Tuesday, January 31, 2006

Pneumococcal Cellulitis - Abstracts

Bacteremic pneumococcal cellulitis compared with bacteremic cellulitis caused by Staphylococcus aureus and Streptococcus pyogenes.

Capdevila O, Grau I, Vadillo M, Cisnal M, Pallares R.

Clinical Research Unit, Hospital de Bellvitge and University of Barcelona, Feixa Llarga s/n, 08907 L' Hospitalet, Barcelona, Spain.

In order to better characterize bacteremic cellulitis caused by Streptococcus pneumoniae, a review was conducted of 10 cases of bacteremic pneumococcal cellulitis, which represented 0.9% of all cases of pneumococcal bacteremia (n=1,076) and 3.2% of all cases of community-acquired bacteremic cellulitis (n=312) that occurred in the Hospital de Bellvitge, Barcelona, from 1984 to 2001. In addition to these 10 cases, 28 cases of bacteremic pneumococcal cellulitis from the literature (Medline 1975-2001) were reviewed.

Pneumococcal cellulitis of the face, neck, and trunk was observed more frequently in patients with systemic lupus erythematosus and hematologic disorders, while pneumococcal cellulitis of the limbs was more common in patients with diabetes, alcoholism, and parenteral drug use. In the Hospital de Bellvitge group, bacteremic cellulitis due to Streptococcus pneumoniae was more frequently associated with severe underlying diseases than that due to Staphylococcus aureus or Streptococcus pyogenes (100%, 57%, and 72%, respectively;P=0.01).

A concomitant extracutaneous focus of infection (e.g., respiratory tract infection) suggesting hematogenous spread with metastatic cellulitis was more frequent in patients with pneumococcal cellulitis, while a local cutaneous entry of microorganisms was feasible in most patients with Staphylococcus aureus or Streptococcus pyogenes cellulitis. The 30-day mortality was 10% in patients with pneumococcal cellulitis, 13% in patients with Staphylococcus aureus cellulitis, and 23% in patients with Streptococcus pyogenes cellulitis (P=0.3). Thus, bacteremic pneumococcal cellulitis is an unusual manifestation of pneumococcal disease and occurs mainly in patients with severe underlying diseases. In most cases, pneumococcal cellulitis has a different pathophysiologic mechanism than cellulitis caused by Staphylococcus aureus or Streptococcus pyogenes.

PMID: 12783279

[
PubMed - indexed for MEDLINE]

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Clinical syndromes associated with adult pneumococcal cellulitis.

Parada JP, Maslow JN.Department of Medicine, Stricht School of Medicine, Loyola University, Maywood, IL, USA.

Streptococcus pneumoniae is an uncommonly recognized etiology of cellulitis in adults. A review of the literature uncovered 30 cases of pneumococcal skin infection in adults. Typically, all patients with pneumococcal cellulitis had an underlying chronic illness, or were immunocompromised by drug or alcohol abuse. Pneumococcal cellulitis presents as two distinctive clinical syndromes: one with extremity involvement in individuals with diabetes and substance abuse; and a second involving the head, neck and upper torso in individuals with systemic lupus erythematosis, nephrotic syndrome and hematologic disorders. For each there are statistically significant associations between the location of pneumococcal cellulitis and underlying clinical disorders. In contrast to other common bacterial etiologies, pneumococcal cellulitis is frequently associated with blood stream invasion, tissue necrosis and suppurative complications. Patients often require surgical interventions and prolonged hospitalizations. A high degree of suspicion and early aggressive management is needed for those presenting with cellulitis characterized by bullae and violaceous color.

Pub Med

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Pneumococcal Cellulitis

Case Based Pediatrics For Medical Students and Residents

Department of Pediatrics, University of Hawaii John A. Burns School of Medicine.

A 2-year-old male presents to the emergency department with a chief complaint of left thigh swelling, fever, irritability, and unwillingness to stand upright for the last 2 days. He has been scratching at mosquito bites that he had gotten while weekend camping about 1 week ago.
Exam: VS T 39.5, P 110, R 26, BP 120/70. Growth parameters are normal for age. He is fussy, somewhat distractible, but clearly uncomfortable. He is continuously scratching at a left upper inner thigh lesion measuring 6 x 3 cm. The skin over the area is indurated, erythematous and tense, and tender. No fluctuance or wound drainage is noted. There is no joint involvement. Some tender lymph nodes are palpable in the left inguinal region.


