Infectious anaerobics in dentistry

 

Clinical infections At all locations Anaerobes were isolated from infections. The frequency and types of isolates however vary and depend on the source of the microbial flora or the adjacent mucocutaneous sites.

Central nervous system (CNS) These include: brain abscess (BA), subdural empyema, epidural abscess, and meningitis. BA also results from infection with the head, mastoid, sinus, oropharynx, dental or lung. Ear or mastoid infection tends to spread to the temporal lobe or cerebellum whereas frontal lobe abscess is often caused by facial sinusitis. Hematogenic spread occurs frequently following dental, oropharyngeal or pulmonary infections, and rarely from endocarditis. Meningitis may follow infection with shunting of the respiratory or cerebrospinal fluid. Shunt infections are generally caused by the skin flora (i.e., P. acnes) and by enteric organisms (i.e., B. fragilis) in ventriculoperitoneal shunts that perforate the gut. C. Perfringens may cause BA and meningitis following a head injury or intracranial surgery[6].

 

Prevotella, Porphyromonas, Bacteroides, Fusobacterium and Peptostreptococcus spp are among the anaerobes usually recovered from BAs complicating respiratory and dental infections. Often, microaerophilic and other streptococci are isolated too. Early administration of antimicrobials may prevent abscess formation at the encephalitis level. Once an abscess has formed, it may require surgical excision or drainage, combined with a long course of antibiotics (4e8 weeks). Some advocate abscess removal, although others advocate recurrent aspirations. The techniques used are aspiration by burr hole and full excision following craniotomy. Repeated aspirations are preferred in multiple abscesses or abcèses in essential brain areas. Recommended after intraventricular rupture of the abscess is open craniotomy with, debridement, intraventricular lavage and intraventricular as well as intravenous antibimicrobial (s). An alternative approach to reducing surgical drainage is extended high-dose antibiotics. Such infections are recommended for antimicrobials with sufficient intracranial penetration: metronidazole, penicillins, meropenem and chloramphenicol.[7]

 

 

 

Head and neck, and upper airways

 

Anaerobes can be recovered from a variety of infections of the head and neck and upper respiratory tract, particularly in chronic forms. These include chronic otitis media, sinusitis and mastoiditis, tonsillary, peritonsillary and retropharyngeal abscesses, infections of the deep neck, parotitis, sialadenitis, thyroiditis, odontogenic infections, and postoperative and nonoperative head and neck wounds and abscesses. The isolates that predominate are Prevotella, Porphyromonas, Bacteroides, Fusobacterium, Peptostreptococcus spp. Most dental infections include anaerobes; endodontal infections (e.g. pulpitis) and parodontal infections (gingivitis and parodontitis and periimplantitis), periapical and dental abscesses, perimandibular spatial infection and post-extraction infection. Dental infections can also involve microaerophilic streptococci and Streptococcus salivarius. Angina of Vincent is a distinct type of ulcerative gingivitis; Fusobacterium spp contains the causative species. And spirochetes anaerobic. Ludwig angina is a mouth-floor connective tissue infection and Lemierre 's syndrome is characterized by thrombosis and suppurative thrombophlebitis of the inner jugular vein along with septic emboli spread to the lungs and other locations; [F. The prevalent species is necrophorum. Broad neck infections (e.g. mediastinitis following esophagus perforation, retropharyngeal abscess extension or cellulite extension, dental abscess) are typically polymicrobial[8].

 

 

Otitis media Peptostreptococcus spp.; And 5e15 percent of acute otitis media find P. acnes. These species and AGNB were present in 42 percent of patients with severe otitis media's culture-positive aspirates. In half of patients with chronic suppurative otitis media, anaerobes were recovered. Mastoiditis and cholesteatom infected. The infection is always polymicrobial; AGNB, peptostreptococci, Pseudomonas aeruginosa, and Staphylococcus aureus were the principal isolates. Anaerobes were isolated from 23 of 24 (96%) chronic mastoiditis specimens and most intracranial abscesses complicating chronic suppurative otitis media. Children with acute and chronic mastoiditis were also isolated from fusobacterium spp. Many of these organisms can make b-lactamase which can contribute to the high rate of b-lactam antibiotics failure. 6.4. 6.4. Of acute sinusitis predominate rhinosinusitis Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis. Once the infection is chronic and oxygen levels drop, the bacterial sinus flora changes from aerobic to anaerobic. In patients with chronic sinusitis, an elevated serum antibody level to prevotella and fusbacterium was demonstrated. Although anaerobes are generally isolated from only about 7% of acute sinusitis (mostly due to dental infection), they can recover from up to 67% of chronic infection. Sinus infection may spread through veins that are anastomised or adjacent to the CNS. Complications include cellulite in the ear, meningitis, sinus thrombosis in the cavern, and abscesses in the epidural, subdural and brain[9].

