Ординатура / Офтальмология / Английские материалы / Basic Sciences in Ophthalmology_Velayutham_2009
.pdf
Microbiology |
363 |
catarrhalis, it was renamed Neisseria catarrhalis in the 1960s because of its morphologic similarity to Neisseria spp. Then, in 1970, it was elevated to the status of a distinct genus, Branhamella, on the basis of DNA homology. In 1979 this organism was placed into the genus Moraxella, of which Branhamella may be a subgenus. A component of the normal bacterial flora of the upper airways, M. catarrhalis has been increasingly recognized as a cause of otitis media, sinusitis, and bronchopulmonary infection.
BACTERIOLOGY
On Gram's staining, M. catarrhalis organisms appear as gram-negative cocci, sometimes occurring in pairs and retaining the side-by-side kidney-bean configuration of Neisseria. These cocci tend to retain crystal violet during the decolorizing step and may be confused with Staphylococcus aureus. Moraxella colonies grow well on blood or chocolate agar but may be overlooked because of their resemblance to Neisseria spp. (a major component of the normal pharyngeal flora). Moraxella is readily distinguishable from Neisseria spp. by biochemical tests.
OTITIS MEDIA AND SINUSITIS
M. catarrhalis has repeatedly been shown to be the third most common bacterial isolate from middle-ear fluid of children who have otitis media, being surpassed only by Streptococcus pneumoniae and nontypable Haemophilus influenzae. Recent studies have shown that this organism is also a prominent isolate from sinus cavities in acute and chronic sinusitis.
PNEUMONIA
M. catarrhalis causes acute exacerbations of chronic bronchitis (increased production and/or purulence of sputum), purulent tracheobronchitis (the latter also involving fever and leukocytosis), and pneumonia. The great majority of infected persons are >50 years old and have a long history of cigarette smoking and underlying chronic obstructive pulmonary disease (COPD).
Symptoms of M. catarrhalis infection have been regarded as modest in severity. Both cough and the amount and purulence of sputum are usually increased above baseline. Chills are reported in one-quarter of patients, pleuritic pain in one-third, and malaise in 40%. Most patients have peak temperatures of <38.3°C (<101°F), and peripheral white blood cell counts are <10,000/uL in nearly one-quarter of cases.
Diagnosis
Microscopic examination of a good sputum specimen following Gram's staining regularly reveals profuse organisms, and culture can be done.
364 |
Basic Sciences in Ophthalmology |
Treatment
Treatment of M. catarrhalis infection with a penicillin/clavulanic acid combination seems highly appropriate. Cephalosporins, especially those of the second and third generations, are effective alternatives.
KLEBSIELLA
K. pneumoniae is the most important Klebsiella species medically, causing community-acquired, long-term-care, and hospital infections. K. oxytoca is primarily a pathogen in long-term-care and hospital settings. K. rhinoscleromatis and K. ozaenae are usually isolated from patients in tropical climates. Klebsiella species are broadly prevalent in the environment and colonize mucosal surfaces of mammals. In healthy humans, nurseries. The most common clinical syndromes are pneumonia, UTI, abdominal infection, surgical site infection, soft tissue infection, and subsequent bacteremia. K. rhinoscleromatis is the causative agent of rhinoscleroma, a slowly progressive (months to years) mucosal upper respiratory infection that causes necrosis and occasional obstruction of the nasal passages. K. ozaenae has been implicated as a cause of chronic atrophic rhinitis.
Diagnosis
Culture on McConkey agar reveals pink Lactose fermenting colonies which can be subjected for biochemical tests.
Treatment
Sensitive to Ampicillins, cephalosporins and quinolones.
PSEUDOMONAS AERUGINOSA
P. aeruginosa is a small, nonsporulating, aerobic gram-negative rod belonging to the family Pseudomonadaceae. It is motile by virtue of its single polar flagellum. More than half of all clinical isolates produce the blue-green pigment pyocyanin; this pigment is helpful in the identification of the organism and accounts for the species name aeruginosa, which refers to the distinctive color of copper oxide.
Most P. aeruginosa infections are acquired in the hospital, where intensive care units account for the highest rates of infection. According to the National Nosocomial Infections, the organism is transmitted to patients via the hands of hospital personnel or via fomites. While some infecting strains of P. aeruginosa appear to be endemic within the hospital, others are traced to a common source associated with a specific outbreak or epidemic. Epidemiologic investigation is facilitated by serotyping (immunotyping) of strains on the basis of differences
Microbiology |
365 |
in lipopolysaccharide (LPS) structure and by the use of molecular techniques such as pulsed-field gel electrophoresis.
