B. Sulfamethoxydiazine (Sulfameter, Sulla) IX. TOXICITY AND SIDE EFFECTS: C. Sulfadimethoxine (Madribon) A. Fever D. Sulphormethoxine-Very long-acting; thera- B. Rash, urticaria peutic blood levels for 1 week. C. Cyanosis, methemoglobinemia D. Nausea, vomiting, diarrhea V. POORLY ABSORBED SULFONAMIDES: E. Hepatitis, jaundice for local use in the intestinal tract only. F. Hematuria, albuminuria, crystalluria, toxic A. Succinylsulfathiazole (Sulfasuxidine): nephritis. 1. Dosage-3.0 Gm q 4 h p.o. G. Headache, mental depression, psychosis, 2. Maximum effect usually not achieved un- peripheral neuritis. til 7th day of therapy. H. Leukopenia, agranulocytosis, purpura, aplas- B. Phthalylsulfathiazole (Sulfathalidine): tic anemia, hypoprothrombinemia, hemolytic ane- 1. Dosage-1.5 Gmq4hp.o. mia. 2. Double this dosage in the presence of I. Severe hypersensitivity reactions - anaphy- diarrhea. laxis, periarteritis nodosa and other collagen dis- 3. Effect produced in 5-7 days. eases, Stevens-Johnson syndrome. C. Para-nitrosulfathiazole (Nisulfazole): Used X. only for intrarectal instillation in treatment of PRECAUTIONS: proctitis or non-specific colitis. A. Keep careful record of urine output - try to maintain output of at least 1200-1500 ml/24 VI. TOPICAL SULFONAMIDES: hrs. B. Alkalinization of urine-sodium bicarbonate A. Mafenide (Sulfamylon): Used on skin as (12-15 Gm/day) may be used for this purpose 10% cream. Unlike other sulfonamides, effective when full systemic doses of sulfonamides are used, in presence of pus and necrotic tissue and does not when there is difficulty in being sure of adequate sensitize readily when used topically. Of value in fluid intake and output, and when such adjunctive prevention and therapy of burn infection due to therapy is not contraindicated. Pseudomonas. C. Check fresh urine specimens for RBC's, B. Ophthalmic preparations: Sodium sulfaceta- albumin and sulfa crystals. mide (Sulamyd) and sulfisoxazole diolamine are the only products suitable for topical use in the eye; D. Weekly blood counts. they are available as solutions (30%) and oint- ments (10%). ANTIBIOTICS AND ANTIBACTERIALS, C. Vaginal preparations: These include sulfi- GENERAL soxazole and triple sulfonamide combinations SYDNEY M. FINEGOLD, M.D., AND ALVIN DAVIS, M.D. made up as creams or tablets. They are used in nonspecific vaginitis and cervicitis. I. PENICILLIN G (Benzylpenicillin): 1. Spectrum and Uses: Highly active against VII. SULFAPYRIDINES: Gram-positive cocci other than beta lactamase- A. Sulfapyridine: Too toxic for general use, but producing staphylococci; Gram-negative cocci; best drug available for dermatitis Gram-positive bacilli; fusiforms and some other herpetiformis. Gram-negative anaerobic bacilli; and (in high dos- B. Salicylazosulfapyridine (Azulfidine): Ofvalue age) Proteus mirabilis. Oral penicillin G is useful in ulcerative colitis, particularly in preventing re- in many urinary tract infections due to E. coli and lapse. Value in regional enteritis less well estab- P. mirabilis. lished. 2. Types of Preparations, Route of Administra- tion and Dosage: VIII. SULFONAMIDES IN GENERAL: a. Crystalline aqueous penicillin G: A. Desired peak blood level-8-15 mg/100 ml (1) Peak blood levels - generally 1-2 (except poorly absorbed compounds). units/ml for each one million units intra- B. Mode of action-bacteriostatic. muscular/day.

