Staphylococci Case File

Staphylococci Case File

Eugene C.Toy, MD, Cynthia Debord, PHD, Audrey Wanger, PHD, Gilbert Castro, PHD, James D. Kettering, PHD, Donald Briscoe, MD

CASE 21

While on call on a Saturday night in July, you receive a call from the mother of a 15-year-old man who developed the acute onset of nausea, vomiting, and diarrhea shortly after returning from an outdoor party that was held at the home of a friend. At the party, a picnic lunch of hamburgers, hot dogs, potato salad, baked beans, and lemonade was served. The food was served on an outdoor picnic table, and the guests were free to eat at any time during the party. None of the food tasted spoiled or tainted. His symptoms started abruptly about an hour after he returned home, which was approximately 4 hours after he had eaten. He currently is unable to keep down anything. He does not have a fever and has not passed any blood in his stool or vomitus. Prior to calling you, your patient’s mother spoke with the hostess of the party, who said that she had heard from three other guests who became ill with similar symptoms.

◆ What organism is the most likely cause of this patient’s illness?

◆ Your patient’s mother requests that you call in a prescription for an antibiotic to treat the infection. What is your response?

ANSWERS TO CASE 21: STAPHYLOCOCCI

Summary: A 15-year-old male with gastroenteritis after eating food at an outdoor picnic. Several other participants also developed similar symptoms.

◆ Most likely organism causing this infection: Staphylococcus aureus.

◆ Response to request to treat with antibiotic: No, the gastroenteritis is caused by a preformed toxin, not by the ingested staphylococci, therefore antibiotic therapy would be of no help.

CLINICAL CORRELATION

Staphylococcus aureus is a common colonizer of the human nasopharynx and skin. Infection occurs when the normal skin barrier is disrupted by either surgery or trauma.

Staphylococcus aureus causes numerous infections, ranging from simple localized skin and soft tissue infections to disseminated disease, such as bacteremia, endocarditis, osteomyelitis, and septic arthritis. Many of the infections caused by S. aureus are toxin mediated, such as toxic shock syndrome, scalded skin syndrome, and gastroenteritis.

Previously thought to be a nosocomial infection seen in hospitalized patients, community acquired MRSA has become a significant public health concern. The majority of these strains produce a toxin called Panton- ValentineLeukocidin (PVL) that is associated with more severe disease, including skin and soft tissue infections and necrotizing pneumonia.

Staphylococcal food poisoning, the second most reported cause of food poisoning in the United States, is a result of the presence of enterotoxin. Food is contaminated by a human carrier, with processed meats, custard-filled baked goods, potato salad, or ice-cream being common vectors. The toxin rapidly produces nausea, vomiting, and diarrhea, usually within 2–6 hours of ingestion. Further toxin is not produced by the ingested S. aureus, and the disease also rapidly resolves, usually within 12–24 hours.

Staphylococcal species also frequently colonize human skin but can cause disease in certain situations. Although there are more than 20 other species, the majority of the species isolated are Staphylococcus epidermidis. The most common predisposing factor for disease with staphylococci not (S. aureus) is the presence of artificial devices in the patient such as catheters and replacement joints. Staphylococcus epidermidis produces a slime that allows it to adhere to plastics and form a biofilm that makes it very difficult for antibiotics to penetrate.

APPROACH TO SUSPECTED STAPHYLOCOCCAL INFECTION

Objectives

1. Know the structure, physiology, and virulence factors associated with S. aureus and the coagulase-negative staphylococci.
2. Know the diseases caused by staphylococci and the mechanisms by which staphylococci develop antibiotic resistance.

Definitions

Biofilm: Bacteria grow on an artificial surface and form a conglomerate with secreted polysaccharides and glycopeptides.

Superantigens: Antigens, most often bacterial toxins, that recruit a large number of T lymphocytes to an area.

Enterotoxins: Substances produced by bacteria that are toxic to the GI tract that cause diarrhea and/or vomiting.