Pathogenesis
Infections caused by P. aeruginosa usually begin with bacterial attachment and superficial colonization of cutaneous or mucosal surfaces and progress to localized bacterial invasion and damage to underlying tissues. The infection may remain anatomically localized or may spread by direct extension to contiguous structures. This process may continue with bloodstream invasion, dissemination, the systemic inflammatory-response syndrome (SIRS), multipleorgan dysfunction, and ultimately death. Not only is local infection more likely to occur in immunocompromised hosts, such as those with profound neutropenia, but it is more likely to culminate in bloodstream invasion and dissemination. Endotoxin, which is a structural component of the bacterial outer membrane, is thought to play a pivotal role in the pathogenesis of the sepsis syndrome or SIRS.
P. aeruginosa produces a number of extracellular virulence factors.
Clinical Manifestations and Diagnosis
Respiratory tract infections: Primary pneumonia, or non-bacteremic pneumonia, results from aspiration of upper respiratory tract secretions; often develops in patients with chronic lung disease, congestive heart failure, or AIDS; and is most common in an intensive care setting in association with mechanical ventilator use. Fever, chills, severe dyspnea, cyanosis, productive cough, apprehension, confusion, and other signs of severe systemic toxicity characterize this acute, often life-threatening infection. Chest roentgenograms typically show bilateral bronchopneumonia with nodular infiltrates and small areas of radiolucency; pleural effusions are common; empyema is relatively uncommon; and lobar consolidation is occasionally seen. Cavitary lesions are particularly common in AIDS patients with P. aeruginosa pneumonia. Pathologic lesions include alveolar necrosis, focal hemorrhages, and microabscesses.
The clinical features of P. aeruginosa bacteremia are similar to those of other forms of bacteremia. Common primary sites of infection include the urinary tract, gastrointestinal tract, lungs, skin and soft tissues, and intravascular foci, including indwelling central venous catheters. Fever, tachypnea, tachycardia, and prostration are common. Disorientation, confusion, or obtundation may be evident. Hypotension can progress to refractory shock. Renal failure, adult respiratory distress syndrome, and disseminated intravascular coagulation occur as complications.
366 |
Basic Sciences in Ophthalmology |
Endocarditis: P. aeruginosa infects native heart valves in injection drug users as well as prosthetic heart valves. The source of P. aeruginosa strains infecting drug users appears to be standing water contaminating drug paraphernalia. Foreign materials mixed with heroin may cause injury to valve leaflets or mural endocardium, with resulting fibrosis and an increased risk for valve infection. Exposure of the tricuspid valve to both trauma and bacteria apparently accounts for the high incidence of tricuspid involvement in association with injection drug use.
Ear infections: P. aeruginosa is often found in the external auditory canal, particularly under moist conditions and in the presence of inflammation or maceration (as in “swimmer's ear”). Moreover, this organism is the predominant pathogen associated with external otitis, a usually benign inflammatory process affecting the external auditory canal. The ear is painful or merely itchy, there is a purulent discharge, and pain is elicited by pulling on the pinna. The external canal appears edematous and is filled with detritus that often prevents visualization of the tympanic membrane.
P. aeruginosa occasionally penetrates the epithelium overlying the floor of the external auditory canal at the junction between bone and cartilage and invades underlying soft tissue. The ensuing invasive process, which involves soft tissue, cartilage, and cortical bone, is typically slow but destructive. Termed malignant external otitis, this condition occurs predominantly in elderly diabetic patients but is reported occasionally in infants with other underlying diseases and rarely in elderly nondiabetic patients.
Eye infections P. aeruginosa causes bacterial keratitis or corneal ulcer and endophthalmitis in the human eye. Keratitis due to P. aeruginosa may result from even minor corneal injury, which interrupts the integrity of the superficial epithelial surface and permits bacterial access to the underlying stroma. Corneal ulcer may complicate contact lens use, particularly when extended-wear soft contact lenses are involved. Contact lens solutions or the lenses themselves may be the source of the organism, which is probably inoculated into the eye at sites of minor lens-induced corneal damage. Patients who have sustained serious burns, have undergone ocular irradiation or tracheostomy, have been exposed to the intensive care environment, and/or are in a coma are also susceptible to P. aeruginosa-associated corneal ulcers. P. aeruginosa keratitis usually starts as a small central ulcer; spreads concentrically to involve a large portion of the cornea, sclera, and underlying stroma; and in some cases progresses to posterior corneal perforation.
