Antibiotics (Properties, Application, Interaction) - M.P. Cherenko 1999

Non-spore-forming anaerobic infection

Alongside the long-known form of anaerobic clostridial infection—gas gangrene—non-sporulating anaerobic (non-clostridial) infection has become significantly widespread in recent decades. It is caused by vegetative anaerobic saprophytic microflora of the family Bacteroidaceae. The elucidation of the latter's role in the Etiology of modern surgical infection is due to advancements in microbiological research, particularly research technologies under anaerobiotic conditions, which have revealed the causative agents of anaerobic non-clostridial microflora in the exudate and Tissues of the infection focus. These studies resolved those paradoxical cases of surgical infection where microbiologists, using older Research Methods, failed to detect microbes in wound or abscess samples and thus concluded that the pus was "sterile".

The group of non-sporulating anaerobes includes about 20 species of microorganisms, among which the most prominent roles are played primarily by the bacteroids B. fragilis and B. melaninogenicum, and to a lesser extent by fusobacteria (Fusobacterium necrophorum, nucleatum, etc.). These Gram-negative microorganisms are permanent residents of the mucous membrane of the oropharynx, Large Intestine, female genital tract, biliary and urinary tracts, etc. In the large intestine, The ratio of anaerobes to aerobes is 300–1000 to 1. Infection caused by these non-sporulating microorganisms is of endogenous origin—it enters the tissues when the mucous membrane or the entire thickness of the wall of the aforementioned tracts (sites of vegetation) is damaged during trauma, including surgical trauma, as well as necrotic, inflammatory, or tumor lesions. Most commonly, this infection occurs when the resistance of the human mucous membrane itself and the overall body resistance decrease due to general disorders (Heart Failure, Diabetes Mellitus, Blood diseases, immunodeficiency states, oncological diseases, other general illnesses, and chronic infections, etc.). This infection frequently complicates diseases and surgeries of the large intestine, as well as biliary tract diseases (cholelithiasis, etc.). Today, it has been clearly established that in 75–85% of patients, infectious complications following surgical interventions and abdominal organ diseases develop with the participation of anaerobic non-clostridial microflora.

As a rule, these microorganisms (bacteroids, fusobacteria, etc.) are present in sources of infection in associations with other causative agents of purulent and Putrefactive infection—both aerobes and facultative anaerobes, whether pathogenic or opportunistic (staphylococci, peptostreptococci, Escherichia coli, Proteus vulgaris, etc.).

Anaerobic infection should be regarded as a tissue lesion/disease (primarily adjacent to the permanent habitat of anaerobes—mucous membranes and membranes) or systemic body intoxication (Sepsis). The specific interaction features within associations of obligate anaerobes, facultative anaerobes, and aerobes involve the mutual enhancement of pathogenic properties (synergism). By consuming oxygen, aerobes create better conditions for the vital activity of anaerobes (lowering the oxidation-reduction potential in tissues); moreover, through The production of Enzymes by anaerobes—particularly beta-lactamases—they contribute to Antibiotic Resistance in other Bacteria. Some members of the association produce substances that accelerate the growth of other anaerobic microorganisms; for example, pseudodiphtheroids vegetating on the mucous membrane produce vitamin K, which is required for the growth of B. melaninogenicum, while the latter produce toxins. The most common bacteroid, B. fragilis, is a lactamase-producing microorganism that causes other microbes in the pathogenic association to become insensitive to Antibiotics.

An important prerequisite for this infection is tissue Hypoxia resulting from various causes: both general Circulatory Disorders and local ones—decreased tissue perfusion, including compression by a bandage or cast (tourniquet necrosis). It is precisely for these reasons that anaerobic non-clostridial infection is observed predominantly in elderly patients (over 50 years of age) with manifestations of atherosclerosis, Hypertension, diabetes mellitus, and other general systemic and Metabolic Disorders.