364 NOVEMBER 1969 * II I* 5 (2) Probenecid (Benemid) 0.5 Gm q 6 h million units supplies 975 mg (25 mEq) of will usually raise levels 11/2 to 2 times. potassium. b. Procaine penicillin G suspended in oil or c. Allergic reactions ranging from minor skin water: reactions to anaphylactic shock and death occur. (1) With single intramuscular dose of The best prophylaxis is a careful history com- 300,000 to 600,000 units, peak serum levels bined with discriminate use of this drug. The are usually 0.75 unit/ml or less and serum usual skin tests and conjunctival tests with peni- concentrations of at least 0.04 unit/ml (ad- cillin G are unreliable. Use of penicillinase equate for highly sensitive organisms such as (Neutrapen) for treatment of penicillin allergy pneumococci and Group A beta-hemolytic should be condemned because there is no proof streptococci) persist for from 20 to 24 hours. of its effectiveness and because it may actually Frequency of administration depends on increase the hazard. preparation and dosage used. d. Hemolytic anemia, neutropenia. (2) Increasing dosage primarily prolongs 4. Mode of Action: Bactericidal. duration of blood level rather than raising peak level; the usual daily maximum should II. ALPHA-PHEENOXY-PENICILLINS:* be 1.2 million units. A. Phenoxymethyl penicillin (penicillin V, Pen- c. Procaine penicillin G in sesame oil and Vee, V-Cillin): This compound is better absorbed 2 % aluminum monostearate: on oral administration than penicillin G and is A single 200,000 unit dose behaves much more acid stable. The antibiotic spectrum of the like procaine penicillin, but 600,000 unit two agents is similar. Both are susceptible to doses result in levels of 0.03 units/ml or staphylococcal beta lactamase. Most infections higher for more than 90 hours. which will respond to oral therapy can be treated d. Benzathine penicillin G (dibenzylethylene- with 250-500 mg q 8 h. Infections such as osteo- diamine dipenicillin G, DBED, Bicillin): myelitis or subacute bacterial endocarditis (when they can be treated orally) require >50-1,000 mg (1) Very insoluble salt. 300,000 unit dose useful for 0.03 q 4-6 h. Penicillin V is not ordinarily intramuscularly gives levels above unit/ therapy of urinary tract infections. ml for over 5 days with peak levels above 0.15 unit/ml uncommon at any time. Doses B. Phenoxyethyl penicillin (phenethicillin, Syn- of 600,000 units and 1,200,000 units intra- cillin, Maxipen, Chemipen, Broxil, Dargil, Alpen): muscularly result in prolongation of levels This compound is very similar to penicillin V. to 12 and 28 days, respectively. (The oral form is poorly absorbed and should not be III. BETA LACTAMASE-RESISTANT PEN- used.) ICILLINS: * (2) Chiefly useful as a prophylactic agent A. Methicillin (Staphcillin, Celbenin, Dimocil- and in the treatment of early syphilis. lin): (3) Painful on injection. Allergic reac- 1. Spectrum and Uses: Active vs staphylo- tions, when they occur, may be severe and cocci resistant to penicillin G (beta lactamase- prolonged. producers). Distinctly inferior to penicillin G e. Oral penicillin G: vs. other organisms. For urinary tract infections, 400,000 units 2. Routes of Administration and Dosage q6h. a. Intramuscularly 1 Gm q 3-6 h. 3. Toxicity, Side Effects, and Precautions: b. Intravenously 1-4 Gm q 4-12 h (12 Gm a. Central nervous system toxicity may occur or more/day in severe infections). It is best when unusually high doses are used and/or im- given in 50-100 ml over a 30 minute period paired renal function exists. q 4-6 h. (The drug is relatively unstable, par- b. The amount of potassium injected must be ticularly at acid pH's. Make up just before considered when very large doses of crystalline use.) aqueous potassium penicillin are used in the These agents exhibit cross-allergenicity with penicillin G. Probe- presence of impaired renal function. Each 15 necid blocks excretion of all penicillins. All are bactericidal.

CALIFORNIA MEDICINE 365 The Western Journal of Medicine 3. Toxicity, Side Effects and Precautions 4. Miscellaneous: Preferred over oral oxacil- a. Sensitivity reactions, as with peni- lin because of better absorption and thus higher cillin G. and more prolonged blood levels. Not suitable b. Renal damage (hypersensitivity?) for treatment of meningitis. fever, albuminuria, pyuria, hematuria, oligu- D. Dicloxacillin (Dynapen, Veracillin): ria to anuria, nitrogen retention, edema, and 1. Spectrum and Uses: Same as for oxacillin. eosinophilia may occur. This is apparently 2. Routes of Administration and Dosage: reversible, but complete recovery may take Available only for oral use. Dosage is 0.25-1.0 months. Gmq6h. c. Bone marrow depression (neutropenia) 3. Toxicity, Side Effects and Precautions: occurs occasionally. Same as for cloxacillin. d. Hemolytic anemia. 4. Miscellaneous: Peak serum levels approx- e. Each 4 Gm of drug supplies 230 mg imately twice those with cloxacillin at compar- (10 mEq) of sodium (drug supplied as so- able dosage. dium salt). E. Nafcillin (Unipen): 4. Miscellaneous. Moderately resistant staph- 1. Spectrum and Uses: Similar to oxacillin. ylococci have been isolated rarely. When other agents are to be administred simultaneously, 2. Routes of Administration and Dosage: they should be given separately rather than be- a. Oral-absorption not reliable. ing mixed with the methicillin. b. Intramuscularly-0.5 Gm q 4-6 h. c. Intravenously-0.5-1.0 Gm q 4 h. May B. Oxacillin (Prostaphlin, Resistopen): be administered by method described for 1. Spectrum and Uses: Similar to methicillin, methicillin. but somewhat more active on a weight basis. 