DISCUSSION

Characteristics of Staphylococcus

Staphylococci belong to the family Micrococcaceae, which includes the genus Micrococcus in addition to Staphylococcus. Staphylococci grow rapidly on multiple culture media, in a wide range of environments, including up to 10 percent sodium chloride, and in a broad range of temperatures. Staphylococcus aureus is a nonmotile, nonspore forming, facultative anaerobic grampositive coccus that commonly colonizes healthy humans and is a frequent cause of disease. It is frequently identified as growing in clusters or clumps. This is a result of the effect of bound coagulase (“clumping factor”), which binds fibrinogen, converts it to insoluble fibrin, and results in aggregation. Staphylococcus aureus is the only Staphylococcus found in humans which produces coagulase; other staphylococcal species are commonly identified as coagulase-negative staphylocci.

Staphylococcus aureus produces at least five cytolytic toxins, two exfoliative toxins, eight enterotoxins, and toxic shock syndrome toxin. Some of these toxins act as superantigens, which recruit host defense cells that liberate cytokines and, therefore, produce systemic effects. Heating will kill the S. aureus organisms, but not inactivate the enterotoxins, because they are stable to heating at 100∞C (112∞F) for 30 minutes and are resistant to breakdown by gastric acids.

Of growing public health concern is the rapid spread of antibiotic resistance within S. aureus isolates. Almost all S. aureus produces penicillinase, a β-lactamase specific for penicillin. Many isolates have also acquired a gene that codes for an altered penicillin binding protein, PBP2, providing antibiotic resistance to semisynthetic penicillins and cephalosporins as well, including methicillin and nafcillin. Some of these genes will also be associated with resistance to non–β-lactamase antibiotics, such as quinolones and macrolides. Some S. aureus isolates have been identified recently with reduced sensitivity to vancomycin. The mechanism of this resistance is unknown. Genes that confer resistance can be transferred between organisms by plasmid transfer, transduction and cell-to-cell contact.

Diagnosis

The initial diagnosis of staphylococcal infection may be difficult because many of the skin and soft tissue infections mimic those of streptococci. Definitive diagnosis is made by Gram stain and culture of the infected site as well as blood. Staphylococci are large gram-positive cocci grouped in clusters (Figure 21-1). Staphylococci grow rapidly on routine laboratory media.

Figure 21-1. Gram stain of Staphylococcus aureus showing gram-positive cocci in clusters. (Reproduced, with permission, from Brooks G, Butel J, Morse S. Jawetz, Melnick, and Aldelburg’s Medical Microbiology, 23rd ed. New York: McGraw-Hill, 2004:224.)

Their colony morphology is different from streptococci in that the colonies are larger, white or yellow instead of grey. They also can be differentiated from streptococci by a positive catalase test (reactivity with hydrogen peroxide). Staphylococcus aureus is β-hemolytic on blood agar medium and is differentiated from the other Staphylococcus species by production of coagulase or positive latex agglutination for Staphylococcus protein A. Further confirmation of the identification of S. aureus is not necessary; however, many commercially available identification systems can identify the organism based on biochemical reactivity. A selective media such as mannitol salts agar, which also differentiates S. aureus from other staphylococcal species is available, but not often used in clinical laboratories.

Staphylococcal gastroenteritis is usually self-limited with symptoms disappearing within 12 hours, and therefore diagnosis is made clinically based on incubation period and history of others eating similar foods with same symptoms. Staphylococcus saprophyticus is the only other staphylococcal species that is identified as a consequence of its association with urinary tract infections in young women. Staphylococcus saprophyticus is differentiated from the other coagulase negative staphylococci by its susceptibility to novobiocin, which is tested by disk diffusion. Staphylococcus lugdunensis has recently gained attention as a significant cause of bacteremia and endocarditis. These organisms look morphologically like Staphylococcus epidermidis, but clinically resemble Staphylococcus auereus. Their distinguishing feature is that they are PYR positive.

Treatment and Prevention

Treatment of local wound infections without systemic symptoms does not usually require treatment with antibiotics; however, in the cases of more complicated infections or presence of fever, antimicrobial therapy is usually warranted. Although nafcillin is the drug of choice for staphylococcal infections, because of the high percentage of strains that are resistant to methicillin and nafcillin, initial treatment is usually with vancomycin until the susceptibility results are available. Oral antibiotics, such as dicloxacillin, rifampin and sulfamethoxazole and trimethoprim (SMX-TMP) or clindamycin can also be used dependent on the susceptibility of the isolate. Treatment of Staphylococcus non-aureus is with vancomycin, because the majority of isolates are resistant to nafcillin.

