The hallmark of vertebral osteomyelitis is back pain, being present in 85 to 100% of patients. Localized vertebral percussion tenderness is present in >80% of cases, but fever is present in anywhere from 18 to 83% of cases in various case series. A significant minority of patients have signs of nerve compression (such as limb weakness) at presentation, and one-quarter of patients with vertebral osteomyelitis will ultimately develop paralysis or significant neurologic dysfunction ⁸⁵. Among 133 consecutive patients with SAB and concomitant vertebral osteomyelitis, the most frequent primary foci or portals of entry of infection were the skin (21%) and urinary tract (10%). However, 71/133 patients (53%) had no identified primary focus ⁸⁶. Comparisons between vertebral osteomyelitis caused by MRSA and that caused by MSSA have found that patients with infections due to MRSA have more comorbidities and are more likely to have had recent nonspinal surgery (390). Lumbar vertebrae are most frequently affected, followed by thoracic and then cervical regions. Notably, the diagnosis of vertebral osteomyelitis is frequently delayed, with an interval of >1 month from symptom onset to diagnosis for the majority of patients ⁸⁵. Delayed diagnosis has been associated with poorer longer-term outcomes, including death, chronic pain, and residual disability ⁸⁵.

The peripheral WBC (white blood cell) count is raised in a variable proportion of patients with osteomyelitis, but the erythrocyte sedimentation rate (ESR) and serum C-reactive protein (CRP) level are raised in 95 to 100% of patients with acute osteomyelitis. A systematic review of 14 studies of vertebral osteomyelitis found that the reported yield from blood cultures for a microbiological diagnosis was 58% (range, 30 to 78%) ⁸⁷. Therefore, in the appropriate clinical and radiological settings, positive blood cultures can eliminate the need for diagnostic biopsy or aspiration of infected bone for culture. However, bone biopsy for culture and histology should be pursued if blood cultures are negative, as it provides a higher diagnostic yield (77%; range, 47 to 100%) ⁸⁷. Where possible, the biopsy specimen is best obtained prior to antibiotic treatment. Several investigators have found that the microbiological yield from biopsy specimens of patients on antibiotics is ∼50% lower than that from biopsy specimens obtained prior to antibiotic treatment ⁸⁸. Where an initial percutaneous biopsy specimen is negative, there may be value in obtaining a second percutaneous biopsy specimen. Gras et al. ⁸⁹ examined a cohort of 136 patients with vertebral osteomyelitis who were all blood culture negative and who had not received antibiotics in the previous 2 weeks. Performance of a second biopsy after an initial negative result led to a microbiological diagnosis in 80% (74/93) of cases, versus 44% (60/136) with only one biopsy specimen. While significantly more invasive, open surgical biopsy is also more likely to yield a diagnosis than needle biopsy. For example, in a series of 70 patients from Missouri, an open biopsy had a 93% diagnostic yield, compared with 48% for radiologically guided needle biopsy ⁹⁰. In summary, a microbiological diagnosis should be sought to guide subsequent therapy. One suggested approach to the diagnosis of vertebral osteomyelitis begins with blood cultures, followed by an initial percutaneous biopsy, a second percutaneous biopsy if the initial biopsy specimen is sterile, and an open biopsy if clinically indicated ⁹¹.

The short-term mortality rates for osteomyelitis are substantial, at 2.8 to 7.7% for nonvertebral osteomyelitis ⁹² and 6 to 16% for vertebral osteomyelitis ⁸⁵. Furthermore, health care costs ⁹³ and rates of long-term functional impairment ⁸⁵ are also high. Akiyama et al. ⁹⁴ found that for vertebral osteomyelitis, higher mortality rates were significantly associated with older age (patients aged 60 to 69, 70 to 79, and ≥80 years), compared with those aged ≤59 years), hemodialysis use, diabetes, liver cirrhosis, malignancy, and infective endocarditis .