3. Toxicity, Side Effects and Precautions: As There is greater protein binding with this agent. with oxacillin. 2. Routes of Administration and Dosage: 4. Miscellaneous - Significant biliary excre- a. Oral-not recommended (cloxacillin or tion. dicloxacillin are preferred oral agents. b. Intramuscularly-0.5-1.0 Gm q 4 h. IV. BROAD-SPECTRUM PENICILLINS:* c. Intravenously-0.5 Gm or more q 4 h. A. Ampicillin (Penbritin, Polycillin): May be administered by method described for methicillin. 1. Spectrum and Uses: a. Active vs most strains of Proteus mira- 3. Toxicity, Side Effects and Precautions: bilis and occasional strains of other Proteus a. Sensitivity reactions as with penicillin G. species. Active vs most strains of H. influ- b. Neutropenia (rare). enzae, Salmonella and Shigella, and about c. Reversible SGOT elevations are occa- 50% of E. coli strains. sionally noted. b. Similar to penicillin G in its activity vs 4. Miscellaneous - cross-resistance with Gram-positive cocci and vs anaerobes except methicillin. Greater amount of biliary excre- that it is more effective vs many strains of tion than with methicillin. Not suitable for treat- enterococcus. ment of meningitis. c. Susceptible to action of beta lactamase C. Cloxacillin (Tegopen): and therefore not effective vs most strains of S. aureus. 1. Spectrum and Uses: Same as for oxacillin. 2. Routes of Administration and Dosage: 2. Routes of Administration and Dosage: a. Oral-0.5-1.0 Gm q 4-6 h (probably Available only for oral use. Dosage is 0.5-1.0 best given one-half hour to an hour before Gmq6h. meals). 3. Toxicity, Side Effects and Precautions: b. Intramuscularly-0.5-1.0 Gm q 4-6 h. a. Same as for oxacillin. c. Intravenously - 1.0-2.0 Gm or more b. Nausea, epigastric distress, diarrhea, Thesw agents exhibit cross-allergenicity with penicillin G. Probe. bitter taste. necid blocks excretion of all penicillins. All are bactericidal.

366 NOVEMBER 1969 * II I* 5 q 4 h; may be administered in the same way as a. Intramuscularly-0.5-1.0 Gm q 6 h. recommended for methicillin. Approved use of drug at the time of this 3. Toxicity, Side Effects and Precautions: writing restricts maximum daily dose to 4 a. Sensitivity reactions as with penicillin G. Gm/day. b. Bone marrow depression. b. Intravenously-0.5-1 Gm q 6 h. May C. SGOT elevation (occasional). be administered by method described for d. Diarrhea (may be fulminant). methicillin. Maximum approved dose by this e. Moniliasis and other superinfections are route is 4 Gm/day as well. more frequent than with other (narrower 3. Toxicity, Side Effects and Precautions: spectrum) penicillins. a. Nephrotoxicity has occurred when drug 4. Miscellaneous - Significant biliary excre- is administered in doses in excess of 4 Gm/ tion. day. This has usually occurred in patients with impaired renal function. However, all V. CEPHALOSPORINS: patients treated with this drug should be ob- A. Cephalothin (Keflin): served carefully and frequent urinalysis and 1. Spectrum and Uses: serum creatinine levels should be obtained. a. Active vs most strains of P. mirabilis This drug should not be used in patients with and some strains of other Proteus species and impaired renal function. vs most strains of Salmonella and Shigella. b. Cross allergenicity with cephalothin and Active vs approximately 50% of strains of possibly with penicillins as well. Klebsiella-Enterobacter and E. coli. It is not c. Hematologic abnormalities - transient particularly active vs H. influenzae. leukopenia, eosinophilia, hemolytic anemia b. Similar to penicillin G in its activity vs (rare). Gram-positive cocci other than S. aureus but d. Superinfections, particularly Pseudo- less active vs pneumococci. It is less active monas. vs most anaerobes. 4. Mode of Action-bactericidal. c. Resistant to beta lactamase and there- VI. STREPTOMYCIN: fore effective vs S. penicillin-resistant aureus. 1. Spectrum and Uses: Should never be used 2. Routes of Administration and Dosage: alone because of extremely rapid development Not acid-stable; must be given parenterally. of resistance by various bacteria. In combina- a. Intramuscularly-0.5 Gm q 6 h for tion with other agents, this drug is useful in average case. Up to 1.0 Gm q 4 h in severe tuberculosis, enterococcal infections, in endo- or relatively resistant infections. carditis due to various organisms, in granuloma b. Intravenously-0.5 Gm q 6 h to 2.0 inguinale, and in Pasteurella infections. Gm q 3 h or more. May be administered by method described for methicillin. 2. Routes of Administration and Dosage: Intramuscularly-0.5-1.0 Gm q 12 h to 1.0 Gm 3. Toxicity, Side Effects and Precautions: 2-3 times weekly. a. Probably cross-allergenic with penicil- 3. Peak Blood Levels: 20-40 mcg/ml after lins. Same type of side effects as with pen- dose of 0.5-1.0 Gm. icillins. Side b. SGOT elevation 4. Toxicity, Effects and Precautions: (occasional). a. Dermatitis c. Superinfections, particularly with Pseu- (may be severe), drug fever. domonas. b. Nephrotoxicity. c. VIII nerve damage- primarily vesti- 4. Mode of Action-bactericidal. bular. B. Cephaloridine (Loridine): d. Bone marrow depression (uncommon). 1. Spectrum and Uses: e. Intraperitoneal, intrapleural, or rapid a. Essentially the same as for cephalothin, intravenous administration, particularly in as- except that it is more active against suscept- sociation with ether anesthesia, may result in ible anaerobic organisms than is cephalothin. curare-like effect with respiratory paralysis. 2. Routes of Administration and Dosage: Neostigmine is the antidote of choice. available only for parenteral use. 5. Mode of Action: Bactericidal.

