++
Anaerobes form the predominant bacterial components of the normal
human skin and mucous membranes. They are responsible either alone
or in combination with aerobes for a wide variety of infections
ranging from superficial skin infections to intra-abdominal and
intracranial infections.
+++
Epidemiology
and Pathogenesis
++
Anaerobic organisms are widely distributed in nature. They are
present in the soil as well as the skin, mucous membranes, and gastrointestinal
tracts of animals and humans. Only a few of these organisms have
been identified as responsible for disease in humans (eTable 249.1).
++
++
Infection with these organisms usually results secondary to disruption
in the normal skin or mucous membrane barriers of the host, resulting
in entry of the bacteria into deeper tissues and leading to, at
times, potentially severe infections from an individual’s
own endogenous flora. Although some are strict anaerobes, others
may be facultative anaerobes, able to survive in conditions with or
without oxygen. The presence of devitalized tissues, low oxygen
tension, and low pH serve to greatly contribute to the pathogenesis
of anaerobic infections. Other conditions that may play a role include
host defense mechanisms, virulence factors (bacterial adherence
factors), production of toxins (eg, Clostridium species),
and the presence of other bacteria in polymicrobial infections.
++
Due to their fastidious nature, as well as inconsistent use of
adequate methods for isolation and identification, anaerobic bacteria
are not easily isolated, which makes their exact frequency difficult
to ascertain.1 Although anaerobes have been reported
to account for 8% to 11% of episodes of bacteremia
in adults, anaerobic organisms have rarely been isolated from blood cultures
in pediatric patients.2,3 This may partly be explained
by higher prevalence of chronic or debilitating conditions in adults,
like malignant neoplasms, secondary immunodeficiencies, diabetes,
obstetric and gynecologic surgery, and the presence of decubitus
ulcers.
+++
Clinical Manifestations
++
Commonly encountered diseases caused by anaerobic bacteria in
children are listed in Table 249-1. The principal
sites of infection are deep soft tissue infections around the mouth
and oropharynx, peritonitis and peritoneal abscesses following appendicitis,
or bowel rupture, and brain and lung abscesses. In females, beyond menarche,
anaerobic bacteria may cause different pelvic infections, such as
salpingitis, tuboovarian abscesses, pelvic inflammatory disease, as
well as bacterial vaginosis. Recently, various eye infections have
been associated with contact lens use, such as conjunctivitis and
keratitis. Overuse of antibiotics leading to pseudomembranous colitis,
which may be quite refractory to treatment, has also emerged as
a significant problem, more so in adults than in children.
++
++
Clinically differentiating anaerobic from aerobic infections
is often difficult. Although anaerobic infections may be more putrid,
there is generally no gas formation unless C perfringens are
present. Bacteremia, although rare, has been associated with a high
mortality rate (15%–35%) and is invariably
secondary to a primary focal infection.2 Disease
in neonates and immunocompromised children is often more severe
and needs to be recognized and treated early.
+++
Central Nervous
System Infections
++
Although not commonly isolated, anaerobes can cause a variety
of central nervous system infections including those that are relatively
common (ie, brain abscess, subdural empyema) to the rare epidural
abscess and meningitis. Chronic infections of the adjacent structures
(ie, ears, mastoids, sinuses, and teeth) commonly predispose to
these infections, either as a result of direct extention or less
commonly due to bacteremia. Meningitis may also follow the infection
of a cerebrospinal fluid shunt with skin flora such as Propionibacterium
acnes. Anaerobes of enteric origin (ie, Bacteroides
fragilis) may be isolated when these shunts perforate the
gut. Following intracranial surgery or trauma, infections with Clostridium perfringens tend
to be seen more commonly than infections with the other anaerobes.
Respiratory and dental infections leading to brain abscess as a secondary
complication are generally caused by Prevotella, Porphyromonas,
Bacteroides, Fusobacterium, and Peptostreptococcus,
as well as microaerophilic and other streptococci.1
++
Treatment generally consists of aspiration along with appropriate
antimicrobial therapy that includes metronidazole, penicillins,
and carbapenems. Chloramphenicol may also be considered in this
situation when there is no other alternative.
++
Recent studies illustrate the importance of anaerobic bacteria
in ocular infections such as conjunctivitis, keratitis, and dacrocystitis.