Control of S. aureus involves strict adherence to hand washing policies, particularly in the hospital setting. The organism can easily be spread from person to person. Colonization with S. aureus is usually transient; however, an attempt can be made in some situations to decolonize the nares by using intranasal mupirocin and/or the skin by using oral anti-staphylococcal antibiotics in combination with topical agents.

COMPREHENSION QUESTIONS

[21.1] A 12-year-old girl was playing soccer when she began to limp. She has pain in her right leg and right upper thigh. Her temperature is 38.9°C (102°F). X-ray of the femur reveals that the periosteum is eroded, suggestive of osteomyelitis. Blood culture yields gram-positive bacteria. The most likely etiologic agent is which of the following?

A. Listeria monocytogenes

B. Salmonella enteritidis

C. Staphylococcus aureus

D. Staphylococcus saprophyticus

E. Streptococcus pneumoniae

[21.2] An outbreak of staphylococcal infection involving umbilical cords of seven newborn babies was reported in the nursery. Bacteriologic survey reveals that two nurses have a large number of S. aureus in the nasopharynx. What test should be performed to determine whether these nurses may have been responsible for the outbreak?

A. Bacteriophage typing

B. Coagulase testing

C. Nasopharyngeal culture on mannitol salt agar

D. Protein A typing

E. Serologic typing

[21.3] Virulence factors of S. aureus include all of the following except one. Which one is this exception?

A. β-lactamases

B. Coagulase

C. Enterotoxins

D. M Protein

E. Protein A

[21.4] Short incubation food poisoning, caused by ingestion of preformed enterotoxin, is caused by which bacteria listed below?

A. Staphylococcus aureus

B. Staphylococcus epidermidis

C. Enterococcus faecalis

D. Streptococcus pneumoniae

E. Streptococcus pyogenes

Answers

[21.1] C. Staphylococci, especially S. epidermidis, are normal flora of the human skin and respiratory and gastrointestinal tracts. Nasal carriage of S. aureus, the pathogen, occurs in 20–50 percent of humans. Abscesses are the typical lesion of S. aureus. From any one focus, organisms may enter the bloodstream and lymphatics to spread to other parts of the body. In osteomyelitis, the primary focus is generally in a terminal blood vessel of the metaphysis of a long bone, which may lead to necrosis of bone and chronic suppuration. Staphylococcus saprophyticus is usually a nonpathogenic normal flora organism. Listeria is usually transmitted in unpasteurized dairy products, whereas Salmonella enteritidis is primarily intestinal. Streptococcus pneumoniae is primarily a respiratory pathogen, although it is an important central nervous system pathogen in children.

[21.2] A. Bacterial viruses (bacteriophages or phages) can attach to separate receptors on the cell walls of various strains of S. aureus. Different specific receptors have been identified and used as the basis of epidemiologic typing of pathogenic S. aureus strains. Typical cultures from the outbreak and strains obtained from personnel can be subjected to a standardized procedure using a series of bacteriophages that attack S. aureus strains. This procedure can readily identify the source of the outbreak organism if it came from a medical care worker.

[21.3] D. M proteins are virulence factors of group A streptococci (S. pyogenes). All of the other listed virulence factors may be found routinely in S. aureus bacteria.

[21.4] A. Of the options given the best answer is S. aureus, as a result of enterotoxin production in food. None of the other strains listed produce enterotoxins that result in short-term gastroenteritis.

MICROBIOLOGY PEARLS ❖ Staphylococcus aureus is a common cause of community-acquired and nosocomial wound infections. ❖ Treatment of S. aureus is with nafcillin if the isolate is susceptible, or alternatively with vancomycin. ❖ Staphylococcus aureus is differentiated from the other staphylococcal species by production of coagulase.

REFERENCES

Murray PR, Rosenthal KS, Pfaller MA. Staphylococcus and related organisms In: Murray PR, Rosenthal KS, Pfaller MA. Medical Microbiology, 5th ed. St. Louis, MO: Mosby, 2005:202–16. 

Moreillon P, Que Y, Glauser MP. Staphylococcus aureus (including staphylococcal toxic shock). In: Mandell GL, Bennett JE, Dolin R, eds. Principles and Practice of Infectious Diseases, 6th ed. Philadelphia, PA: Churchill Livingstone, 2005:321–51.

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