Administration Of Chloramphenicol Research Articles

Role of Oxidative Stress in Reproductive Toxicity Induced by Co‐administration of Chloramphenicol and Multivitamin–Haematinics Complex in Rats

Concurrent administration of chloramphenicol (CAP) with multivitamin-haematinics complex (MHC) is a common practice to cushioning anticipated anaemic effect of CAP in most developing countries. This study investigated the mechanism involved in CAP-induced reproductive toxicity as well as the effects of its co-administration with MHC in male rats. CAP and MHC were administered orally at therapeutic doses of 28 mg/kg body-weight and 0.08 ml/kg body-weight, respectively, every 6 hr for 10 days. After exposure, while there was body-weight loss in CAP, MHC and CAP plus MHC-treated animals, there were no treatment-related changes in the absolute and relative weights of the testes in all treated groups. Alone, MHC treatment markedly decreased catalase (CAT), glutathione S-transferase (GST), and 5' nucleotidase (5' NTD) activities whereas it resulted in significant increase in superoxide dismutase (SOD) activity. Activities of SOD, CAT and GST as well as H(2)O(2) levels were not significantly affected in CAP and CAP plus MHC-treated rats whereas GSH level and 5' NTD activity were markedly decreased in CAP plus MHC-treated rats. Significant increase in testicular alkaline phosphatase activity, lipid peroxidation and sperm abnormalities were accompanied by reduction in epididymal sperm number, sperm motility and live-dead ratio in all treatment groups whereas aminotransferase activities were unaffected. Treatment-related degeneration of the testes was evident in all treated animals. In summary, while MHC-induced testicular toxicity via oxidative stress, CAP did not and their combination is implicated in reproductive dysfunction within the time course of our investigation.

Serogroup distribution and antimicrobial resistance of nasopharyngeal isolates of Streptococcus pneumoniae among Beijing children with upper respiratory infections (2000–2005)

The aims of this study were to estimate pneumococcal carriage rate, antimicrobial resistance and serogroup distribution of nasopharyngeal isolates of Streptococcus pneumoniae among children with acute upper respiratory infections (AURIs) aged 1 month to 5 years attending outpatient department of the Beijing Children's Hospital between 2000 and 2005. Susceptibilities to penicillin, amoxicillin-clavulanic acid, ceftriaxone, cefuroxime, cefaclor, erythromycin, tetracycline, sulfamethoxazole-trimethoprim and chloramphenicol were assessed using the E-test and disc diffusion. We also analyzed the correlation between antibiotic consumption and rates of resistance. The prevalence of penicillin-nonsusceptible pneumococci increased from 26% during 2000-2001 and 21% during 2002-2003 to 31.5% in 2004-2005. The percentage of S. pneumoniae resistant to cefaclor and cefuroxime increased from about 6% during 2000-2001 to about 23% during 2004-2005 (P<0.01). The frequency of resistance to erythromycin ranged from 87% to 94%. Tetracycline and co-trimoxazole resistance rates were greater than 80%. We conclude that resistance rates for most antibiotics are increasing, possibly due to misues of antibiotics in the hospital setting. However, chloramphenicol resistance was found to decrease, which correlated with the cessation of chloramphenicol administration in 1999. Pneumococcal strains (n=519) were analyzed by serogroup, and only 296 were found to be seven-valent pneumococcal conjugate vaccine-related serotype isolates. This serotype distribution is important for surveillance of the new conjugate vaccine.

