Papel dos Anaeróbios

Carlos M. Luna MD

Profesor de Medicina, Hospital de Clinicas, Universidad de Buenos Aires, Argentina

Papel dos Anaeróbios nas Infecções Supurativas

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Most common Etiology of CAP

Streptococcus pneumoniaeHaemophilus influenzaeAerobic gram-negative bacilliPseudomonas aeruginosaStaphylococcus aureus

Mycoplasma pneumoniaeChlamydia pneumoniaeChlamydia psitacciCoxiella burnettiLegionella species

Mycobacterium tuberculosis

Influenza A and B, adenovirusparainfluenza 1,2 y 3

Pathogenic fungi

Pneumocystis carinii

Aspirative

Postobstructive

Unknown

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Pneumonia

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Absceded Pneumonia

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Peptostreptococcus Bacteroides Fusobacterium

Role of Anaerobes in Lung Infections

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Role of Anaerobes in Lung Infections

1: Obligate aerobic; 2: Obligate anaerobic (avoid oxygen); 3: Facultative bacteria (mostly at the top, but can be found all along the test tube), 4: Microaerophiles (upper part of the test tube but not at the top); 5: Aerotolerant bacteria (not affected by oxygen, and they are evenly spread)

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Role of Anaerobes in Lung Infections

Anaerobes are the predominant constituents of the normal flora that inhabits the mucosal surfaces of the gingival crevice.

The crevicular fluid flora normally is predominantly gram-positive and the predominant anaerobic is Actinomyces.

If periodontitis is present, the flora becomes predominantly gram-negative (Porphyromonas, Prevotella, Bacteroides, and Fusobacterium).

Over 200 microbial species are found in the crevicular fluid in numbers of 1012 CFU/g.

Levison ME. Curr Opin Infect Dis. 2001; 14:187.

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Anaerobic Bacteria

Anaerobic bacteria are the most overlooked bacterial pathogens of the lower respiratory tract.

They are often infrequently recovered from this site because of improper specimen collection and lack of appropriate anaerobic identification techniques.

Isolation of anaerobics in two studies was around 65% of cases of empyema .

However, in various other studies, incidence of anaerobes in empyema is as high as 76-100 %to as low as 31-39%.

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When to think in Anaerobes?

Alcoholism: S. pneumoniae, oral anaerobes, K. pneumoniae, Acinetobacter sp, M. tuberculosis.

Aspiration pneumonia: Gram – negative enteric bacilli, oral anaerobes.

Lung abscess: CA – MRSA, oral anaerobes, endemic fungal pneumonia, M. tuberculosis, atypical mycobacteia

Injection drug use: S. aureus, anaerobes, M. tuberculosis, S. Pneumoniae.

Mandell L, et al. IDSA/ATS CAP guidelines. CID 2007;44:S27

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Role of Anaerobes in Lung Infections

Anaerobic bacteria are the causative agent of aspiration pneumonia, lung abscess and empyema.

These agents are especially abundant in the upper and lower respiratory tracts.

Anaerobic agents should be taken into account also in alcoholic patients, in those presenting non-resolving pneumonia, in pulmonary infections in lung cancer patients.

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Risk Factors for Specific Pathogens in CAP (n:346)

Condition Associated Pathogens

Respiratory P. aeruginosa, EGNB, M. catarrhalisDiabetes M. tuberculosisAlcohol abuse M. tuberculosisHepatic S. pneumoniaeNeurological Aspiration PneumoniaAge 65 Aspiration PneumoniaAge < 65 M. pneumoniae, H. influenzae, C. pneumoniaeCurrent smoker M. tuberculosis

Luna CM, et al. Chest 2000;118: 1434

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Role of Anaerobes in Lung Infections

Anaerobes are the causative bugs of various infectious diseases. The need of special techniques and equipment for culture hampers the detection from clinical specimens.

Transtracheal and percutaneous lung aspiration and protected brush are used to obtain specimens for culture to avoid oropharyngeal contamination. Culture is difficult, biochemical tests or gas-liquid chromatography used for identification are troublesome and time-consuming.

Finegold SM. 1989; Anaerobic infections in humans.Hill RT, et al. J Gen Microbiol 1989; 135:3271.

Holland JW, et al. J Clin Microbiol 1979; 10:121.

Bartlett JG, et al. Chest 1987;91:901.

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Anaerobes in Pleuropulmonary Infections

76 anaerobes and 122 aerobes were isolated in 100 patients with pleuropulmonary infections: empyema (64), pleural effusion (19) and lung abscess (17).

In 14% only anaerobes and in 58% mixed, aerobes + anaerobes were encountered.

Amongst anaerobes gram-negative bacilli included Prevotella melaninogenicus, Fusbocterium spp and Bacteroides spp predominate. Amongst the gram-positive Peptostreptococcus spp. Coliform bacteria and Pseudomonas aeruginosa were the predominant aerobes.

De A, et al. Indian J Med Microbiol 2002: 20: 150

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Necrotizing Pneumonia and Pulmonary Gangrene

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Necrotizing Pneumonia and Pulmonary Gangrene

Necrotizing pneumonia and pulmonary gangrene are complications of severe CAP and represent distinct entities along the spectrum of pulmonary infections.

Early recognition and treatment of these complications are critical because patients often require intensive care unit monitoring, mechanical ventilation, aggressive drainage of infected fluid, and possible surgical intervention.

