Brain abscess

Often polymicrobial (14–28% of cases)

Child: anaerobes (40%), aerobic and anaerobic viridans streptococci (GPC in chains), S. aureus (GPC), S. pneumoniae (GPDC), S. pyogenes (GPC in chains); less common: Enterobacteriaceae (GNR), P. aeruginosa (GNR), H. influenzae (GNCB), N. meningitidis (GNDC).

Adults: Viridans streptococci (anaerobic streptococci, S. milleri) (70%).

Enterobacteriaceae (GNR) (23–33%), S. aureus (GPC) (10–15%), N. meningitidis, Listeria sp., anaerobes (20–40%) including bacteroides (GNR), prevotella (GNR), fusobacterium (GNR), eubacterium (GPR), and propionibacterium (GPR), and more rarely S. pneumoniae, Rhodococcus sp., Group B streptococci (GPC in chains), nocardia (GPR), actinomyces (GPR), T. solium (cysticerci), Entamoeba histolytica, Schistosoma sp., and fungi (1%).

Immunocompromised: T. gondii, Cryptococcus neoformans, nocardia (GPR), Listeria sp. (GPR), mycobacteria (AFB), Aspergillus sp., C. albicans, coccidioides, Zygomycetes (mucor, rhizopus), E. histolytica.

Posttraumatic: S. aureus (GPC), viridans streptococci (GPC in chains), Enterobacteriaceae (GNR), coagulase-negative staphylococci (GPC), Propionibacterium acnes (GPR).

Blood for bacterial and fungal cultures.

Brain abscess aspirate for Gram stain (82%), bacterial (88%), AFB, fungal cultures, and cytology.

Lumbar puncture is dangerous and contraindicated.

Sources of infection in the ears, sinuses, lungs, or bloodstream should be sought for culture when brain abscess is found.

CT scan and MRI are the most valuable imaging procedures (see Chapter 6) and can guide brain biopsy if a specimen is needed.

Serum toxoplasma antibody in HIV-infected patients may not be positive at initiation of presumptive therapy. If negative or if no response to empiric therapy, biopsy may be needed to rule out lymphoma, fungal infection, or tuberculosis. Biopsy material should be sent for toxoplasma antigen (detected by direct fluorescent antibody, DFA).

Detection of toxoplasma DNA in blood or CSF samples by PCR techniques is now available from specialized or reference laboratories. PCR for toxoplasma is not useful once therapy has been started. A positive PCR result must be interpreted in the context of the clinical presentation.

(See also Toxoplasma antibody, Chapter 3.)

Occurs in patients with otitis media and sinusitis; cyanotic congenital heart disease and right-to-left shunting (eg, tetralogy of Fallot) or arteriovenous vascular abnormalities of the lung (eg, Osler-Weber-Rendu).

Mortality 8–25%.

Most toxoplasmosis abscesses are multiple and are seen on MRI in the basal ganglia, parietal and frontal lobes (ring-enhancing lesions with contrast on CT scan).

Stereotactic CT-guided aspiration of abscess material facilitates microbiologic diagnosis.

Hicks CW et al. Identifying and managing intracranial complications of sinusitis in children: a retrospective series. Pediatr Infect Dis J 2011;30:222. [PubMed: 21416657]

Prasad KN et al. Analysis of microbial etiology and mortality in patients with brain abscess. J Infect 2006;53:221. [PubMed: 16436297]

Shachor-Meyouhas Y et al. Brain abscess in children—epidemiology, predisposing factors and management in the modern medicine era. Acta Paediatr 2010;99:1163. [PubMed: 20222876]

Encephalitis

Arboviruses (California encephalitis group, St. Louis encephalitis, eastern and western equine encephalitis, West Nile virus, Japanese encephalitis virus in summer and fall), enteroviruses (coxsackie, echo, polio), HSV (10–20%), Bartonella henselae, lymphocytic choriomeningitis virus, tick-borne encephalitis virus, measles, rubella, VZV, rabies (Central and South America, India, Africa), Nipah virus (Malaysia), Chikungunya virus (India and Nepal), Creutzfeldt-Jakob.

Immunocompromised: CMV, VZV, EBV, West Nile virus, JC virus, HIV, Toxoplasma gondii.

CSF for pressure (elevated), cell count (WBCs elevated but variable [10–2000/mcL], mostly lymphocytes), protein (elevated, especially IgG fraction), glucose (normal), RBCs (suggestive of herpesvirus or other necrotizing virus). Repeat examination of CSF after 24 hours often useful. (See CSF [enteroviruses, HSV-2, mumps] profiles, Table 8–8).

CSF cultures for viruses or bacteria (low yield).

CSF PCR for CMV (33%), HSV (98%), VZV, EBV, JC virus, enterovirus, and West Nile virus.

Identification of HSV DNA in CSF by PCR techniques is now the definitive diagnostic test. HSV DNA by PCR may not be detectable early in course of illness.

Stool culture for enterovirus (2–5 days), which is frequently shed for weeks (especially in children) or in late illness.

For rabies, direct fluorescent antibody staining of skin biopsy from nape of neck (50% positive in first week) or RT-PCR on CSF or saliva.

Single serum for Bartonella (cat-scratch disease) IgM and IgG.

Test single serum for West Nile virus IgM antibody or CSF IgM antibody, or PCR of serum or CSF.

Paired sera for arboviruses and other viruses should be drawn immediately (acute specimen) and after 1–3 weeks of illness (convalescent specimen).

Urine PCR and/or serum PCR are options for diagnosis of enteroviruses.

All patients with suspected encephalitis should undergo MRI with gadolinium (most sensitive) unless contraindicated. CT scan with contrast less sensitive (50% sensitive). Temporal lobe lesions are suggestive of herpes simplex encephalitis.

Polyradiculopathy is highly suggestive of CMV in AIDS.

Consult with laboratory regarding availability of serological tests.

Baringer JR. Herpes simplex infections of the nervous system. Neurol Clin 2008;26:657. [PubMed: 18657720]

Hayes EB et al. West Nile virus: epidemiology and clinical features of an emerging epidemic in the United States. Annu Rev Med 2006;57:181. [PubMed: 16409144]

Long SS. Encephalitis diagnosis and management in the real world. Adv Exp Med Biol 2011;697:153. [PubMed: 21120725]

Aseptic meningitis

Acute: Enteroviruses (coxsackie, echo, polio) (90%), mumps, HSV, HIV (primary HIV seroconversion), VZV, lymphocytic choriomeningitis virus, adenovirus, parainfluenza virus 3, West Nile virus, St. Louis encephalitis virus and California group encephalitis viruses (rare).

Recurrent benign lymphocytic meningitis: HSV-2 (Mollaret meningitis).

CSF for pressure (elevated), cell count (WBCs 10–100/mcL, polomorphonuclear neutrophils (PMN searly, lymphocytes later), protein (normal or slightly elevated), and glucose (normal). On repeat CSF after 24–48 hours, an increase in lymphocytes is seen. (See CSF profiles, Table 8–8.)

CSF viral culture can be negative despite active viral infection. Enteroviruses can be isolated from the CSF in the first few days after onset (positive in 40–80%) but only rarely after the first week.

