Other conditions that may mimic cellulitis include deep vein thrombosis, which can be diagnosed with a compression leg ultrasound, and stasis dermatitis, which is inflammation of the skin from poor blood flow. Signs of a more severe infection such as necrotizing fasciitis or gas gangrene that would require prompt surgical intervention include purple bullae, skin sloughing, subcutaneous edema, and systemic toxicity. Misdiagnosis can occur in up to 30% of people with suspected lower-extremity cellulitis, leading to 50,000 to 130,000 unnecessary hospitalization and $195 to $515 million in avoidable healthcare spending annually in the United States.

Associated musculoskeletal findings are sometimes reported. When it occurs with acne conglobata, hidradenitis suppurativa, and pilonidal cysts, the syndrome is referred to as the follicular occlusion triad or tetrad.

Lyme disease can be misdiagnosed as staphylococcal- or streptococcal-induced cellulitis. Because the characteristic bullseye rash does not always appear in people infected with Lyme disease, the similar set of symptoms may be misdiagnosed as cellulitis. Standard treatments for cellulitis are not sufficient for curing Lyme disease. The only way to rule out Lyme disease is with a blood test, which is recommended during warm months in areas where the disease is endemic.

In those who have previously had cellulitis, the use of antibiotics may help prevent future episodes. This is recommended by CREST for those who have had more than two episodes.

The Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score can be utilized to risk stratify people having signs of cellulitis to determine the likelihood of necrotizing fasciitis being present. It uses six serologic measures: C-reactive protein, total white blood cell count, hemoglobin, sodium, creatinine and glucose. A score greater than or equal to 6 indicates that necrotizing fasciitis should be seriously considered. The scoring criteria are as follows:

- CRP (mg/L) ≥150: 4 points

- WBC count (×10/mm)

- <15: 0 points

- 15–25: 1 point

- >25: 2 points

- Hemoglobin (g/dL)

- >13.5: 0 points

- 11–13.5: 1 point

- <11: 2 points

- Sodium (mmol/L) <135: 2 points

- Creatinine (umol/L) >141: 2 points

- Glucose (mmol/L) >10: 1 point

As per the derivation study of the LRINEC score, a score of ≥6 is a reasonable cut-off to rule in necrotizing fasciitis, but a LRINEC <6 does not completely rule out the diagnosis. Diagnoses of severe cellulitis or abscess should also be considered due to similar presentations. 10% of patients with necrotizing fasciitis in the original study still had a LRINEC score <6. But a validation study showed that patients with a LRINEC score ≥6 have a higher rate of both mortality and amputation.

Diagnosis is by a swab of the affected area for laboratory testing. A Gram stain is performed to show Gram-positive cocci in chains. Then, the organism is cultured on blood agar with an added bacitracin antibiotic disk to show beta-hemolytic colonies and sensitivity (zone of inhibition around the disk) for the antibiotic. Culture on agar not containing blood, and then performing the catalase test should show a negative reaction for all streptococci. "S. pyogenes" is CAMP and hippurate tests negative. Serological identification of the organism involves testing for the presence of group-A-specific polysaccharide in the bacterium's cell wall using the Phadebact test.

The rapid pyrrolidonyl arylamidase (PYR) test is used for the presumptive identification of group A beta-hemolytic streptococci. GBS gives a negative finding on this test.

Early diagnosis is difficult as the disease often looks early on like a simple superficial skin infection. While a number of laboratory and imaging modalities can raise the suspicion for necrotizing fasciitis, the gold standard for diagnosis is a surgical exploration in the setting of high suspicion. When in doubt, a small "keyhole" incision can be made into the affected tissue, and if a finger easily separates the tissue along the fascial plane, the diagnosis is confirmed and an extensive debridement should be performed.

Computed tomography (CT scan) is able to detect approximately 80% of cases while MRI may pick up slightly more.

Immediate treatment is very important for someone with orbital cellulitis. Treatment typically involves intravenous (IV) antibiotics in the hospital and frequent observation (every 4–6 hours). Along with this several laboratory tests are run including a complete blood count, differential, and blood culture.

