Anaerobic Pulmonary Infections Research Articles

Anaerobic Pulmonary Infections in Children

Pulmonary infections due to anaerobic bacteria usually occur in children prone to aspiration. The source of the anaerobic bacteria is the oropharyngeal bacterial flora, where these organisms outnumber aerobic and facultative organisms in a 10:1 ratio. The most common lower respiratory tract infections where anaerobic bacteria are recovered mixed with aerobic organisms are aspiration pneumonia, lung abscess, and empyema. The predominant isolated anaerobic bacteria are Peptostreptococcus, Fusobacterium, pigmented Prevotella, and Porphyromonas spp. and Bacteroides fragilis group. Management of these infections includes the administration of antimicrobials effective against the anaerobic as well as the aerobic pathogens.

Pleural Effusions in the Pediatric Population

1. Ori Efrati, MD* 2. Asher Barak, MD* 1. *The Pediatrics Pulmonary Unit, Sheba Medical Center, Tel HaShomer Hospital, Ramat Gan, Israel After completing this article, readers should be able to: 1. Describe the anatomic pleural cavity. 2. Delineate the most likely causes for pediatric pleural effusions. 3. Distinguish between exudate and transudate. 4. Describe the diagnostic radiographic and laboratory examinations for pleural effusions. 5. Describe the management of parapneumonic effusion. 6. Describe other types of pleural effusions. Pleural effusions (liquid in the pleural space), which occur less frequently in children than in adults, can be caused by a variety of infectious and noninfectious diseases. Most of the information about pleural effusions is derived from adult studies. Causes of pleural effusions in children differ significantly from those in adults. Among adults, the most frequent cause is congestive heart failure (transudate), and bacterial pneumonia and malignancy are the most frequent causes of exudate. Pleural effusions in children most commonly are infectious (50% to 70% parapneumonic effusion); congestive heart failure is a less frequent cause (5% to 15%), and malignancy is a rare cause. Parapneumonic effusion is defined as fluid in the pleural space in the presence of pneumonia, lung abscess, or bronchiectasis. Nontuberculous bacterial pneumonia constitutes the most frequent origin of pleural effusion in children. Establishing a specific causative agent depends on the patient’s age, underlying disease, standard of laboratory culture method, and initiation of antibiotic therapy. Staphylococcus aureus is the single most common pathogen causing empyema (29% to 35% of cases), especially among infants younger than 2 years of age. Streptococcus pneumoniae is the cause in up to 25% of cases of empyema. Haemophilus influenzae is a less frequent pathogen but still is significant in the development of parapneumonic effusion in children up to 5 years of age. Group A streptococci have re-emerged as significant agents causing empyema in later childhood. Anaerobic pulmonary infection is uncommon, and more than 90% of affected patients manifest periodontal infections, altered consciousness, …

Anaerobic Pleuropulmonary Infection*

Obligate anaerobes are the predominant constituents of normal oropharyngeal flora and produce pleuropulmonary infection in patients who are prone to aspirate. Obtaining material from these patients for culture from the site of infection that is uncontaminated by normal flora is problematic. In-vitro cultivation of obligate anaerobes requires rigorous anaerobic techniques and susceptibility testing of obligate anaerobes is not standardized in many clinical microbiology laboratories. Few clinical trials of drugs have been done in patients with laboratory documented or putative anaerobic pulmonary infection. For these reasons the diagnosis and therapy of anaerobic pulmonary infection are frequently empirical and guided by published studies of in-vitro activity against collected clinical isolates. Several new drugs that have in-vitro activity against obligate anaerobes have recently become available for empirical treatment of pneumonia.

Anaerobic pleuropulmonary infection.