Detection of enteroviral RNA, HSV DNA, or VZV DNA in CSF by PCR from specialized or reference laboratories.

Paired sera (acute and convalescent) for antibody titers: mumps, West Nile virus, and VZV.

Consult with laboratory regarding availability of diagnostic tests for other viruses.

CT or MRI of head should be performed before lumbar puncture to evaluate for mass lesions or hydrocephalus if focal neurologic signs or papilledema are present.

Aseptic meningitis is acute meningeal inflammation in the absence of pyogenic bacteria or fungi. Diagnosis is usually made by examination of the CSF, PCR of CSF, or serologic assays and by ruling out other infectious causes of acute mental status changes or seizures (eg, toxoplasmosis, Lyme disease, neurosyphilis, tuberculosis, Rocky Mountain spotted fever, ehrlichiosis, fungal infection, and parasitic infection). Consider noninfectious causes such as nonsteroidal anti-inflammatory drugs and other medications.

Enteroviral aseptic meningitis is rare after age 40.

10–30% of patients with primary genital HSV-2 infection can have stiff neck, headache, and photophobia suggestive of recurrent meningitis.

Irani DN. Aseptic meningitis and viral myelitis. Neurol Clin 2008;26:635. [PubMed: 18657719]

Lee BE et al. Aseptic meningitis. Curr Opin Infect Dis 2007;20:272. [PubMed: 17471037]

Poulikakos PJ et al. A case of recurrent benign lymphocytic (Mollaret’s) meningitis and review of the literature. J Infect Public Health 2010;3:192. [PubMed: 21126724]

Bacterial meningitis

Neonate: Group B streptococci (GPC) (70%), L. monocytogenes (GPR) (20%), S. pneumoniae (GPC) (10%), E. coli (GNR) and Klebsiella sp (GNR) (1%), and other streptococci.

Infant: S. pneumoniae (GPC) (47%), N. meningitidis (GNDC) (30%), group B streptococci (GPC) (18%), Listeria monocytogenes (GPR), H. influenzae (GNCB) (5%).

Child: N. meningitidis (60%), S. pneumoniae (25%), H. influenzae (8%), and other streptococci.

Adult: S. pneumoniae (60%), N. meningitidis (20%), L. monocytogenes (6%), group B streptococci (4%), other Hemophilus sp., and staphylococci (1%), Ehrlichia chaffeensis (rare).

Postneurosurgical: S. aureus (GPC), S. pneumoniae, P. acnes (GPR), coagulase-negative staphylococci (GPC), pseudomonas (GNR), E. coli (GNR), other Enterobacteriaceae, Acinetobacter (GNR).

Alcoholic patients and the elderly: In addition to the adult organisms, Enterobacteriaceae, pseudomonas, H. influenzae.

CSF for pressure (>180 mm H2O), cell count (WBCs 5000–20,000/mcL, >50% PMNs), protein (150–500 mg/dL), glucose (low <40 mg/dL). (See CSF profiles, Table 8–8.)

CSF for Gram stain of cytocentrifuged material (positive in 70–80%).

CSF culture for bacteria (positive in 70–85%).

Blood culture positive in 40–60% of patients with pneumococcal, meningococcal, and H. influenzae meningitis.

CSF antigen tests are no longer considered useful because of their low sensitivity and false-positive results.

The first priority in the care of the patient with suspected acute meningitis is therapy, then diagnosis. Start antimicrobial agents based on Gram stain, or if no bacteria are seen, start empiric antibiotics immediately based on patient age and any underlying disease process. Adjunctive dexamethasone therapy has proved beneficial, especially for pneumococcal meningitis. If lumbar puncture is performed, administer antimicrobial therapy with dexamethasone immediately after CSF collection.

The mortality rate for pneumococcal meningitis is about 20%, with 25–50% of patients having long-term neurologic complications.

With recurrent N. meningitidis meningitis, suspect a terminal complement component deficiency. With other recurrent bacterial meningitides, suspect a CSF leak; S. pneumoniae is most likely pathogen.

Therapy usually includes a 3rd generation cephalosporin plus vancomycin until culture results return. This will cover the most common pathogens as well as H. influenzae. Add ampicillin if L. monocytogenes is suspected. Therapy can be narrowed once the pathogen is identified and susceptibility results are determined.

For S. pneumoniae, there has been an increase in prevalence of penicillin- and cephalosporin-resistant strains, so susceptibility testing of pneumococcal strains is very important to guide therapy.

Bamberger DM. Diagnosis, initial management, and prevention of meningitis. Am Fam Physician 2010;82:1491. [PubMed: 21166369]

Brouwer MC et al. Epidemiology, diagnosis, and antimicrobial treatment of acute bacterial meningitis. Clin Microbiol Rev 2010;23:467. [PubMed: 20610819]

Kim KS. Acute bacterial meningitis in infants and children. Lancet Infect Dis 2010;10:32–42. [PubMed: 20129147]

Nudelman Y et al. Bacterial meningitis: epidemiology, pathogenesis and management update. Drugs 2009;69:2577. [PubMed: 19943708]

Fungal meningitis

C. neoformans (spherical, budding yeast), C. immitis (spherules), H. capsulatum.

Immunocompromised: Aspergillus sp, Pseudallescheria boydii, Candida sp., sporothrix, blastomyces.

CSF for pressure (normal or elevated), cell count (WBCs 50–1000/mcL, mostly lymphocytes), protein (elevated), and glucose (normal or decreased).

Serum cryptococcal antigen (CrAg) test (latex agglutination) for C. neoformans (>90% sensitive and specific). (This test can be performed on CSF specimens.)

For other fungi, collect at least 5 mL of CSF for fungal culture. Initial cultures are positive in 40% of coccidioides cases and 27–65% of histoplasma cases. Repeat cultures are frequently needed.

Cultures of blood, bone marrow, skin lesions, or other involved organs, if clinically indicated.

CSF India ink preparation for cryptococcus is not recommended. Cytospin Gram stain procedure concentrates CSF and can demonstrate round, budding yeast.

Serum coccidioidal serology is a serum immunodiffusion test for antibodies against the organism (75–95%). CSF serologic testing is rarely necessary. (See Coccidioides serology, Chapter 3.)

Complement fixation tests for coccidioides or histoplasma antibodies are available from reference laboratories or public health department laboratories (see Chapter 3) and can give titers that can be used to follow treatment.

Histoplasma antigen can be detected in urine (90%), blood (70%), or CSF (61%) in cases of histoplasma meningitis.

The clinical presentation of fungal meningitis in non-immunocompromised and immunocompromised patients is that of an indolent chronic meningitis.

Before AIDS, cryptococcal meningitis was seen both in patients with cellular immunologic deficiencies and in patients who lacked obvious defects (about 50%).

In AIDs patients, cryptococcus is the most common cause of meningitis and may present with normal CSF findings.

Titer of CSF CrAg can be used to monitor therapeutic success (falling titer) or failure (unchanged or rising titer) or to predict relapse during suppressive therapy (rising titer) in immunocompetent patients, though not in patients with AIDS.