CALIFORNIA MEDICINE 367 The Western Journal of Medicine VII. TETRACYCLINES: lower dose levels) in the presence of impaired 1. Spectrum and Uses: Active against many kidney function and/or pregnancy. Gram-positive and Gram-negative bacteria, vs d. DMCT-May show, in addition to items rickettsiae, Mycoplasma and Chlamydia (Bed- listed above in 4. a, nephrogenic diabetes insipi- sonia). Most S. aureus are resistant. Twenty per- dus. cent of Group A beta-streptococci are resistant, e. Special toxicity in the presence of impaired and occasional pneumococci are resistant. renal function (may be delayed). 2. Routes of Administration and Dosage: (1) Increasing azotemia, acidosis, hyper- phosphatemia. a. Oral- (1) Tetracycline, oxytetracycline, and (2) Anorexia, nausea, emesis. chlortetracycline-250-500 mg q 6 h. (3) Weight loss. (2) Demethylchlortetracycline and metha- (4) Increased urinary losses of nitrogen cycline-150mgq6hor 300 mgq 12h. and sodium. (3) Doxycycline-100 mg q 12 h x 3 These effects may be avoided by reduced doses, then 100 mg daily. dosage. They are reversible. Anabolic steroids may prevent or retard these effects also. b. Intramuscularly- f. Special toxicity with outdated drug-Fan- (1) Tetracycline and oxytetracycline - coni syndrome may occur (reversible). 100 mgq 8-12h. (2) Rolitetracycline-350-700 mg daily 5. Mode of Action: Bacteriostatic. in 1 or 2 injections. 6. Miscellaneous: The antibacterial activity of c. Intravenously- tetracycline is counteracted by certain multivalent (1) Tetracycline, oxytetracycline, and metallic ions. Therefore, it is best to avoid concur- chlortetracycline-500 mg q 8-12 h (by slow rent administration of such things as aluminum drip only). hydroxide gel, milk, etc. (2) Rolitetracycline-350-700 mg q 12 h 7. Types of Tetracycline Preparations Avail- (over 15-30 minute period). able: a. Tetracycline (Achromycin, Cosa-tetracyn, 3. Peak Blood Levels: Panmycin, Polycycline, Steclin, Sumycin, Tetra- a. Oral or Intramuscular-0.5-3.0 mcg/ml. cyn, Tetrex). b. Intravenous-8-10 mcg/ml. b. Oxytetracycline (Terramycin). 4. Toxicity, Side Effects, and Precautions: c. Chlortetracycline (Aureomycin). a. Oral. d. Demethylchlortetracycline (Declomycin, (1) Nausea, vomiting, anorexia, epigastric DMCT). distress. e. Methacycline (Rondomycin). (2) Diarrhea, flatulence, proctitis. f. Doxycycline (Vibramycin). (3) Stomatitis, glossitis. g. Rolitetracycline (Syntetrin, Velacycline). (4) Dermatitis. These drugs are very similar chemically and (5) Accumulation in teeth and bones- biologically. There may be some quantitative may cause pigmentation and enamel defects differences in antibacterial activity against cer- in teeth of children. tain species or strains; oxytetracycline seems to (6) Anaphylactoid reactions (rare). be generally superior to the others against Pseu- (7) Phototoxic reactions (more common domonas. There is virtually complete cross- with DMCT). resistance between the various agents. (8) Vaginitis. b. Intramuscular-local pain. VIII. CHLORAMPHENICOL (Chloromycetin) c. Intravenous. 1. Spectrum and Uses: Active against many (1) Thrombophlebitis Gram-positive and Gram-negative bacteria, rickett- (2) Hepatotoxicity may be seen with daily siae and Chlamydia (Bedsonia). Best drug for doses exceeding 1.5 grams. With intravenous typhoid fever. In a number of localities, signficant usage this may be accentuated (or found at numbers of staphylococci are resistant.