The clinical manifestations of P. aeruginosa keratitis include a rapidly expanding, necrotic stromal infiltrate in the bed of an epithelial injury; surrounding epithelial edema; an anterior chamber reaction; and mucopurulent discharge adherent to the ulcer's surface. Corneal ulcer due to P. aeruginosa may advance rapidly to involve the entire cornea in < 2 days or may evolve
Microbiology |
367 |
subacutely over several days. Systemic symptoms are uncommon. Complications include corneal perforation, anterior chamber involvement, and endophthalmitis.
P. aeruginosa endophthalmitis is typically a rapidly progressive, sightthreatening condition that demands immediate therapeutic intervention. It may complicate penetrating injuries of the eye, intraocular surgery, hematogenous spread from other sites of Pseudomonas infection, or posterior perforation of corneal ulcers. Clinical manifestations may include eye pain, conjunctival hyperemia, chemosis, lid edema, decreased visual acuity, hypopyon, severe anterior uveitis, and signs of possible vitreous involvement. Panophthalmitis may result from this intraocular infection.
Urinary tract infections: P. aeruginosa is one of the most common causes of complicated and nosocomial infections of the urinary tract. These infections may result from urinary tract catheterization, instrumentation, surgery, or obstruction; they may arise from persistent foci (e.g. the prostate or stones) and may be chronic or recurrent. The urinary tract may be a target for bloodborne infection in patients with P. aeruginosa bacteremia but more often is the source of bacteremia. Chronic P. aeruginosa infections of the urinary tract are relatively common among patients with indwelling urinary catheters, altered urinary tract anatomy secondary to diversionary procedures, and paraplegia.
The clinical features of urinary tract infections due to P. aeruginosa are usually indistinguishable from those of other bacterial infections. However, P. aeruginosa infections exhibit a propensity for persistence, chronicity, resistance to antibiotic therapy, and recurrence. More unusual forms of urinary tract involvement peculiar to P. aeruginosa include (1) ulcerative lesions of the renal pelvis, ureters, and bladder that cause sloughing of vesical membranes in the urine; and (2) ecthyma-like lesions of the renal cortex that are seen in association with Pseudomonas sepsis.
Diagnosis
Culture on nutrient agar, blood agar and MacConkey agar. Pigmented colonies will be seen (Fig. 33.7).
Treatment
Aminoglycosides, Quinolones and Imepenem are effective. Usually 2 drug combination is effective.
BRUCELLA
Brucellosis is a zoonosis transmitted to humans from infected animals. Its clinical features are not disease specific. Brucellosis has many synonyms derived from the geographical regions in which the disease occurs
368 |
Basic Sciences in Ophthalmology |
Fig. 33.7: Slimy pigmented colonies on nutrient agar which is oxidase positive
(e.g. Mediterranean fever, Malta fever, Gibraltar fever, Cyprus fever); from the remittent character of its fever (e.g. undulant fever); or from its resemblance to malaria and typhoid (e.g. typhomalarial fever, intermittent typhoid).
Etiology
Human brucellosis can be caused by any of four species: Brucella melitensis (the most common and most virulent cause of brucellosis worldwide) is acquired primarily from goats, sheep, and camels; B. abortus from cattle; B. suis from hogs; and B. canis from dogs. These small aerobic gram-negative bacilli are unencapsulated, nonmotile, non-spore-forming, facultative intracellular parasites that cause lifelong infection in animals. Brucellae are killed by boiling or pasteurization of milk and milk products. They survive for upto 8 weeks in unpasteurized, white, soft cheese made from goat's milk and are not killed by freezing. The organisms remain viable for upto 40 days in dried soil contaminated with infected-animal urine, stool, vaginal discharge, and products of conception and for longer periods in damp soil.
Pathogenesis
Serum opsonizes Brucella organisms for ingestion by polymorphonuclear leukocytes and activated macrophages. Brucellae resist intracellular phagocytic killing by mechanisms such as the suppression of the myeloperoxide-hydrogen peroxide-halide system and the production of superoxide dismutase. The pathogen-phagocyte interaction plays a key role in determining the severity and outcome of brucellosis. The organisms surviving within and escaping from the phagocytes multiply and reach the bloodstream via the lymphatics,
Microbiology |
369 |
subsequently localizing in the liver, spleen, bones, kidneys, lymph nodes, heart valves, nervous system, and testes. In these organs, the bacteria are ingested by macrophages and survive by inhibition of phagosome-lysosome fusion. In infected tissues, inflammatory responses or noncaseating granulomas typically develop, and caseating granulomas and abscesses have been described.