Ginsberg L et al. Chronic and recurrent meningitis. Pract Neurol 2008;8:348. [PubMed: 19015295]

Honda H et al. Central nervous system infections: meningitis and brain abscess. Infect Dis Clin North Am 2009;23:609. [PubMed: 19665086]

Li SS et al. Cryptococcus. Proc Am Thorac Soc 2010;7:186.[PubMed: 20463247]

Wheat LJ et al. Diagnosis and management of central nervous system histoplasmosis. Clin Infect Dis 2005;40:844. [PubMed: 15736018]

Williams PL. Coccidioidal meningitis. Ann N Y Acad Sci 2007;1111:377. [PubMed: 17363442]

Spirochetal meningitis/neurologic diseases

B. burgdorferi (neuroborreliosis), T. pallidum (neurosyphilis), leptospira, other borreliae

Neuroborreliosis: CSF for pressure (normal or elevated), cell count (WBCs elevated, mostly lymphocytes), protein (may be elevated), and glucose (normal).

Serum and CSF for serologic testing for antibody by ELISA or IFA. False-positive serologic tests may occur. Western blots should be used to confirm borderline or positive results. CSF serology for anti-B. burgdorferi IgM (90%). PCR is very specific for detecting Borrelia DNA, but sensitivity is variable owing to stage of disease and type of body fluid tested. (See Lyme disease serologies, Chapter 3.)

Acute syphilitic meningitis: CSF for pressure (elevated), cell count (WBCs 25–2000/mcL, mostly lymphocytes), protein (elevated), and glucose (normal or low). (See CSF profiles, Table 8–8.)

Serum VDRL. (See VDRL, serum, Chapter 3.)

CSF VDRL is the preferred test (see Chapter 3), but is only 66% sensitive for acute syphilitic meningitis.

Neurosyphilis: CSF for pressure (normal), cell count (WBCs normal or slightly increased, mostly lymphocytes), protein (normal or elevated), glucose (normal), and positive CSF VDRL.

Serum RPR or VDRL with confirmatory FTA-ABS, or TP PA testing should be done with a positive serum result before CSF VDRL is performed.

Traditionally, nontreponemal serologic tests (RPR or VDRL) are used as screening tests for detection of syphilis. Because of the lack of specificity for these tests, positive screening tests must be confirmed with FTA-ABS or TP PA treponemal-specific assays. A new syphilis testing algorithm using treponemal tests for screening followed by a nontreponemal serology test has been proposed.

Leptospirosis: CSF cell count (WBCs <500/mcL, mostly monocytes), protein (slightly elevated), and glucose (normal).

Urine for dark-field examination of sediment to detect leptospira organisms.

Blood and CSF dark-field examination positive only in acute phase prior to meningitis.

Serum for serology for IgM by EIA (93% specificity) and ELISA.

Neurosyphilis is a late stage of infection and can present with meningovascular (hemiparesis, seizures, aphasia), parenchymal (general paresis, tabes dorsalis), or asymptomatic (latent) disease. In HIV-infected patients, neurosyphilis can present in secondary syphilis.

Because there is no single highly sensitive or specific test for neurosyphilis, the diagnosis must depend on a combination of clinical and laboratory data. Therapy of suspected neurosyphilis should not be withheld on the basis of a negative CSF VDRL if clinical suspicion is high.

In HIV neurosyphilis, treatment failures may be common.

Lyme disease can present as a lymphocytic meningitis, facial palsy, or painful radiculitis.

Leptospirosis follows exposure to urine of infected rodents, small animals, or livestock.

Kent ME et al. Reexamining syphilis: an update on epidemiology, clinical manifestations, and management. Ann Pharmacother 2008;42:226. [PubMed: 18212261]

O’Connell S. Lyme borreliosis: current issues in diagnosis and management. Curr Opin Infect Dis 2010;23:231. [PubMed: 20407371]

Sena AC et al. Novel Treponema pallidum serologic tests: a paradigm shift in syphilis screening for the 21st century. Clin Infect Dis 2010;51:700. [PubMed: 20687840]

Stoner BP. Current controversies in the management of adult syphilis. Clin Infect Dis 2007;44 (Suppl 3):S130. [PubMed: 17342666]

Toyokawa T et al. Diagnosis of acute leptospirosis. Expert Rev Anti Infect Ther 2011;9:111. [PubMed: 21171882]

Victoriano AF et al. Leptospirosis in the Asia Pacific region. BMC Infect Dis 2009;9:147. [PubMed: 19732423]

Parasitic meningo-encephalitis

T. gondii, Naegleria fowleri, T. solium (cysticerci), Acanthamoeba (granulomatous amebic encephalitis GAE), Balamuthia sp. (GAE), Angiostrongylus (eosinophilic meningoencephalitis), Trypanosoma sp.

CSF for pressure (normal or elevated), cell count (WBCs 100–1000/mcL, chiefly monocytes, lymphocytes), protein (elevated), glucose (normal to low). Serum serology to detect antibodies for T. gondii, E. chaffeensis, A. phagocytophilum.

Toxoplasmosis: CT or MRI of brain, serology, Giemsa-stained touch prep of brain tissue, CSF PCR.

Naegleria: CSF wet mount for amebic trophozoites, or hematoxylin and eosin stain of brain tissue. Serologic tests not helpful.

Cysticercosis: Characteristic findings on CT and MRI are diagnostic. Serology is less sensitive.

Balamuthia: Culture not helpful. Indirect immunofluorescence or PCR of brain tissue to detect organism.

Angiostrongyliasis: CSF pressure (normal or elevated), cell count (WBC eosinophilic pleocytosis), protein (elevated), glucose (normal). CSF wet mount, ELISA serology.

Trypanosomiasis: Blood-Giemsa stain on thick and thin smears. CSF wet mount. Serologic tests by ELISA, IFA have 93–98% sensitivity and 99% specificity in acute stages. Serologic tests may be negative in chronic stages.

Naegleria follows exposure to warm, fresh, and polluted water (eg, swimming pools, sewers, fresh-water lakes).

Pereira-Chioccola VL et al. Toxoplasma gondii infection and cerebral toxoplasmosis in HIV-infected patients. Future Microbiol 2009;4:1363. [PubMed: 19995194]

Ramirez-Avila L et al. Eosinophilic meningitis due to Angiostrongylus and Gnathostoma species. Clin Infect Dis 2009;48:322. [PubMed: 19123863]

Visvesvara GS. Amebic meningoencephalitides and keratitis: challenges in diagnosis and treatment. Curr Opin Infect Dis 2010;23:590. [PubMed: 20802332]

Tuberculous meningitis

M. tuberculosis (MTb),

CSF for pressure (elevated), cell count (WBCs 100–500/mcL, PMNs early, lymphocytes later), protein (elevated), glucose (decreased). (See CSF profiles, Table 8–8.)

CSF for AFB stain. Stain is positive in only 30%; culture may be negative in 15–25% of cases. Cytocentrifugation and repeat smears increase yield.

CSF for AFB culture (positive in <70%). Repeated sampling of the CSF during the first week of therapy is recommended; ideally, 3 or 4 specimens of 5–10 mL each should be obtained (87% yield with 4 specimens). CSF PCR available but sensitivity of most assays is low (50%). Positive CSF PCR is helpful with appropriate clinical picture, but negative PCR does not rule out tuberculous meningitis.