He is prescribed cephalexin and anti-pyretics. In follow-up the next day, the erythematous region is slightly darker (a shift from red toward a shade of purple). Tiny blisters are also noted over the area. These changes are expected and treatment is continued. On follow-up day 2, the fever has resolved and the cellulitis appears to be clearly improving. His parents are instructed to finish the course of antibiotics. He is next seen in follow-up 7 days later, at which time, his cellulitis is resolved.

The basic response to infection is fever. The local, dermatological acute inflammatory reaction of cellulitis stems specifically from granulocytic infiltrations, hyperemia, and capillary leakage. This is the basis for the skin disruption inherent in cellulitis. The patient may guard the tender area. If the cellulitic area overlies a mobile area such as a joint, the patient may display resistance or anxiety with limb movement, either passive or active.

The specific visual characteristics (appearance) of the cellulitic region can provide important clues as to the organism(s) involved, with implications for treatment and prognosis. Clinical presentation, treatment, and prognosis differ depending on the causative organism and the location of the cellulitis. The remainder of this chapter will be stratified by these factors.

Group A strep cellulitis

Generally, cellulitis suggests the presence of a skin infection due to group A beta-hemolytic streptococci (GABHS, also known as Strep pyogenes). GABHS cellulitis is a painful, erythematous, indurated infection of the skin and subcutaneous tissues. It is classically described as large lesions, erythroderma in color (magenta), slightly raised at the border, with a small, central open skin lesion (frequently an insect bite). It is common for varicella lesions to become secondarily infection with GABHS. GABHS cellulitis may present with scarlet fever.

Abscess formation beneath the cellulitis is very uncommon. GABHS is penicillin and cephalosporin sensitive.

Staph aureus cellulitis

Staph aureus is commonly cultured from impetigo lesions, albeit usually as a secondary pathogen, along with GABHS. Some of these lesions develop into cellulitis, which may be primarily caused by GABHS or alternatively, caused primarily by Staph aureus. Staph aureus cellulitis is typically smaller (than the larger GABHS cellulitis) and is frequently associated with an abscess or pustule. In many of these cases, the abscess is the major problem (i.e., incision and drainage is required), as opposed to the cellulitis which is relatively less of a problem.

H. flu type b cellulitis

H. influenzae type b (Hib) used to account for in 5-14% of the cellulitis cases in young children. More than 85% of children with H. influenzae type b cellulitis are 2 years of age or younger. Hib is a particularly virulent organism which is frequently associated with sepsis. A common location for Hib cellulitis was the periorbital and buccal region. Cellulitis is a complication of H. influenzae septic arthritis 10-30% of cases. Fortunately, there has been a substantial decline in the incidence of invasive infection caused by Hib with the practice of routine immunization of infants against this organism, to the point where Hib infection is almost non-existent. Hib is covered by high generation cephalosporins (e.g., ceftriaxone) and by broad spectrum oral drugs such as amoxicillin-clavulanate and cefuroxime.

Pasteurella/animal bite cellulitis

Cellulitis and lymphangitis typically appears 24-36 hours after mammalian bite injuries. The etiologies of infections following mammalian bites are polymicrobial and consist of mixed anaerobic and aerobic bacteria. In one study, an average of three different bacterial species was isolated from infected dog bites while a mean of five different species was recovered from infected human bites. Because of the numerous bacterial species in mammalian oral cavities and on the victim's skin, contamination of bite injuries is universal. Pasteurella multocida is sensitive to penicillins, but it is less sensitive to cephalosporins. Amoxicillin-clavulanate is generally used for animal bites to cover Pasteurella, staph aureus and anaerobes.