Anaerobic non-sporulating microflora is most frequently present in such forms of infection as oropharyngeal infection (gingivitis, stomatitis, paratonsillar abscess, Ludwig's angina, etc.), paraesophageal Phlegmon, Peritonitis, intra-abdominal abscess (particularly pelvic), cholangitis and Liver abscess, Brain abscess, aspiration Pneumonia and lung abscess, suppuration of bite wounds, abdominal wall phlegmon, gangrenous fasciitis, vaginitis, acute paraproctitis, etc. However, this infection most commonly complicates Diseases of the Abdominal cavity, especially the large intestine and female genital Organs, or surgeries on these organs (diffuse or localized peritonitis, abdominal wall phlegmon—cellulitis, fasciitis, etc.). Therefore, in these forms of infection, one must always keep in mind the possible involvement of anaerobic non-clostridial microflora among its pathogens and conduct appropriate clinical and Laboratory studies for accurate Diagnosis and targeted, effective Treatment.

The involvement of this microflora in the infectious process makes its course and prognosis much more complex and severe. Anaerobic Gram-negative sepsis, which usually arises from uncontrolled local foci of this infection, poses a particularly great threat to the patient. Suspicion of an anaerobic non-clostridial infection should be prompted by the following clinical signs:

1. Foul-smelling odor (putrefactive or colibacillary) of discharges from the wound or other infection foci.

2. Dark (brownish or even black) color of the exudate, its serous-turbid nature, often with fat droplets in it, or liquid purulent-putrid exudate.

3. Predominantly necrotic (gangrenous) nature of morphological Changes in the tissues of the infection focus (necrotic cellulitis, fasciitis) and significant spread of the process with largely unremarkable Skin changes, especially in the initial stage (prior to the disruption of skin blood supply due to necrosis of underlying tissues and fascia, as well as vascular thrombosis).

4. Septic Shock accompanied by jaundice.

5. Septic thrombophlebitis.

6. Localization of the infection focus adjacent to mucous membranes, within the surrounding tissues.

Anaerobic sepsis most frequently occurs in peritonitis, including intra-abdominal abscesses, and septic thrombophlebitis, which is often complicated by brain, lung, liver, and bone abscesses. It is accompanied by a very high mortality rate (over 50%).

Along with important local signs of anaerobic non-clostridial infection, it is characterized by significant manifestations of general intoxication—tachycardia, decreased blood pressure, fever, dyspeptic disorders, anemia, cyanotic skin color, etc. In sepsis, signs of shock appear—hypotension, tachycardia, hypovolemia, sweating, hyperthermia, cyanosis of the Lips and skin with facial flushing (in the hyperdynamic phase of sepsis).

Quite often, gas is present in the discharge (pus) within foci of anaerobic non-sporulating infection, but unlike anaerobic clostridial infection—where gas is found both in wound discharges and, most notably, in the tissues—in anaerobic non-clostridial infection, gas is present only in the exudate (pus). Muscles in non-clostridial infection remain virtually unchanged, although they may turn pinkish-gray (in the area of the infection focus), but they are not necrotic.

Microbiological Diagnostics of both clostridial and non-clostridial anaerobic infection are difficult and require a long time to isolate the culture. Non-sporulating anaerobes are very fastidious regarding media and highly sensitive to oxygen (even a negligible level of it leads to their death). Therefore, material for examination is taken from the infection focus under conditions of strict asepsis and anaerobiosis or minimal exposure to air. The exudate taken with a sterile needle (after expelling air from it with the plunger) is injected through a puncture into a sterile vial containing a chemical scavenger—a residual oxygen reducer. Viscous exudate (pus) and tissue detritus from the focus should be collected with a cotton swab on a stick (stored in a sterile test tube) and transferred into another sterile oxygen-free container. The material is immediately sent to the microbiological laboratory, where it is cultured and examined in anaerobiotic devices (anaerostats). Results (culture) are usually obtained in a week.

Due to the complexity and duration of microbiological testing, the initial clinical treatment strategy is based on the patient's physical examination findings. Antibiotics active against Gram-positive pyogenic microflora, as well as ANTIBIOTICS AND CHEMOTHERAPEUTIC agents active against non-clostridial anaerobes, are prescribed.

Among antibiotics against pyogenic infection, Aminoglycosides (particularly gentamicin), Cephalosporins, and penicillin group drugs (specifically semisynthetic ones, such as ampicillin at a dose of 20,000,000–30,000,000 IU per day, and ampiox) are most frequently used. Tienam and chlorquinolones (ciprofloxacin) are also used. Among antibiotics and drugs directed against anaerobic non-clostridial infection, clindamycin, chloramphenicol (levomycetin), lincomycin (especially effective against B. fragilis), metronidazole, and certain cephalosporins (such as cefoxitin, active against B. fragilis, as well as cefotaxime and cefuroxime, which are resistant to beta-lactamases synthesized by many anaerobic microorganisms) are employed. Kanamycin is also active against Pseudomonas aeruginosa.