Although anaerobes are part of the normal flora of the conjunctival
sac, this does not exclude their ability to become pathogenic given
the correct milieu (eg, injuries, foreign bodies, and underlying
diseases). Apart from this direct contamination is a frequent mode
of transmission. In studies that employed adequate methods for isolation,
anaerobes were recovered from about a third of patients with conjunctivitis,
half of the time in pure culture.4
++
Conjunctivitis associated with anaerobic bacteria is not distinguishable
from inflammation caused by other bacteria, although patients who
use contact lenses may be at higher risk of developing infections
caused by these organisms. Although the vast majority of cases of
acute conjunctivitis, are caused by viruses as well as aerobic bacteria,
such as Staphylococcus aureus, Streptococcus pneumoniae,
and Haemophilus influenzae, anaerobic gram-positive
cocci (eg, Peptosteptococcus) have also been recovered in
significant numbers from these patients. Other bacteria that have
been recovered include Propionobacterium, B fragilis,
pigmented Prevotella, Porphyromonas, Fusobacteria,
and Bifidobacteria. Often these are found in conjunction
with other aerobic bacteria. In addition to this, Chlamydia
trachomatis and Neisseria gonorrheae have
been isolated from sexually active adolescents. Corneal ulcerations
on the other hand have been associated with S pneumoniae, Pseudomonas species,
and Peptostreptococcus.
++
Keratitis, a relatively serious infection that may result in
corneal scarring, opacification, and blindness, although mostly
associated with a variety of aerobic gram-positive
and gram-negative bacteria, has been reported in conjunction with Clostridium
perfringens, in which case it can result in a fulminant
endophthalmitis. This has been associated with perforating ocular
injuries. Clostridium tetani has also been associated
with ocular trauma. Corneal susceptibility to infection is secondary
to its continuous exposure, as well as avascularity. Anaerobic bacteria
should also be considered in cases of chronic dacrocystitis.
++
The treatment for anaerobic ocular infections depends on the
severity as well as the site of infection. Simple cases of conjunctivitis
may be treated with topical antibiotics. Bacitracin is very effective
against pigmented Prevotella and Porphyromonas as
well as Peptosptreptococcus species but is usually
not effective against B fragilis and Fusobacterium.
Similarly, erythromycin is active against pigmented Prevotella and Porphyromonas,
miroaerophilic and anaerobic streptococci, Clostridium species,
as well as gram-positive non-spore-forming anaerobic bacilli but
has poor activity against gram-negative anaerobic bacilli. Chloramphenicol
has very good activity against most anaerobes, however, caution should
be used even when used topically because absorption from the conjunctivae
can occur and may rarely cause aplastic anemia even when administered
locally. Sulfonamides, quinolones, polymyxin B, and aminoglycoside
preparations may also not be very effective against most anaerobes. The newer
third- and fourth-generation quinolones, such as levofloxacin and
moxifloxacin, have shown better activity than ciprofloxacin and
ofloxacin, including superior activity against the gram-positive
organisms that are most commonly involved in keratitis and endophthalmitis.5
++
Complications such as the presence of a corneal ulcer as well
as more severe infections involving the lacrimal glands and cases
of endophthalmitis will need to be treated aggressively with broad-spectrum
antimicrobials that include anaerobic coverage. In addition, early
surgical intervention should be initiated where indicated. Every
effort should be made to send appropriate aerobic and anaerobic
cultures. This applies particularly to neonates with blockage of
the nasolacrimal duct where infection is often a concern.
+++
Head and Neck
Infections
++
Anaerobes may be isolated in cases of acute as well as chronic
infections involving the ears, sinuses, mastoids, and other head
and neck structures.6 Members of the oropharyngeal flora
(ie, Prevotella, Porphyromonas, Bacteroides, Fusobacterium, and Peptostreptococcus)
are the predominant anaerobic flora involved in these infections.
In addition to these, Streptococcus salivarius and
microaerophilic streptococci may be involved in the pathogenesis
of dental infections.
++
Anaerobes have been isolated from approximately 5% to
15% of cases of acute otitis media as well as 50% of
cases of chronic suppurative otitis media, including those with
the presence of a cholesteotoma. These can accelerate the absorption
of bone which is enhanced by organic acids produced by anaerobic
bacteria.1,7-9
++
Recovery of anaerobes in up to 75% of tonsils of children
with recurrent group A beta hemolytic streptococcus (GABHS) as well
as 40% of those with non-GABHS has been one of the possible
explanations offered for the failure of penicillin to treat these
infections. Selection of beta-lactamase producing strains of aerobic
as well as anaerobic bacteria may render penicillin ineffective
in these situations.1,10-12
++
Other infections, such as thyroiditis, have been associated with
anaerobic bacteria, such as anaerobic gram-negative bacteria as
well as Peptostreptococcus species.