Obligate anaerobes are the predominant constituents of normal oropharyngeal flora and produce pleuropulmonary infection in patients who are prone to aspirate. Obtaining material from these patients for culture from the site of infection that is uncontaminated by normal flora is problematic. In-vitro cultivation of obligate anaerobes requires rigorous anaerobic techniques and susceptibility testing of obligate anaerobes is not standardized in many clinical microbiology laboratories. Few clinical trials of drugs have been done in patients with laboratory documented or putative anaerobic pulmonary infection. For these reasons the diagnosis and therapy of anaerobic pulmonary infection are frequently empirical and guided by published studies of in-vitro activity against collected clinical isolates. Several new drugs that have in-vitro activity against obligate anaerobes have recently become available for empirical treatment of pneumonia.

Anaerobic Infections of the Lung.

Although the landmark investigational period for anaerobic pathogens occurred more than 20 years ago, pleuropulmonary infections caused by these pathogens remain an important cause of morbidity and mortality. Despite heightened awareness of pathogenicity and new diagnostic methods, the actual incidence of anaerobes in pulmonary infections--especially those occurring in hospitalized patients--remains controversial. Further complicating the management of these infections is the changing antimicrobial susceptibility of oral anaerobes, which has mandated the abandonment of penicillin monotherapy in seriously ill patients. This article reviews the pathogenesis of anaerobic pulmonary infections, their clinical presentations, and current management issues.

Lung abscess and other anaerobic pulmonary infections

Anaerobes are ubiquitous members of the normal flora of the body. Anaerobic lung infections are relatively uncommon in children. Most of these infections are the result of aspiration of oral flora. Predisposing factors include underlying illness, impaired consciousness, seizures, swallowing dysfunction, intubation, foreign body aspiration, and periodontal disease. Types of lung infection include aspiration pneumonitis, necrotizing pneumonia, lung abscess, and empyema. Most anaerobic infections are polymicrobial. Definitive diagnosis is difficult because of the fastidiousness of the agents and the frequent failure to obtain appropriate specimens. Therapy often requires drainage, as well as antibiotics. Resistance to penicillin among the oral anaerobes has increased over the last 20 years. Current antibiotics of choice include clindamycin, cefoxitin, penicillin with metronidazole, or combinations of a penicillin and a β-lactamase inhibitor.

Bacteriologic Diagnosis in Anaerobic Pleuropulmonary Infections

Four types of specimens are viewed as having established reliability for the detection of anaerobic bacteria that cause pulmonary infections: blood, pleural fluid, transtracheal aspirates, and transthoracic aspirates. Blood cultures are obviously appropriate diagnostic methods but are positive in <2% of cases [ 1 ] in which the diagnosis is established by alternative methods. Pleural fluid also has unchallenged merit as a specimen but only for the minority of patients with empyema. For most patients with infections restricted to the pulmonary parenchyma, the only diagnostic methods with clearly established merit involve transtracheal aspiration and transthoracic needle aspiration. Transthoracic needle aspiration was done extensively in the preantibiotic era, but more recently its use has been largely restricted to a relatively few practitioners and a highly selective patient population. We are not aware of any practitioner who is doing transthoracic needle aspirations with any frequency for patients with anaerobic pulmonary infections, although the merit of this technique has been established in at least two studies of lung abscess by investigators in France [2] and Spain [3]. There has been extensive experience with transtracheal aspiration that verifies the utility of this technique in obtaining uncontaminated specimens from the lower airways of patients with anaerobic pulmonary infections [4-7] and also establishes the role of anaerobes in lung abscess and aspiration pneumonia [1, 5-7]. Transtracheal aspiration became popular in the late 1960s but almost disappeared from clinical practice after ~ 10 years of extensive use. Several factors contributed to this decline in its use: reports of severe complications, escalating interest in alternative techniques such as fiberoptic bronchoscopy, failure of hospitals to credential qualified physicians for performing this technique (as they do for bronchoscopy), and a common perception that empirical use of antibiotics has largely supplanted any need to es-

Treatment of anaerobic pulmonary infections.

Treatment of anaerobic pulmonary infections.