368 NOVEMBER 1969 * III * 5 2. Routes of Administration and Dosages: 4. Toxicity, Side Effects, and Precautions: a. Oral-0.5 Gm q 6 h. Occasionally higher a. Diarrhea, occasional nausea and vomit- dosages are indicated. ing. b. Intramuscular-Must not be used by this b. Mild rash (infrequent). route; absorption not dependable. c. Anaphylaxis (rare). c. Intravenous - Chloramphenicol succinate d. Intrahepatic cholestasis with jaundice is 0.5 Gm q 4-6 h, each dose administered in 50 seen occasionally in patients on erythromycin ml over 15 minute period. estolate. Eosinophilia (in the peripheral blood) 3. Peak Blood Levels: 10-20 mcg/ml, by any of occurs with this. The syndrome is a hypersen- above routes. sitivity phenomenon, occurring typically when 4. Toxicity, Side Effects and Precautions: the drug is taken for 10 days or more or in a. Bone marrow depression (any or all ele- repeated courses. The symptoms may recur, ments); may be fatal. In rare instances, there is in sensitive patients given another course, idiosyncratic bone marrow depression unrelated within 48 hours or even after a single dose. to dosage; apparently more common in white e. Intramucular injection usually very female children and after multiple courses. In painful. most patients, however, toxicity is well corre- 5. Mode of Action: Bacteriostatic lated with dosage and blood levels and with B. Oleandomycin, triacetyloleandomycin (Cy- duration of treatment. Elevation of serum iron clamycin, Matromycin, TAO): and drop in reticulocyte count are early signs of These agents have similar activity and there is toxicity. Complete blood counts should always marked cross-resistance between them and erythro- be done at regular intervals. mycin as well. Erythromycin is significantly more b. "Gray syndrome" in premature and neo- active than these drugs and since resistance devel- natal infants. ops relatively easily to any of these agents, the c. Optic or peripheral neuritis (rare). other agents should not be used except under very 5. Mode of Action: Primarily bacteriostatic. unusual circumstances where it is demonstrated 6. Miscellaneous: There may be a greater haz- that an organism is sensitive to one of them and ard of toxicity in patients with impaired liver func- not to erythromycin and another better agent is tion. Biliary excretion is poor. not available. Both intrahepatic cholestasis and hepatocellular IX. MACROLIDES: abnormality occur with triacetyloleandomycin; a A. Erythromycin (Erythrocin, Ilosone, Iloty- significant percentage of patients receiving 1 Gm/ cin): day for over two weeks may show such changes. 1. Spectrum and Uses: Active against Gram- Oleandomycin shows little toxicity. positive organisms primarily. Fifteen percent or more of S. aureus strains are resistant in some X. LINCOMYCIN (Lincocin): areas. Usefulness in staphylococcal infections 1. Spectrum and Uses: Active against Gram- (as a single agent) limited by initial resistance positive coccal organisms (including most strains or development of resistance. Also useful in of S. aureus) and anaerobes (with the exception of Hemophilus and Mycoplasma infections. Bacteroides fragilis). No activity against H. influ- 2. Routes of Administration and Dosage: enzae. Moderate activity vs. Mycoplasma. a. Oral or Intravenous-0.5 Gm q 6 h. 2. Routes of Administration and Dosage: b. Intramuscular - 100 mg q 8-12 h. a. Oral-0.5-1.0 Gm q 6 h. Give deep intramuscularly. b. Intramuscular-600 mg q 12 h. 3. Peak Blood Levels: c. Intravenous-600 mg q 6-8 h. a. Erythromycin base or stearate (Ilotycin, 3. Peak Blood Levels: Erythrocin) 0.5-3.0 mcg/ml. a. Oral-3-5 mcg/ml b. Erythromycin estolate (propionyl ery- b. Parenteral-6-13 mcg/ml. thromycin lauryl sulfate, Ilosone)-Levels 4. Toxicity and Side Effects: 2-3 times those with erythromycin base or a. Diarrhea. stearate and more consistent. This compound b. Occasional nausea, emesis or abdominal is available only for oral administration. distress.

CALIFORNIA MEDICINE 369 The Western Journal of Medicine c. Occasional rash or urticaria. tive organisms. Ineffective, or relatively so, d. Local reactions to intramuscular injection against Pseudomonas, streptococci, pneumo- (inflammation). cocci, anaerobes, Brucella. Some Klebsiella- e. Neutropenia-rare, reversible. Aerobacter strains are resistant. A significant f. Abnormal SGOT levels (occasional). number of S. aureus strains at many institutions 5. Miscellaneous: One-way cross-resistance with are extremely resistant. This resistance is high erythromycin; strains of S. aureus resistant to linco- enough to exceed concentrations of drug used mycin are also resistant to erythromycin. topically or achieved in G.I. tract after oral administration. XI. NOVOBIOCIN (Albamycin): 2. Routes of Administration and Dosage: 1. Spectrum and Uses: Sometimes useful in a. Intramuscular - 15 mg/kg/day or less Proteus (particularly P. mirabilis and P. vulgaris) (usually 1 Gm/day or less). Divided into infections. Should not be used for pneumococcal 2-4 doses. or streptococcal infections. Rarely of use in treat- b. Intravenous - same as intramuscular. ment of staphylococcal infections at the present Give very slowly. Avoid this route entirely, if time. possible, particularly in presence of impaired 2. Routes of Administration and Dosage: renal function. a. Oral-0.25 to 0.5 Gm q 6 h or 0.5-1.0 c. Oral-1.5 Gm q 4-6 h. Loading dose Gm q 12 h. of 1.0 Gm q h x 4 may be used when rapid b. Intramuscular or intravenous - Same as effect is desired. Some workers prefer to never for oral. Incompatible with dextrose-containing exceed 4.0 Gm/day orally. solutions. Give slowly intravenously. 