Tuesday 10 July 2012

Chloromycetin Sodium Succinate


Generic Name: Chloramphenicol
Class: Chloramphenicol
VA Class: AM150
CAS Number: 56-75-7



  • Serious and fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) can occur after short-term or prolonged therapy.a Chloramphenicol-associated aplastic anemia (terminating in leukemia) has been reported.a (See Hematologic Effects under Cautions.)




  • Use only when other potentially less hazardous anti-infectives cannot be used or would be ineffective.a Do not use for trivial infections or when not indicated (e.g., for colds, influenza, throat infections, prophylaxis).a




  • It is essential that adequate blood studies be performed during chloramphenicol treatment.a While such studies may detect early peripheral blood changes (e.g., leukopenia, reticulocytopenia, granulocytopenia) before they become irreversible, such studies cannot be relied on to detect bone marrow depression prior to development of aplastic anemia.a




  • To facilitate appropriate blood studies and observation, patient should be hospitalized while receiving chloramphenicol.a




Introduction

Antibacterial; broad-spectrum antibiotic used only in serious infections caused by susceptible bacteria when less hazardous anti-infectives are ineffective or contraindicated.132 a


Uses for Chloromycetin Sodium Succinate


Meningitis


Treatment of meningitis caused by susceptible bacteria, including Neisseria meningitidis, Haemophilus influenzae, or Streptococcus pneumoniae.106 112 132 144 149 a Generally used only when penicillins and cephalosporins are contraindicated or ineffective.101 102 104 105 106 132 149 A regimen of ampicillin and chloramphenicol may be used as an alternative to cefotaxime or ceftriaxone for treatment of H. influenzae meningitis.132


Do not use for treatment of meningitis caused by penicillin-resistant S. pneumoniae132 149 unless the chloramphenicol minimum bactericidal concentration (MBC) is ≤4 mcg/mL.132 149


Do not use for treatment of meningitis caused by Listeria monocytogenes144 or gram-negative bacilli.147


Anthrax


Alternative for treatment of anthrax,165 166 170 especially anthrax meningoencephalitis.165 166


Component of multiple-drug parenteral regimens recommended for treatment of inhalational anthrax that occurs as the result of exposure to B. anthracis spores in the context of biologic warfare or bioterrorism.164 167 Initiate treatment with IV ciprofloxacin or doxycycline and 1 or 2 other anti-infective agents predicted to be effective (e.g., chloramphenicol, clindamycin, rifampin, vancomycin, clarithromycin, imipenem, penicillin, ampicillin);164 167 if meningitis is established or suspected, use IV ciprofloxacin (rather than doxycycline) and chloramphenicol, rifampin, or penicillin.164


Brucellosis


Treatment of brucellosis; used with or without streptomycin as an alternative to a tetracycline regimen.106


Burkholderia Infections


Treatment of infections caused by Burkholderia cepacia (e.g., in cystic fibrosis patients, immunocompromised patients).106 Co-trimoxazole considered drug of choice; chloramphenicol, ceftazidime, or imipenem are alternatives.106


Treatment of glanders caused by B. mallei; used in conjunction with streptomycin as an alternative to tetracycline and streptomycin.106


Treatment of melioidosis caused by B. pseudomallei; used in a multiple-drug regimen with doxycycline and co-trimoxazole.106 154 Ceftazidime or imipenem monotherapy may be preferred.106 152 153 154 156 B. pseudomallei is difficult to eradicate and relapse of melioidosis is common.152 153 154 156


Chlamydial Infections


Treatment of psittacosis (ornithosis) caused by Chlamydia psittaci.106 132 Alternative to tetracyclines.106


Clostridium Infections


Alternative to penicillin G or clindamycin for treatment of infections caused by Clostridium perfringens.106 132


Ehrlichiosis


Treatment of ehrlichiosis caused by Ehrlichia chaffeensis.106 159 160 Recommended as an alternative to tetracyclines,106 but efficacy has not been established.132 159


Plague


Alternative for treatment of plague caused by Yersinia pestis, including naturally occurring or endemic plague or pneumonic plague that occurs following exposure to Y. pestisin the context of biologic warfare or bioterrorism.106 132 133 168 Regimen of choice is streptomycin (or gentamicin) with or without doxycycline.106 132 168 170 Alternatives include doxycycline (or tetracycline), chloramphenicol, co-trimoxazole (may be less effective than other alternatives), or ciprofloxacin (or another fluoroquinolone).132 168 170


Treatment of plague meningitis; drug of choice.132 170


Rat-bite Fever


Alternative to penicillin G for treatment of rat-bite fever caused by Streptobacillus moniliformis or Spirillum minus.132


