Antibiotics and Antifungal
Antibiotics Antifungal Drugs - Antibiotics Antifungal Therapy - Antifungal Antibacterial
Deep - Tissues, Organs
Deep infections are Candidiasis, Aspergillosis, Coccidiomycosis, Histoplasmosis etc
Antifungal Antibiotics List
Substances that destroy fungi by suppressing their ability to grow or reproduce. They differ from FUNGICIDES, INDUSTRIAL because they defend against fungi present in human or animal tissues.
Polyenes - Amphotericin B, Nystatin, Hamycin, Natamycin
Heterocyclic benzofurans - Griseofulvin
Antibiotics and antifungal agents
Despite its falling incidence, herpes simplex infection remains common. Most primary infections, which may be asymptomatic, are acquired in childhood, where they manifest as gingivostomatitis. The incidence of herpes virus infections is higher in deprived areas. A retrospective review of 43 cases of gingivostomatitis among children admitted to a regional infectious diseases unit over a 24 month period suggests that general practitioners are uncertain about the diagnosis and treatment of this condition. While our sample may be biased, it suggests that current practices should be reviewed.
The 43 cases were clinically similar, and of the 25 which were investigated virologically, 22 had positive cultures for herpes simplex virus. An obvious prodrome, lasting between one and three days, was noted in only eight cases. Four patients had been unwell in the week leading up to admission (two with gastroenteritis and two with chest infections). Treatment prior to hospitalization consisted of: nystatin (five patients), amphotericin (one), aminopenicillin (ampicillin, amoxycillin or co-amoxiclav) (nine), erythromycin (four) and aminopenicillin plus nystatin (five). Two of the five patients who received acyclovir prior to admission had received antibiotics beforehand. In the three instances when an antibiotic had been prescribed for prodromal symptoms it was erythromycin. This is likely to represent the choice of antibiotic for 'pyrexia of unknown origin' and it seems unlikely that erythromycin increases the incidence of ulceration. Bacterial culture grew light growths of normal oral flora, and occasional light growths of yeasts. From discussion at the time of admission, and because nystatin was the commonest therapeutic agent prescribed prior to admission, it appeared that many of the cases were being misdiagnosed as thrush or bacterial stomatitis. At the time of presentation all of the children had painful mouths (often present before ulcertion), displaying typical shallow, greywhite, based ulcers in the anterior part of the mouth, and 23 had secondary lesions. The greyish-white ulcers are quite distinct from the white raised lesions which are the usual sign of candidiasis in children. The latter are confined to mucosal surfaces and are less associated with systemic illness. Many children have light growths of candida on oral swabs, as did a number in this series. We did not use antifungal agents in these circumstances and had no problems with thrush.
Only five children had received acyclovir prior to admission, without obvious benefit. Our policy is to give acyclovir in the first two days of illness (except for very mild lesions), though there is no conclusive evidence to show benefit at present.4 Certainly treatment probably needs to be given very early. No children required intravenous fluids or had late complications.
Herpetic gingivostomatitis may be diagnosed on clinical grounds,5 and if confirmation is required, herpes simplex virus is easily cultured. Thrush should be easily distinguishable, and if treatment for possible bacterial stomatitis is desired, penicillin V is active against all normal pathogens, and is less likely to cause adverse events than many agents.
Specific organ toxic effects
Patients with reactions to locally applied sulfonamides will usually respond to a simple patch test with a 50 per cent sulfonamide powder in hydrous lanolin applied to the skin after light scarification.
Subjects who develop hypersensitivity reactions to systemic sulfonamides usually fail to respond to skin tests but show an immediate allergic reaction when tested by intradermal injection of serum from a patient receiving the appropriate sulfonamide.
For a positive result the test serum must contain at least 2 mg. per 100 ml. and should come from a patient who has been taking sulfonamides for at least five days.
Sometimes the sensitivities are specific for a particular sulfonamide. On other occasions, particularly after local therapy, the patients react to all sulfonamides and also to the common radicle sulfanilic acid. They may also show reactions to procaine, which possesses the same amino-phenyl radicle.
Patients can sometimes be desensitized by a week's course of increasing oral doses twice daily, starting with 0.1 Gm.
Hypersensitivity to penicillin presents a far more serious problem than with any other antibiotic. The initial contact may be hidden. Usually two types of reactions are seen, urticaria and fever and that of immediate profound shock which may be fatal in a few minutes. This usually follows injection, but may take place after oral administration, local application, or following a minute dose, as a test for sensitivity.
To avoid this type of reaction one must take a careful history of previous reactions. Routine sensitivity tests show only the less dangerous type of hypersensitivity. Patients with asthma and other known sensitivities are exceptional risks and should be given other antibiotics. Penicillin should only be used when there is ample justification.
De Week has suggested using penicilloylpolypeptide compound for skin testing, as he believes the actual hapten responsible for the sensitivity is not the penicillin-protein combination but penicillenic acid or a penicilloyl derivative of it. This substance is slowly formed from penicillin in solution. Penicillenic acid can induce sensitivity but the penicilloyl-polypeptide compound does not induce hypersensitivity although it can detect it.
Blood dyscrasias. The most serious complication of sulfonamide therapy is damage to blood-forming organs. Anemia, purpura, and agranulocytosis may result. It can follow a short course but in the majority of cases it follows a prolonged schedule of high dosage. Hypersensitivity may be a factor.