Characterization of the pulmonary inflammatory response to an anaerobic bacterial challenge.

Anaerobic bacteria from the oral flora are important causes of aspiration pneumonia and lung abscess. However, the pulmonary antibacterial response to these organisms has not been well described. To define this, mice were intratracheally inoculated with 10(9) Bacteroides gingivalis, a member of the B. melaninogenicus group, and a common clinical isolate from periodontal disease and anaerobic pulmonary infections. Studies after intratracheal challenge included bacteriologic and histopathologic examination, pulmonary cellular response, lactic dehydrogenase (LDH) and albumin levels in lung lavage fluid, and wet lung weight. Overall mortality was 25%. In the surviving animals, pulmonary lavage showed a marked recruitment of polymorphonuclear leukocytes that was associated with significant bacterial killing by 48 h. Histopathologic examination showed an acute, severe necrotizing bronchopneumonia. Pulmonary abscess formation occurred in 37% of animals. Severe parenchymal damage was further documented by a marked increase in LDH levels in lavage fluids. Mean LDH levels in lavage fluid increased to 850 +/- 25 units/first lavage at 24 h postchallenge compared with control values of 65 +/- 10 units/first lavage. Lung lavage also demonstrated an extensive influx of serum albumin consistent with injury to the alveolar capillary membrane. Albumin levels in lung lavage were highest at 24 h after intratracheal challenge (3.25 +/- 0.3 mg/first lavage), whereas lavage fluid from control mice had nondetectable albumin levels. Wet lung weights maximally increased from 0.12 +/- 0.01 g in control mice to 0.28 +/- 0.03 g 24 h after bacterial-challenge. These data demonstrate tht B. gingivalis causes marked inflammation in the lung that progresses to severe bronchopneumonia and lung abscess.(ABSTRACT TRUNCATED AT 250 WORDS)

Pulmonary Disease: An Annotated Bibliography of Recent Literature

Pulmonary Disease: An Annotated Bibliography of Recent Literature

Recent developments in the management of anaerobic infections.

Anaerobic bacteria are recognized with increasing frequency as etiologic agents in a variety of infectious diseases. The pathogenic significance of these microbes is supported by experimental studies with animals, chemotherapeutic trials, and definition of specific virulence factors by microbial analysis. In vitro sensitivity tests show that many clinically significant anaerobic species are resistant to penicillin; susceptibility to an expanding array of alternative antimicrobial agents is quite variable. Nevertheless, clinical trials suggest that several antibiotic regimens are equally effective. These studies provide guidelines for empiric selection of agents, although in vitro studies or the unique properties of some drugs must be considered in occasional cases. Several commonly accepted tenets held in the past may now be challenged: some abscesses do not require surgical drainage; plasmids conferring resistance to clindamycin in Bacteroides fragilis appear prevalent in some institutions; clindamycin may be the preferred agent for treatment of serious anaerobic pulmonary infections; and metronidazole is the only new agent advocated for anaerobic infections that offers potential advantages over prior agents.

Failure of Penicillin in Anaerobic Necrotizing Pneumonia

Penicillin is considered to be the drug of choice in anaerobic pulmonary infections. The patient presented here illustrates some of the reasons for the failure of penicillin therapy in an anaerobic necrotizing pneumonia. Experimental and clinical evidence to date suggests a need for reappraisal of penicillin therapy in such infections.

Chemoprophylaxis of anaerobic pulmonary infections. An experimental study in rabbits.

Chemoprophylaxis of anaerobic pulmonary infection due to aspiration was studied in a rabbit model with the view of comparing the efficacy of procaine penicillin, clindamycin, chloramphenicol, doxycycline and cefoxitin. The antibiotic treatment was commenced immediately following transtracheal inoculation of a mixture of Bacteroides fragilis, Streptococcus morbillorum, Fusobacterium nucleatum and Eubacterium lentum. Treatment was stopped after 48 h and lungs were examined for evidence of infection on the 10th day. Only clindamycin and carbencillin were highly efficacious in chemoprophylaxis and both drugs prevented pulmonary infection in 7 of 8 (87%) of the animals tested.