Intraosseous Drug Administration in Children and Adults During Cardiopulmonary Resuscitation

To review and assess the available literature on the use of intraosseous (IO) drug administration during cardiopulmonary resuscitation, addressing the benefits and risks of using this method of drug delivery in children and adults. The MEDLINE (1950-July 2007) database was searched for pertinent abstracts, using the key term intraosseous infusions. Additional references were obtained from the bibliographies of the articles reviewed. Manufacturer Web sites were used to obtain information about IO insertion devices. All available English-language clinical trials, retrospective studies, and review articles describing IO drug administration were reviewed. Studies conducted in animal models to evaluate the effectiveness and safety of IO drug administration were also included. IO access uses the highly vascularized bone marrow to deliver fluids and medications during cardiopulmonary resuscitation. This route, developed in the 1940s, has been revived in the past decade as a means of achieving rapid vascular access when intravenous access cannot be obtained. The primary advantage of IO access is the high success rate (approximately 80%). Most trained providers can place an IO line within 1-2 minutes. A number of small-scale studies and retrospective reviews have established the usefulness of this route for the delivery of many commonly used resuscitation drugs. In addition, animal models have demonstrated rapid drug delivery to the systemic circulation. While all resuscitation drugs can be given by the IO route, administration of ceftriaxone, chloramphenicol, phenytoin, tobramycin, and vancomycin may result in lower peak serum concentrations. The most common adverse effect seen with IO use, extravasation, has been reported in 12% of patients. Compartment syndrome, osteomyelitis, and tibial fracture are rare, but have also been reported. IO administration is a safe and effective method for delivering drugs during cardiopulmonary resuscitation. It should be considered whenever intravenous access cannot be rapidly obtained.

Effects of phenylalanine and glycine on some toxic effects of chloramphenicol

We investigated the effects of concurrent administration of the amino acids, phenylalanine and glycine, on chloramphenicol (CAP)-induced haematotoxicty and histopathological effects in rats infected with Klebsiella pneumonia. The study was carried out for 21 days in which haematological and histopathological changes were monitored in the infected animals treated with either of these amino acids or their combination and chloramphenicol. After 7 days of treatment, the amino acids suppressed the decreases recorded in anaemia-related haematological parameters. The order of potency is as follows: CAP/glycine > CAP/glycine/phenylalanine > CAP/phenylalanine > CAP alone > negative control. These decreases were significantly (P CAP/glycine > CAP/phenylalanine > CAP alone > control. With the exception of the group which received chloramphenicol alone, all other treatment groups exhibited increases or no changes in PCV, HB and RBC on day 21 relative to day 7 values. The WBC counts in all the animals in the treated groups were decreased, with CAP/glycine treated group being the most remarkable. Of all the combinations used in the study, only CAP/glycine was effective in protecting the liver against the toxic effects of CAP. No appreciable protection was noted in the spleen of any of the groups. Phenylalanine, glycine and their combination when given concomitantly significantly, reduced the anaemia and histopathological changes associated with chloramphenicol administration. Key words: chloramphenicol toxicity, glycine, haematotoxicity, phenylalanine.

Eriobotrya japonica Counteracts Reactive Oxygen Species and Nitric Oxide Stimulated by Chloramphenicol

Chloramphenicol is a toxic antibiotic used for certain infections, though aplastic anaemia is one of its side-effects. The results of our experiments showed that blood cells suffered oxidative stress in the presence of chloramphenicol, with a significant increase in reactive oxygen species (ROS) detected by luminol-chemiluminescence (CL). The extract of fruits of Eriobotrya japonica markedly decreased ROS in leukocytes and erythrocytes, the oxidative stress caused by this antibiotic. Nitro Blue Tetrazolium (NBT) assay with purified leukocytes demonstrated that the antioxidant action of E. japonica caused an intracellular reduction in ROS, and that the extracts decreased these promoters of oxidative stress to normal levels in the cytoplasm. Determinations of nitric oxide (NO) generation indicated that E. japonica extracts also inhibited the stimuli of NO provoked by chloramphenicol. This study showed that the immediate antioxidant effect of E. japonica could be associated with the action of vitamin A. The protective action of this fruit was seen on mature leukocytes and erythrocytes, beneficial effect on blood cells suggest that its extract could be used as an antioxidant agent complementing the administration of chloramphenicol, as a modern-day extension to its traditional use in Chinese medicine.