Delay in treatment may result in overwhelming sepsis, multiorgan system failure, and even death.

Tzeng DZ, et al. Clin Pulm Med 2007; 14: 166

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Necrotizing Pneumonia and Pulmonary Gangrene

Bacteroides fragilis, and other gram-negative anaerobes are known to have procoagulant activity.

Aerobics causing necrotizing pneumonia include K. pneumoniae, P. aeruginosa, other gram-negatives, S. aureus, and S. pneumoniae.

S. aureus and some gram-negatives produce enzymes that digest tissue; S. pneumoniae and most gram-negative aerobes have procoagulant properties like anaerobics.

As anaerobes are difficult to culture, it is reasonable to treat, even if cultures are negative, in severely ill patients.

Karmy-Jones R, et al. Clin Pulm Med 2003; 10: 17

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Anaerobic Necrotizing Lung Infection

The necrotizing infection is referred to as a lung abscess if each cavity is 2 cm or more in diameter.

If there are multiple, small cavities, each less than 2 cm in diameter, the process is usually referred to as necrotizing pneumonia.

Both lung abscess and necrotizing pneumonia are thought to be different manifestations of the same pathogenetic processes.

Extension of the anaerobic pulmonary infection to the pleural space may result in anaerobic empyema.

Levison ME. Curr Opin Infect Dis. 2001; 14:187.

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Etiology of Microorganisms in AcuteLung Abscess.

In a third-world setting, acute community-acquired lung abscess is associated with dental caries, poorly controlled epilepsy, previously damaged lungs, and alcohol abuse.

In more developed populations, however, this disease is now uncommon except in patients immunocompromised by drugs or disease or as a postobstructive complication.

Anaerobic organisms have been identified as the most common pathogens in studies in which percutaneous lung or transtracheal aspiration techniques have been used.

Pohlson EC, et al. Am J Surg 1985; 150:97Pena Grinan N, et al. Chest 1990; 97:69

Bartlett JG, et al. Am J Med 1974; 56:202

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Lung Abscess, Analysis of 66 cases.

Sixty six patients treated between 1979 and 1991 in the Juntendo University Hospital, Tokyo.

The most commonest anaerobes were Bacteroides spp, Peptostreptococcus, Fusobacterium spp., micro-aerophilic Streptococcus and Veillonella.

The mortality was higher in P. aeruginosa, Klebsiella spp. and Candida spp. cases.

The prognosis of lung abscess patients depend on the presence of underlying diseases and on superinfection with aerobes.

Mori T, et al. Intern Med 1993;32:278

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Aspiration Pneumonia and Dysphagia in the Elderly

CAP is a major cause of death in nursing homes.

Oropharyngeal aspiration is an important etiologic factor leading to pneumonia in the elderly.

The incidence of neurologic diseases increase with aging and are associated with dysphagia, impaired cough reflex and increased risk of oropharyngeal aspiration.

Elderly with clinical signs of dysphagia or with CAP should perform swallow evaluation. A multidisciplinary approach to swallowing management include diet, oral care, and consideration for using ACE inhibitor.

Marik PE, et al. Chest 2003; 124: 801.

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Diagnosis and Therapy of Anaerobe’s Pleuropulmonary Infections

Because of the difficulties the recovery of obligate anaerobes from clinical specimens and their in-vitro antimicrobial susceptibility testing, the microbial diagnosis frequently remains based on the clinical presentation, especially predisposition to aspiration or the putrid odor of the breath or infected material (sputum or pleural fluid).

Antimicrobial therapy consequently often remains empirical and based on published studies of in-vitro activity against the presumed anaerobic pathogens.

Karmy-Jones R, et al. Clin Pulm Med 2003; 10: 17

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Role of Anaerobes in Lung Infections

Amoxicillin/clavulanic, metronidazole, chloramphenicol, piperacillin/tazobactam and meropenem remain very useful antimicrobials for treating anaerobic infections.

Cefoxitin, cefotetan and clindamycin were less active. In particular, only 62%, 52% and 48% of B. fragilis group strains were susceptible, respectively

Anti-anaerobic activity of the new antibiotics is interesting, with MIC50 and MIC90 of 1 and >32 mg/L for moxifloxacin, 2 and 4 mg/L for linezolid and 0.5 and 8 mg/L for tigecycline.

Wybo I, et al. J Antimicrob Chemother. 2007;59:132.

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Treatment of Anaerobic Infections

Since anaerobic infections are generally polymicrobial, (anaerobes mixed with aerobic organisms), therapy should provide coverage of both types of pathogens.

Antimicrobials is to limit the local and systemic spread of infection. Surgical drainage, debriding and increasing tissue oxygenation is essential.

The most effective antimicrobials are metronidazole, carbapenems, chloramphenicol, combinations of β-lactam + a β-lactamase inhibitor, tigecycline and clindamycin.

Brook I. Expert Rev Anti Infect Ther 2007;5:991.

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Summary

Anaerobic bacteria are the most overlooked bacterial pathogens of the lower respiratory tract.

They are infrequently recovered because of improper specimen collection and lack of appropriate techniques.

Anaerobic bacteria are the causative agent of aspiration pneumonia, lung abscess and empyema.

Therapy includes antimicrobial coverage for aerobes and anaerobes to limit the local and systemic spread and surgical drainage and debriding.

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Thanks for your atention!!

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