- Antibiotic therapy – Since orbital cellulitis is commonly caused by "Staphylococcus" and "Streptococcus" species both penicillins and cephalosporins are typically the best choices for IV antibiotics. However, due to the increasing rise of MRSA (methicillin-resistant "Staphylococcus aureus") orbital cellulitis can also be treated with Vancomycin, Clindamycin, or Doxycycline. If improvement is noted after 48 hours of IV antibiotics, healthcare professions can then consider switching a patient to oral antibiotics (which must be used for 2–3 weeks).

- Surgical intervention – An abscess can threaten the vision or neurological status of a patient with orbital cellulitis, therefore sometimes surgical intervention is necessary. Surgery typically requires drainage of the sinuses and if a subperiosteal abscess is present in the medial orbit, drainage can be performed endoscopically. Post-operatively, patients must follow up regularly with their surgeon and remain under close observation.

Bacterial infections of the orbit have long been associated with a risk of catastrophic local

sequelae and intracranial spread.

The natural course of the disease, as documented by Gamble (1933), in the pre-antibiotic era,

resulted in death in 17% of patients and permanent blindness in 20%.

The diagnosis of Ludwig's angina is clinical. History and physical examination are usually enough to establish the diagnosis.

Diagnosis of nocardiosis can be done by a doctor using various techniques. These techniques include, but are not limited to: a chest x-rays of the lung, a bronchoscopy, a brain/lung/skin biopsy, or a sputum culture.

However, diagnosis may be difficult. Nocardiae are gram positive weakly acid-fast branching rod-shaped bacteria and can be visualized by a modified Ziehl–Neelsen stain like Fite-Faraco method. In the clinical laboratory, routine cultures may be held for insufficient time to grow nocardiae, and referral to a reference laboratory may be needed for species identification. Infiltration and pleural effusion are usually seen via x-ray.

The prognosis of nocardiosis is highly variable. The state of the host's health, site, duration, and severity of the infection all play parts in determining the prognosis. As of now, skin and soft tissue infections have a 100% cure rate, and pleuropulmonary infections have a 90% cure rate with appropriate therapy. The cure rate falls to 63% with those infected with dissemented nocardiosis, with only half of those surviving infections that cause brain abscess. Additionally, 44% of people who are infected in the spinal cord/brain die, increasing to 85% if that person has an already weakened immune system. Unfortunately, there is not a preventative to nocardiosis. The only recommendation is to protect open wounds to limit access.

CBC, ESR, blood cultures, and sinus cultures help establish and identify an infectious primary source. Lumbar puncture is necessary to rule out meningitis.

Sinus films are helpful in the diagnosis of sphenoid sinusitis. Opacification, sclerosis, and air-fluid levels are typical findings. Contrast-enhanced CT scan may reveal underlying sinusitis, thickening of the superior ophthalmic vein, and irregular filling defects within the cavernous sinus; however, findings may be normal early in the disease course.

A MRI using flow parameters and an MR venogram are more sensitive than a CT scan, and are the imaging studies of choice to diagnose cavernous sinus thrombosis. Findings may include deformity of the internal carotid artery within the cavernous sinus, and an obvious signal hyperintensity within thrombosed vascular sinuses on all pulse sequences.

Cerebral angiography can be performed, but it is invasive and not very sensitive. Orbital venography is difficult to perform, but it is excellent in diagnosing occlusion of the cavernous sinus.

For those with a history of intravenous drug use, an X-ray is recommended before treatment to verify that no needle fragments are present. In this population if there is also a fever present infectious endocarditis should be considered.

Recovery from an anaerobic infection depends on adequate and rapid management. The main principles of managing anaerobic infections are neutralizing the toxins produced by anaerobic bacteria, preventing the local proliferation of these organisms by altering the environment and preventing their dissemination and spread to healthy tissues.

Toxin can be neutralized by specific antitoxins, mainly in infections caused by Clostridia (tetanus and botulism). Controlling the environment can be attained by draining the pus, surgical debriding of necrotic tissue, improving blood circulation, alleviating any obstruction and by improving tissue oxygenation. Therapy with hyperbaric oxygen (HBO) may also be useful. The main goal of antimicrobials is in restricting the local and systemic spread of the microorganisms.