DNA hybridization probes are available for rapid identification of mycobacteria from culture.

Tuberculous meningitis is usually secondary to rupture of a subependymal tubercle from pulmonary focus or may be a consequence of miliary tuberculosis rather than blood-borne invasion.

Because CSF stain and culture are not sensitive for tuberculous meningitis, diagnosis and treatment should be based on a combination of clinical and microbiologic data.

Evidence of inactive or active extrameningeal tuberculosis, especially pulmonary, is seen in 75% of patients.

Garg RK. Tuberculous meningitis. Acta Neurol Scand 2010;122:75. [PubMed: 20055767]

Garg RK et al. Tuberculous meningitis in patients infected with human immunodeficiency virus. J Neurol 2011;258:3. [PubMed: 20848123]

Thwaites GE et al. Update on tuberculosis of the central nervous system: pathogenesis, diagnosis, and treatment. Clin Chest Med 2009;30:745. [PubMed: 19925964]

Conjunctivitis

Neonate (ophthalmia neonatorum): C. trachomatis (15–50%), N. gonorrhoeae (GNDC), HSV.

Children and adults: adenovirus, staphylococci (GPC), HSV, H. influenzae (GNCB), S. pneumoniae (GPDC), S. pyogenes (GPC), VZV, N. gonorrhoeae (GNDC), M. lacunata (GNCB), M. catarrhalis, Bartonella sp. (Parinaud oculoglandular syndrome).

Adult inclusion conjunctivitis/trachoma: C. trachomatis.

Acute hemorrhagic conjunctivitis (acute epidemic keratoconjunctivitis): enterovirus, coxsackievirus.

Conjunctival Gram stain is especially useful if gonococcal infection is suspected.

Bacterial culture for severe cases (routine bacterial culture) or suspected gonococcal infection.

Conjunctival scrapings or smears by direct immunofluorescent monoclonal antibody staining for C. trachomatis.

Cell culture for chlamydia.

Detection of chlamydial DNA on ocular swabs by PCR techniques may be available in research laboratories.

Ocular HSV and VZV PCR may be available in reference laboratories.

The causes of conjunctivitis change with the season. Adenovirus occurs mainly in the fall, H. influenzae in the winter.

Gonococcal conjunctivitis is an ophthalmologic emergency.

Cultures are usually unnecessary unless chlamydia or gonorrhea is suspected or the case is severe.

Consider noninfectious causes (eg, allergy, contact lens deposits, trauma).

Hu VH et al. Epidemiology and control of trachoma: systematic review. Trop Med Int Health 2010;15:673. [PubMed: 20374566]

O’Brien TP et al. Acute conjunctivitis: truth and misconceptions. Curr Med Res Opin 2009;25:1953. [PubMed: 19552618]

Keratitis

Bacteria: P. aeruginosa (GNR), staphylococci (GPC), S. pneumoniae (GPDC), Haemophilus sp. (GNCB), Moraxella sp.

Virus: HSV (dendritic pattern on fluorescein slit-lamp examination), VZV.

Contact lens: Acanthamoeba, Enterobacteriaceae (GNR).

Fungus: Candida, fusarium, aspergillus, rhodotorula, other filamentous fungi.

Parasite: O. volvulus (river blindness), microsporidia (HIV).

Corneal scrapings for Gram stain, KOH, and culture. Routine bacterial culture is used for most bacterial causes, viral culture for herpes, and special media for acanthamoeba (can be detected with trichrome or Giemsa stain of smears).

Treatment depends on Gram stain appearance and culture.

Corneal biopsy may be needed if initial cultures are negative.

Ocular viral DFA for HSV and VZV.

Prompt ophthalmologic consultation is mandatory.

Acanthamoeba infection occurs in soft contact (extended-wear) lens wearers and may resemble HSV infection on fluorescein examination (dendritic [“branching”] ulcer).

Bacterial keratitis is usually caused by contact lens use or trauma. Fungal (ie, Fusarium sp.) keratitis is usually caused by trauma.

Increased resistance noted among all bacterial isolates (eg, coagulase-negative staphylococci) to ciprofloxacin (20–38%) and cefazolin (19–40%). Resistance to bacitracin, trimethoprim-sulfamethoxazole and vancomycin remains unchanged.

Ahearn DG et al. Fusarium keratitis and contact lens wear: facts and speculations. Med Mycol 2008;46:397. [PubMed: 18608899]

Chang DC et al; Fusarium Keratitis Investigation Team. Multistate outbreak of Fusarium keratitis associated with use of a contact lens solution. JAMA 2006;296:953. [PubMed: 16926355]

Cronau H et al. Diagnosis and management of red eye in primary care. Am Fam Physician 2010;81:137. [PubMed: 20082509]

Joslin CE et al. Epidemiological characteristics of a Chicago-area Acanthamoeba keratitis outbreak. Am J Ophthalmol 2006;142:212. [PubMed: 16876498]

Endophthalmitis

Spontaneous or postoperative:

Coagulase-negative staphylococci (70%) (GPC), S. aureus (10%) (GPC), viridans group streptococci (5%) (GPC in chains), S. pneumoniae (5%) (GPDC), gram-negative rods (6%) (eg, E. coli, Klebsiella sp., Pseudomonas sp.), and other gram-positive organisms (4%) (eg, group B streptococci, Listeria sp.).

Trauma: Bacillus sp. (GPR), fungi, coagulase negative staphylococci (GPC), streptococci (GPC), and gram-negative rods.

Postfiltering bleb created to control glaucoma: Viridans group streptococci (57%) (GPC in chains), S. pneumoniae (GPDC), H. influenzae (GNCB), M. catarrhalis (GNCB), S. aureus (GPC), S. epidermidis (GPC), enterococci (GPC), gram-negative rods.

IV drug abuse: Add Bacillus cereus.

Culture material from anterior chamber, vitreous cavity, and wound abscess for bacteria, mycobacteria, and fungi. Traumatic and postoperative cases should have aqueous and vitreous aspiration for culture and smear (56%).

Endophthalmitis refers to bacterial or fungal infections and is an inflammatory process of the ocular cavity and adjacent structures. Rapid diagnosis is critical, because vision may be compromised.

Bacterial endophthalmitis usually occurs as a consequence of ocular surgery (cataract surgery), 75% within first postoperative week. Prophylactic antibiotics are of unproven benefit, though topical antibiotics are widely used.

Also consider retinitis in immunocompromised patients, caused by CMV, HSV, VZV, and toxoplasma (retinochoroiditis), which is diagnosed by retinal examination.

Maguire JI. Postoperative endophthalmitis: optimal management and the role and timing of vitrectomy surgery. (Lond) 2008;22:1290. [PubMed: 18356929]

Schwartz SG et al. Endophthalmitis after intravitreal injections. Expert Opin Pharmacother 2009;10:2119. [PubMed: 19586422]

Otitis media

Infant, child, and adult: S. pneumoniae (23%) (GPDC), H. influenzae (36%) (GNCB), M. catarrhalis (3%) (GNDC), S. aureus (GPC), S. pyogenes (GPC in chains), viruses (eg, respiratory syncytial virus [RSV], influenza virus, rhinovirus, enteroviruses, human metapneumovirus), M. pneumoniae, C. trachomatis or pneumoniae, anaerobes, fungi (eg, Blastomyces dermatitidis, Candida sp., Aspergillus sp.).