3. Peak Blood Levels: 3. Peak Blood Levels: 20-40 mcg/ml; consider- a. Parenteral-20-35 mcg/ml. able protein binding. b. Oral-negligible except with severe he- 4. Toxicity, Side Effects, and Precautions: patic disease, renal disease, or in the presence a. Neutropenia-typically mild and revers- of extensive bowel ulceration. ible. Pancytopenia reported rarely. Hemolytic 4. Toxicity, Side Effects, and Precautions: anemia-rare. a. Nephrotoxicity-azotemia is chief man- b. Rashes - incidence 10-20%. Occur after ifestation. Seen more often in patients with 7th to 9th day. May be readily managed with pre-existing impairment of renal function. antihistamines as a rule. Recovery slow (4-6 weeks) but apparently c. Urticaria, drug fever, eosinophilia. complete as judged by the usual clinical de- d. Appearance of a yellow pigment in the terminations. Seen in older patients in absence plasma (which may interfere with the determi- of obvious evidence of pre-existing impaired nation of serum bilirubin and icteric index) may renal function. mask evidence of true liver damage and is there- b. Ototoxicity - both branches of VIII fore an indication for discontinuing the drug. nerve may be involved, but primarily the e. In neonates and young infants, tlere may auditory. Related to dosage, blood level, be interference with conjugation of bilirubin. duration of therapy, impaired renal function 5. Mode of Action: Usually bacteriostatic. (pre-existing or caused by drug), and previ- ous perceptive hearing loss. May occur even 6. Miscellaneous: There is relatively poor dis- with oral therapy in patients with poor renal tribution in tissues. function, etc. More likely to occur with con- XII. KANAMYCIN - NEOMYCIN - PAROMO- comitant or sequential use of other ototoxic MYCIN GROUP: agents. Essentially irreversible. Observe pa- tients closely for such early evidences of oto- A. Kanamycin (Kantrex): toxicity as tinnitus, "fullness" in the ear, and/ 1. Spectrum and Uses: Safest of group for or audiometric evidence of loss of acuity. Loss parenteral administration. Poorly absorbed oral- of acuity at 4000 and 8000 cycles typically ly; oral usage is for intestinal infections or for occurs before subjective hearing loss. "bowel sterilization." Very effective against a c. Pain at injection site occasionally-usu- wide variety of Gram-positive and Gram-nega- ally prevented by procaine.

370 NOVEMBER 1969 * III * 5 d. Curare-like effect with respiratory pa- 3. Peak Blood Levels: ralysis or arrest-may follow intraperitoneal, Oral - negligible, except in patients with intrapleural, or rapid intravenous administra- severe hepatic failure, renal disease, or exten- tion, particularly in association with ether an- sive bowel ulceration. esthesia. Calcium gluconate or neostigmine 4. Toxicity, Side Effects, and Precautions: should be tried as antidotes. Qualitatively similar to kanamycin, but more e. Since kanamycin is dialyzable, consid- toxic. Here, neostigmine is probably antidote of eration should be given to utilizing dialysis choice for neuromuscular block. Deafness may promptly in patients with early evidence of progress for extended periods after therapy has toxicity. been stopped and blood levels are no longer B. Gentamicin (Garamycin): demonstrable. 1. Spectrum and Uses: Active against most 5. Mode of Action: Bactericidal. Gram-negative bacteria including E. coli, Pseu- D. Paromomycin (Humatin): domonas aeruginosa and Proteus species. Kana- Similar to kanamycin and neomycin and shows mycin is more active against Proteus species and cross-resistance with them. Used only orally. May some strains of Klebsiella-Enterobacter but gen- be more effective in intestinal amebiasis than re- tamicin is effective against some strains of lated compounds. Klebsiella-Enterobacter which are resistant to XIII. POLYMYXIN-COLISTIN GROUP: kanamycin. It is the drug of choice for serious A. Polymyxin B Sulfate (Aerosporin): Pseudomonas infections, recognizing that occa- sional strains may be resistant. Its role in the 1. Spectrum and Uses: Effective vs. most management of staphylococcal infection remains Gram-negative bacilli other than Proteus. Dif- to be defined. It is ineffective against strepto- fuses poorly into body cavities and tissues. Sus- cocci, pneumococci, and anaerobes. ceptible to inactivation by constituents of cells and tissues. Orally, there is very little absorption 2. Routes of Administration and Dosage: so it is useful for some enteric infections. a. Intramuscular-0.4-1.0 mg/kg q 8 h. 2. Routes of Administration and Dosage: In serious infections, doses of 1.5 mg/kg a. Intramuscular - 2.5 mg/kg body q 8 h have been used for limited periods. weight/day; give in 3 divided doses (q 8 h). b. Topical. Average dosage is 50 mg q 8 h intramuscu- 3. Peak Blood Levels: With normal renal larly. May be diluted with procaine. function, doses indicated do not usually produce b. Oral - 10-20 mg/kg/day, divided serum levels in excess of 10 mcg/ml. into 4 doses (not absorbed). 