Metronidazole vs Clindamycin Treatment of Anaerobic Pulmonary Infection

Metronidazole has important in vitro bactericidal activity against strict anaerobic bacteria and has been used successfully in the treatment of infection due to these organisms. In this randomized study, the efficacy of metronidazole was compared with clindamycin in the treatment of patients with anaerobic lung abscess or necrotizing pneumonia. Six patients with lung abscesses and one with necrotizing pneumonia received metronidazole; six patients with lung abscesses, three with necrotizing pneumonia, and one with pneumonia and empyema received clindamycin. Three patients with lung abscesses and one with necrotizing pneumonia failed to respond to metronidazole treatment. One clindamycin-treated patient died of causes unrelated to antibiotic therapy. The results of this study suggest that metronidazole treatment of anaerobic pulmonary infections is less effective than currently available therapy.

Metronidazole vs clindamycin treatment of anerobic pulmonary infection. Failure of metronidazole therapy

Metronidazole has important in vitro bactericidal activity against strict anaerobic bacteria and has been used successfully in the treatment of infection due to these organisms. In this randomized study, the efficacy of metronidazole was compared with clindamycin in the treatment of patients with anaerobic lung abscess or necrotizing pneumonia. Six patients with lung abscesses and one with necrotizing pneumonia received metronidazole; six patients with lung abscesses, three with necrotizing pneumonia, and one with pneumonia and empyema received clindamycin. Three patients with lung abscesses and one with necrotizing pneumonia failed to respond to metronidazole treatment. One clindamycin-treated patient died of causes unrelated to antibiotic therapy. The results of this study suggest that metronidazole treatment of anaerobic pulmonary infections is less effective than currently available therapy.

The Gram-negative bacillary pneumonias

With increasing age, chronic underlying disease, and debility, the oropharyngeal flora are colonized with aerobic gram-negative bacilli. In this debilitated population, gram-negative bacillary pneumonias (GNBP) are increasingly common. GNBP account for two of every three pneumonia deaths today. As a group, the mortality of GNBP is about 50%. Although the original epidemiologic surveys were done 15 years ago, there is little evidence for an improving case fatality rate despite the appearance of aminoglycoside antibiotics, carbenicillin, and cephalosporins. In susceptible patients, GNBP pneumonias occur both in the community and as nosocomial infections. Recognition of the dangers of contaminated reservoir nebulizers or other similar devices used in inhalation therapy has led to epidemiologic measures within hospitals that have markedly decreased the incidence of this nosocomial GNBP. The role of Gram stain and culture of expectorated sputum and similar examinations of specimens obtained by transtracheal aspiration, fiberoptic bronchoscopy, and lung biopsy in the diagnosis of GNBP are discussed in this review (see Criteria for Diagnosis). In the presence of pulmonary emphysema, congestive heart failure, mixed gram-negative bacillary infections, or the use of immunosuppressive drugs, typical characteristics of individual GNBP may not be apparent. Typical features of Pseudomonas aeruginosa, Escherichia coli, Enterobacter, Proteus, Hemophilus, and anaerobic pulmonary infections are described. Early recognition and institution of appropriate antibacterial agents are emphasized, particularly in GNBP caused by Pseudomonas aeruginosa, Escherichia coli, or Friedländer's bacillus, where the mortality approaches 70%. The mortality of GNBP, including Enterobacter, Proteus, Hemophilus, and anaerobic GNBP, is about 20%. The latter figure is the same as the mortality of pneumococcal pneumonia in similar patients.