Traumatic Late Flap Dehiscence and Enterobacter Keratitis Following LASIK

To report a case of traumatic flap dehiscence and Enterobacter keratitis 34 months after LASIK. A 36-year-old man sustained a flap dehiscence following traumatic right eye gouging by a seagull claw. He presented the following day with uncorrected visual acuity (UCVA) in the affected eye of 3/200 and organic foreign body deposits underneath the flap. Systemic and topical antibiotics were administered and urgent surgical debridement and replacement of the LASIK flap was performed. An Enterobacter species was cultured from an intraoperative swab. After a prolonged postoperative course, including administration of topical ofloxacin, tobramycin, chloramphenicol, and dexamethasone, UCVA returned to 20/20. Good visual outcome after early debridement and appropriate antibiotics was achieved. Patients should be injury advised to seek prompt ophthalmic consultation after LASIK.

Chloramphenicol decreases brain glucose utilization and modifies the sleep–wake cycle architecture in rats

We studied the effects of chloramphenicol on brain glucose utilization and sleep-wake cycles in rat. After slightly anaesthetized animals were injected with [18F]fluoro-2-deoxy-D-glucose, we acquired time-concentration curves from three radiosensitive beta microprobes inserted into the right and left frontal cortices and the cerebellum, and applied a three-compartment model to calculate the cerebral metabolic rates for glucose. The sleep-wake cycle architecture was analysed in anaesthetic-free rats by recording electroencephalographic and electromyographic signals. Although chloramphenicol is a well-established inhibitor of oxidative phosphorylation, no compensatory increase in glucose utilization was detected in frontal cortex. Instead, chloramphenicol induced a significant 23% decrease in the regional cerebral metabolic rate for glucose. Such a metabolic response indicates a potential mismatch between energy supply and neuronal activity induced by chloramphenicol administration. Regarding sleep-wake states, chloramphenicol treatment was followed by a 64% increase in waking, a 20% decrease in slow-wave sleep, and a marked 59% loss in paradoxical sleep. Spectral analysis of the electroencephalogram indicates that chloramphenicol induces long-lasting modifications of delta-band power during slow-wave sleep.

The changing epidemiology of meningococcal meningitis after introduction of bivalent A/C polysaccharide vaccine into school-based vaccination programs in Egypt

Background: The strategy recommended by the World Health Organization (WHO) to curtail outbreaks of meningococcus in Africa is enhanced surveillance with administration of oily chloramphenicol as well as vaccination when incidence thresholds are exceeded. The role of capsular polysaccharide meningococcal vaccine in outbreak prevention has been the subject of considerable debate. The Egyptian Ministry of Health and Population initiated a school-based vaccination program with bivalent A/C capsular polysaccharide vaccine in 1992. This investigation reviews data on meningococcal meningitis in Egypt comparing years before and after introduction of the vaccine. Methods: This is a retrospective review of several sources to examine the rates and serogroups of meningococcal meningitis before and after the introduction of the meningococcal A/C vaccine in Egypt. Findings: Between 1967 and 1991, outbreaks of meningococcal disease were documented with a periodicity of 8 years in Egypt. However, there has not been an outbreak since 1991 and over the same period, there has also been a progressive decline in the baseline incidence of meningococcus. Also, a shift from a serogroup A to serogroup B predominance in meningococcal disease was noted during the study period. These data suggest that there has been an alteration in the epidemiology of meningococcal disease in Egypt that coincided with the implementation of the school-based vaccination program. Interpretation: Routine use of the bivalent A/C meningococcal vaccine may be an alternative for the control and prevention of meningococcal disease in high-risk areas including the “meningitis belt”.

Chloramphenicol Treatment for Rabbit Syphilis

Penicillin, the recommended treatment for rabbit syphilis, sometimes induces adverse effects. The efficacy of oral chloramphenicol was evaluated in 39 cases of rabbit syphilis to establish a safe and efficient treatment for this disease in companion rabbits. All cases clinically improved and recovered promptly. Fourteen of 39 cases (35.9%) relapsed, but most remained chloramphenicol sensitive. Since safety take priority over efficacy in treating syphilis in companion rabbits, chloramphenicol should be chosen as a first-line agent, as a general rule. Three-week administration of chloramphenicol may be adequate at the initial onset of disease. When relapse occurs repeatedly or the rabbit owner cannot administer the medicine adequately, treatment with penicillin should be considered.