Orbital and periorbital cellulitis

Periorbital (preseptal) cellulitis involves inflammation of the lids and periorbital tissues without signs of true orbital involvement, such as proptosis or limitation of eye movement. It presents as a red and swollen infection limited to the superficial tissue layers anterior to the orbital septum. History usually yields an antecedent respiratory infection or bacteremia. Historically, H. influenzae type b was an important cause, and presented with fever, edema, tenderness, warmth of the lid, and, occasionally, purple discoloration (violaceous hue). However, streptococcal organisms are the most common cause of bacteremia associated with periorbital cellulitis in the post Hib-vaccinated era (9). S. pneumonia, Staphylococcus aureus, and group A beta-hemolytic streptococci cause clinically indistinguishable preseptal cellulitis (2). The latter two pathogens are more likely when fever is absent and with an interruption of the integument (e.g., an insect bite) (1).

Distinguishing periorbital from orbital cellulitis can be difficult. If proptosis, extraocular movement dysfunction, or visual deficits are clearly present, then orbital cellulitis is likely. However, in the absence of these findings, the diagnosis is unclear. In periorbital cellulitis, the lid swelling may be so severe, that it is not possible to tell if proptosis is present. A CT scan of the orbits will reliably distinguish periorbital from orbital cellulitis. Since the difference between the two can be important, a CT scan of the orbits has become routine in the evaluation of most patients with severe periorbital cellulitis and/or suspected orbital cellulitis.

Orbital cellulitis refers to a condition involving not only edema of the conjunctiva (chemosis), and inflammation and swelling of the eyelids, but also involvement of the tissues of the orbit, with subsequent proptosis (limitation of movement of the eye). In general, orbital cellulitis may follow direct infection of the orbit from a wound, metastatic deposition of organisms during bacteremia, or direct extension or venous spread of infection from contiguous sites such as the lids, conjunctiva, globe, lacrimal gland, nasolacrimal sac, or paranasal sinuses. The most common cause of orbital cellulitis in children is paranasal sinusitis, with the most frequent pathogenic organisms being Haemophilus influenzae, Staphylococcus aureus, group A beta-hemolytic streptococci, and Streptococcus pneumonia. Orbital cellulitis must be recognized promptly and treated aggressively. Hospitalization and systemic antibiotic therapy are usually indicated. In some cases surgical intervention is necessary to drain infected sinuses, or a subperiosteal or orbital abscess. Intravenous treatment for 10 to 14 days is highly recommended, along with repeated eye exams (visual acuity, pupillary reactivity, extraocular movements, and visual fields) to evaluate possible progression of infection and/or involvement of the optic nerve (10). As a worst case scenario, orbital cellulitis can lead to the complication of brain abscess, especially in the frontal lobe.

Finally, orbital cellulitis is an infrequent presenting sign of retinoblastoma. The severe clinical implications of retinoblastoma (enucleation may be inevitable) warrants vigilance for a white pupillary reflex (leukocoria, the reflection of light off the white tumor), pseudohypopyon (tumor cells layered inferiorly in front of the iris caused by tumor seeding in the anterior chamber of the eye), and hyphema (blood layered in the anterior chamber) secondary to iris neovascularization or vitreous hemorrhage.

Erysipelas

Erysipelas is an acute, well-demarcated aggressive infection of the skin with lymphangitis involving the face (associated with pharyngitis) and extremities (wounds). The skin is erythematous and indurated. The advancing margins of the lesions have raised, firm borders. The skin lesion usually is associated with fever, vomiting, and irritability. In some cases, streptococci break through the lymphatic barrier (lymphangitis), and subcutaneous abscesses, bacteremia, and metastatic foci of infection are observed. Bacteremia and death have been associated with streptococcal cellulitis, and progression may be so rapid that there may be no response to treatment with penicillin. The popular press has termed severe cases of GABHS cellulitis (necrotizing fasciitis) as "flesh eating bacteria".

Lymphangitis

Lymphangitis is an inflammation of the lymphatics draining an area of infection (i.e., a cellulitis site). On exam, tender red streaks extend proximally from the infected site. S. aureus and group A strep are the most frequent pathogens. A history of impetigo is also suggestive of cellulitis, in that, cellulitis has been reported in approximately 10% of patients with nonbullous impetigo but rarely follows the bullous form. There is no correlation between the number of lesions and clinical involvement of the lymphatics or development of cellulitis in association with streptococcal impetigo. The history is consistent with pruritic lesions subject to frequent scratching and secondary infection (including insect bites, pediculosis and scabies). This is followed by the development of a vesicle or vesiculopustule with an erythematous base that erodes through the epidermis into the dermis to form an ulcer with elevated margins. A dry crust that contributes to the persistence of the infection obscures the ulcer. Lesions may be spread by autoinoculation, may be as large as 4 cm, and occur most frequently on the legs or pruritic areas within reach.