Classification
Brucellosis is classified according to whether or not the disease is active (i.e. symptoms or progressive tissue damage and significantly raised Brucella agglutinin levels with or without positive cultures) and whether or not there is localized infection. The state of activity and the site of localization have a significant impact on recommended treatment. Classification of brucellosis as acute, subacute, serologic, bacteremic, or of mixed types serves no purpose in diagnosis and management.
Clinical Manifestations and Complications
Brucellosis is a systemic disease with protean manifestations. Its features may mimic those of other febrile illnesses. The incubation period lasts for about 1 to 3 weeks but may be as long as several months, depending on the virulence of the organisms, their route of entry, the infecting dose, and the host's preexisting health status. The onset of symptoms may be either abrupt (over 1 to 2 days) or gradual (> 1 week). The most common symptoms are fever, chills, diaphoresis, headaches, myalgia, fatigue, anorexia, joint and low-back pain, weight loss, constipation, sore throat, and dry cough. Physical examination often reveals no abnormalities, and patients can look deceptively well. Some patients, in contrast, are acutely ill, with pallor, lymphadenopathy, hepatosplenomegaly, arthritis, spinal tenderness, epididymoorchitis, rash, meningitis, cardiac murmurs, or pneumonia. The fever of brucellosis has no distinctive pattern but may exhibit diurnal variation, with normal temperatures in the morning and high temperatures in the afternoon and evening.
Bones and joints: Although monoarticular septic arthritis occurs, 30 to 40% of patients have reactive asymmetric polyarthritis involving the knees, hips, shoulders, and sacroiliac and sternoclavicular joints. The total white cell count in synovial fluid ranges from 4000 to 40,000/mL, typically with about 60% polymorphonuclear leukocytes. The synovial fluid glucose concentration may be reduced and the protein concentration elevated; cultures of synovial fluid are positive in about 50% of cases.
Infection with Brucella organisms commonly causes osteomyelitis of the lumbar vertebrae, starting at the superior end plate (an area with a rich blood supply) and occasionally progressing to involve the entire vertebra, disk space, and adjacent vertebrae. Extraspinal Brucella osteomyelitis is rare. In Brucella
370 |
Basic Sciences in Ophthalmology |
septic arthritis and osteomyelitis, the peripheral white cell count is typically normal, while the erythrocyte sedimentation rate may be either normal or elevated.
Heart: Cardiovascular complications of brucellosis include endocarditis, myocarditis, pericarditis, aortic root abscess, mycotic aneurysms, thrombophlebitis with pulmonary aneurysm, and pulmonary embolism. Brucella endocarditis may develop on valves previously damaged by rheumatic fever or congenital malformation but also occurs on previously normal valves.
Respiratory tract: Brucellae can produce respiratory symptoms. A flulike illness with sore throat, tonsillitis, and dry cough is common and usually mild. Hilar and paratracheal lymphadenopathy, pneumonia, solitary or multiple pulmonary nodules, lung abscess, and empyema have been reported.
Gastrointestinal tract and hepatobiliary system: Gastrointestinal manifestations of Brucella infection are generally mild and may include nausea, vomiting, constipation, acute abdominal pain, and/or diarrhea.
Genitourinary tract: The various genitourinary infections attributed to brucellae include unilateral or bilateral epididymoorchitis, which is rarely associated with testicular abscess. Prostatitis, seminal vesiculitis, dysmenorrhea, amenorrhea, tuboovarian abscess, salpingitis, cervicitis, acute pyelonephritis, glomerulonephritis, and massive proteinuria have also been documented. Brucella organisms have been cultured from the urine in upto 50% of cases of genitourinary tract infection.
Central nervous system: Neurobrucellosis is uncommon but serious and includes meningitis, meningoencephalitis, multiple cerebral or cerebellar abscesses, ruptured mycotic aneurysms, myelitis, Guillain-Barre syndrome, cranial nerve lesions, hemiplegia, sciatica, myositis, and rhabdomyolysis. Papillitis, papilledema, retrobulbar neuritis, optic atrophy, and ophthalmoplegia due to lesions in cranial nerves III, IV and VI may occur in Brucella meningoencephalitis.