4. Toxicity, Side Effects, and Precautions: c. Intravenous-Same dosage as intramus- a. Similar to that indicated for kanamycin. cular, but never over 200 mg per day. Ad- b. Ototoxicity - both branches of VIII minister each dose over 60 to 90 minute nerve may be involved, but the vestibular period. branch is involved more often. Predisposing d. Topical-0.1 to 0.25% concentration. factors as described under kanamycin prob- e. Intrathecal -Treatment of choice for ably apply to this drug as well. Pseudomonas meningitis. 5-10 mg in 10 ml of N/S first day, then 5 mg daily for 3 C. Neomycin (Mycifradin): days, then 5 mg every other day. 1. Spectrum and Uses: Very similar to kana- 3. Peak Blood Levels: About 2 mcg/ml. mycin. Should not be used parenterally because 4. Toxicity, Side Effects, and Precautions: of greater toxicity. Cross-resistance with other a. Nephrotoxicity; rising creatinine is indi- members of group may be seen. cation for lowering dosage or discontinuing 2. Routes of Administration and Dosage: drug. Renal shutdown rare. Changes usually a. Oral-as with kanamycin. reversible, as far as is known. b. Topical-5 mg/ml or Gm. Caution: b. Neurotoxicity - Paresthesias, ataxia, large volumes of irrigating fluid or prolonged weakness of legs, dizziness. Entirely revers- administration may produce enough absorp- ible, but may be disturbing enough to patient tion to cause toxicity. to force cessation of treatment.

CALIFORNIA MEDICINE 371 The Western Journal of Medicine c. Very painful on injection for most pa- XV. BACITRACIN: tients. 1. Spectrum and Uses: Active against Gram- d. Drug fever. positive organisms primarily. Rarely used paren- e. The possibility of neuromuscular block- terally at present. ade with respiratory paralysis should be kept 2. Routes of Administration and Dosage: in mind when this agent is used intraperitone- a. Parenteral - 50,000 to 100,000 units ally, intrapleurally, or intravenously. Calcium daily, divided into 4 doses (q 6 h) intramuscu- gluconate counteracts this effect experimen- larly. Should be diluted in procaine in normal tally. saline. Give deep intramuscularly. B. Colistin methanesulfonate (Coly-Mycin): b. Intrathecal - 5,000 to 10,000 units in Similar to polymyxin B. Should not be used normal saline daily (for staphylococcal menin- intravenously or intrathecally (contains dibucaine). gitis). Very well tolerated by CNS. Intramuscular dosage-5.0 mg/kg per day in di- c. Topical-500 to 1,000 units/ml or Gm. vided doses (q 6 h). Much less pain at intramus- 3. Peak blood levels after parenteral use-0.3 cular injection sites. (However, polymyxin given to 3.0 units/ml. intravenously avoids this problem.) Toxicity com- parable to polymyxin B when both are used at full 4. Toxicity, Side Effects, and Precautions: therapeutic dosage. Currently more expensive than a. Pain at injection site. polymyxin B. b. Nephrotoxicity - renal tubular necrosis may occur. If patient's blood urea nitrogen or XIV. VANCOMYCIN (Vancocin): creatinine is normal and remains so, toxicity 1. Spectrum and Uses: Active against essentially will usually be minimal and reversible. Watch all Gram-positive organisms; ordinarily should be urinary output carefully. reserved for infections not readily treatable with 5. Mode of Action: Bactericidal. less toxic agents. 2. Routes of Administration and Dosage: XVI. NITROFURANS: a. Oral- 4 grams/day. Absorption negli- A. Nitrofurantoin (Furadantin) gible, so useful only for staphylococcal entero- 1. Spectrum and Uses: Useful only for uri- colitis. nary tract infections. Most urinary tract infec- b. Intravenous - Parenteral administration tions with E. coli, staphylococci and enterococci must be by the intravenous route. Dosage-2 respond. About 50% of infections due to Pro- Gm daily, preferably 1 Gm q 12 h in volume of teus species or Klebsiella-Enterobacter respond. 50-100 ml administered over 15-30 minutes. Pseudomonas is resistant and may cause super- 3. Peak Blood Levels: 5-20 mcg/ml. infection. 4. Toxicity, Side Effects, and Precautions: 2. Routes of Administration and Dosage: a. Thrombophlebitis - less common when a. Oral-50-100 mg q 6 h. given intermittently rather than by constant b. Intravenous (Furadantin sodium)-180 intravenous drip. mg in 500 ml of diluent q 12 h (60 drops/ b. Rash, urticaria, drug fever. minute). Reduce dosage for patients under c. Anaphylactoid reactions-rare. 120 lbs. Dissolve crystals just prior to use. d. Nephrotoxicity - particularly in patients 3. Blood Levels: Negligible. with previous impairment of renal function. 4. Toxicity, Side Effects, and Precautions: e. Ototoxicity-much less frequent than with a. Nausea, vomiting-minimized by taking kanamycin. Related to high blood levels, drug with food. whether due to impaired renal function or not. b. Headache, malaise, dizziness. f. Leukopenia (rare). c. Rash, urticaria, other sensitivity reac- 5. Mode of Action: Bactericidal. tions (including pulmonary infiltrates). 6. Miscellaneous: It appears to be very difficult A. Hemolytic anemia in certain susceptible to induce resistance to this drug either in vitro or patients (people with red cells having glucose- in vivo. 6-phosphate dehydrogenase deficiency).

