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A single 75-mg dose of sodium colistimethate was administered intramuscularly to 39 subjects with varying degrees of renal function; 17 of the subjects were undergoing dialysis therapy. Se...

Dr. E. B. Edmondson in our laboratory has reported on the in vitro susceptibilities of members of the Klebsiella-Enterobacter-Serratia group of organisms to 11 antimicrobials including gentamicin [1]. Bacteriological methods employed to differentiate between Klebsiella, Enterobacter kanamycin sulfate, tetracycline, chloramphenicol, polymyxin B sulfate, colistimethate, gentamicin sulfate, and nitrofurantoin sodium in trypticase soy agar (BBL) and stored at 4 C. Bacterial strains to be tested were inoculated into trypticase soy broth (BBL) and incubated 4-6 hr until a

A previously well 4-year-old child died following administration of ten times the recommended dosage of colistimethate sodium. The clinical course was marked by acute renal failure and neuromyal paralysis and at autopsy acute tubular necrosis was the major finding.

A MARKED increase in the incidence of systemic infections due to gram-negative enteric bacilli has been observed in hospitalized patients since the advent of antibiotic therapy.1 , 2 Many of these micro-organisms are relatively insensitive or resistant in vitro to the action of commonly used antibiotics.3 , 4 However, most strains of escherichia, klebsiella-aerobacter and pseudomonas species are susceptible in vitro to colistin,3 , 4 which has been shown to be effective in therapy of infections caused by these micro-organisms.4 5 6 7 To achieve therapeutic serum levels of colistin, intramuscular administration of colistimethate sodium§ must be employed.8 Colistin is excreted in the urine,9 , 10 and excessively high serum concentrations . . .

To the Editor:— In the article by Drs. Hinman and Wolinsky, "Nephrotoxicity Associated With the Use of Cephaloridine" (200:724, 1967), the following was reported:Klebsiellawas isolated from the sputum of a patient with pneumonia; and was found to be susceptible to tetracycline, chloramphenicol, streptomycin, sulfisoxazole, kanamycin, polymyxin B and cephalothin; but was resistant to ampicillin by the disk method. By the tube dilution method, the minimum inhibitory concentration for cephaloridine was 25μg/ml. We consider this level to indicate relative resistance, and accordingly would not use cephaloridine in such a case. The patient had been previously treated with penicillin, chloramphenicol, and streptomycin, and then cephaloridine, up to 12 gm intravenously in 24 hours, was used. We do not recommend more than 4 gm daily intravenously. Sodium colistimethate was also administered. Prior to cephaloridine therapy, blood urea nitrogen levels were 13 and 23 mg/100 ml, but with this drug the

Neutral solutions of aminomethanesulfonates are largely dissociated into hydroxymethylamino compounds and sulfite (and bisulfite) ions. Identical solutions are formed either by dissolving pure crystalline aminomethanesulfonic acids or by combining the amine, formaldehyde, and sulfite at appropriate pH. Solutions of aminomethanesulfonates can react with an additional molecule of formaldehyde bisulfite to give a disubstituted amine, which in turn dissociates to give more sulfite ion. Neutral solutions of sodium colistimethate comprise complex equilibria in which individual molecules are substituted by varying numbers of meth-anesulfonate or hydroxymethyl groups, possibly as many as 10, but with three or four of these species more highly favored than the rest (possibly for steric as well as statistical reasons). When more than three molecules each of formaldehyde and sulfite are available for reaction with colistin, no evidence for the existence of free colistin is found. Furthermore, the likelihood for the simultaneous existence of five unreacted amino groups in one molecule is very small.

A 70-year-old man with myasthenia gravis received a single intramuscular injection of colistimethate sodium (150 mg) for a urinary tract infection. He developed a respiratory arrest with a complete flaccid paralysis three hours later. All muscles but those associated with respiration improved rapidly following intramuscular neostigmine methylsulfate (2 mg) and intravenous edrophonium chloride (10 mg) administration. A combination of ventilation support and anticholinesterase therapy brought about recovery in 11 days. Carbenicillin effectively eradicated the Pseudomonas infection without causing neuromuscular impairment.

Excerpt To the editor: I have read the paper on sodium colistimethate by Dr. Koch-Weser in the June issue of the ANNALS(72:857-868, 1970). The report raises certain questions. A prospective study o...

Staphylococcus aureus showed decreased susceptibility to penicillin, vancomycin, sodium cephalothin, and tetracycline, but increased susceptibility to sodium colistimethate, at a pressure of 68 atm in helium or helium-oxygen gas. Susceptibility of Streptococcus pyogenes was unchanged by pressurization.

