Antibiotic resistance of oral anaerobic bacteria and their effect on the management of upper respiratory tract and head and neck infections

Anaerobes of oral origin are common in chronic upper respiratory tract and other head and neck infections. Anaerobes are the predominant components of the normal human oropharyngeal flora, and are therefore a common cause of bacterial infections of the upper respiratory tract that are of endogenous origin. These bacteria can be isolated in chronic otitis media, sinusitis, and tonsillitis, and their complications. Anaerobes also predominate in deep oral and neck infections and abscesses. Their isolation requires appropriate methods of collection, transportation, and cultivation of specimens. In addition to their active pathogenic role in these infections, many anaerobes express an indirect effect through their ability to produce the enzyme beta-lactamase. This enables these organisms to shield non-beta-lactamase-producing bacteria (BLPB) from penicillins. Inadequate therapy against BLPB may lead to clinical failures. Treatment of anaerobic infection is complicated by their slow growth, their polymicrobial nature, and the growing resistance of anaerobic bacteria to antimicrobials. Antimicrobial therapy is often the only form of therapy needed, whereas in other instances it is an important adjunct to a surgical approach. Because anaerobes generally are isolated mixed with aerobic organisms, therapy should provide for adequate coverage of both types of pathogens.     

The role of anaerobic bacteria in upper respiratory tract and other head and neck infections

Anaerobes are common pathogens in chronic upper respiratory tract and head and neck infections. They can be recovered in chronic otitis media and sinusitis, play a role in tonsillitis, and predominate in complications of these infections, causing deep oral and neck infections and abscesses. In addition to their direct pathogenicity, they play an indirect role through the production of the enzyme β-lactamase, “shielding” non-β-lactamase-producing bacteria from penicillins. Failure to provide adequate therapy against anaerobes may lead to clinical failures. Management of anaerobic infection is complicated by the slow growth of these organisms, by their polymicrobial nature, and by their growing resistance to antimicrobials. Antimicrobials are often the only form of therapy needed, but surgical approach is needed in some cases. Because anaerobes often are mixed with aerobic organisms, the antimicrobials given should provide adequate coverage against all pathogens.     

Microbiology of sinusitis

Most sinus infections are viral, and only a small proportion develops a secondary bacterial infection. Rhinoviruses, influenza viruses, and parainfluenza viruses are the most common causes of sinusitis. The most common bacteria isolated from pediatric and adult patients with community-acquired acute purulent sinusitis are Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Streptococcus pyogenes. Staphylococcus aureus and anaerobic bacteria (Prevotella and Porphyromonas, Fusobacterium and Peptostreptococcus spp.) are the main isolates in chronic sinusitis. Pseudomonas aeruginosa and other aerobic and facultative gram-negative rods are commonly isolated from patients with nosocomial sinusitis, the immunocompromised host, those with HIV infection, and in cystic fibrosis. Fungi and Pseudomonas aeruginosa are the most common isolates in neutropenic patients. The microbiology of sinusitis is influenced by the previous antimicrobial therapy, vaccinations, and the presence of normal flora capable of interfering with the growth of pathogens.     

Biofilms in pediatric respiratory and related infections

Bacteria can grow as free-floating, planktonic bacteria or complex communities called biofilms. Biofilms promote bacterial growth and diversity and offer bacteria unique environments, including aerobic and anaerobic layers, that facilitate resistance to antimicrobial therapies. Respiratory and related structures provide ideal environments for the development of bacterial biofilms, which predispose patients to recurrent and chronic infections. Biofilms are important for the persistence of chronic rhinosinusitis, pulmonary infections in cystic fibrosis, chronic otitis media, and device-related infections. Antimicrobial therapy that is proven effective against planktonic bacteria is often insufficiently effective against the defenses of biofilms. Furthermore, biofilms modify themselves following exposure to antimicrobial therapy, thus developing increased resistance. Understanding the nature of biofilms in common pediatric infections is essential to comprehending the expected course of bacterial illness and identifying treatments that are most likely to be beneficial against more resistant biofilms.     