Risk of osteomyelitis and septic arthritis

Although the risk of osteomyelitis and septic arthritis is fairly rare unless a penetrating wound is present, the relationship between osteomyelitis and cellulitis deserves special attention, in that a progression to osteomyelitis from cellulitis mandates a far more aggressive and prolonged antibiotic course, not to mention possible orthopedic surgical debridement. Thus, when a diagnosis of cellulitis is made, the comorbid presence of osteomyelitis must also be strongly considered especially when corroborated by a history of a penetrating wound. At the very least, cellulitis accompanied by point tenderness or joint pain is highly suggestive of osteomyelitis. Attempts at diagnosis are complicated by the fact that cellulitis of structures in proximity to bone can mimic osteomyelitis.


To effectively discern cellulitis with possible underlying osteomyelitis, combining technetium bone scanning with other radionuclide scanning techniques or MRI scanning may be useful. In a three phase bone scan, focal increased uptake in the initial phase, with subsequent decline in the later phases (especially the bone phase), is suggestive of cellulitis without osteomyelitis. In osteomyelitis, localized uptake is seen in all three phases, especially in the bone phase.
If the history, physical exam, or radiological studies suggest deep cellulitis near a joint, the level of suspicion is raised with regard to an infection in the respective joint, not to mention osteomyelitis, synovitis, septic bursitis and pyomyositis in nearby muscles. Deep cellulitis is also consistent with psoas or retroperitoneal abscesses. Cellulitis overlying a joint can interfere with studies crucial to the diagnosis of septic arthritis. If a cellulitic area is traversed during arthrocentesis for a workup for septic arthritis, the results can be confounded if organisms are introduced into a previously sterile uninvolved joint.


Cellulitis and immunodeficiency

The presence of cellulitis in the face of concomitant immunodeficiency requires inpatient treatment. Deficient expression of leukocyte adherence glycoproteins can present as cellulitis or small (<1>

Defects in the normal host response may be reflected in study findings that are disproportionately severe when compared to relatively benign findings on the physical exam. For example, deep cellulitis may be quite impressive on a CT of a neutropenic patient who has only mild superficial swelling or erythema. Indeed, surface pus formation is unusual at sites of even severe cellulitis in such patients.

Cellulitis in children with burns illustrates not only the acute effects of interrupted skin and mucous membrane barriers, presence of necrotic tissue, long-term administration of antibiotics and prolonged intravenous or urinary catheterization, but also the concomitant abnormal immune response to infection, including neutrophil dysfunction. The resulting neutrophil chemotactic defect, combined with an associated hypogammaglobulinemia is a perfect scenario for cellulitis with Pseudomonas aeruginosa being the most common organism.

In the neonatal period, cellulitis can be a manifestation of invasive infection, as is bacteremia with a septic-like clinical picture, pneumonia, respiratory distress syndrome with shock, conjunctivitis, scalp abscess, or meningitis. Cellulitis may be the presenting sign of immunodeficiency in an infant. Cellulitis, delayed separation of the umbilical cord and gingivitis is consistent with an infant with leukocyte adhesion deficiency. Cellulitis of the labia majora, pyogenic skin infections, oral ulcerations, or abscesses has been the presenting manifestations of autoimmune neutropenia of infancy.

Cellulitis of the perirectal area, sites of iatrogenic puncture (central venous catheter insertion, venipuncture, lumbar puncture, and bone marrow biopsy), or abrasions is a setup for gram negative dissemination. In the context of vaginitis, beta-hemolytic streptococcus is a common cause in prepubertal girls and may present with perianal cellulitis with local itching, pain, blood-streaked stools, erythema, and proctitis (3).