Inhibition of NADH oxidation by chloramphenicol in the freely moving rat measured by picosecond time-resolved emission spectroscopy.

Owing to the lack of methods capable to monitor the energetic processes taking place within small brain regions (i.e. nucleus raphe dorsalis, nRD), the neurotoxicity of various categories of substances, including antibiotics and psycho-active drugs, still remains difficult to evaluate. Using an in vivo picosecond optical spectroscopy imaging method, we report that chloramphenicol (CAP), besides its well-known ability to inhibit the mitochondria protein synthesis, also influences the NADH/NAD+ redox processes of the respiratory chain. At a 200-mg/kg dose, CAP indeed produces a marked increase in the fluorescent signal of the nRD which, according to clear evidence, is likely to be related to the NADH concentration. This effect also implies an efficient inhibition of complex I of the respiratory chain by CAP. It refers to the mechanism through which the adverse effects of the antibiotic may take place. It could explain why paradoxical sleep, a state needing aerobic energy to occur, is suppressed after CAP administration. The present approach constitutes the first attempt to determine by fluorescence methods the effects of substances on deep brain structures of the freely moving animal. It points out that in vivo ultrafast optical methods are innovative and adequate tools for combined neurochemical and behavioural approaches.

Trends in ophthalmic antimicrobial utilization pattern in Bahrain between 1993 and 2000: a resurgence of chloramphenicol?

The occurrence of aplastic anemia following topical administration of ophthalmic chloramphenicol is controversial and debated internationally. We have determined the influence of such debate on the utilization of ophthalmic chloramphenicol in Bahrain, through studying the utilization patterns of ophthalmic antimicrobial preparations by the Ministry of Health, with an emphasis on chloramphenicol, between 1993 and 2000. Cost-implications of these patterns are examined. Information on the annual purchase of ophthalmic antimicrobial drug preparations and their unit price was obtained from the Directorate of Materials Management, Ministry of Health, and analyzed. In 1993, the 3 most commonly purchased ophthalmic antibacterial preparations were oxytetracycline 1% eye ointment (40.1%); sulfacetamide 10% and 20% eye drops (25.3%); and chloramphenicol 0.5% eye drops and 1% eye ointment (10.8%). In 2000, oxytetracycline remained the most frequently purchased preparation (33%), followed by chloramphenicol (21.2%). Between 1993 and 1999, chloramphenicol purchases fluctuated between 10% to 16.4% with a remarkable increase to 21.2%, in 2000. Chloramphenicol accounted for 8.6% and 15.1% of cost of total ophthalmic preparations purchased in 1993 and 2000, respectively. Despite continued concerns of potential risks of ophthalmic chloramphenicol, this preparation is extensively utilized in Bahrain. We are of the opinion that for minor infections, chloramphenicol ophthalmic preparations should be replaced by safer alternatives. Further, we recommend that their use be reserved for ocular infections that are resistant to other antimicrobials, and that ophthalmologists, at the secondary care level, should supervise such treatment.

Rabbit syphilis diagnosed clinically in household rabbits.

This paper deals with 16 cases presented from April to December 2001 and diagnosed clinically as rabbit syphilis, because they showed distinct lesions around the nose and/or mouth, responded to chemotherapy, and the "Rapid Plasma Reagin" test was positive. Twelve cases exhibited initial symptoms and four were relapses. Lesions around the genitalia and/or anus as well as the nose and/or mouth were seen in 8 cases, and 6 cases indicated sneezing. Fifteen cases were successfully treated with oral administration of chloramphenicol, and one was treated with long-acting penicillin by intramuscular injection. The mean age of onset was 8.8 months. As none of these cases had any mating history, the disease was likely to be maternally transmitted.