Treatment of Anaerobic Pleuropulmonary and Soft-Tissue Infections

To the Editor.— The article by Goldstein et al (242:435, 1979) regarding the antibiotic therapy of anaerobic pleuropulmonary and soft-tissue infections indicated that erythromycin was a reasonable alternative to penicillin in the treatment of penicillin-allergic patients with anaerobic pulmonary infections. The majority of their patients with favorable outcomes had either empyemas, in which pleural drainage plays an important if not primary role, or soft-tissue infections. Only one of four patients with an anaerobic lung abscess or aspiration pneumonia had a complete cure, although two patients did have an initial response with subsequent relapse. We believe their data and our recent experience with the failure of erythromycin in two clinical anaerobic pulmonary abscesses do not presently support the use of this agent in the therapy for anaerobic pulmonary infections. Report of Cases.—Case 1.— A 43-year-old woman with a history of alcohol abuse was evaluated for malaise, a nonproductive cough,

Lung Disease: State of the Art

The editor of the American Review of Respiratory Disease Journal has collected 14 articles that appeared in the State of the Art section for the years 1974 and 1975. Leading workers in different fields of pulmonology were invited to provide an updated review of a particular topic. The intention was to aid the practicing physician in caring for their patients with lung diseases. The articles average 27 pages in length. The references total an impressive 1,900, with an average of 136 per article, reflecting the breadth with which the subjects are reviewed. Two articles deal with aerobic Gram-negative bacillary and anaerobic pulmonary infections, respectively, which are therapeutically the most difficult of common bacterial lung and pleural infections. Despite its remarkably decreased prevalence in the United States, pulmonary tuberculosis is reviewed in two articles devoted primarily to chemotherapy. The introduction of fiberoptic bronchoscopy has revolutionized the practice of pulmonology, analogous to

Treatment of Anaerobic Pulmonary Infections: Carbenicillin Compared to Clindamycin and Gentamicin

Twenty-three patients with anaerobic infections of the lung were treated with either two antibiotics, clindamycin and gentamicin (11 patients) or with a single antibiotic, carbenicillin (12 patients). Cultures were obtained prior to therapy, either by transtracheal needle aspiration (17 patients) or thoracocentesis (six patients). Anaerobic bacteria were found in all. Fifteen patients had aerobic and facultative bacteria in addition. The anerobic isolates were peptostreptococci (12), peptococci (12), Bacteroides organisms (eight), clostridia (three), actinomycetes (two), eubacteria (one), and fusobacteria (one). Aerobes included streptococci (nine), enterococci (seven), Neisseria organisms (two), Klebsiella organisms (one), Citrobacter organisms (one), Pseudomonas organisms (one), Mycobacterium tuberculosis (two), and Nocardia (one). The two patients with pulmonary tuberculosis with anaerobic and superinfection received antituberculosis chemotherapy in addition. Therapeutic response was considered excellent in both groups. This suggests that carbenicillin may be used as a single antibiotic in the treatment of anaerobic and mixed infections of the lung.

Management of anaerobic infections.

Anaerobic infections are reviewed with emphasis on management. Most anaerobic pulmonary infections respond to penicillin G, even when Bacteroides fragilis (penicillin-resistant) is present. Clindamycin is suitable in penicillin-sensitive patients. Intraabdominal infections have a complex flora usually involving anaerobes, especially B. fragilis. It is desirable to use antimicrobial therapy to cover potential pathogens of all types. Surgical drainage and debridement are extremely important considerations. Anaerobic bacteria were found in 72% of 200 patients with female genital tract infections and were the exclusive isolates in 30%. Surgical therapy is primary, but antimicrobial and anticoagulant therapy are also important. A variety of soft-tissue infections involve anaerobes. Surgery is the major therapeutic approach. Anaerobic endocarditis is uncommon but may be difficult to manage. Chloramphenicol is ordinarily the drug of choice for brain abscess. New antimicrobial agents, which are under investigation and are promising, include new penicillins, new cephalosporins, new tetracyclines, and metronidazole.