Treatment of anaerobic non-clostridial infection is comprehensive. Its foundation is surgical intervention, consisting of wide opening of the infection focus with drainage, removal of exudate and necrotic tissues (excising all dead tissues). Wounds are left open and provided with wide aeration, and washed with hydrogen peroxide (1%) or potassium permanganate (1:1000) solutions. Hyperbaric Oxygenation is also utilized (postoperatively once daily for 45–60 minutes at a pressure of 0.2–0.4–0.6 atm) along with treatment in aromatherapy chambers.

Surgical intervention is supplemented with antimicrobial agents, specifically antibiotics and chemotherapeutic agents active against pyogenic aerobic and anaerobic microflora.

It is crucial to correct general disorders, salt and protein deficiencies, dehydration, and hypovolemia, and to normalize the blood composition. Controlling concomitant diseases—particularly cardiac disorders, diabetes mellitus, hypertension, respiratory failure, etc.—is of great importance.

Diligent patient care—including maintaining patients and their beds in a proper sanitary condition, combating pressure ulcers (frequent repositioning of the patient in bed, wiping the sacral skin with camphor alcohol, placing rubber rings underneath, etc.), a high-calorie and vitamin-rich diet, timely and painless wound dressing, and timely reoperation in case of infection progression, as well as active flushing of cavities and abscesses—all these measures are essential components of therapy and keys to the patient's recovery.

Prevention of non-clostridial anaerobic infection, due to its endogenous nature, is difficult and limited to early diagnosis and timely treatment of surgical diseases of those organs that serve as the source of this infection (digestive tract organs, especially the large and rectum, biliary and urinary tracts, oropharynx, etc.), measures to limit contamination during interventions on these organs and adjacent soft tissues by the contents of these organs and exudate (pus) in the affected areas, drainage of cavities and infected wounds, and in certain cases, delayed primary suturing of skin wounds.

A very important role in prevention is played by preoperative patient preparation, especially in interventions on the digestive tract: mechanical bowel cleansing and prophylactic administration of a daily dose of broad-spectrum antibiotics 2 hours before surgery, combating hospital-acquired infection, and strict adherence to aseptic rules.

GANGRENOUS STOMATITIS AND NOMA (Cancer AQUOSUS)

One of the rare forms of non-spore-forming anaerobic infection is gangrenous stomatitis, or noma (cancer aquosus). Originating in the oral mucosa (the cheek or Gums, presenting as gingivitis), this source of wet gangrene can spread through the entire thickness of the cheek tissue, resulting in perforation, and further involve the palate, Tongue, Nose, and other adjacent areas. As necrotic tissues break down and slough off, they sometimes create massive facial defects, leaving the Oral Cavity gaping and exposing the jaws and Teeth. This gangrenous-perforative stomatitis is caused by fusobacterial associations, occasionally involving anaerobic streptococci (with Cl. perfringens frequently isolated). It occurs primarily in children aged 2–12 who are debilitated by childhood infectious diseases, parasitic infestations, blood disorders (such as leukemia), or immunodeficient states—in other words, children with severely compromised Immunity. Contributing factors include poor oral hygiene, dental disease, and periodontitis. The disease typically manifests as acute sepsis characterized by high fever and rapid-onset anemia, and carries a high mortality rate. Under adverse conditions, gangrenous stomatitis may also develop in adults. It was notably documented among soldiers of European nations during World War I, which is why it is also known as trench Mouth.

The Development of this oral infection (“trench mouth”) is promoted by stress combined with poor Nutrition and inadequate hygiene.

Treatment must be comprehensive, comprising systemic anti-infective therapy (appropriate antibiotics, ciprofloxacin, sulfonamides, metronidazole, immunomodulators, general supportive care—especially vitamin supplementation—along with detoxification therapy, etc.) combined with local interventions (sanitation of local infection foci involving debridement of necrotic tissue and antiseptic treatment). Subsequent tissue defects caused by noma are managed through plastic surgery.

Today, noma is virtually nonexistent in our country. Thanks to timely therapeutic measures, gangrenous stomatitis is usually restricted to mucosal involvement, typically avoiding cheek perforation.