 

 

 

Parotitis Aerobic (S. aureus, streptococci, Gram-negative bacteria) and anaerobic (Peptostreptococcus, Bacteroides and pigmented Prevotella and Porphyromonas spp.) bacteria cause acute suppurative parotitis. Empirical therapy should be targeted on both. When pus has formed, drainage can be indicated.

 

Cervical lymphadenitis S are organisms that cause acute unilateral infection linked to facial trauma or impetigo. Aureus and group A Streptococci b-hemolytic (GABHS). In chronic infections bartonella henselae and mycobacteria are essential. Anaerobes (mostly Fusobacterium and Peptostreptococcus spp.) were 25 percent isolated and linked to dental, parodontal or tonsillary infection[10].

 

 

 

Antimicrobial treatment Effective control of mixed aerobic / anaerobic infection includes aggressive antimicrobial administration against both components. When selecting effective antimicrobials a range of factors should be considered. They should be effective against all targeted species, induce minimal to no resistance, attain sufficient levels in the infected site and reduce toxicity. Due to the development of resistance, not achieving sufficient tissue levels, incompatible drug interaction and the development of an abscess, antimicrobials may fail to clear the infection. Antimicrobials are ineffective in treating abscesses. The abscess capsule reduces their penetration, and their activity may be impaired by low pH and the presence of binding proteins or inactivating enzymes (i.e. b-lactamase). For aminoglycosides and quinolones, low pH and the anaerobic conditions are detrimental

.

Penicillins

 

Penicillin G is active and effective against many essential anaerobic isolates except for B at dose levels that may be clinically attained. Fragile. A number of studies confirmed a high degree of B resistance. Penicillin fragilis, some species needing up to 256 units / ml or more for inhibition and suggesting that other non-fragilis species can develop penicillin resistance. While some anaerobic streptococcal infections that need large doses of penicillin (20-30 megabytes per day), most clinicians prefer to use penicillin G to treat anaerobic streptococcal infections in the absence of serious allergy to penicillin. Amoxacillin, ampicillin, and penicillin V show similar activity to that Penicillin G used by most other than B anaerobes. Fragilis, while methicillin, nafcillin, oxacillin, cloxacillin and dicloxacillin may not be as predictable. When used in large doses, carbenicillin and ticarcillin do inhibit many anaerobes. Some 5 % to 10% of Bacteroides fragiIis strains, however, are resistant, treatment is costly, and undesirable side effects such as platelet dysfunction and hypokalaemia may occur. Prolonged high-dose ticarcillin or carbenicillin treatment is also expensive. 

Semisynthetic acylureido penicillins, azlocillin and mezlocillin, have aerobic spectra similar to carbenicillin, but mezlocillin is significantly more active against Bacteroides fragilis than carbenicillin.[11] Mezlocillin can be useful in infections of this area because of its spectrum against aerobic and anaerobic organisms such as those found in pelvic infections. Piperacillin, a penicillin derivative of piperazine, has excellent action against Bacteroides fragilis, inhibiting 80 percent of strains at 25 / xg / ml. Clinical trials in Japan recording efficacy of piperacillin are now being extended in other countries. Currently penicillin G is the standard by which other penieillins, and indeed most other antibiotics, must be judged in the treatment of anaerobic infection with nonBacteroides. Penicillin G is involved in lung abscess, anaerobic osteomyelitis, and intracranial abscess with adequate results. Table I compares the concentrations of penicillin and other antibiotics in intracranial pus used to treat anaerobic intracranial infections.