++
Human infection with Fusobacterium necrophorum usuallyinvolves F
necrophorum subsp funduliforme as opposed
to infection with F necrophorumsubsp necrophorum,
which is a common pathogen in animals. Lemierresyndrome,
or postanginal sepsis, is the most common life-threateningmanifestation.
Tonsillitis is followed by septic thrombophlebitisof
the internal jugular vein and is then followed by septicemia with
septicemboli in lungs and other sites.13
++
Recent evidence suggests thatF necrophorum can
be limited to the throat and cause persistentor
recurrent tonsillitis. F necrophorum is unique
among non-spore-forminganaerobes, mainly for its
virulence and association with Lemierresyndrome
as a monomicrobial infection and also because itseems
probable that it may be an exogenously acquired infection.The
source of infection is unclear; suggestions include acquisitionfrom
animals or human-to-human transmission. Approximately 10%of
published cases are associated with infectious mononucleosis,which
may facilitate invasion. Recent work suggests that genetic mutations
leading to hypercoagulability may predispose to internal jugular
vein thrombophlebitis when infected with fusobacterium.13Lemierre syndrome
was a relatively common entity in the preantibioticera
but seemed to virtually disappear with widespread use ofantibiotics
for upper respiratory tract infection. In the lastseveral
years, however, there has been a rise in incidence, possibly relatedto
a decrease in antibiotic usage for sore throat. Coinfection with Fusobacterium necrophorum and Arcanobacterium haemolyticum in
a case of Lemierre syndrome has been reported.14
+++
Pleuropulmonary
Infections
++
Severe periodontal or gingival disease as well as aspiration
of oropharyngeal secretions or gastric contents are the major risk
factors associated with the development of pleuropulmonary disease which
can range from uncomplicated pneumonia to severe necrotizing pneumonia
with the formation of empyema or lung abscess. Like most anaerobic
infections, these are generally polymicrobial in nature. The predominant
anaerobes to be isolated in these situations include Prevotella, Porphyromonas,Fusobacterium, and Peptostreptococcus. These
may be mixed with aerobic organisms such as alpha hemolytic as well
as microaerophilic streptococci and in nosocomial-acquired pneumonia
gram-negative organisms such as Pseudomonas spp, Enterobacteriaceae.
S aureus may be isolated as well.15
+++
Intra-Abdominal
Infections
++
Perforation of abdominal viscera, either traumatically or during
surgery, may lead to peritonitis as well as the formation of intra-abdominal
abscesses. The specific microorganisms involved here are the normal
flora of the gastrointestinal tract where the anaerobic bacteria
outnumber aerobes in a ratio of 1:1000 to 1:10,000. These infections
often tend to be biphasic, with the initial infection being caused
by Enteriobacteriaceae followed by a later phase
with the development of abscesses from which B fragilis or Peptostreptococcus may
be isolated. Because Bacteroides species tend to
make up 25% of the anaerobes in the gut, infections with
these organisms are seen most commonly. Members of the Clostridium species
are another common group of anaerobic organisms to be isolated in
these situations. Combination therapy is generally initiated, often
incorporating an aminoglycoside along with a penicillin-beta-lactamase
(ie, ticarcillin-clavulanate) or third- or fourth-generation cephalosporin
and, depending on the severity of the illness, a carbapenem.1
+++
Osteomyelitis
and Septic Arthritis
++
These infections also tend to be polymicrobial with osteomyelitis
after trauma and fracture most commonly involving the long bones, whereas
osteomyelitis involving the spine may be seen following decubitus
ulcers. Cranial and facial bones may be involved as well, particularly
following trauma.1
++
Anaerobic streptococci and Bacteroides are the
most common organisms at all sites, including bites and cranial
infections. Pigmented Prevotella as well as Porphyromonas are
other common organisms isolated in these infections. Clostridia may
be isolated in compound fractures involving the lower extremities
and pelvis.
++
Septic arthritis involving anaerobes may be seen following hematogenous
or direct spread of infection, trauma, as well as in association with
prosthetic joints.
+++
Infections of
the Female Genital Tract Including Pelvic Inflammatory Disease
++
Genital tract infections mimic other infections caused by anaerobes
in the sense that they are usually polymicrobial. This includes bacterial
vaginosis, endometritis, salpingitis, tuboovarian abscesses, as
well as intrauterine-device-associated infections. The predominant
anaerobic bacteria include Prevotella species, Peptostreptococcus, Porphyromonas, and Clostridium species.