Diabetic foot infections. Bacteriologic analysis

Diabetic patients with foot infections were prospectively evaluated over a two-year period. Cultures from reliable specimens avoiding contamination with foot ulcers were obtained in 54 infectious episodes. Staphylococcus species, Enterococcus species, Corynebacterium species, and various species of Enterobacteriaceae were commonly isolated. Common anaerobic isolates included Peptostreptococcus magnus, Peptostreptococcus prevotii, and Bacteroides species. Results of cultures from 94 unreliable specimens were similar. Results of reliable and unreliable specimens obtained simultaneously in 26 patients agreed in seven (27%), but antibiotics selected for organisms isolated from unreliable specimens would have adequately covered pathogens found in the reliable culture in 24 (93%). Diabetic foot infections usually involve mixed bacterial flora, including aerobic, facultatively anaerobic, and anaerobic microorganisms. Specimens should be obtained from infected tissue that does not communicate directly with the foot ulcer if possible. If such specimens are not available, cultures of purulent exudate within the foot ulcer or soft-tissue sinuses may provide useful information on which to base decisions about antibiotic therapy. Broad-spectrum beta-lactam antibiotics or a combination of antibiotics active against facultatively anaerobic cocci and bacilli as well as anaerobes provide the best empirical antimicrobial coverage in these patients.     

Bacteria isolated from chronic upper and lower respiratory tract infections and the associated therapeutic strategies--in paranasal sinusitis

Nasal sinusitis, tonsillitis, and pharyngolaryngitis typify upper respiratory tract infections, while bronchitis and pneumonia typify lower respiratory tract infections. Cases of paranasal sinusitis with severe suppuration are reportedly becoming less frequent, while those of chronic catarrhal paranasal sinusitis and edematous allergic paranasal sinusitis are becoming more so, The primary factor in paranasal sinusitis, a typical infectious disease encountered in otolaryngology, is bacterial infection. The main causative bacteria are Streptococcus pneumoniae, reported in 13.4% of cases, Haemophilus influenzae in 12.8% Moraxella catarrhalis in 5.5%, Staphylococcus aureus in 26.5%, Pseudomonas aeruginosa in 5.2%, and anaerobes. The incidence of strains resistant to antimicrobial agents has grown for S. pneumoniae, H. influenzae, and M. catarrhalis and decreased for S. aureus and P. aeruginosa. Acute exacerbation or severe suppuration in chronic paranasal sinusitis requires the administration of antimicrobial agents, with the same agent administered 2 weeks for maximal effect. First-line agents are AMPC/CVA, SBTPC, CDTR-PI, CFPN-PI, and GFLX for adults, with ASPC, SBPC, ACPC, CTRX, CMZ, FMOX, PAPM/BP, and MEPM injected in severe cases. Attention must be paid to strains that resist cephems and macrolides, such as PISP, PRSP, and BLNAR. In refractory chronic paranasal sinusitis, attention must also be paid to biofilms produced by S. aureus and P. aeruginosa. Suitable antimicrobial agents should be determined for treating of chronic paranasal sinusitis, in addition to the best procedure to ensure early recovery from inflammation, such as puncturing or irrigating the maxillary sinus, injecting a suitable agent, nebulization, and/or surgically widening the middle meatus.     

The Role of Fluoroquinolones in the Treatment of Skin and Soft Tissue Infection

Skin and soft tissue infections vary widely in their nature and severity, and their nomenclature is complex. Most are readily recognized and easily treated, but more severe infections may masquerade in forms similar to those of more innocent infections, causing delay in diagnosis and treatment that may result in loss of limb or life. Antimicrobial therapy is clearly beneficial for both recovery from these infections as well as preventing disease progression. The fluoroquinolones are potent broad-spectrum antimicrobial agents. The older fluoroquinolones mainly have excellent in vitro activity against gram-negative bacilli and borderline activity against clinically important gram-positive organisms, but newer fluoroquinolones were developed to have enhanced activity against both gram-positive and anaerobic organisms while retaining broad-spectrum anti-gram-negative activity. Several comparative trials using fluoroquinolones suggest that the efficacy of these agents is similar to that ofà-lactam antimicrobial agents. Additional clinical trials are necessary to determine the overall role of newer fluoroquinolones as alternatives for skin and soft tissue infections.     