Chloramphenicol Induced Hearing Loss

Background: With the widespread use of the drug Chloramphenicol in treatment of typhoid fever, a number of cases of deafness are coming to light following such treatment. However the pattern and level of the resulting hearing impairment has not received much attention in the literature. Method: A prospective study of ototoxicity over a 3- year period by means of questionnaire, clinical and otological examination and audiological tests to identify cases of significant hearing loss attributable to Chloramphenicol administration. Result: Out of a total of 49 cases of drug ototoxicity seen during a 3- year period, 21 cases (43%) were due to Chloramphenicol and the deafness was most commonly associated with parenteral administration, though actual doses could not be ascertained from the histories. Hearing impairment was bilateral and severe to profound at onset in most cases (66%), with no improvement noticed even after cessation of drug use. Follow-up tests where possible, carried out 6 to 12 months later showed no improvement in thresholds. Conclusion: Hearing impairment as a complication of Chloramphenicol usage is severe in most cases and associated with poor prognosis both in respect of chances of spontaneous recovery as well as the degree of concommitant hearing handicap. The need to prevent this grave iatrogenic tragedy by limiting the use of this drug is stressed. (Nig J Surg Res 2001; 3: 75 – 80) KEY WORDS: Hearing Loss, Chloramphenicol, Typhoid Fever, Handicap

Potential risk factors associated with thrombocytopenia in a surgical intensive care unit.

We conducted a retrospective chart review of 193 patients admitted during a 3-month period to determine the frequency of and potential risk factors associated with thrombocytopenia, and the association of acquired thrombocytopenia with length of stay in a surgical-trauma intensive care unit (SICU) and mortality. All records were reviewed beginning 24 hours after admission. Patients were followed for the duration of SICU stay or until death. Data collected and analyzed as potential risk factors for thrombocytopenia were age, gender, admitting diagnosis, classification (trauma, surgical, medical), APACHE II score, medical history, all scheduled drugs with start and stop dates, select laboratory values, arterial or central line placement, and complications. Thrombocytopenia occurred in 25 (13%) patients. These patients were more likely (p<0.05) than those without thrombocytopenia to have the following potential risk factors: presence of a central or arterial line (76% vs 46%, p<0.025), nonsurgical diagnosis (60% vs 37%, p<0.05), diagnosis of sepsis (p<0.001), and administration of phenytoin (p<0.01), piperacillin (p<0.005), imipenem-cilastatin (p<0.001), and vancomycin (p<0.005). A longer SICU stay (mean 21 vs 4.5 days, p<0.05) and increased mortality (16% vs 4%, p<0.05) were significantly associated with thrombocytopenia. Cefazolin administration was significantly associated with nonthrombocytopenia (p<0.05). Factors not associated with thrombocytopenia were age, gender, and administration of histamine2-receptor antagonists, heparin, enoxaparin, penicillins, ceftazidime, ceftriaxone, chloramphenicol, and amphotericin B. A central or arterial line was the only factor associated with the development of thrombocytopenia in a multiple linear regression analysis (p=0.0003, multiple r=0.2580). Thrombocytopenia is not a common occurrence in the SICU, but is associated with a longer SICU stay and increased mortality.

The myelotoxicity of chloramphenicol: in vitro and in vivo studies: II: in vivo myelotoxicity in the B6C3F mouse

1. Chloramphenicol continues to be widely used in many parts of the world despite its known haematotoxicity. Until now, elucidation of the mechanisms involved and any attempt at amelioration of the toxic effects have been hampered by the lack of an animal model. 2. In this study neither acute nor chronic administration of chloramphenicol as its succinate ester in the drinking water produced anaemia in mice as assessed by changes in peripheral blood parameters. 3. Chloramphenicol could not be detected in the bone marrow when the antibiotic was administered either in the drinking water or by gavage, although it was detected in the serum. 4. In marrow taken from mice after chloramphenicol succinate administration and cultured in vitro, depression of the differentiation of immature committed erythroid progenitors occurred 15 min after administration of the antibiotic by gavage. However, recovery was beginning to occur at 48 h after administration of chloramphenicol succinate at 50 and 200 mg/kg and this was then followed by an 'overshoot' response at the higher dose. A toxic effect was therefore achieved in the bone marrow but this was probably masked in the peripheral blood by enhanced proliferation. 5. Morphological evidence of apoptosis was seen in erythroid and myeloid precursors in mice treated with 200 mg/kg. 6. The data suggest that the effect of chloramphenicol was at the differentiation stage of the committed marrow progenitor cells rather than at the replication stage of the stem cells and therefore this response appears to mimic the reversible bone marrow depression seen in the treated patient.