++
In addition to these infections, more than one million women
in the United States are treated for pelvic inflammatory disease
(PID) annually. Although C trachomatis and N gonorrheae are
the organisms most frequently associated with PID, up to 70% of
cases are neither gonococcal nor chlamydia related. Anaerobic gram-negative
rods are frequently involved in these infections, although isolation
is often difficult for reasons mentioned elsewhere in this chapter. Treatment
includes the use of doxycycline or a macrolide in combination with
cefoxitin, cefotetan, clindamycin, or metronidazole. Recently, randomized
clinical trials using moxifloxacin, ofloxacin, clindamycin-ciprofloxacin,
and azithromycin among women with mild to moderate PID found clinical cure
rates of 90% to 97%. Although single-drug therapy
holds promise for milder cases, further studies are needed to show
the efficacy of these regimens in treating anaerobes associated
with these regimens as well as preventing adverse reproductive sequelae, the
ultimate goal for effective and early treatment of PID.16
++
In addition to infections in older children, anaerobes colonize
the newborn during vaginal delivery and have been recovered from several
types of newborn infections, including cellulitis, aspiration pneumonia,
bacteremia, conjunctivitis, omphalitis, and infant botulism. The
wide range of endogenous infections caused by anaerobes in neonates
as well as older children is not surprising being that they form
the predominant component of the normal human skin and mucosa.
++
Given the overall low incidence of anaerobic infections in children,
the routine use of anaerobic blood cultures in childhood illness
has been debated. However, with the reemergence of anaerobic bacteremia,
the evidence favors obtaining anaerobic blood cultures.2,17,18 Diagnosis
made on clinical grounds can prove difficult because the clinical
features of anaerobic bacteremia are not very different from those associated
with other types of bacteremias in children. Diagnosis may also
be delayed due to the more fastidious growth requirements and time
needed for identification of these bacteria. Knowledge of host risk
factors as well as organ system involved may aid in the diagnosis. Presence
of a foul odor in the clinical specimen or site from which the specimen
was obtained may also provide a useful clue to the diagnosis. Antimicrobial
susceptibility studies for anaerobic bacteria are often not available
from hospital laboratories; however, they should be requested in
exceptional and life-threatening cases.
++
Because of the mortality associated with anaerobic infections,
it is important to establish timely appropriate therapy. Infections
involving anaerobes are often polymicrobial making antibiotic combinations
useful. Patients should be started on broad-spectrum antibiotics
effective against aerobic as well as anaerobic organisms. Site of
the infection, antimicrobial resistance patterns when available,
pharmacokinetics of the different drugs used, as well as potential
side effects should all be taken into consideration when deciding on
an antimicrobial agent. Penicillin G remains the drug of choice
against most non-beta-lactamase-producing organisms, including anaerobic
streptococci, Clostridium species other than C
difficile, and nonsporulating anaerobic bacilli. This makes
it appropriate for treatment of most oropharyngeal infections. Metronidazole
and clindamycin have excellent activity against anaerobes, including
those producing β-lactamase (eg, Bacteroides).
Clindamycin is superior to penicillin for serious lung infections.
Antibiotic combinations with β-lactamase inhibitors
(amoxicillin/clavulanic acid, ticarcillin/clavulanic acid,
ampicillin/sulbactam, piperacillin/tazobactam)
have become increasingly popular due to their broad-spectrum aerobic
and anaerobic activity as well as the ability to overcome β-lactamase
production. Second-generation cephalosporins cefotetan and cefoxitin
also have good anaerobic activity, although cefoxitin is relatively
inactive against most species of clostridium except C perfringens.
++
The carbapenems (imipenem, ertapenem, meropenem) all have excellent
anaerobic activity. Chloramphenicol also has excellent in vitro
activity against most anaerobes; however, its use has been limited
by the availability of safer antibiotics. The macrolides have moderate
to good in vitro activity against anaerobic bacteria other than B
fragilis and Fusobacterium. Although the
newer quinolones (moxifloxacin, levofloxacin) have better anaerobic
activity especially against the B fragilis group,
their use in children is limited due to the possible adverse effects
on cartilage. Vancomycin has good activity against all gram-positive
anaerobes including C difficile.1
++
In addition to antimicrobial therapy, drainage of any abscesses
and debridement of necrotic tissue are important. Certain types
of adjunct therapy, such as hyperbaric oxygen, although controversial
may also be considered in certain circumstances.