Tigecycline: the answer to beta-lactam and fluoroquinolone resistance?

Patients with serious bacterial infections such as intra-abdominal infections and complicated skin and soft tissue infections are often treated empirically because a delay in appropriate initial antimicrobial therapy has been shown to significantly increase morbidity and mortality. Furthermore, pathogens that have developed resistance to mainstay therapeutic options are increasing in prevalence making these infections a challenge for physicians. Treatment guidelines for surgical and intra-abdominal infections recommend selection of an agent or a combination of agents with activity to cover both Gram-positive, Gram-negative organisms and anaerobes. Recommended agents include second-generation cephalosporins with anaerobic coverage, beta-lactam/beta-lactamase inhibitor agents, fluoroquinolone/metronidazole combinations and carbapenems. However, the effectiveness of these agents has come into question as once susceptible organisms are now showing signs of resistance to such antimicrobial therapies. Alternative agents specifically designed to overcome mechanisms of microbial resistance have been sought. The result of that search has been the development of a new class of antimicrobials termed glycylcyclines. The first of these novel antibacterials is tigecycline, with a broad spectrum of activity that includes coverage against vancomycin-resistant enterococci, methicillin-resistant S. aureus, and many species of multidrug-resistant Gram-negative bacteria. Tigecycline also has activity against most penicillin-susceptible and resistant Gram-positive organisms. Clinical trial experience with tigecycline has shown it to be at least as effective as current recommended regimens for the treatment of intra-abdominal infections and complicated skin and soft tissue infections. This new agent thus holds promise as an alternative to the beta-lactams and fluoroquinolones for the initial empiric treatment of serious bacterial infections.     

Bacteriology of maxillary sinusitis in relation to character of inflammation and prior treatment

By antral aspiration, 200 sinus secretions were obtained from the same number of adult patients with maxillary sinusitis. The bacteriological findings were related to the character of the secretions as well as to the duration of symptoms, previous antibacterial treatment and possible dental genesis. Pathogens were isolated in 87% of 54 patients with untreated acute sinus empyema, Streptococcus pneumoniae being the most prevalent (57%). In 47 cases of treatment failure Haemophilus influenzae predominated and was found in 60% of the purulent secretions. In all, 11% of the 47 cases showed growth of beta-lactamase-producing H. influenzae, corresponding to 18% of all H. influenzae in this group. Staphylococcus aureus and anaerobic bacteria were infrequent findings except in purulent sinus secretion from patients with a long history. In contrast to patients with sinus empyema, no pathogens were found in the majority of 37 patients with non-purulent sinusitis.     

Respiratory tract infections in the elderly, advances and limitations in the diagnosis and treatment]

Advances and limitations in the diagnosis and treatment of respiratory tract infections were discussed in relation to the prognosis of the elderly patients. Haemophilus influenzae and Streptococcus pneumoniae are the major pathogens in the community-acquired respiratory tract infections. On the other hand, methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa are the major pathogens in the nosocomial respiratory tract infections. Detection of MRSA-PBP genes and antibiotic sensitivity tests are important for the diagnosis of MRSA. Vancomycin or arbekacin is the first-choice antibiotic for the treatment of severe infection caused by MRSA, and a combination therapy using one of the above agents and a partner antibiotic is necessary in some cases of MRSA infections. Reports concerning the significance of anaerobic bacteria in respiratory tract infections in Japan have been rare, presumably because procedures to recover anaerobic bacteria from specimens other than sputum, for example transtrancheal aspiration (TTA), bronchoscopic procedure and transcutaneous lung biopsy, are required for the diagnosis of the anaerobic respiratory tract infections. Nowadays, identification of cytomegalovirus (CMV) is a prerequisit for the rapid diagnosis of CMV infection. Therefore attempts are being made to detect a specific substance, for example messenger RNA during the stage of reactivation of CMV. Prophylaxis as well as treatment is necessary for the control of acute exacerbation of chronic respiratory tract infections. In this regard, long-term administration of a small dose of erythromycin or new-quinolone is promising.     