Screening for chloramphenicol residues in the tissues and fluids of treated cattle by the four plate test, Charm II radioimmunoassay and Ridascreen CAP-Glucuronid enzyme immunoassay.

The administration of chloramphenicol (CAP) is banned in food animals in the European Union (EU). It is, therefore, important to have adequate screening methods to determine if residues of CAP and its major metabolite, chloramphenicol-glucuronide (CAP-Gluc), are present in samples taken for monitoring purposes. Six castrated male cattle were treated with a single intramuscular injection of 10 mg kg-1 CAP. Animals were sampled once daily for urine and were slaughtered at 3 and 6 d post-injection. Samples of bile, kidney, liver and diaphragmatic muscle were removed at slaughter. All matrices were analysed using the four plate test (FPT) bioassay, the Charm II radioimmunoassay and a Ridascreen CAP-Glucuronid competitive enzyme immunoassay (EIA). The FPT detected CAP residues in urine samples taken up to 2 d post-treatment. The Charm assay detected CAP in the urine for up to 4 d post-treatment. The EIA detected CAP throughout the 6 d sampling period. Samples of bile were positive by both the EIA and the Charm assay at day 3 and day 6. No zones of inhibition were obtained using the FPT in bile or diaphragm either with or without sample pre-treatment with beta-glucuronidase. However, the kidney and the liver from one animal killed at day 6 gave larger zones of inhibition after treatment with beta-glucuronidase, indicating the presence of CAP. The kidneys of all treated animals slaughtered at day 3 were positive by both the EIA and the Charm assay but none of the kidneys at day 6 tested positive by either method. Owing to technical difficulties, the Charm assay was not suitable for the analysis of liver. The EIA failed to detect CAP in the liver of any treated animal. It is concluded that urine appears to be the best matrix for screening purposes. The sensitivity of the FPT is inadequate for the determination of CAP residues were minimal withdrawal periods have been observed. The Charm assay and the EIA were suitable for the detection of both CAP and CAP-Gluc in tissues and body fluids for longer periods post-administration. The EIA was more sensitive for the determination of low concentrations of CAP and its metabolite.

Oral administration of antibiotics: a rational alternative to the parenteral route.

Much early experience with antibiotic therapy involved oral administration of sulfonamides, penicillins, tetracyclines, and chloramphenicol. Newer acid-labile, less-soluble agents created the need for intravenous (i.v.) administration, and i.v. technology (hyporeactive catheter polymers, infusion pumps, etc.) improved to where i.v. administration became normative for the treatment of serious infections. Recently, this preference is being reconsidered in light of agents that are highly effective orally, growing appreciation that i.v. treatment has serious complications, and economic pressures to provide the best care at the lowest cost. This article presents a brief history of administration routes and reviews the rationale for considering oral treatment for serious infections, including consideration of pharmacokinetics and minimum inhibitory concentrations. Published reports supporting the efficacy of orally administered antibiotics either as sole treatment or following an initial parenteral course are reviewed in detail, and examples of programs that educate physicians about the rationale, acceptibility, and benefits of oral administration are given.

Influence of mitochondrial protein synthesis inhibition on deafferentation-induced ultrastructural changes in nucleus magnocellularis of developing chicks.