Other manifestations: Conjunctival splashing with live attenuated B. abortus vaccine (S19) during animal vaccination may cause conjunctivitis, keratitis, and corneal ulcers, with progression to systemic disease in some cases. Uveitis, optic neuritis, retinopathy, retinal detachment, and endophthalmitis may result from hematogenous spread.
The bone marrow of Brucella-infected patients frequently contains noncaseating granulomas. Among the hematologic complications of brucellosis are anemia, leukopenia, and thrombocytopenia.
Endocrinologic findings reported in brucellosis include thyroiditis with abscess formation, adrenal insufficiency, and the syndrome of inappropriate secretion of antidiuretic hormone.
Microbiology |
371 |
Diagnosis
The combination of potential exposure, consistent clinical features, and significantly raised levels of Brucella agglutinin (with or without positive cultures of blood, body fluid, or tissues) confirms the diagnosis of active brucellosis. The organism's identity is confirmed by phage typing, DNA characterization, or metabolic profiling. Use of a CO2 detection system (such as BACTEC; Becton Dickinson, Sparks, MD) for blood culture provides a more sensitive and rapid culture result than standard methods, with positivity usually apparent after only 2 to 5 days of incubation. Serum antibodies to Brucella can be detected by several methods, including standard tube agglutinins (STA), the 2-mercaptoethanol agglutination test, Coomb’ test, enzyme-linked immunosorbent assay, and polymerase chain reaction (PCR). B. abortus antigens, which are commonly used for serologic tests, cross-react with B. melitensis and B. suis but not with B. canis. The specific antigen required for assay of antibodies to B. canis is not commercially available.
A high titer of specific IgM suggests recent exposure, while a high titer of specific IgG suggests active disease. Lower titers of IgG may indicate past exposure or treated infection.
Cooperation and consultation with a clinical microbiology laboratory are important when brucellosis is suspected. It may be necessary to observe culture bottles for upto 6 weeks before organisms become detectable. Subcultures should be prepared on duplicate blood agar plates (with and without an atmosphere of 10% CO2) and special media (such as a bloodor serum-enriched peptone-based medium) or with a rapid CO2 detection system.
Treatment
Gentamicin, Netilmycin, Streptomycin are effective as well as Doxycycline.
MYCOBACTERIUM TUBERCULOSIS
Definition
Tuberculosis, one of the oldest diseases known to affect humans, is caused by bacteria belonging to the Mycobacterium tuberculosis complex (Fig. 33.8). The disease usually affects the lungs, although in upto one-third of cases other organs are involved. If properly treated, tuberculosis caused by drug-susceptible strains is curable in virtually all cases. If untreated, the disease may be fatal within 5 years in more than half of cases. Transmission usually takes place through the airborne spread of droplet nuclei produced by patients with infectious pulmonary tuberculosis.
372 |
Basic Sciences in Ophthalmology |
Fig. 33.8: M. tuberculosis seen under fluorescent microscope
Etiologic Agent
Mycobacteria belong to the family Mycobacteriaceae and the order Actinomycetales. Of the pathogenic species belonging to the M. tuberculosis complex, the most frequent and important agent of human disease is M. tuberculosis itself. The complex includes M. bovis (the bovine tubercle bacillus, once an important cause of tuberculosis transmitted by unpasteurized milk and currently the cause of a small percentage of cases in developing countries), M. africanum (isolated in a small proportion of cases in West and Central Africa), and M. microti (the "vole" bacillus, a closely related but rarely encountered organism).
M. tuberculosis is a rod-shaped, non-spore forming, thin aerobic bacterium measuring about 0.5 μm by 3 μm. Mycobacteria, including M. tuberculosis, do not stain readily and are often neutral on Gram's staining. However, once stained, the bacilli cannot be decolorized by acid alcohol, a characteristic justifying their classification as acid-fast bacilli (AFB). Acid fastness is due mainly to the organisms' high content of mycolic acids, long-chain cross-linked fatty acids, and other cell wall lipids.
Infection: M. tuberculosis is most commonly transmitted from a patient with infectious pulmonary tuberculosis to other persons by droplet nuclei, which are aerosolized by coughing, sneezing, or speaking. The tiny droplets dry rapidly; the smallest (<5 to 10 μm in diameter) may remain suspended in the air for several hours and may gain direct access to the terminal air passages when inhaled. There may be as many as 3000 infectious nuclei per cough. In the past, a frequent source of infection was raw milk containing M. bovis from tuberculous cows. Other routes of transmission of tubercle bacilli, such as through the skin or the placenta, are uncommon and of no epidemiologic significance.