The available parenteral antimicrobials for most infections are metronidazole, clindamycin, chloramphenicol, cefoxitin, a penicillin (i.e. ticarcillin, ampicillin, piperacillin) and a beta-lactamase inhibitor (i.e. clavulanic acid, sulbactam, tazobactam), and a carbapenem (imipenem, meropenem, doripenem, ertapenem). An antimicrobial effective against Gram-negative enteric bacilli (i.e. aminoglycoside) or an anti-pseudomonal cephalosporin (i.e. cefepime ) are generally added to metronidazole, and occasionally cefoxitin when treating intra-abdominal infections to provide coverage for these organisms. Clindamycin should not be used as a single agent as empiric therapy for abdominal infections. Penicillin can be added to metronidazole in treating of intracranial, pulmonary and dental infections to provide coverage against microaerophilic streptococci, and Actinomyces.

Oral agents adequate for polymicrobial oral infections include the combinations of amoxicillin plus clavulanate, clindamycin and metronidazole plus a macrolide. Penicillin can be added to metronidazole in the treating dental and intracranial infections to cover "Actinomyces" spp., microaerophilic streptococci, and "Arachnia" spp. A macrolide can be added to metronidazole in treating upper respiratory infections to cover "S. aureus" and aerobic streptococci. Penicillin can be added to clindamycin to supplement its coverage against "Peptostreptococcus" spp. and other Gram-positive anaerobic organisms.

Doxycycline is added to most regimens in the treatment of pelvic infections to cover chlamydia and mycoplasma. Penicillin is effective for bacteremia caused by non-beta lactamase producing bacteria. However, other agents should be used for the therapy of bacteremia caused by beta-lactamase producing bacteria.

Because the length of therapy for anaerobic infections is generally longer than for infections due to aerobic and facultative anaerobic bacteria, oral therapy is often substituted for parenteral treatment. The agents available for oral therapy are limited and include amoxacillin plus clavulanate, clindamycin, chloramphenicol and metronidazole.

In 2010 the American Surgical Society and American Society of Infectious Diseases have updated their guidelines for the treatment of abdominal infections.

The recommendations suggest the following:

For mild-to-moderate community-acquired infections in adults, the agents recommended for empiric regimens are: ticarcillin- clavulanate, cefoxitin, ertapenem, moxifloxacin, or tigecycline as single-agent therapy or combinations of metronidazole with cefazolin, cefuroxime, ceftriaxone, cefotaxime, levofloxacin, or ciprofloxacin. Agents no longer recommended are: cefotetan and clindamycin ( Bacteroides fragilis group resistance) and ampicillin-sulbactam (E. coli resistance) and ainoglycosides (toxicity).

For high risk community-acquired infections in adults, the agents recommended for empiric regimens are: meropenem, imipenem-cilastatin, doripenem, piperacillin-tazobactam, ciprofloxacin or levofloxacin in combination with metronidazole, or ceftazidime or cefepime in combination with metronidazole. Quinolones should not be used unless hospital surveys indicate >90% susceptibility of "E. coli" to quinolones.

Aztreonam plus metronidazole is an alternative, but addition of an agent effective against gram-positive cocci is recommended. The routine use of an aminoglycoside or another second agent effective against gram-negative facultative and aerobic bacilli is not recommended in the absence of evidence that the infection is caused by resistant organisms that require such therapy.

Empiric use of agents effective against enterococci is recommended and agents effective against methicillin-resistant "S. aureus" (MRSA) or yeast is not recommended in the absence of evidence of infection due to such organisms.

Empiric antibiotic therapy for health care-associated intra-abdominal should be driven by local microbiologic results. Empiric coverage of likely pathogens may require multidrug regimens that include agents with expanded spectra of activity against gram-negative aerobic and facultative bacilli. These include meropenem, imipenem-cilastatin, doripenem, piperacillin-tazobactam, or ceftazidime or cefepime in combination with metronidazole. Aminoglycosides or colistin may be required.

Antimicrobial regimens for children include an aminoglycoside-based regimen, a carbapenem (imipenem, meropenem, or ertapenem), a beta-lactam/beta-lactamase-inhibitor combination (piperacillin-tazobactam or ticarcillin-clavulanate), or an advanced-generation cephalosporin (cefotaxime, ceftriaxone, ceftazidime, or cefepime) with metronidazole.

Clinical judgment, personal experience, safety and patient compliance should direct the physician in the choice of the appropriate antimicrobial agents. The length of therapy generally ranges between 2 and 4 weeks, but should be individualized depending on the response. In some instances treatment may be required for as long as 6–8 weeks, but can often be shortened with proper surgical drainage.