Excerpt To the Editor:The recent article by Goodwin and Friedman, "The Effects of Renal Impairment, Peritoneal Dialysis, and Hemodialysis on Serum Sodium Colistimethate Levels" (Ann. Intern. Med. 6...

SODIUM COLISTIMETHATE (Coly-Mycin Injectable) [Colomycin] has been shown to be of value in the treatment of certain types of infection (Carroll and Malette, 1961; 1 Edgar and Dickinson, 1962; 2 Sandrucci, 1956 3 ), but its value in the treatment of meningitis has not been established. Marsden and Hyde (1962) 4 reported the successful treatment of two children with meningoceles suffering from meningitis. Sandrucci (1958) 5 found sodium colistimethate diffused well into the cerebrospinal fluid (CSF) of children and that the diffusion levels obtained in children with inflamed meninges were even higher. Boger and Gavin (1961) 6 also reported that sodium colistimethate diffused into the CSF of adults with uninflamed meninges. For these reasons it was thought that this drug might be of value in the treatment of infection in hydrocephalic children; and the results obtained were compared with those obtained with chloramphenicol, the ability of which to diffuse into the

TOPICAL mafenide (Sulfamylon) acetate B in a hydrophilic base has recently been shown to effectively reduce the mortality from burn wound sepsis both in the laboratory and clinically. This therapy has been based largely on the work of Teplitz 1 and Lindberg 2 and subsequently substantiated in our laboratory showing that the mortality is directly related to the degree of burn wound sepsis as measured by eschar and subeschar bacterial counts and that the bacterial invasion of a burn wound occurs at a predictable rate. Topical mafenide has been shown by Lindberg 3 to be progressively less effective if the initial application is delayed until 48 hours postburn or longer. Systemic antibiotics have not significantly reduced burn mortality probably due to their inability to achieve effective concentrations in the burn with its damaged vascularity, 4,5 and still remain within safe systemic levels of the antibiotic. Sodium colistimethate (Coly-Mycin Injectable) has

To the Editor:— After reading the article by Parisi and Kaplan ( 194 : 298,1965) describing apnea, muscle weakness, and ptosis in association with colistimethate therapy, we feel obligated to caution physicians that neuromuscular effects due to this drug may be quite common. We recently saw a patient who repeatedly developed episodes of ptosis and profound muscular weakness of the extremities in response to small doses (75 mg every 12 hours) of sodium colistimethate. Her renal function was normal, and the maximum blood level of the drug was 2μgm/ml. This value is within or below the recommended therapeutic range. Edrophonium, 10 mg, administered intravenously improved her extremity weakness, but had no effect on her facial weakness. Fortunately, toxicity due to the colistimethate was considered, and she became asymptomatic when the antibiotic was discontinued. It is conceivable that had this patient received the customary dose of the drug (300 mg), or had there

W ITH great success we have 11 Ibeen using Thayer-Martin (T-M) medium with vancomycin, colistimethate, and nystatin (VCN) inhibitor (1,2) for the culture of Neisseria gonorrhoeae (3) Specimens from a number of patients with purulent discharges containing large numbers of Gram-negative diplococci, however, have yielded no growth of gonococci on this medium. Our suspicions that some gonococci were suppressed by one of the three antibiotics of T-M medium were confirmed by the work of Reyn (4) who reported that 3 percent of gonococcal strains from 171 cultures were suppressed on a medium containing 3 1?g per milliliter of vancomycin. We thereupon embarked on a study to examine the sensitivity of various wild strains of gonococci to the VCN inhibitor used in the T-M medium and to determine to a limited extent whether vancomycin was the inhibitory substance.

To the Editor.— We wish only to call attention to one small error in an otherwise fine report. The statement by Hardy et al ( 212 :1345, 1970) is made that the infant received "colistin sulfate 4 mg/day intramuscularly." There are two considerably different forms of the antibiotic colistin available. First is colistin sulfate which is essentially the sulfate salt of the colistin base. Second is the methane sulfonate derivative of this base, namely, colistimethate sodium. The former product is referred to as Coly-Mycin S Oral Suspension and is used only for the treatment of enteric infections. Because of its toxicity, it is never administered intramuscularly. The second product is referred to as Coly-Mycin M Intramuscular (Injectable) which has a considerably lesser toxicity and is the form generally used for intramuscular systemic therapy. Admittedly, the similarity of the names for both forms of this antibiotic leads easily to confusion but, in

Infections caused by bacteria of the tribe Mimeae were reviewed.Mima polymorphaorHerellea vaginicolawas isolated by culture from 56 living patients and 9 autopsy cases, with pure cultures of these organisms from 11 living patients. Mimeae were found to be opportunistic pathogens with a highly variable degree of virulence. In three febrile patients, blood cultures yielded a pure growth ofH vaginicola, establishing the apparent pathogenicity of these organisms. Many of the infections were associated with an iatrogenic portal of entry, such as an intravascular catheter, with over half of the 18 wound infections occurring in head- and neck-surgery cases. Sodium colistimethate, kanamycin sulfate, methenamine mandelate, and polymyxin B sulfate were found to be the most effective therapeutic agents.