372 NOVEMBER 1969 * II I. 5 e. Peripheral neuritis - particularly in pa- XVIII. AMPHOTERICIN B (Fungizone): tients with impaired renal function or predis- 1. Spectrum and Uses: Effective against both position to neuritis (diabetes, avitaminosis, North and South American blastomycosis, histo- etc.). plasmosis, moniliasis, sporotrichosis, cryptococco- 5. Mode of Action: Primarily bacteriostatic. sis (torulosis), aspergillosis, mucormycosis and 6. Miscellaneous: Macrodantin is a macro- coccidioidomycosis. crystalline form of nitrofurantoin which is prob- 2. Routes of Administration and Dosage: ably comparable in activity and which may offer a. Intravenous -Start with daily dose of 5 the advantage of fewer gastrointestinal side mg and increase gradually (by 5-10 mg/ effects. day) to maintain dosage of 50-70 mg every B. Furazolidone (Furoxone): other day. Drug must be administered in 5% 1. Spectrum and Uses: This nitrofuran is dextrose in water using 100 to 150 ml of solu- used for treatment of enteric disease due to tion for each 10 mg of drug. Administer over Shigella and Giardia. not less than 6 hour period, using small gauge 2. Route of Administration and Dosage: 100 needle. Analgesics, antihistamines, sedatives, mgm orally q 6 h. etc. may be used to minimize reactions. Total 3. Toxicity, Side Effects, and Precautions: dosage should not exceed 2.0-3.0 Gm, if pos- a. Reactions similar to those described for sible. nitrofurantoin. b. Intrathecal or intraventricular* - Dilute b. Disulfiram-like reactions may occur drug in sterile distilled water to a concentration after alcohol in patients on this drug. of 0.25 mg/ml. The initial dose should not c. Urine may turn brown (not a sign of exceed 0.1 mg. This should be administered toxicity). slowly after first diluting solution with 6-8 vol- 4. Blood Levels: Drug absorbed poorly; umes of spinal fluid. Increase dosage at rate of blood levels low. 0.1 mg for each subsequent injection to maxi- very mum of 0.5-0.7 mg. Solutions must be made XVII. NALIDIXIC ACID (NegGram): fresh each time. Injections should be given 3-4 x weekly, preferably alternating between lumbar 1. Spectrum and Uses: Useful primarily for uri- and cisternal sites after the first few lumbar in- nary tract infections. May be useful in therapy of jections. Ordinarily, this schedule is followed for Shigella and enteropathogenic E. coli enteritis and approximately one month and then maintenance the Salmonella carrier state, but available studies injections of 0.5 mg are given intracisternally are not adequate to allow one to properly judge its once weekly for at least two more months. Intra- place in the management of these conditions. In ventricular therapy may be used in place of the case of urinary tract infection, it is most useful lumbar or cisternal intrathecal therapy. against Proteus but may also be useful in infec- c. Topical-Amphotericin may also be used tions due to E. coli, Klebsiella-Enterobacter and locally in the pleural space, joints, directly into occasionaly strains of Pseudomonas, staphylococci superficial lesions, etc., in selected cases. and enterococci. 3. Toxicity, Side Effects, and Precautions: 2. Routes of Administration and Dosage: Avail- a. Fever, chills, headache, nausea, vomiting. able only for oral use. The usual initial dose is 4.0 b. Phlebitis. Gm/day given in four divided doses. If therapy is c. Anemia; requires transfusion at times. continued for longer than 7-10 days, dosage should d. Nephrotoxicity-Unique nephropathy in- be reduced to 2.0 Gm/day. volving hyperkaluria, nephrocalcinosis and other 3. Toxicity, Side Effects, and Precautions: features suggestive of renal tubular acidosis. a. Nausea, emesis, occasionally diarrhea. Decreased glomerular perfusion is another fea- b. Rash, urticaria, drug fever, eosinophilia, ture. Renal toxicity probably best followed by photosensitivity. endogenous creatinine clearance. c. Occasional elevation of SGOT. e. Arachnoiditis may follow intrathecal ther- d. Occasional neural disturbances - head- apy. ache, drowsiness, dizziness, visual disturbances, Repeated intraventricular injection is feasible only when a device acute toxic psychosis, convulsions. such as an Ommaya valve has been implanted surgically.

CALIFORNIA MEDICINE 373 The Western Journal of Medicine