 

Cefoxitin and cephalosporins

Most of the commonly used parenteral cephalosporins are not specifically suggested to treat anaerobic or mixed aerobic-anaerobic infections due to inadequate activity against Bacteroides fragilis. It is acceptable to do activity against many other anaerobes. Cephapirin or cephalothin are about 10 per cent of B inhibitory. Fragilis strains that are attainable in blood. In comparison, cefoxitin is very active against B. Fragilis; 80% of strains are 16 / xg / ml inhibited. Cefoxitin is highly active against C, too. Perfringens ... Perfringens. Statements in the literature suggesting that cefoxitin is less active against non-perfringens clostridia, are offset in part by other studies showing that cefoxitin 's efficacy against mandatory anaerobes is comparable to that of carbenicillin and clindamycin Reported experience with cefoxitin in the treatment of a wide range of anaerobic infections has been beneficial (see Table II). In abdominal and gynecological infections due to a mixture of anaerobic and aerobic organisms cefoxitin may offer us the option to use a single agent for treatment. I have studied cefoxitin as a single agent on the IM route for treating mixed extremity infections in patients with diabetes and peripheral vascular disease with cure or improvement in any case. Cefamandole, a new member of the cephalosporin family, extends to the bone, joints, and spinal fluid. Cefamandole has a wide aerobic spectrum and is active against multiple anaerobic non-bacteroidal bacteria. This agent has been useful in the treatment of aerobic and anaerobic bacteria-infections. Cefamandole 's favorable pharmacokinetics justify our continued interest in this compound in the treatment of bone, joint, central nervous system and lung polymicrobial infections

 

chloramphenicol and clindamycin

In a supplement to the Journal of Infectious Diseases, clindamycin use in anaerobic infections has been definitively reviewed. Some clostridia non-perfringens are resistant to clindamycin, as are bacteria used off by other strains. There are far too many studies recording clindamycin 's clinical efficacy in anaerobic infections such as osteomyelitis, genital infections, abdominal sepsis and lung abscesses to list here. However, the importance of clindamycin was diminished by the pseudomembranous colitis problem, which was also documented (although much less frequently) with other anaerobic drugs such as ampicillin, tetracycline, and chloramphenicol. Anaerobes that are highly resistant to chloramphenicol can be hard to find. Because of both the extreme idiosyncratic aplastic anaemia and the dose-related depression of erythropoeisis, the prudent clinician avoids using chloramphenicol except in the critically ill patient or the patient with intracrane suppuration. These complications restrict the use of chloramphenicol, which is highly effective in treating anaerobic infections , especially those of the central nervous system, when used appropriately. The efficacy of clindamycin and chloramphenicol in the treatment of anaerobic infections has not been tested in prospective trials, to my knowledge. Conventional doses of both drugs produce levels in the blood that exceed most B's minimum inhibitory concentration. Forms of fragilis (Goodman, 1976). Administered as a single agent, clindamycin has been reported as an adequate treatment for mixed anaerobic / aerobic infections [14].

 

 

Tetracyclines may be chemically inactivated in anaerobic environments where there is low potential for oxidation-reduction. At the acid pH and low redox potential that can be found in necrosis areas, erythromycin is probably not at all involved. Tetracycline resistance (over 1 / xg / ml of doxycycline) is present in 21% of Clostridium perfringens strains. It is clear that Bacteroides fragilis, Bacteroides melaninogenicus, other species of bacteroides and anaerobic Grampositive bacilli are susceptible to erythromycin but generally immune to fusobacteria. A recent analysis by Lacey highlights the low toxicity of erythromycin and points out that in treating anaerobic infections this drug may have more to offer than most of us commonly believe. Both of these drugs may be useful for patients needing prolonged oral therapy for infections caused by species that have been shown to be immune to these antibiotics.

 

 

 

metronidazole

 

Essentially all the required clinically relevant anaerobic bacteria are susceptible to metronidazole which is reliably bactericidal. Microaerophilic and carboxyphilic streptococci, most often contained in the brain's fronti ~ l or temporal lobe abscesses, are usually immune. Intracranial infections include B. Fragilis is routinely acquired only from otogenic brain abscesses, and only usually in combination with aerobic organisms. Opinions about the value of metronidazole for central nervous system anaerobic infections vary from favourable to cautionary to its use. In non-central nervous system infections

Metronidazole performed well. Dr. Tally reported promising outcomes after treating metronidazole septic anaerobic infections, as did Dr. Ledger following treatment of postpartum pelvic infections. A metronidazole analog, tinidazole, has far more favorable pharmacokinetics and was compared to clindamycin and doxycycline in the treatment of anaerobic wound infections in immunocompromised hosts. Tinidazole has been effective against all anaerobes except Gram-positive cocci, and has been as effective in treating anaerobic infections in cancer patients as clindamycin. Metronidazole does cross the barrier to the blood-brain. Toxicity, resistant organism colonisation, and super-infection are uncommon. There is a parenteral form available in the United States for investigational use in the treatment of anaerobic infections. A continuing problem during these trials will be the mutagenic potential of long-term metronidazole treatment [15].