THE HE CURRENT medical literature reflects an increasing recognition of druginduced renal disease. 1 The clinical effectiveness of the antibiotic, colistin, in a variety of bacterial infections has been well established. 2-8 To date, disturbances of kidney function attributed to this drug have usually been minimal and completely reversible. This is a report of four patients in whom acute renal failure developed during treatment with sodium colistimethate (Coly-Mycin Injectable) (Table). Report of Cases Case 1 (Fig 1). —B.I., a 75-year-old obese woman, was admitted to Presbyterian-St. Luke's Hospital for treatment of a fracture of the femur. On admission, the urinalysis was normal and the blood urea nitrogen (BUN) was 9 mg/100 ml. On the third hospital day, the head of the femur was replaced by a prosthesis. Low-grade fever was noted during the postoperative period. A small diffuse opacity of the right middle lobe of the lung was seen on

To the Editor:— I have read with interest a number of Clinical Notes inThe Journalin the past 18 months on antibiotic-related respiratory depression ( 190 :421, 1964; 194 :298, 1965; 196 :181, 1966). Particularly disturbing is the consistency of the theme of reports of apnea induced by the closely related polypeptide antibiotics polymyxin B sulfate and sodium colistimethate. In each of these reports the patients were receiving large or maximally recommended doses of these agents; there was indication of neurologic dysfunction (dysphagia, circumoral paresthesias, blurred vision) hours to days prior to sustained apnea. In spite of symptoms of neurotoxicity, drug administration was continued in unchanged dosages. Two of the patients were azotemic at the inception of therapy (which is in itself an indication for lowered dosage), and the third became azotemic during treatment. In one case, serum concentration of the drug at the time of the apneic episode was

Excerpt To the Editor:Dr. Kunin has been a leading proponent of correct antibiotic usage. He has performed an important service by calling attention to the urgent necessity of reducing dosage in th...

RESPIRATORY PARALYSIS has been increasingly publicized as a side effect encountered in antibiotic therapy. Recently Perkins 1 incriminated sodium colistimethate, a congener of polymyxin B, as a cause of apnea in man. We have observed a patient who experienced respiratory arrest during colistimethate therapy and have obtained additional data pertinent to the interrelationship. Report of a Case A 66-year-old woman had intermittent, severe acute pyelonephritis for four years prior to November 1963, when she underwent right nephrectomy for multiple cortical abscesses. At that time chemical diabetes was discovered. In December 1963. she was readmitted with left pyelonephritis. On examination she was in a toxic condition and dehydrated. Temperature was 101.4 F (38.6 C), pulse rate 92, and blood pressure 120/80 mm Hg. Carotid pulses were normal. She had a grade 2/6 systolic ejection murmur at the left sternal border and a healed right flank incision. Neurological examination showed intact cranial

96 Incidence of nephrotoxicity associated with concomitant colistimethate and vancomycin use in cystic fibrosis patients M. Adeola1, A. Coralic1, S. Hart1, T.L. Barto2, M. Katz2,3. 1The Methodist Hospital, Pharmacy, Houston, United States; 2Baylor College of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Houston, United States; 3Texas Children’s Hospital Pavilion for Women, Houston, United States

96 Incidence of nephrotoxicity associated with concomitant colistimethate and vancomycin use in cystic fibrosis patients M. Adeola1, A. Coralic1, S. Hart1, T.L. Barto2, M. Katz2,3. 1The Methodist Hospital, Pharmacy, Houston, United States; 2Baylor College of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Houston, United States; 3Texas Children’s Hospital Pavilion for Women, Houston, United States

96 Incidence of nephrotoxicity associated with concomitant colistimethate and vancomycin use in cystic fibrosis patients M. Adeola1, A. Coralic1, S. Hart1, T.L. Barto2, M. Katz2,3. 1The Methodist Hospital, Pharmacy, Houston, United States; 2Baylor College of Medicine, Division of Pulmonary, Critical Care, and Sleep Medicine, Houston, United States; 3Texas Children’s Hospital Pavilion for Women, Houston, United States