Rickettsial Infections


Alternative to tetracyclines for treatment of Rocky Mountain spotted fever and other rickettsial infections.102 104 105 106 132 135


Tularemia


Alternative to streptomycin (or gentamicin) for treatment of tularemia caused by Francisella tularensis,106 132 133 169 including naturally occurring or endemic tularemia or tularemia that occurs following exposure to F. tularensis in the context of biologic warfare or bioterrorism.169 170


Typhoid Fever


Treatment of typhoid fever caused by susceptible Salmonella typhi.106 132 134 136 139 140 a Drugs of choice are third generation cephalosporins (e.g., ceftriaxone, cefotaxime) or fluoroquinolones (e.g., ciprofloxacin, ofloxacin); chloramphenicol is an alternative.106 132 139 150 151


Do not use to treat S. typhi carriers.101 104 110 112 a


Vibrio Infections


Treatment of cholera caused by Vibrio cholerae.106 123 128 129 130 Alternative to tetracyclines;123 128 129 130 132 used as an adjunct to fluid and electrolyte replacement in moderate to severe disease.106 132


Chloromycetin Sodium Succinate Dosage and Administration


General


Because differences between therapeutic and toxic plasma concentrations of chloramphenicol are narrow and because of interindividual differences in metabolism and elimination of the drug, most clinicians recommend that plasma concentrations of chloramphenicol be monitored in all patients.101 102 104 105 107 108 109 114 115 Some experts suggest chloramphenicol dosage be adjusted to maintain plasma concentrations at 5–20 mcg/mL.101 102 104 105 107 108


Administration


Chloramphenicol is administered IV.a Do not administer IM since this route may be ineffective.a


Administer IV chloramphenicol no longer than necessary; change to an oral regimen of another appropriate anti-infective as soon as practical.a


Repeated courses of chloramphenicol should be avoided if at all possible.a


IV Administration


Reconstitution

Reconstitute vial containing 1 g of chloramphenicol by adding 10 mL of an aqueous diluent (e.g., sterile water for injection, 5% dextrose injection) to provide a solution containing 100 mg/mL.a


Rate of Administration

Inject calculated dose IV over a period of ≥1 minute.a


Dosage


Available as chloramphenicol sodium succinate; dosage expressed in terms of chloramphenicol.a


Pediatric Patients


General Dosage for Neonates

IV

25 mg/kg daily given in 4 equally divided doses every 6 hours during the first 2 weeks of life.102 112 a Full-term neonates >2 weeks of age may receive 50 mg/kg daily given in 4 equally divided doses every 6 hours.a


General Dosage for Children >1 Month of Age

IV

50 mg/kg daily given in equally divided doses every 6 hours.102 112 132 a


Up to 100 mg/kg daily may be required in infections caused by less susceptible organisms or if necessary to achieve adequate CSF concentrations.112 132 a However, because of concern that toxic chloramphenicol concentrations may occur with this high dosage, some clinicians suggest that 75 mg/kg daily be used initially in the treatment of these infections.102 105 Dosage should be reduced to 50 mg/kg daily as soon as possible.112 a


General Dosage for Pediatric Patients with Immature Metabolic Processes

IV

25 mg/kg daily will usually produce therapeutic blood concentrations in young infants and other pediatric patients in whom immature metabolic functions are suspected.a


Monitoring chloramphenicol plasma concentrations is particularly important in these patients.a


Anthrax

Treatment of Anthrax (Inhalational, GI, Meningeal, Septicemia)

IV

50–75 mg/kg daily given in 4 divided doses.165


Meningoencephalitis caused by B. anthracis may require 1 g every 4 hours.166


Used in multiple-drug regimens that initially include IV ciprofloxacin or IV doxycycline and 1 or 2 other anti-infectives predicted to be effective.164 167


Duration of treatment is 60 days if anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.164 167


Plague

IV

25 mg/kg 4 times daily for 10 days for treatment of pneumonic plague that occurs as the result of exposure to Y. pestis in the context of biologic warfare or bioterrorism.168


Initial loading dose of 25 mg/kg followed by 15 mg/kg 4 times daily for 10–14 days for treatment of plague meningitis.170


Tularemia

IV

15 mg/kg 4 times daily given for 14–21 days for treatment of tularemia that occurs as the result of exposure to F. tularensis in the context of biologic warfare or bioterrorism.169


Typhoid Fever

IV

50 mg/kg daily in equally divided doses every 6 hours given for 14–15 days.134 139 140


Adults


General Adult Dosage

IV

50 mg/kg daily given in equally divided doses every 6 hours.102 112 a


In infections caused by less susceptible organisms or if necessary to achieve adequate CSF concentrations, up to 100 mg/kg daily may be required.112 c However, because of concern that toxic plasma chloramphenicol concentrations may occur with this high dosage, some clinicians suggest that 75 mg/kg daily be used initially in the treatment of these infections.102 105 Dosage should be reduced to 50 mg/kg daily as soon as possible.112 c