"S. pyogenes" infections are best prevented through effective hand hygiene. No vaccines are currently available to protect against "S. pyogenes" infection, although research has been conducted into the development of one. Difficulties in developing a vaccine include the wide variety of strains of "S. pyogenes" present in the environment and the large amount of time and number of people that will be needed for appropriate trials for safety and efficacy of the vaccine.

Abscesses should be differentiated from empyemas, which are accumulations of pus in a preexisting rather than a newly formed anatomical cavity.

Other conditions that can cause similar symptoms include: cellulitis, a sebaceous cyst and necrotising fasciitis. Cellulitis typically also has an erythematous reaction, but does not confer any purulent drainage.

Antibiotics are aimed at gram positive bacteria. Medical attention should be sought if symptoms persist beyond 2–3 days.

The diagnosis of osteomyelitis is complex and relies on a combination of clinical suspicion and indirect laboratory markers such as a high white blood cell count and fever, although confirmation of clinical and laboratory suspicion with imaging is usually necessary.

Radiographs and CT are the initial method of diagnosis, but are not sensitive and only moderately specific for the diagnosis. They can show the cortical destruction of advanced osteomyelitis, but can miss nascent or indolent diagnoses.

Confirmation is most often by MRI. The presence of edema, diagnosed as increased signal on T2 sequences, is sensitive, but not specific, as edema can occur in reaction to adjacent cellulitis. Confirmation of bony marrow and cortical destruction by viewing the T1 sequences significantly increases specificity. The administration of intravenous gadolinium-based contrast enhances specificity further. In certain situations, such as severe Charcot arthropathy, diagnosis with MRI is still difficult. Similarly, it is limited in distinguishing bone infarcts from osteomyelitis in sickle cell anemia.

Nuclear medicine scans can be a helpful adjunct to MRI in patients who have metallic hardware that limits or prevents effective magnetic resonance. Generally a triple phase technetium 99 based scan will show increased uptake on all three phases. Gallium scans are 100% sensitive for osteomyelitis but not specific, and may be helpful in patients with metallic prostheses. Combined WBC imaging with marrow studies have 90% accuracy in diagnosing osteomyelitis.

Diagnosis of osteomyelitis is often based on radiologic results showing a lytic center with a ring of sclerosis. Culture of material taken from a bone biopsy is needed to identify the specific pathogen; alternative sampling methods such as needle puncture or surface swabs are easier to perform, but do not produce reliable results.

Factors that may commonly complicate osteomyelitis are fractures of the bone, amyloidosis, endocarditis, or sepsis.

Impetigo is usually diagnosed based on its appearance. It generally appears as honey-colored scabs formed from dried serum, and is often found on the arms, legs, or face. If a visual diagnosis is unclear a culture may be done to test for resistant bacteria.

Other conditions that can result in symptoms similar to the common form include contact dermatitis, herpes simplex virus, discoid lupus, and scabies.

Other conditions that can result in symptoms similar to the blistering form include other bullous skin diseases, burns, and necrotizing fasciitis.

A boil may clear up on its own without bursting, but more often it will need to be opened and drained. This will usually happen spontaneously within two weeks. Regular application of a warm moist compress, both before and after a boil opens, can help speed healing. The area must be kept clean, hands washed after touching it, and any dressings disposed of carefully, in order to avoid spreading the bacteria. A doctor may cut open or "lance" a boil to allow it to drain, but squeezing or cutting should not be attempted at home, as this may further spread the infection. Antibiotic therapy may be recommended for large or recurrent boils or those that occur in sensitive areas (such as the groin, breasts, armpits, around or in the nostrils, or in the ear). Antibiotics should not be used for longer than one month, with at least two months (preferably longer) between uses, otherwise it will lose its effectiveness. If the patient has chronic (more than two years) boils, removal by plastic surgery may be indicated.

Furuncles at risk of leading to serious complications should be incised and drained if antibiotics or steroid injections are not effective. These include furuncles that are unusually large, last longer than two weeks, or occur in the middle of the face or near the spine. Fever and chills are signs of sepsis and indicate immediate treatment is needed.

Staphylococcus aureus has the ability to acquire antimicrobial resistance easily, making treatment difficult. Knowledge of the antimicrobial resistance of "S. aureus" is important in the selection of antimicrobials for treatment.