Management of osteomyelitis

The management of vertebral osteomyelitis caused by Staph aureus requires prolonged courses of antibiotics. Jensen et al. ⁸⁶ found that among 114 patients with bacteremic Staph aureus osteomyelitis, recurrence was more likely in patients receiving <8 weeks of antibiotic therapy than in those receiving ≥8 weeks of therapy. Park et al. ⁹⁵ determined that for 62 patients with vertebral osteomyelitis due to MRSA, patients receiving <8 weeks of antibiotic treatment were 4.8 times more likely to relapse than those receiving ≥8 weeks of therapy. There was no such association for 77 patients with MSSA infections ⁹⁵. In contrast, Roblot et al. ⁹⁶ determined that for 120 patients, outcomes were similar for 36 patients treated at one center with a median of 6 weeks of total therapy and for 84 patients treated at another center with a median of 10 weeks total therapy. These data and other observational data have led to recommendations that range from 6 weeks ⁹⁶ to 12 weeks ⁹¹ of antibiotic treatment. Most recently, Bernard et al. ⁹⁷ compared antibiotic treatments for 6 weeks and 12 weeks for patients with pyogenic vertebral osteomyelitis. In an open-label, noninferiority clinical trial design powered to achieve an absolute margin of 10%, 359 patients from 71 French medical care centers were randomly assigned to either of the treatment durations. Of these infections, 145 (41%) were due to S. aureus, 95% (n = 137) of which were due to MSSA. The primary endpoint was defined as the proportion of patients who were classified as being cured at 1 year by a masked independent validation committee. In an intention-to-treat analysis, 6 weeks of antibiotic treatment was noninferior to 12 weeks of antibiotic treatment, suggesting that the standard duration of antibiotic treatment for patients with this infection could be reduced to 6 weeks ⁹⁷ . Where clinical improvement is slow, undrained or unremoved foci exist, the CRP level is slow to normalize, or infection is due to MRSA, we consider it prudent to extend antibiotic therapy to at least 8 weeks. For patients responding well to initial i.v. therapy, observational data suggest that a switch to oral therapy after 2 weeks may be safe. Results reported by Bernard et al. ⁹⁷ are also supportive in that the overall rate of treatment success in their randomized clinical trial was 91% with a median duration of 14 days of i.v. therapy.

Osteoarticular Infections in Children

The incidence of osteoarticular infections in children ranges from 7 to 22 per 100,000 person-years based on studies from Europe ⁹⁸. These infections are more common in males than in females (with incidences in French children of 24 per 100,000 person-years for boys and 19 per 100,000 person-years for girls) and in toddlers than in other age groups ⁹⁹. Some ethnic groups may be at higher risk, with Maori and Pacific Islander populations being overrepresented in a study involving 813 cases of acute osteomyelitis in New Zealand ¹⁰⁰. In the United States, community associated-MRSA has become considerably more prominent as a cause of acute osteoarticular infections since 2000. In a study of 158 cases in Tennessee, the proportion of osteoarticular infections due to community associatedA-MRSA rose from 4% to 40% from 2000 to 2004 ¹⁰¹. Similarly, the proportion of cases of acute osteomyelitis due to CA-MRSA was 6% in 1999 to 2001 compared to 31% in 2001 to 2003 in Dallas, TX ¹⁰². In Houston, TX, between 2001 and 2010, 195 of 376 (52%) cases of Staph aureus osteomyelitis were due to MRSA ¹⁰³.

Clinical manifestations and outcomes of Acute osteomyelitis

Acute hematogenous osteomyelitis in children presents with fever and malaise, local pain, and point tenderness and most commonly involves the metaphysis of the tibia or the femur, resulting in limping or an inability to walk ¹⁰⁴. The pain is often poorly localized but becomes more focal over time. The hallmark of the pain is its constant nature. Overlying redness and swelling are often present, which may create diagnostic confusion. For diagnostic purposes, CRP analysis is highly sensitive and thus has value in excluding the diagnosis of acute osteoarticular infection. In a prospective study of 265 osteoarticular infections in children, using a cutoff of 20 mg/liter, CRP analysis had a sensitivity of 95% for the diagnosis of acute osteomyelitis; and the combination of CRP and ESR (with a cutoff 20 mm/h) analyses provided a sensitivity of 98% ¹⁰⁵. Additionally, CRP analysis can be used to monitor the response to antibiotic treatment ¹⁰⁵. Peltola and Paakkonen provide an excellent diagnostic algorithm for acute osteomyelitis in children ¹⁰⁴.