Antimicrobial activity of Lactobacillus against microbial flora of cervicovaginal infections

ObjectiveTo assess the probiotic nature of Lactobacillus in preventing cervical pathogens by studying the effectiveness of antimicrobial activity against vaginal pathogens.MethodsLactobacilli were isolated from healthy vaginal swabs on selective media and different pathogenic bacteria were isolated by using different selective media. The Lactobacillus strains were tested for the production of hydrogen peroxide and antimicrobial compounds along with probiotic properties.ResultsOf the 10 isolated Lactobacillus strains, strain 1, 3 and 6 are high hydrogen peroxide producers and the rest were low producers. Results of pH and amines tests indicated that pH increased with fishy odour in the vaginal fluids of cervicovaginal infection patients when compared with vaginal fluids of healthy persons. The isolates were found to be facultative anaerobic, Gram-positive, non-spore-forming, non-capsule forming and catalase-negative bacilli. The results of antimicrobial activity of compounds indicated that 280 and 140 μg/mL was the minimum concentration to inhibit the growth of both pathogens and test organisms respectively.ConclusionsThe results demonstrated that Lactobacillus producing antimicrobial compounds inhibits the growth of cervical pathogens, revealing that the hypothesis of preventing vaginal infection by administering probiotic organisms has a great appeal to patients, which colonize the vagina to help, restore and maintain healthy vagina.     

Recovery of potential pathogens and interfering bacteria in the nasopharynx of smokers and nonsmokers

BACKGROUND: Active smoking and passive exposure to cigarette smoke are associated with colonization by some potentially pathogenic species of bacteria and an increased risk of respiratory tract infection in both adults and children. In an attempt to explain these observations, this study compared the frequency of isolation of potential pathogens, and aerobic and anaerobic bacteria that possess interfering capabilities (ie, interfering with the in vitro growth of potential pathogens) in the nasopharynx of smokers to their recovery in nonsmokers. METHODS: Nasopharyngeal specimens for cultures were taken from 20 smokers and 20 nonsmokers. Potential pathogens, and aerobic and anaerobic bacteria with interfering capabilities against these organisms were identified. RESULTS: Fourteen potential pathogens (0.7 per patient) were isolated from nasopharyngeal cultures obtained from 11 of the 20 smokers, and 4 (0.2 per patient) were recovered from 3 of the 20 nonsmokers (p < 0.01). In vitro bacterial interference between two aerobic (alpha-hemolytic and nonhemolytic streptococci) and two anaerobic species (Prevotella and Peptostreptococcus species), and four potential pathogens (Streptococcus pneumoniae, Haemophilus influenzae [non-type b], Moraxella catarrhalis, and Streptococcus pyogenes) was observed. Bacterial interference was noted in 61 instances against the four potential pathogens by 22 normal flora isolates that were recovered from the group of smokers, and in 155 instances by 50 isolates from the group of nonsmokers (p < 0.01). CONCLUSIONS: These findings illustrate for the first time that the nasopharyngeal flora of smokers contains fewer aerobic and anaerobic organisms with interfering capabilities and more potential pathogens compared with those of nonsmokers.     

Bacteriological study of diabetic foot infections

AIMS: The polymicrobial nature of diabetic foot infection has been well documented in the literature. Patients with diabetic foot infection not exposed to antibiotics are not well studied before. The relative frequency of bacterial isolates cultured from community-acquired foot infections that are not exposed to antimicrobial agents for 30 days is studied. In addition, the bacterial comparative in vitro susceptibility to the commonly used antibacterial agents is assessed. METHODS: This is a prospective study in which the infected wounds of 86 consecutive diabetic patients seen in the diabetic foot clinic in Adan Teaching Hospital were cultured when visiting the clinic. The patients did not receive antimicrobial therapy 30 days prior to taking the cultures. The specimen was cultured using aerobic and anaerobic microbiological techniques. Isolates were tested for susceptibility to commonly used antimicrobial therapy. RESULT: Staphylococcus aureus was the most common isolate, being recovered from 38.4% of cases. Other organisms were Pseudomonas aeruginosa (17.5%) and Proteus mirabilis (18%), anaerobic gram-negative organisms (10.5%), mainly Bacteroides fragilis. Imipenem, meropenem, and cefepime were the most effective agents against gram-negative organisms. Vancomycin was the most effective against gram-positive organisms. CONCLUSION: S. aureus and P. aeruginosa were the most common causes of diabetic foot infections. Anaerobic organisms are still a common cause for infection, although the prevalence is less. These wounds may require use of combined antimicrobial therapy for initial management.     

