Intrathecal Use of Colistin

This letter reports a case of meningitis caused by a multiresistant gram-negative rod that was successfully treated with intrathecal colistin. A 41-year-old female was admitted to the intensive care unit due to subarachnoid hemorrhage. The computerized tomography scan showed intraventricular bleeding, enlargement of the lateral ventricles, and a decrease in size of the fourth ventricle. The patient underwent a craneotomy for clipping of an aneurysm and we performed an external drainage.

The patient developed fever 8 days after the drainage. The cerebrospinal fluid (CSF) white cell count, red cell count, and chemistry are show in Table 1.

TABLE 1.

Clinical parameters and microbiology of CSF

Parameter (unit) or test	Value or result on indicated date (mo-day-yr)
	1-10-99	1-18-99	1-19-99	1-23-99
Dextrose in CSF (mg/dl)	67	69	9	65
Leukocyte count in CSF (cells/mm3)	3	2,100	1,200	50
Protein in CSF (g/liter)	0.1	0.4	3.6	1.2
Lactic acid in CSF (mg/dl)	14.9	14	70	60
Chloride in CSF (meq/ml)	131	121	118	115
Gram stain		GNRa	GNR
CSF culture		A. calcoaceticus	A. calcoaceticus

^aGNR, gram-negative rods. 

The CSF culture grew Acinetobacter calcoaceticus (now Acinetobacter baumannii). The susceptibility results were as follows: resistant to ampicillin-sulbactam, piperacillin, piperacillin-tazobactam, ceftazidime, cefepime, imipenem, meropenem, aztreonam, gentamicin, and amikacin (NCCLS document M2-A6); susceptible only to colistin. The MIC of colistin was 0.5 μg/ml, and the MIC of amikacin was 128 μg/ml (NCCLS document M7-A4).

The treatment consisted of 5 mg per day of intrathecal colistin on day 1 and 10 mg of intrathecal colistin per 24 h for 21 days thereafter.

The CSF Gram stain and culture became negative after 24 h, whereas the blood chemistry normalized at 48 h.

The inhibitory and bactericidal activities of the CSF were measured right before the intrathecal injection of colistin. Both values were 1/8 CSF dilution.

The patient had a successful outcome. Six weeks after finishing the intrathecal treatment, the patient underwent the last drainage with no complications.

Some cases of bacterial meningitis cannot always be treated intravenously with conventional antimicrobial agents. Patients with meningitis due to multiresistant gram-negative rods should be treated intrathecally with polymixin B or colistin; however, due to their toxicity, these agents are not currently used (1, 4, 6).

Multiresistant Acinetobacter spp. are frequently the etiologic agent of nosocomial infections, and 90% of these strains are susceptible to colistin (MIC at which 90% of the isolates are inhibited, 2 mg/liter) (3). The MIC of colistin for the strains that caused the infection in our patient was 0.5 mg/ml (2).

At the present time, no reported data about intrathecal colistin treatment has been published.

Recently, Levin et al. reported 60 patients with nosocomial infections by Pseudomonas aeruginosa and Acinetobacter baumannii who were treated with colistin intravenously. Only four of five cases with good resolution had central nervous system infections; however, none of them had received intrathecal treatment (5).

We conclude that in cases of meningitis caused by multiresistant gram-negative rods, intrathecal administration of the old antibiotic colistin could be considered as an effective alternative treatment.