With regard to acute osteomyelitis caused by Staph aureus, Ju et al. ¹⁰⁶ found four clinical parameters that could predict the probability of acute osteomyelitis in children due to MRSA compared to MSSA: temperature of >38°C, hematocrit level of <34%, white blood cell count of >12,000 cells/μl, and CRP level of >13 mg/liter. However, this study suffers from having only 11 patients with MRSA and a lack of genotyping data and from its single-center design ¹⁰⁶. An attempt to validate this clinical prediction algorithm among 58 patients (MRSA, n = 16; MSSA, n = 42) in Phoenix, AZ, found the algorithm to have a poor predictive value ¹⁰⁷. Without genotyping data, it seems likely that the study by Ju et al. and previous studies that also compared cases of acute osteomyelitis due to MRSA versus MSSA found discriminators between USA300 and other Staph aureus clones rather than between MRSA and MSSA per se.

With the emergence of community associated-MRSA, deep venous thrombosis (DVT) adjacent to the site of osteomyelitis has been described by several groups ¹⁰⁸. Deep venous thrombosis (DVT) with acute osteomyelitis has been associated with MRSA, PVL-positive strains of Staph aureus and USA300 in particular ¹⁰⁹. Compared to patients with acute osteomyelitis but no DVT, those with DVT were consistently unwell, likely to be bacteremic, and likely to have pulmonary involvement (presumably due to septic pulmonary emboli), and MRSA was overrepresented. Thus, a high index of suspicion for DVT is required for children with acute osteomyelitis who are critically unwell or who have pulmonary involvement, and Doppler ultrasound screening near the site of infection should be considered ¹¹⁰.

Nonetheless, most large series suggest that for acute osteomyelitis in children, outcomes are generally favorable. Only 1 child out of 1,000 with osteomyelitis died in a case series from France ⁹⁹, and of 131 prospectively monitored cases in Finland, only 2 children developed mild sequelae (varus deformity of tibia and ankle pain during exercise) ¹¹¹. The mean length of hospital stay was 8.6 days in the French series ⁹⁹.

Management of Acute osteomyelitis in Children

Empirical treatment for acute osteomyelitis in children is dictated by the local antibiogram of Stph aureus. Where the prevalence of MRSA is <10% among community Staph aureus strains, an antistaphylococcal penicillin or cephalosporin is recommended; where the prevalence of community associated-MRSA is >10% and the rate of clindamycin resistance is <10%, clindamycin is recommended; and where both the prevalence of community associated-MRSA and the rate of clindamycin resistance are >10%, vancomycin should be used ¹⁰⁴. If the child is severely ill and has suspected acute osteomyelitis or septic arthritis, it is prudent to treat the child with both vancomycin and an antistaphylococcal β-lactam until bacterial susceptibilities are known ¹⁰³.

For pediatric acute osteomyelitis caused by MSSA, an early switch to oral therapy appears safe. A prospective study of 70 children with either septic arthritis or osteomyelitis demonstrated that an algorithmic approach resulted in 59% of children converting to oral therapy after 3 days of i.v. therapy and 86% converting to oral therapy after 5 days. All 70 children had good outcomes at 1 year of follow-up ¹¹². Similarly, Peltola et al. switched 131 patients to oral therapy after a median of 3 to 4 days of i.v. therapy, with excellent outcomes ¹¹³. An early switch to oral therapy is particularly important for children, as the risk for central line-related complications is high. Ruebner et al. ¹¹⁴ found that of 75 patients who received >2 weeks of treatment for acute osteomyelitis through a central venous catheter, 41% developed at least one central venous catheter-related complication.