Clinical evaluation of anaerobic infections in patients with bronchopulmonary infections diagnosed by transtracheal aspiration]

We evaluated the clinical and bacteriologic features in the patients with bronchopulmonary infections isolated anaerobes from transtracheal aspirates between April 1990 and March 1998. Some anaerobe was isolated in 42 (10.9%) in 387 patients whom we performed transtracheal aspiration (TTA), in 42 (15.7%) of 268 in whom some organism was isolated from TTA, or in 42 (16.3%) of 257 patients in whom some bacterium excluding acid-fast bacteria, fungi or mycoplasma from TTA. The isolation rate of anaerobic bacteria was 93.3% in the patients with lung abscess, 22.7% in the patients with nosocomial pneumonia, 19.4% in the patients with community-acquired pneumonia, 26.7% in the patients with acute exacerbation of chronic lower respiratory tract infection (CLRTI), 1.6% in the patients with persistent infection of CLRTI, and 3.0% in the patients with acute bronchitis, respectively. The major anaerobes, isolated from TTA, were Peptostreptococcus micros and Prevotella melaninogenica. The aerobic bacteria were isolated with anaerobic bacteria in 32 of 42 patients at the same time. The quantitive grade of colonial growth of anaerobes was equal to or more than aerobes in the patients with lung abscess and pneumonia. We mostly administrated 3rd generation cephems or carbapenems with or without clindamycin for the treatment of anaerobic infections. Forty-one of 42 patients were cured only by the therapy of antimicrobial agents, but pneumonia patient with lung cancer died in spite of adequate antimicrobial therapy. These results suggest that the anaerobic infections are important in the bronchopulmonary infections.     

Osteomyelitis due to Veillonella parvula: case report and review.

Anaerobic gram-negative cocci of the genus Veillonella are generally normal flora of the oropharynx and upper respiratory tract. When isolated in clinical specimens, these bacteria are usually regarded as commensal organisms rather than as pathogens. We report a case of spinal osteomyelitis in which Veillonella parvula was isolated in pure culture from bone as well as blood. Osteomyelitis of the spine due to anaerobic bacteria may occur more frequently than has been recognized, and anaerobic cultures of biopsy specimens should be routinely performed.     

Spotlight on Cefditoren Pivoxil in Bacterial Infections

Cefditoren pivoxil (Spectracef, Meiact) is a third-generation oral cephalosporin with a broad spectrum of activity against pathogens, including both Gram-positive and -negative bacteria, and is stable to hydrolysis by many common beta-lactamases. Cefditoren pivoxil is approved for use in the treatment of acute exacerbations of chronic bronchitis (AECB), mild-to-moderate community-acquired pneumonia (CAP), acute maxillary sinusitis, acute pharyngitis/tonsillitis, and uncomplicated skin and skin structure infections (indications may differ between countries). In clinical trials in adults and adolescents, cefditoren pivoxil demonstrated good clinical and bacteriological efficacy in AECB, CAP, acute maxillary sinusitis, acute pharyngitis/tonsillitis, and uncomplicated skin and skin structure infections, and was generally well tolerated. Thus, cefditoren pivoxil is a good option for the treatment of adult and adolescent patients with specific respiratory tract or skin infections, particularly if there is concern about Streptococcus pneumoniae with decreased susceptibility to penicillin, or beta-lactamase-mediated resistance among the common community-acquired pathogens.     

Bone infections involving anaerobic bacteria.