Neonate: Same as above plus Enterobacteriaceae (GNR), group B streptococcus (GPC).

Endotracheal intubation: Pseudomonas sp. (GNR), Klebsiella (GNR), Enterobacteriaceae (GNR).

Chronic: P. aeruginosa (GNR), anaerobes, M. tuberculosis (AFB).

Tympanocentesis aspirate for Gram stain and bacterial culture in the patient who has a toxic appearance. Otherwise, microbiologic studies of effusions are so consistent that empiric treatment is acceptable.

CSF examination if clinically indicated.

Nasopharyngeal swab may be substituted for tympanocentesis.

Blood culture in the toxic patient.

Peak incidence of otitis media occurs in the first 3 years of life, especially between 6 and 24 months of age.

In neonates, predisposing factors include cleft palate, hypotonia, mental retardation (Down syndrome).

Tympanocentesis is indicated if the patient fails to improve after 48 hours or develops fever. It may hasten resolution and decrease sterile effusion.

Persistent middle ear effusion may require placement of ventilating or tympanostomy tubes.

Bullous myringitis suggests mycoplasma.

Emerging antibiotic resistance should be considered in choice of empiric antibiotic therapy.

There is emerging resistance of S. pneumoniae to macrolides, to erythromycin and to penicillin, so appropriate therapy should rely on local antibiograms.

M. catarrhalis organisms produce β-lactamase (90%), as do H. influenzae organisms (~33–50%). This lessens usefulness of amoxicillin, the usual drug of choice.

Coker TR et al. Diagnosis, microbial epidemiology, and antibiotic treatment of acute otitis media in children: a systematic review. JAMA 2010;304:2161. [PubMed: 21081729]

Vergison A et al. Otitis media and its consequences: beyond the earache. Lancet Infect Dis 2010;10:195. [PubMed: 20185098]

Wald ER. Acute otitis media and acute bacterial sinusitis. Clin Infect Dis 2011;52(Suppl 4):S277. [PubMed: 21460285]

Otitis externa

Acute localized: S. aureus (15%) (GPC), anaerobes (32%), S. pyogenes (GPC in chains), H. influenzae, other gram-positive cocci.

“Swimmer’s ear”: Pseudomonas sp. (40%) (GNR), fungi (6%) (eg, Aspergillus sp., Candida sp.).

Chronic: Usually secondary to seborrhea or eczema.

Diabetes mellitus, AIDS (“malignant otitis externa”): P. aeruginosa (GNR), Aspergillus sp., Candida sp.

Furuncle of external canal: S. aureus.

Ear drainage for Gram stain and bacterial culture, especially in malignant otitis externa.

CT or MRI can aid in diagnosis by demonstrating cortical bone erosion or meningeal enhancement.

Infection of the external auditory canal is similar to infection of skin and soft tissue elsewhere.

If malignant otitis externa is present, exclusion of associated osteomyelitis and surgical drainage may be required.

Carfrae MJ et al. Malignant otitis externa. Otolaryngol Clin North Am 2008;41:537. [PubMed: 18435997]

Kaushik V et al. Interventions for acute otitis externa. Cochrane Database Syst Rev 2010;(1):CD004740. [PubMed: 20091565]

Rosenfeld RM et al; American Academy of Otolaryngology–Head and Neck Surgery Foundation. Clinical practice guideline: acute otitis externa. Otolaryngol Head Neck Surg 2006;134(4 Suppl):S4. [PubMed: 16638473]

Sinusitis

Acute: S. pneumoniae (GPDC) (20–43%), H. influenzae (GNCB) (21–35%), M. catarrhalis (GNDC) (2–10%), other streptococci (3–9%) (GPC), anaerobes (1–9%), viruses (4%) (adenovirus, influenza, parainfluenza), S. aureus (GPC) (1–8%).

Chronic (child): Viridans and anaerobic streptococci (GPC in chains) (23%), S. aureus (19%), S. pneumoniae, H. influenzae, M. catarrhalis, P. aeruginosa (GNR) in cystic fibrosis.

Chronic (adult): Coagulase-negative staphylococci (GPC) (36%), S. aureus (GPC) (25%), viridans streptococci (GPC in chains) (8%), corynebacteria (GPR) (5%), anaerobes (6%), including Bacteroides sp., Prevotella sp. (GNR), peptostreptococcus (GPC), Fusobacterium sp. (GNR).

Hospitalized with nasogastric tube or nasotracheal intubation: Enterobacteriaceae (GNR), Pseudomonas sp. (GNR).

Fungal: Zygomycetes (rhizopus), aspergillus, P. boydii, other dematiaceous mold.

Immunocompromised: P. aeruginosa (GNR), CMV, Aspergillus sp. and other filamentous fungi plus microsporidia, Cryptosporidium parvum, Acanthamoeba in HIV-infected patients.

Clinical diagnosis.

Nasal aspirate for bacterial culture is not usually helpful due to respiratory flora contamination of aerobes and anaerobes.

Maxillary sinus aspirate for bacterial culture may be helpful in severe or atypical cases.

Diagnosis and treatment of sinusitis are usually based on clinical and radiologic features. Microbiologic studies can be helpful in severe or atypical cases.

Sinus CT scan (or MRI) is better than plain x-ray for diagnosing sinusitis, particularly if sphenoid sinusitis is suspected. However, sinus CT scans should be interpreted cautiously, because abnormalities are also seen in patients with the common cold.

Acute and chronic sinusitis occur frequently in HIV-infected patients, may be recurrent or refractory, and may involve multiple sinuses (especially when the CD4 cell count is <200/mcL).

Acute sinusitis often results from bacterial superinfection following viral upper respiratory infection.

Mehrtens JM et al. Acute sinusitis. Adolesc Med State Art Rev 2010;21:187. [PubMed: 21047024]

Orlandi RR et al. Fungus and chronic rhinosinusitis: weighing the evidence. Otolaryngol Head Neck Surg 2010;143:611. [PubMed: 20974327]

Ryan MW. Evaluation and management of the patient with “sinus.” Med Clin North Am 2010;94:881. [PubMed: 20736100]

Wang X et al. Chronic rhinosinusitis. Adv Otorhinolaryngol 2011;70:114. [PubMed: 21358193]

Pharyngitis

Exudative: S. pyogenes (GPC) (15–30%), viruses (rhinovirus, coronavirus, adenovirus) (30%), group C and G streptococci (GPC) (5%), herpes simplex virus (HSV) (4%), parainfluenza and influenza virus A and B (2–4%), Epstein-Barr virus (mononucleosis) (1%), HIV (1%) N. gonorrhoeae (GNDC) (1%), C. diphtheriae (GPR) (≤1%), Arcanobacterium hemolyticum (GPR) (≤1%) M. pneumoniae, C. pneumoniae.

Membranous: C. diphtheriae (GPR), C. pseudodiphtheriticum (GPR), HSV, Epstein-Barr virus.