Chloramphene

Chloramphenicol, a natural antibiotic containing a nitrobenzene chain, exerts its antibacterial action by binding to the 50S subunit of the bacterial ribosome, inactivating peptidyl transferase enzymes and thereby inhibiting the formation of bacterial peptide bonds. Chloramphenicol is bacteriostatic at rising therapeutic concentrations. The drug is highly soluble in lipids and is widely distributed to all body tissues. In the central nervous system, therapeutic concentrations are attained only though the blood brain barrier is intact; sufficient concentrations are even reached within the prostate. Chloramphenicol is biotransformed by glucuronyl transferase into a glucuronide conjugate in the liver, an enzyme deficient in cats and neonates younger than 6 weeks of age. Metabolite excretion is primarily renal, with 5 to 10 per cent of the active drug being found in urine. Absorption following oral administration is excellent, with serum concentrations often comparable to those obtained by intravenous administration in humans. 

The primary adverse effect of chloramphenicol on dogs and cats is dose-dependent hematologic toxicity. Depression of the bone marrow results from inhibition of protein synthesis with mitochondria. Cats are particularly susceptible to toxicity caused by chloramphenicol due to a relative deficiency in the activity of the hepatic glucuronyl transferase. Depression of the central nervous system and reversible suppression of the bone marrow have been observed in cats treated with 60 mg of chloramphenicol per kg per day. The dosage of chloramphenicol in cats is recommended to not exceed 50 mg per kg per day. In dogs treated with chloramphenicol, dose-related neutropenia and occasional cases of aplastic anemia have been observed.[16] Chloramphenicol is more active against all strains of anaerobic bacteria than any other antibiotic and is considered by some to be the medication of choice for the treatment of severe anaerobic infection when the presence and sensitivity of infectious species is uncertain. There is also broad-spectrum anti-aerobic pathogens development, including both gram-negative bacilli and gram-positive cocci. Reliable action against B strains which are resistant to penicillin. Fragilis is the greatest advantage of chloramphenicol over penicillins in treating anaerobic infections. Clinically, however, chloramphenicol in vivo activity often fails to yield parallel findings from in vitro susceptibility studies. At least part of this effect can be due to the in vivo reduction of the active nitro group of chloramphenicol, a reaction which does not appear to occur in vitro. In man, concerns about possible adverse hematological effects have largely limited chloramphenicol to the treatment of brain abscesses. The relative inexpense of chloramphenicol makes it an enticing alternative to other more costly antibiotics for the treatment of anaerobic infections in dogs and cats. Chloramphenicol is well known for treating aspiration pneumonia, a mixed infection that often includes oral anaerobic bacteria, and for treating central nervous system anaerobic infections [17].

 

IMPIENAM

 

Imipenam, the first of a new 13-lactam class of antibiotics known as carbapenams, has substantial activity against most medically important bacterial species, including multi-resistant Pseudomonas strains. Imipenam undergoes significant renal tubular metabolism, and is thus paired with cilastatin, a renal tubular dipeptidase inhibitor. The combination results in much higher concentrations of imipenam in urine, and thus decreases the nephrotoxicity associated with imipenam administration alone.

 Imipenam 's activity against anaerobic bacteria is greater than that of all other 13-lactam antibiotics and is considered equivalent to clindamycin, chloramphenicol, and metronidazole. Obviously, a potent broad-spectrum, relatively non-toxic antibiotic such as imipenam provides considerable advantages for the treatment of severe mixed infections , particularly when information about culture and susceptibility is not known. While it has good effectiveness in humans, there has been little clinical experience in veterinary medicine with this antibiotic. Antibiotics with Limited Efficacy Against Anaerobes Anaerobic bacteria are universally immune to aminoglycoside antibiotics, due to the fact that aminoglycoside transfer across the bacterial cell membrane involves enzymes that lack anaerobic bacteria. [18]

 