Over 700 cases of anaerobic osteomyelitis have been reported in the literature. Nonetheless, most reviews of osteomyelitis have paid little attention to the potential role of anaerobes in bone infections. There have, as yet, been no prospective studies of osteomyelitis utlizing optimal anaerobic transport and culture techniques. In a retrospective study of osteomyelitis at Wadsworth VA Hospital from 1973--1975, 39 percent of 58 patients with osteomyelitis had an infection involving anaerobes. Anaerobes were isolated from 81 percent of 27 patients whose specimens were cultured anaerobically. Anaerobes were isolated from nine of ten samples of bone. Anaerobic bacteria were part of a mixed flora involving facultative bacteria in all but two cases. All of the patients with anaerobic infection had non-hematogenous osteomyelitis. Non-hematogenous disease comprises 80--90 percent of the osteomyelitis seen in adults. Our experience at Wadsworth VA Hospital and a review of the literature lead us to believe that anaerobes play a much larger role in osteomyelitis than has been appreciated previously. Infections of the calvarium, mastoid, mandible, maxilla and the extremities are most likely to involve anaerobes. Predisposing conditions include paranasal sinusitis, otitis media, periodontal disease, trauma, peripheral vascular disease, peripheral neuropathy and/or chronic osteomyelitis. The presence of a foul odor is a valuable clinical clue to the presence of anaerobes. Bacteroides, fusobacteria and anaerobic cocci have been reported with almost equal frequency from anaerobic bone infections. While Bacteroides fragilis is the most common anaerobe isolated in infections of other organ systems, it does not appear to be a common pathogen in anaerobic bone infections. The role of anaerobes in osteomyelitis is not yet resolved. They have been isolated in pure culture from infected bone, and under those circumstances are clearly pathogenic. Anaerobes are found more frequently as part of a mixed flora with facultative streptococci, gram-negative bacilli, and less often with S. aureus. In this setting it is unclear which organism or organisms are the primary invaders, or whether there is a synergistic mechanism of infection. The reliability of sinus drainage cultures also remains to be determined. Our retrospective study suggests that certain anaerobes isolated from sinus drainage are not present in infected bone. Cultures of bone or an abscess adjacent to bone would be expected to give more reliable data. The majority of anaerobes other than B. fragilis are susceptible to levels of penicillin achievable with parenteral administration of the antibiotic. Anaerobic pathogens should be sought in the situations noted above. We feel that parenteral penicillin should be part of the initial antibiotic regimen in patients with suspected or documented anaerobic bone infection...     

Antimicrobial treatment of sinusitis.

Sinusitis is a common disease. Most cases of acute sinusitis involve the maxillary sinus and occur after viral infections of the upper respiratory tract. The usual pathogens are Streptococcus pneumoniae and Haemophilus influenzae. Moraxella (Branhamella) catarrhalis is also an important pathogen in children. Anaerobic infections are more common in chronic sinusitis. Fungi are frequently observed in granulocytopenic cancer patients but also can occur in apparently normal hosts. Many strains of H influenzae and M catarrhalis observed in patients with sinusitis produce beta-lactamases. Many antimicrobial regimens have proven successful in the treatment of sinusitis, including ampicillin, amoxicillin, trimethoprim-sulfamethoxazole, the tetracyclines, and cefuroxime axetil, but only the latter three drugs are active against most beta-lactamase-producing strains. Nosocomial sinusitis usually occurs in intensive care unit settings and is frequently associated with nasopharyngeal instrumentation. The pathogens observed in nosocomial sinusitis are gram-negative bacilli or staphylococci and frequently require therapy with broad-spectrum penicillins or cephalosporins, an aminoglycoside, or vancomycin.     

Acute and chronic bacterial sinusitis

Sinusitis is one of the most common complaints resulting in physician visits in the United States. An antecedent viral infection of the upper respiratory tract is the most common presentation. Despite its prevalence, most cases resolve spontaneously. Only a small proportion develops a secondary bacterial infection that will benefit from antimicrobial therapy. This article discusses the microbiology and pathogenesis of acute and chronic bacterial sinusitis. The role anaerobic bacterial in chronic and recurrent sinusitis is emphasized, and appropriate antimicrobial regimens are discussed.