Throat swab for culture. Place in sterile tube or transport medium. If N. gonorrhoeae is suspected, use chocolate agar or Thayer-Martin media. If C. diphtheriae is suspected, use Tinsdale or blood agar. Throat swabs are routinely cultured for group A streptococcus only. If other organisms are suspected, this must be stated.

Throat culture has about 70–90% sensitivity and 95% specificity for group A streptococcus.

“Rapid” tests for group A streptococcus can speed diagnosis and aid in the treatment of family members. However, false-negative results may lead to underdiagnosis and failure to treat. Back-up throat cultures are recommended so group A streptococcus is not missed. Sequelae of group A streptococcus infection can be severe such as rheumatic fever, post-streptococcal glomerulonephritis.

Controversy exists over how to evaluate patients with sore throat, although some authors suggest culturing all patients and then treating only those with positive cultures.

Most laboratories only report group A streptococcus from throat culture.

In patients with compatible histories, be sure to consider pharyngeal abscess or epiglottitis, both of which may be life-threatening.

Complications include pharyngeal abscess and Lemierre syndrome (infection with Fusobacterium sp.), which can progress to sepsis and multi-organ failure.

Chan TV. The patient with sore throat. Med Clin North Am 2010;94:923. [PubMed: 20736104]

Wessels MR. Clinical practice. Streptococcal pharyngitis. N Engl J Med 2011;364:648. [PubMed: 21323542]

Laryngitis

Virus (90%) (influenza, rhinovirus, adenovirus, parainfluenza, Epstein-Barr virus), S. pyogenes (GPC) (10%), M. catarrhalis (GNDC), H. influenzae (GNCB), M. tuberculosis, fungus (cryptococcosis, histoplasmosis).

Immunocompromised: Candida sp., CMV, HSV.

Laryngitis usually occurs with common cold or influenzal syndromes.

Fungal laryngeal infections occur most commonly in immunocompromised patients (AIDS, cancer, organ transplants, corticosteroid therapy, diabetes mellitus).

Chronic laryngitis is associated with one or more chronic irritants such as gastric acid, chronic sinusitis, chronic alcohol use, inhaled toxins.

Feierabend RH et al. Hoarseness in adults. Am Fam Physician 2009;80:363. [PubMed: 19678604]

Mau T. Diagnostic evaluation and management of hoarseness. Med Clin North Am 2010;94:945. [PubMed: 20736105]

Laryngotracheobronchitis

Infant/child: RSV (50–75%) (bronchiolitis), adenovirus, parainfluenza virus (HPIV types 1, 2, 3) (80%) (croup), B. pertussis (GNCB) (whooping cough), other viruses, including rhinovirus, coronavirus, influenza, bocavirus, human metapneumovirus.

Adolescent/adult: Usually viruses, M. pneumoniae, C. pneumoniae, B. pertussis.

Chronic adult: S. pneumoniae (GPDC), H. influenzae (GNCB), M. catarrhalis (GNDC), Klebsiella (GNR), other Enterobacteriaceae (GNR), viruses (eg, influenza), aspergillus (allergic bronchopulmonary aspergillosis).

Chronic obstructive airway disease: Viral (25–50%), S. pneumoniae (GPC), H. influenzae (GNCB), S. aureus (GPC), Enterobacteriaceae (GNR), anaerobes (<10%).

Nasopharyngeal aspirate or swab for respiratory virus DFA, for viral culture (rarely indicated), and for PCR for B. pertussis. PCR for pertussis is test of choice; culture and DFA are less sensitive. Cellular examination of early morning sputum will show many PMNs in chronic bronchitis.

Sputum Gram stain and culture for ill adults. In chronic bronchitis, mixed flora are usually seen with oral flora or colonized H. influenzae or S. pneumoniae on culture.

Paired sera for mycoplasmal antibody assays can help make a diagnosis retrospectively in infants and children but are not clinically useful except for seriously ill patients.

Chronic bronchitis is diagnosed when sputum is coughed up on most days for at least 3 consecutive months for more than 2 successive years.

Bacterial infections are usually secondary infections of initial viral or mycoplasma induced inflammation.

Airway endoscopy can aid in the diagnosis of bacterial tracheitis in children.

Cornia PB et al. Does this coughing adolescent or adult patient have pertussis? JAMA 2010;304:890. [PubMed: 20736473]

Everard ML. Acute bronchiolitis and croup. Pediatr Clin North Am 2009;56:119. [PubMed: 19135584]

Sobol SE et al. Epiglottitis and croup. Otolaryngol Clin North Am 2008;41:551. [PubMed: 18435998]

Epiglottitis

Child: H. influenzae type B (GNCB), H. parainfluenzae (GCNB), S. pneumoniae (GPC), S. aureus (GPC), other streptococci (groups A, B, C)

Adult: S. pyogenes (GPC), S. pneumoniae (GPC), Klebsiella sp. (GNR), H. influenzae (GNCB), Pseudomonas sp. (GNR), HSV, viruses (parainfluenza and influenza).

HIV: Candida (fungi) and Pseudomonas sp. (GNR).

Blood for bacterial culture: positive in 50–100% of children with H. influenzae.

Lateral neck x-ray may show an enlarged epiglottis but has a low sensitivity (31%).

Acute epiglottitis is a rapidly moving cellulitis of the epiglottis and represents an airway emergency.

Epiglottitis can be confused with croup, a viral infection of gradual onset that affects infants and causes inspiratory and expiratory stridor. Airway management is the primary concern, and an endotracheal tube should be placed or tracheostomy performed as soon as the diagnosis of epiglottitis is made in children. A tracheostomy set should be at the bedside for adults.

Alcaide ML et al. Pharyngitis and epiglottitis. Infect Dis Clin North Am 2007;21:449. Erratum in: Infect Dis Clin North Am 2007;21:847. [PubMed: 17561078]

Al-Qudah M et al. Acute adult supraglottitis: current management and treatment. South Med J 2010;103:800. [PubMed: 20622745]

Community-acquired pneumonia

Neonate: E. coli (GNR), group A or B streptococcus (GPC), S. aureus (GPC), Pseudomonas sp (GNR), C. trachomatis.

Infant/child (<5 years): Virus, S. pneumoniae (GPC), H. influenzae (GNCB), S. aureus.

Age 5–40 years: Virus, M. pneumoniae, C. pneumoniae (formerly known as TWAR strain), C. psittaci, S. pneumoniae, Legionella sp.

Age >40 without other disease: S. pneumoniae (GPDC), H. influenzae (GNCB), S. aureus (GPC), M. catarrhalis (GNDC), C. pneumoniae, Legionella sp. (GNR), S. pyogenes (GPC), K. pneumoniae (GNR), Enterobacteriaceae (GNR), viruses (eg, influenza).

Cystic fibrosis: P. aruginosa (GNR), Burkholderia cepacia.

Elderly: S. pneumoniae (GPDC), H. influenzae (GNCB), S. aureus (GPC), Enterobacteriaceae (GNR), M. catarrhalis (GNDC), group B streptococcus (GPC), legionella (GNR), nocardia (GPR), influenza.