This disease is diagnosed mainly by the appearance of well-demarcated rash and inflammation. Blood cultures are unreliable for diagnosis of the disease, but may be used to test for sepsis. Erysipelas must be differentiated from herpes zoster, angioedema, contact dermatitis, and diffuse inflammatory carcinoma of the breast.

Erysipelas can be distinguished from cellulitis by its raised advancing edges and sharp borders. Elevation of the antistreptolysin O titer occurs after around 10 days of illness.

Puppies are first presented with what appears to be staphylococcal pyoderma. Definitive diagnosis requires cytologic and histopathologic evaluations. Cytologic examination of papulopustular lesions of juvenile cellulitis reveals pyogranulomatous inflammation with no microorganisms and carefully performed cultures are negative. Biopsies of early lesions reveal multiple discrete or confluent granulomas and pyogranulomas consisting of clusters of large epithelioid macrophages with variably sized cores of neutrophils. Cytological analysis of joint fluid often reveals sterile suppurative arthritis.

A skin and skin structure infection (SSSI), also referred to as skin and soft tissue infection (SSTI) or acute bacterial skin and skin structure infection (ABSSSI), is an infection of skin and associated soft tissues (such as loose connective tissue and mucous membranes). The pathogen involved is usually a bacterial species. Such infections often requires treatment by antibiotics.

Until 2008, two types were recognized, complicated skin and skin structure infection (cSSSI) and uncomplicated skin and skin structure infection (uSSSI). "Uncomplicated" SSSIs included simple abscesses, impetiginous lesions, furuncles, and cellulitis. "Complicated" SSSIs included infections either involving deeper soft tissue or requiring significant surgical intervention, such as infected ulcers, burns, and major abscesses or a significant underlying disease state that complicates the response to treatment. Superficial infections or abscesses in an anatomical site, such as the rectal area, where the risk of anaerobic or gram-negative pathogen involvement is higher, should be considered complicated infections. The two categories had different regulatory approval requirements. The uncomplicated category (uSSSI) is normally only caused by "Staphylococcus aureus" and "Streptococcus pyogenes", whereas the complicated category (cSSSI) might also be caused by a number of other pathogens. In cSSSI, the pathogen is known in only about 40% of cases.

Because cSSSIs are usually serious infections, physicians do not have the time for a culture to identify the pathogen, so most cases are treated empirically, by choosing an antibiotic agent based on symptoms and seeing if it works. For less severe infections, microbiologic evaluation via tissue culture has been demonstrated to have high utility in guiding management decisions. To achieve efficacy, physicians use broad-spectrum antibiotics. This practice contributes in part to the growing incidence of antibiotic resistance, a trend exacerbated by the widespread use of antibiotics in medicine in general. The increased prevalence of antibiotic resistance is most evident in methicillin-resistant "Staphylococcus aureus" (MRSA). This species is commonly involved in cSSSIs, worsening their prognosis, and limiting the treatments available to physicians. Drug development in infectious disease seeks to produce new agents that can treat MRSA.

Since 2008, the U.S. Food and Drug Administration has changed the terminology to "acute bacterial skin and skin structure infections" (ABSSSI). The Infectious Diseases Society of America (IDSA) has retained the term "skin and soft tissue infection".

The definition of OM is broad, and encompasses a wide variety of conditions. Traditionally, the length of time the infection has been present and whether there is suppuration (pus formation) or sclerosis (increased density of bone) is used to arbitrarily classify OM. Chronic OM is often defined as OM that has been present for more than one month. In reality, there are no distinct subtypes; instead there is a spectrum of pathologic features that reflect balance between the type and severity of the cause of the inflammation, the immune system and local and systemic predisposing factors.

- Suppurative osteomyelitis

- Acute suppurative osteomyelitis

- Chronic suppurative osteomyelitis

- Primary (no preceding phase)

- Secondary (follows an acute phase)

- Non-suppurative osteomyelitis

- Diffuse sclerosing

- Focal sclerosing (condensing osteitis)

- Proliferative periostitis (periostitis ossificans, Garré's sclerosing osteomyelitis)

- Osteoradionecrosis

OM can also be typed according to the area of the skeleton in which it is present. For example, osteomyelitis of the jaws is different in several respects from osteomyelitis present in a long bone. Vertebral osteomyelitis is another possible presentation.