Following cochlea removal in developing chicks, about 30% of the neurons in the ipsilateral second-order auditory nucleus, nucleus magnocellularis, undergo cell death. Administration of chloramphenicol, a mitochondrial protein synthesis inhibitor, results in a pronounced increase in deafferentation-induced cell death. In this study, we examined whether the chloramphenicol enhancement of deafferentation-induced cell death reveals the same ultrastructural characteristics that are seen in degenerating nucleus magnocellularis neurons after cochlea removal alone. Unilateral cochlea removal was performed on anaesthetized posthatch chicks. One group of animals was simultaneously treated with chloramphenicol. Six, twelve, or twenty-four hours following cochlea removal, n. magnocellularis neurons were studied by routine transmission electron microscopy. Particular attention was paid to the integrity of the polyribosomes and rough endoplasmic reticulum. Two ultrastructurally different types of neuronal degeneration were observed in the deafferented nucleus magnocellularis neurons: an early onset electron-lucent type that always involved ribosomal dissociation and a late-onset electron-dense type displaying nuclear pyknosis and severely damaged mitochondria. The percentage of nucleus magnocellularis neurons displaying ribosomal disintegration following cochlea removal was found to be markedly increased after chloramphenicol treatment. This finding suggests that mitochondrial function is important for the maintenance of a functional protein synthesis apparatus following deafferentation.

Bacterial Meningitis in Developing Countries

Hemophilus influenza, Streptococcus pneumoniae, and Neisseria meningitidis account for over 75% of all cases of bacterial meningitis. S. pneumoniae is the commonest causative organism in many developing countries, particularly in Africa. In developing countries overall case fatality rates of 33-44% have been reported, rising to over 60% in adult groups. S. pneumoniae accounts for the highest mortality worldwide. Sequela rates of 22-26% of survivors have been found in African studies, mostly of a neurological nature. There have been few reports of AIDS-related bacterial meningitis in the USA, and a recent study from Uganda found no association between HIV infection and meningococcal meningitis. Stronger associations have been found between opportunistic infections, both viral (cytomegalovirus, herpes virus) and non-viral (TB, Toxoplasma gondii, Cryptococcus neoformans). A lumbar puncture and analysis of the cerebrospinal fluid should be performed on suspected cases unless there is suspicion of impending coning (decreasing consciousness or focal neurological signs). The intramuscular administration of chloramphenicol alone is comparable with intravenous use, and can be given as a shorter course of therapy (2 or 3 days) followed by an oral course. The use of adjunct therapy with corticosteroids in children is now commonplace in the USA and Europe. It appears reasonable to use dexamethasone, given early and in high dosage (0.15 mg/kg 6 hourly for 4 days), in those patients who are severely ill. Rifampicin is effective for chemoprophylaxis (10 mg/kg twice daily for 2 days for meningococcal contacts, 20 mg/kg once daily for 4 days for hemophilus contacts, maximum 600 mg per dose). The recent development and introduction of conjugate vaccines for H. influenza (HIB) has led to rapid reductions in the incidence of hemophilus meningitis in many European countries. An important step in improving prognosis is to increase awareness in both health workers and the public, to encourage early hospital referral, and early antibiotic therapy.

CHLORAMPHENICOL AND ACTINOMYCIN-D-INDUCED MODIFICATIONS IN THE CARCINOGEN-METABOLIZING CAPACITIES OF MOUSE-LIVER MICROSOMES

The effect of antibiotics chloramphenicol (CML) and actinomycin-D (AMD) on the modification of the carcinogen metabolizing capacity was studied in vivo in mouse liver microsomes at different durations of treatment, for one day and three and six consecutive days. Following the administration of CML, a significant increase was observed in the activity of the low and high substrate levels of the hepatic microsomal N-nitrosodimethylamine demethylases (NDMAd I and II, respectively). On the contrary, AMD reduced the activity of NDMAd I and II in a time-dependent manner up to 3 days of treatment while no effect was observed when the drug was administered for 6 consecutive days. No effect was observed in the activity of the arylhydrocarbon (benzo(alpha)pyrene) hydroxylase either at the single or the repeated doses of CML only for 6 days of treatment with AMD. The expression of the hepatic content of cytochrome P450 revealed a significant induction at the various treatment intervals with CML. AMD, however, reduced the cytochrome P450 at 1 and 6 days treatment with induction at 3 days of repeated treatment.