Rarely, cellulitis or skin discoloration overlying a fluctuant mass might be the presenting finding in tuberculosis of the superficial lymph nodes, often referred to as scrofula, the most common form of extrapulmonary tuberculosis in children. The tonsillar, anterior cervical, submandibular, and supraclavicular nodes become involved secondary to extension of a primary lesion of the upper lung fields or abdomen. The nodes usually enlarge gradually in the early stages of lymph node disease. They are firm (but not hard), discrete, and nontender. The nodes often feel fixed to underlying or overlying tissue. Disease is most often unilateral, but bilateral involvement may occur because of the crossover drainage patterns of lymphatic vessels in the chest and lower neck.

Cellulitis of the sublingual and submandibular spaces (Ludwig angina) tends to spread rapidly without lymph node involvement or abscess formation. It is an acute, life-threatening entity that may require tracheostomy in the event of respiratory obstruction.

Cellulitis of the auricle and external auditory canal is usually caused by S. pyogenes (GABHS) or occasionally by S. aureus. The skin is red, hot, and indurated, without a sharply defined border. Fever may be present with little or no exudate in the canal.

Cellulitis can be a complication of hidradenitis suppurativa, a chronic, inflammatory, suppurative disorder of the apocrine glands in the axillae or anogenital area, and occasionally, the scalp, posterior aspect of the ears, female breasts, and around the umbilicus. Cellulitis of the lateral nail fold can occur as spicules that have separated from the nail plate, penetrate the soft tissue. Predisposing factors include compression of the side of the toe from poorly fitting shoes, particularly if the great toes are abnormally long and the lateral nail folds are prominent, and improper cutting of the nail in a curvilinear manner rather than straight across. Oral antibiotics are necessary to treat cellulitis of the lateral nail fold.

Lab tests are generally not very helpful in cellulitis. A CBC might help to assess infection severity. A blood culture may be indicated if bacteremia or sepsis is suspected. A gram stain of a leading edge aspirate is done by injecting a small amount of non-bacteristatic saline into the leading edge of the cellulitis, then aspirating back the saline. Leading edge cultures have a low yield and they are usually not obtained. Since introduction of the Hib vaccine, the most common organisms are streptococci. In a series of 243 children admitted with cellulitis, Sadow and Chamberlain (1998) contend that, given a treatment threshold based on a band-to-neutrophil ratio of 0.20 on a CBC differential, routine cultures contribute little to the decision to treat (7). Most cases of early or mild cellulitis, especially those without fever, do not require laboratory testing. Empiric antibiotic treatment is successful in most instances.


Antibiotic treatment is targeted mainly against the usual pathogen, group A strep. Staph aureus is uncommon (unless an abscess is present), but difficult to exclude without a leading edge aspirate culture. GABHS is sensitive to penicillin and cephalosporins. Staph aureus used to be sensitive to anti-Staph aureus penicillins (cloxacillin, dicloxacillin, methicillin, oxacillin, nafcillin) and cephalosporins. However, currently, 25% of Staph aureus are resistant (i.e., methicillin and cephalosporin resistant). If GABHS is very likely, then utilizing a cephalosporin or penicillin is acceptable. However, if Staph aureus is suspected, then there is a 25% failure rate for cephalosporins and anti-Staph aureus penicillins. There is less Staph aureus resistance to clindamycin (also covers GABHS) and trimethoprim-sulfamethoxazole (does not cover GABHS as well). Thus, clindamycin is generally indicated if Staph aureus is suspected. Vancomycin and aminoglycosides are parenteral and can only be used for inpatient treatment of staph aureus. Erythromycin has been used in the past, but GABHS and Staph aureus have high resistance rates to erythromycin. If a satisfactory clinical response is not achieved within 7 days, a culture and sensitivity should be taken of a leading edge aspirate. If a resistant organism is detected, an appropriate antibiotic should be given for an additional 7 days.

Young children (<36>

Finally, aggressive attempts to restore skin integrity should be initiated. The skin should be gently moistened and cleansed. Impetiginous crusts should be softened with warm compresses and removed with an antibacterial soap. Application of an emollient provides lubrication and decreases discomfort. Topical antibiotics are unnecessary once systemic intervention is started.

Pneumococcal Cellulitis

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