Agranulocytosis commonly develops in two to three weeks after the onset of therapy. Fever is often the first sign. The presence of fever at this time should be a warning.
Chloramphenicol is a potentially dangerous bone marrow depressant. Granulocytopenia is uncommon. Purpura and pallor are the first signs. Blood counts show a deficiency of all blood cells. Death is the usual outcome despite transfusions. This complication may appear during the months after cessation of therapy. There seems to be no absolutely safe dosage schedule.
Repeated blood counts can be a safeguard. A diminished reticulocyte count is the earliest sign; the disease is reversible at this stage. This test is as accurate as a bone marrow biopsy. It is advisable to repeat this test every two days.
Gastrointestinal disturbance. The tetracyclines are the chief offenders of the antibiotics to the gastrointestinal tract. Some of the effects may be due to irritation but they are most probably due to superinfection. Three kinds of organisms fill the void left by the flora inhibition induced by these broad-spectrum agents. Candida albicans may proliferate in the mouth, pharynx, and bowel. Proteus and Pseudomonas species resistant to the tetracyclines may become predominant in the bowel. A resistant strain of Staphylococcus aureus may be responsible for a serious superinfection. Diarrhea is the outstanding symptom and should be a stimulus for the search of fecal films for positive stains of the offending organisms.
It is doubtful that vitamin B deficiency is an important factor in this gastrointestinal disturbance. It is also doubtful that one tetracycline is less damaging in this regard than another.
Liver disease. Erythromycin and oleandomycin can produce mild gastrointestinal disturbances, but more threatening is the potential for liver damage. Usually abdominal pain, fever, hepatic enlargement, and raised bilirubin indicate the hepatic involvement. All disturbances clear as the drugs are withdrawn.
Eighth nerve damage. Defects of hearing ranging from decrease in auditory acuity to complete deafness may be noted with vancomycin, kanamycin, and neomycin. This eighth nerve involvement appears to be related to dosage schedule, duration of therapy, and renal efficiency. However, deafness has been reported with small doses, particularly in the presence of impaired renal function. If the kidneys are impaired it is best to use some other agent, e.g., methicillin or oxacillin, for resistant staphylococci.
The most serious effects of streptomycin are vestibular disturbance and deafness with dihydrostreptomycin. Although chances of such side effects are related to total dosage, renal impairment and age in excess of 40 increase the risk. The severity of the threat to vision by a properly diagnosed ocular infection is sufficient justification for the use of these agents in spite of their toxicity.
Thrombophlebitis. The most common complication of vancomycin and amphotericin therapy is thrombophlebitis at the injection site. In order to minimize this, the antibiotic must be diluted adequately, given slowly, leakage avoided, and different veins employed for each injection. The dilution may be in. normal saline or a 5 per cent dextrose solution. The concentration should not exceed 1 per cent and the rate of injection should be 2 ml. per minute
Ampicillin is the first available semisynthetic penicillin that is effective against Gram-negative bacteria. Chemically, it is arpha-amino-benzyl penicillin. It is active against some strains of E. coli, Shigella, and Salmonella. It seems to be equivalent in the strains tested to the action of tetracycline and chloramphenicol. It is quite active against Hemophilus inflnenzae. It is not effective against many strains of Proteus or Pseudomonas, nor is it as effective against nonpenicillinase-producing staphylococci as penicillin G. It is destroyed by penicillinase and therefore is ineffective against penicillinase-producing staphylococci and Gram-negative bacteria such as E. coli and Proteus bacilli, which may also elaborate the enzyme. No parenteral preparation of this is available; it is given orally. Studies in our laboratory to date have shown that this drug penetrates adequately into the normal experimental animal and human eye. It passes readily into the inflamed eye. It is unlikely, because of its lack of effect against penicillinase-producing staphylococci, that it will be of great therapeutic value to ophthalmologists in spite of its penetration performance. However, its ease of penetration makes it potentially useful for combined therapy.
Toxic effects of newer penicillins. Organisms do develop resistance to these agents, and superinfections have already been reported by fungi as well as Gramnegative bacilli. Each of these has the possibility of producing hypersensitivity reactions in the recipient and there may be crossed allergic reactions with people who are sensitive to penicillin G although this does not always occur. Bone marrow depressions have also been reported in a few patients during methicillin therapy so that blood counts must be performed routinely. An elevation of serum glutamic oxaloacetic transaminase (SGOT) has been noted in an occasional patient when treated with oxacillin and ampicillin.
Subconjunctival injections of cloxacillin in rabbits produced corneal opacities and therefore this has not been recommended for ophthalmic use in this manner.
The drug, available commercially, is called cephalothin (Keflin). It is poorly absorbed when taken by mouth and must be given intramuscularly or by intravenous injection. It does not pass readily across bloodaqueous barrier or across the blood-brain barrier. However, when inflammation is present, levels can be detected in these structures. Cephalothin will penetrate into the aqueous of rabbits after subconjunctival injection. This drug, bound to a great extent by the serum proteins, has a broad spectrum but is not effective against Pseudomonas. It does effect Gram-positive cocci including penicillinase-producing staphylococci, the majority of strains of H. influenzae, Proteus, and E. coli. Cross allergies with other antibiotics including penicillins have not been demonstrated.
Cephalothin is a relatively nontoxic drug. Skin eruptions have been noted as well as leukopenia, and elevations of SGOT have been reported. It is rather painful at the site of injection.