Aspiration: S. pneumoniae (GPDC), K. pneumoniae (GNR), Enterobacteriaceae (GNR), Bacteroides sp. and other oral anaerobes.

Fungal: H. capsulatum, C. immitis, B. dermatitidis

Exposure to birthing animals, sheep: C. burnetii (Q fever), rabbits: F. tularensis (tularemia), deer mice: hantavirus, birds: C. psittaci.

Sputum for Gram stain desirable; culture, if empiric therapy fails or patient is seriously ill. An adequate specimen should have <10 epithelial cells and >25 PMNs per low-power field. Special sputum cultures for legionella are available. Legionella urine antigen test is 70–80% sensitive, but only detects Legionella pneumophila serogroup 1 (90% of cases of Legionaire disease), so test may be falsely negative.

Blood for bacterial cultures (2 sets); obtain before antibiotic treatment, especially in ill patients.

Pleural fluid for bacterial culture if significant effusion is present.

Bronchoalveolar lavage or brushings for bacterial, fungal, and viral antigen tests and AFB culture in immunocompromised patients and atypical cases.

Paired sera for M. pneumoniae EIA testing can diagnose infection retrospectively.

Serologic tests for Q fever and for hantavirus (IgM and IgG) are available. Culture of respiratory specimens for C. pneumoniae, C. psittaci strains.

Other special techniques (bronchoscopy with telescoping plugged catheter and protected brush, transtracheal aspiration, transthoracic fine-needle aspiration, or, rarely, open-lung biopsy) can be used to obtain specimens for culture in severe cases, in immunocompromised patients, or in cases with negative conventional cultures and progression despite empiric antibiotic therapy.

About 60% of cases of community-acquired pneumonia have an identifiable microbial cause. Pneumatoceles suggest S. aureus but are also reported with pneumococcus, group A streptococcus, H influenzae, and Enterobacteriaceae (in neonates).

An “atypical pneumonia” presentation (diffuse pattern on chest x-ray with lack of organisms on Gram stain of sputum) should raise suspicion of mycoplasma, legionella, or chlamydial infection. Consider hantavirus pulmonary syndrome if pulmonary symptoms follow afebrile illness.

Aspiration pneumonias are most commonly associated with stroke, alcoholism, drug abuse, sedation, and periodontal disease.

Brar NK et al. Management of community-acquired pneumonia: a review and update. Ther Adv Respir Dis 2011;5:61. [PubMed: 20935033]

Butt S et al. Treatment of community-acquired pneumonia in an ambulatory setting. Am J Med 2011;124:297. [PubMed: 21435417]

Janssens JP. Pneumonia in the elderly (geriatric) population. Curr Opin Pulm Med 2005;11:226. [PubMed: 15818184]

Anaerobic pneumonia/lung abscess

Usually polymicrobial: Anaerobes: Bacteroides sp. (15% B. fragilis), Peptostreptococcus, Prevotella sp., Porphyromonas sp., Fusobacterium sp., micro-aerophilic streptococcus, veillonella, and facultative anaerobes; S. aureus, P. aeruginosa, S. pneumoniae (rare), Klebsiella (rare), H. influenzae type B, legionella, nocardia, actinomyces, fungi, parasites.

Sputum Gram stain and culture for anaerobes are of little value because of contaminating oral flora.

Bronchoalveolar sampling (brush or aspirate or biopsy) for Gram stain and culture will usually make an accurate diagnosis.

Percutaneous transthoracic needle aspiration may be useful for culture and for cytology to demonstrate coexistence of an underlying carcinoma.

Blood cultures are usually negative (80%).

Aspiration is the most important underlying cause of lung abscess.

Without clear-cut risk factors such as alcoholism, coma, or seizures, bronchoscopy is often performed to rule out neoplasm.

Brook I. Anaerobic pulmonary infections in children. Pediatr Emerg Care 2004;20:636. [PubMed: 15599270]

Hogan MJ et al. Interventional radiology treatment of empyema and lung abscesses. Paediatr Respir Rev 2008;9:77. [PubMed: 18513667]

Patradoon-Ho P et al. Lung abscess in children. Paediatr Respir Rev 2007;8:77. [PubMed: 17419981]

Puligandla PS et al. Respiratory infections: pneumonia, lung abscess, and empyema. Semin Pediatr Surg 2008;17:42. [PubMed: 18158141]

Hospital-acquired pneumonia

P. aeruginosa (GNR), Klebsiella (GNR), S. aureus (GPC), Acinetobacter (GNR), Enterobacteriaceae (GNR), S. pneumoniae (GPDC), H. influenzae (GNCB), influenza virus, RSV, parainfluenza virus, adenovirus, oral anaerobes, S. maltophilia (GNR), B. cepacia (GNR).

Mendelson syndrome (see Comments): No organisms initially, then pseudomonas, Enterobacteriaceae, S. aureus, S. pneumoniae.

Sputum Gram stain and culture for bacteria (aerobic and anaerobic) and fungus (if suspected).

Blood cultures for bacteria are often negative (80%).

Endotracheal aspirate or bronchoalveolar sample for bacterial and fungal culture in selected patients.

Ventilator-associated pneumonia (VAP) is difficult to diagnose. Suspect VAP in patient with fever, leukocytosis, purulent respiratory secretions or a progressive radiographic pulmonary infiltrate.

Most cases are related to aspiration. Hospital-acquired aspiration pneumonia is associated with intubation and the use of broad-spectrum antibiotics.

A strong association between aspiration pneumonia and swallowing dysfunction is demonstrable by videofluoroscopy.

Mendelson syndrome is due to acute aspiration of gastric contents (eg, during anesthesia or drowning).

Hospital-acquired pneumonia is the second most common nosocomial infection, accounting for 25% of all ICU infections. Moreover, there has been a dramatic increase in multidrug-resistant bacteria.

Jones RN. Microbial etiologies of hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia. Clin Infect Dis 2010;51(Suppl 1):S81. [PubMed: 20597676]

Torres A et al. Treatment guidelines and outcomes of hospital-acquired and ventilator-associated pneumonia. Clin Infect Dis 2010;51(Suppl 1):S48. Erratum in: Clin Infect Dis 2010;51(9):1114. [PubMed: 20597672]

Wall RJ et al. Evidence-based algorithms for diagnosing and treating ventilator-associated pneumonia. J Hosp Med 2008;3:409. [PubMed: 18951395]

Pneumonia in the immunocompromised host

Child with HIV infection: Lymphoid interstitial pneumonia (LIP).

AIDS: M. avium (31%), P. jiroveci (13%), CMV (11%), H. capsulatum (7%), S. pneumoniae (GPDC), H. influenzae (GNCB), P. aeruginosa (GNR), Enterobacteriaceae (GNR), C. neoformans, M. tuberculosis (AFB), other mycobacteria, C. immitis, P. marneffei, Rhodococcus equi (GPR).

Neutropenic: S. aureus (GPC), Pseudomonas sp. (GNR), Klebsiella sp., enterobacter (GNR), Bacteroides sp. and other oral anaerobes, legionella, candida, aspergillus, mucor.