Polymyxin antibiotics are also unsuccessful, for aminoglycosid-like purposes. Large tetracycline resistance has significantly restricted its utility in the treatment of anaerobic infection. Hirsch and colleagues18 observed resistance to tetracycline from veterinary patients in a variety of isolates of Bacteroides. Erythromycin and lincomycin are found to be fairly ineffective for the anaerobic infection treatment. Neither drug is active against Clostridium perfringens, a pathogen very widespread in animal anaerobic infections. A further common veterinary pathogen, fusobacterium, is also immune to erythromycin. Lincomycin, as the parent compound for clindamycin, has been shown to be considerably less efficient than clindamycin when compared in an experimental model of anaerobic infection in dogs to their treatment efficiency. 8 Sulfonamides also have limited effectiveness in the treatment of anaerobic infections because cellular breakdown by-products, including

Paraminobenzoic acid, in typical anaerobic conditions, occurs in abundance. Some of those compounds competitively inhibit the activity of sulfonamide. There has also been evidence of trimethoprim 's therapeutic ineffectiveness against anaerobic bacteria. In a model for treating anaerobic infections, trimethoprim sulfonamide performed poorly and failed to reduce the production of abscesses or to produce cures. Despite evidence of in vitro activity against necessary animal-isolated anaerobes, trimethoprimsulfamethoxazole was found to be a clinically ineffective treatment for anaerobic infections in dogs and cats, and was associated with a large number of care failures. [19] 

References

1. Hirsch DC, Biberstein EL, Jang SS: Obligate anaerobes in clinical veterinary practice. J Clin Microbiol10:188-191, 1979

2.  Finegold SM: Pathogenic anaerobes. Arch Intern Med 142:1988-1992, 1982

3. Gorbach SL, Bartlett JG: Anaerobic infections. N Engl J Med 290:1177-1184, 1237--1245, 1289-1294 (3 parts), 1974

4.Finegold, S. M. (1977). Therapy for infections due to anaerobic bacteria. Journal oflnfectious Diseases, (S), 135, 25

5.Dow SW, Jones RL: Anaerobic infections. Part I. Pathogenesis and clinical significance. Compend Contin Ed Pract Vet 9:711-720, 1987

6. Finegold SM. Anaerobic infections in humans: an overview. Anaerobe 1995;1:

3e9.

7. Bernardini GL. Diagnosis and management of brain abscess and subdural

empyema. Curr Neurol Neurosci Rep 2004;4:448e56.

8. Brook I, Frazier EH. Microbiology of mediastinitis. Arch Intern Med 1996;156:

333e6.

9. L1 Coltella, Mancinelli L, Onori M, Lucignano B, Menichella D, Sorge R, et al.

Russo C Advancement in the routine identification of anaerobic bacteria by

MALDI-TOF mass spectrometry. Eur J Clin Microbiol Infect Dis 2013;32:

1183e92.

10. Brook I. Aerobic and anaerobic bacteriology of cervical adenitis in children.

Clin Pediatr 1980;19:693e776

11. Chow, A. W., Montgomerie, J. Z. and Guze, L. B. (1974). Parenteral clindamycin for severe anaerobic infections. Archives of Internal Medicine, 134, 78.

12. Ingham, H. R., Selkon, J. B. and Roxby, C. M. (1977). Bacteriological study of otogenic cerebral abscesses: chemotherapeutic role of metronidazole. British Medical Journal, ii, 997

13. Symposium on cefamandole. Moellering, R. C. Jr. (Ed.) (1978). Journal of Infectious Diseases, 137 (S).

14. Gorbach, S. L. and Bartlett, J. G. (1977). The role of clindamycin in anaerobic bacterial infections. Journal of Infectious Diseases, 135, (S).

15. Ledger, W. J., Gee, C., Pollin, P. A., Lewis, W. P., Sutter, V. L. and Finegold, S. M. (1976). A new approach to patients with suspected anaerobic post partum pelvic infections. Transabdominal uterine aspiration for culture and metronidazole for treatment. American Journal of Obstetrics and Gynecology, 126, 1.

16. Watson ADJ, Middleton DJ: Chloramphenicol toxicosis in cats. Am J Vet Res 39:1199- 1203, 1978

17. Bartlett JG: Chloramphenicol. Med Clin North Am 66:91-102, 1982

18. Damper DP, Epstein W: Role of membrane potential in bacterial resistance to aminoglycoside antibiotics. Antimicrob Agents Chemother 20:803-808, 1981

19. Darrell JH, Garrod LP, Waterworth PM: Trimethoprim: Laboratory and clinical studies. J Clin Pathol 21:202-209, 1968