A prospective, quasirandomized, controlled, open-label trial involving 252 children with osteoarticular infections (82/252 with osteomyelitis and 189/252 with Staph aureus [all MSSA]; the proportion of cases of osteomyelitis with MSSA was not reported) in Finland determined that oral clindamycin or a first-generation cephalosporin was equally efficacious as follow-up therapy ¹¹⁵. The same investigators also determined in an randomized control trial involving 131 children with acute osteomyelitis (117 with S. aureus, all MSSA) that 20 days of total therapy resulted in outcomes equivalent to those with 30 days of total therapy ¹¹¹. In children with septic arthritis, a separate Finnish study (517) found that a duration of 10 days of total antibiotic therapy was equivalent to 30 days of therapy. Of 130 cases, only 1 developed a late-onset infection following completion of therapy, and this case was in the 30-day arm of the study. A systematic review ¹¹⁶ noted that the above-mentioned randomized clinical trials are only of moderate quality, principally due to a lack of blinding, and concluded that the recommendations of treatment for acute osteomyelitis of 3 to 4 days of i.v. therapy followed by oral antibiotics for a total treatment duration of 3 weeks should be regarded as being supported by only weak evidence (grade 2B).

Given the severity of osteoarticular infections caused by community associated-MRSA and their conspicuous absence in the Finnish studies, it is unknown whether abbreviated i.v. and subsequent oral therapies can effectively treat acute osteomyelitis due to MRSA. This point is acknowledged by Peltola and Paakkonen ¹⁰⁴ and also in IDSA guidelines for MRSA infections ¹¹⁷. Both reports suggest that acute osteomyelitis due to MRSA should be treated with a minimum of 4 to 6 weeks of total therapy. Additionally, it is recommended that infants <3 months of age receive a longer course of i.v. therapy due to concerns over the absorption and efficacy of oral antibiotics ¹¹⁶.

Only 12% of 130 patients with septic arthritis in a Finnish study ¹¹⁸ required a surgical procedure, and in a separate trial, 62/131 (47%) cases of acute osteomyelitis received resectional surgery to the bone cortex ¹¹¹. However, higher rates of surgery have been noted in the United States. For example, Tuason et al. found that of 57 cases of acute osteomyelitis, 41 (72%) children required surgery, 12 of whom underwent ≥2 surgeries ¹¹⁹. Additional concerns are that hip septic arthritis in children can result in ischemic necrosis of the femoral head and that sequelae of septic arthritis may be more common than for osteomyelitis. An Australian study including 44 children, in whom S. aureus was the causative organism in 76% of cases, found that 10% of children at 12 months had residual joint dysfunction ¹²⁰. Thus, careful clinical assessment and monitoring are mandatory. For patients with extensive disease or where levels of inflammatory markers are not being reduced as expected, ongoing reassessment of the need for surgical intervention is advised.

Adjunctive dexamethasone appears to be a promising intervention to accelerate recovery and decrease residual morbidity in children with native joint septic arthritis. Odio et al. ¹²¹ randomized 123 children with septic arthritis (67% of whom had infections due to Staph aureus) to receive 4 days of adjunctive i.v. dexamethasone in addition to antibiotics. They found that a significantly lower proportion of patients in the dexamethasone group had residual joint dysfunction after 12 months of follow-up (2% versus 26%). Harel et al. ¹²² randomized 49 children to receive 4 days of dexamethasone or placebo for septic arthritis and found more rapid resolution of fever and pain and a shorter duration of i.v. antibiotics in the dexamethasone group. However, it is unclear if these results apply to S. aureus infections, as 65% of patients had no pathogen isolated from joint fluid, and for the remainder of the patients, the most common pathogen was Kingella kingae. More rapid early recovery with dexamethasone was also recently found in a double-blind, nonrandomized, prospective clinical trial enrolling 60 children in Pakistan ¹²³.

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