Transplant recipients: CMV (60–70%), P. aeruginosa (GNR), S. aureus (GPC), S. pneumoniae (GPDC), legionella (GNR), RSV, influenza virus, P. jiroveci, aspergillus, P. boydii, nocardia, strongyloides.

Expectorated sputum for Gram stain and bacterial culture, if purulent. AFB and fungal cultures of respiratory specimens.

Sputum induction or bronchiolar lavage for Giemsa or methenamine silver staining or DFA for P. jiroveci trophozoites or cysts; for mycobacterial, fungal staining and culture, for legionella culture, and for CMV culture.

Nasal washings or swab for viral respiratory direct fluorescent antibody (DFA) and viral culture.

Urine for legionella and histoplasma antigen test.

Blood for CMV quantitative PCR, or fungal galactomannan antigen test or beta-d-glucan assay for transplant patients.

Blood, respiratory specimen, or bone marrow fungal culture for histoplasmosis (positive in 50%), coccidioidomycosis (positive in 30%).

Blood culture for bacteria. Blood cultures are more frequently positive in HIV-infected patients with bacterial pneumonia and often are the only source where a specific organism is identified; bacteremic patients have higher mortality rates.

Histoplasma urine antigen positive in 90% of AIDS patients with disseminated histoplasmosis.

Immunodiffusion is useful for screening for antibodies, and complement fixation for antibody titers for suspected histoplasmosis or coccidioidomycosis.

Serum cryptococcal antigen or culture of respiratory specimens when pulmonary cryptococcosis is suspected.

Serum lactate dehydrogenase (LDH) levels are elevated in 63% and hypoxemia with exercise (Pao2 <75 mm Hg) occurs in 57% of PCP cases.

In pneumocystis pneumonia (PCP), the sensitivities of the various diagnostic tests are: sputum induction 80% (in experienced labs), bronchoscopy with lavage 90–97%, transbronchial biopsy 94–97%.

In PCP, chest x-ray may show interstitial (36%) or alveolar (25%) infiltrates or may be normal (39%), particularly if leukopenia is present.

Recurrent episodes of bacterial pneumonia are common.

Kaposi sarcoma of the lung is a common neoplastic process that can imitate infection in homosexual and African HIV-infected patients.

Carmona EM et al. Update on the diagnosis and treatment of Pneumocystis pneumonia. Ther Adv Respir Dis 2011;5:41. [PubMed: 20736243]

Catherinot E et al. Pneumocystis jirovecii pneumonia. Infect Dis Clin North Am 2010;24:107. [PubMed: 20171548]

Kasperbauer SH et al. Diagnosis and treatment of infections due to Mycobacterium avium complex. Semin Respir Crit Care Med 2008;29:569. [PubMed: 18810690]

Madeddu G et al. Pneumococcal pneumonia: clinical features, diagnosis and management in HIV-infected and HIV noninfected patients. Curr Opin Pulm Med 2009;15:236. [PubMed: 19399965]

Shirley RM et al. Cryptococcal lung disease. Curr Opin Pulm Med 2009;15:254. [PubMed: 19352182]

Mycobacterial pneumonia

M. tuberculosis (MTb, AFB, acid-fast beaded rods), M. kansasii, M. avium-intracellulare complex (MAC), other mycobacteria. (M. abscessus, M. xenopi, M. fortuitum, M. chelonei).

Sputum for acid-fast bacilli (AFB) stain and culture. First morning samples are best, and at least three samples are required. Culture systems detect mycobacterial growth in as little as several days to 8 weeks.

Bronchoalveolar lavage for AFB stain and culture or gastric washings for AFB culture can be used if sputum tests are negative or unable to obtain sputum (children).

Sputum for amplification assays to detect MTb available for confirmation of smear positive (99%), less sensitive for smear negative (75%).

Once AFB has been detected on solid media or in broth culture, nucleic acid hybridization probes or high-performance liquid chromatography can be used to identify the mycobacterial species.

CT- or ultrasound-guided transthoracic fine-needle aspiration cytology can be used if clinical or radiographic features are nonspecific or if malignancy is suspected.

Blood culture for MTb (15%) or MAC.

Pleural fluid culture for MTb (25%).

AFB found on sputum stain do not necessarily make the diagnosis of tuberculosis, because they could represent nonpathogenic mycobacteria.

Tuberculosis is very common in HIV-infected patients, in whom the chest x-ray appearance may be atypical and occasionally (4%) may mimic PCP (especially in patients with CD4 cell counts <200/mcL).

Consider HIV testing if MTb is diagnosed.

Delayed diagnosis of pulmonary tuberculosis is common (up to 20% of cases), especially among patients who are older or who do not have respiratory symptoms.

In any patient with suspected tuberculosis, respiratory isolation is required.

Araújo-Filho JA et al. Extensively drug-resistant tuberculosis: a case report and literature review. Braz J Infect Dis 2008;12:447. [PubMed: 19219288]

Schlossberg D. Acute tuberculosis. Infect Dis Clin North Am 2010;24:139. [PubMed: 20171549]

Zuckerman JM. Prevention of health care-acquired pneumonia and transmission of Mycobacterium tuberculosis in health care settings. Infect Dis Clin North Am 2011;25:117. [PubMed: 21315997]

Empyema

Neonate: E. coli (GNR), group A or B streptococcus (GPC), S. aureus (GPC), Pseudomonas sp. (GNR).

Infant/child (<5 years): S. aureus (60%) (GPC), S. pneumoniae (27%) (GPC), H. influenzae (GNCB), anaerobes.

Child (>5 years)/adult, acute: S. pneumoniae (GPC), group A streptococcus (GPC), S. aureus (GPC), H. influenzae (GNCB), legionella, coagulase-negative staphylococci, viridans streptococci (GPC in chains).

Child (>5 years)/adult, chronic: Anaerobic streptococci, Bacteroides sp., Prevotella sp., Porphyromonas sp., Fusobacterium sp. (anaerobes 36–76%), Enterobacteriaceae, E. coli, Klebsiella pneumoniae, M. tuberculosis, Actinomyces sp.

Pleural fluid for cell count (WBCs 25,000–100,000/mcL, mostly PMNs), protein >50% of serum), glucose (<SERUM, (="" ldh="" (60% of serum). (See Pleural fluid profiles, Table 8–18.)

Blood cultures for bacteria.

Sputum for Gram stain and bacterial culture. Special culture can also be performed for legionella when suspected.

Pleural fluid for Gram stain and bacterial culture (aerobic and anaerobic).

Chest tube drainage is paramount.

The clinical presentation of empyema is nonspecific.

Chest CT with contrast is helpful in demonstrating pleural fluid accumulations due to mediastinal or subdiaphragmatic processes and can identify loculated effusions, bronchopleural fistulae, and lung abscesses.

40–60% of empyemas develop following pneumonia.

About 25% of cases result from trauma or surgery.

Bronchoscopy is indicated when the infection is unexplained. Occasionally, multiple thoracenteses may be needed to diagnose empyema.

Clark J. Microbiology and management of pleural empyema. Adv Exp Med Biol 2009;634:61. [PubMed: 19280849]

Lee SF et al. Thoracic empyema: current opinions in medical and surgical management. Curr Opin Pulm Med 2010;16:194. [PubMed: 20224409]