Anthrax

Treatment of Anthrax (Inhalational, GI, Meningeal, Septicemia)

IV

50–100 mg/kg daily in 4 divided doses.165


Meningoencephalitis caused by B. anthracis may require 1 g every 4 hours.166


Used in multiple-drug regimens that initially include IV ciprofloxacin or IV doxycycline and 1 or 2 other anti-infectives predicted to be effective.164 167


Duration of treatment is 60 days if anthrax occurred as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism.164 167


Plague

IV

25 mg/kg 4 times daily given for 10 days for treatment of pneumonic plague that occurs as the result of exposure to Y. pestis in the context of biologic warfare or bioterrorism.168


Initial loading dose of 25 mg/kg followed by 15 mg/kg 4 times daily given for 10–14 days for treatment of plague meningitis.170


Tularemia

IV

15 mg/kg 4 times daily given for 14–21 days for treatment of tularemia that occurs as the result of exposure to F. tularensis in the context of biologic warfare or bioterrorism.169


Typhoid Fever

IV

50 mg/kg daily in equally divided doses every 6 hours given for 14–15 days.134 139 140


Prescribing Limits


Pediatric Patients


Maximum 25 mg/kg daily in 4 divided doses in neonates <2 weeks of age.a Higher dosage in these neonates should be used only to maintain blood concentrations within a therapeutically effective range.a


Special Populations


Hepatic Impairment


Reduce dosage in proportion to the degree of impairment.a Closely monitor plasma chloramphenicol concentrations, especially in pediatric patients.a


Renal Impairment


Reduce dosage in proportion to the degree of impairment.a Closely monitor plasma chloramphenicol concentrations, especially in pediatric patients.a


Cautions for Chloromycetin Sodium Succinate


Contraindications



  • Known hypersensitivity to chloramphenicol.a




  • History of previous toxic reaction to chloramphenicol.a




  • Trivial infections or when not indicated (e.g., colds, influenza, throat infections, prophylaxis).a



Warnings/Precautions


Warnings


Hematologic Effects

Serious and potentially fatal blood dyscrasias (aplastic anemia, hypoplastic anemia, thrombocytopenia, granulocytopenia) reported with both short-term and prolonged use.a An irreversible type of bone marrow depression leading to aplastic anemia with a high mortality rate has occurred.a


Dose-related, reversible bone marrow depression may occur.a This type of bone marrow depression is characterized by vacuolization of erythroid cells, reduction in reticulocytes and leukopenia, and usually responds promptly to discontinuance of chloramphenicol.a


Hematologic function should be evaluated prior to and approximately every 2 days during chloramphenicol therapy.a Consider that such studies do not exclude the possible later appearance of the irreversible type of bone marrow depression.a


Discontinue chloramphenicol if reticulocytopenia, leukopenia, thrombocytopenia, anemia, or any other blood study findings attributable to the drug occur.a


Sensitivity Reactions


Hypersensitivity Reactions

Fever, macular and vesicular rash, angioedema, urticaria, and anaphylaxis may occur.a


General Precautions


Selection and Use of Anti-infectives

To reduce development of drug-resistant bacteria and maintain effectiveness of chloramphenicol and other antibacterials, use only for treatment or prevention of infections proven or strongly suspected to be caused by susceptible bacteria.a


When selecting or modifying anti-infective therapy, use results of culture and in vitro susceptibility testing.a


Chloramphenicol may be initiated pending results of in vitro susceptibility testing, but should be discontinued if the causative organism is found to be susceptible to potentially less hazardous anti-infectives.a A decision to continue use of chloramphenicol rather than switching to a less hazardous anti-infective should be based on severity of the infection, susceptibility of the causative organism to the other anti-infectives, and efficacy of the various drugs in the specific infection type.a


Repeated courses of chloramphenicol should be avoided if at all possible.a Treatment should not be continued longer than required to produce a cure with little or no risk or relapse.a


Superinfection

Possible emergence and overgrowth of nonsusceptible bacteria or fungi.a Discontinue drug and institute appropriate therapy if superinfection occurs.a


CNS Effects

Headache, mild depression, metal confusion, and delirium have been reported.a


Optic and peripheral neuritis reported, usually following long-term therapy.a Promptly discontinue chloramphenicol if this occurs.a


Sodium Content

Contains approximately 52 mg (2.25 mEq) of sodium per g of chloramphenicol sodium succinate.a


Specific Populations


Pregnancy

Category C.a


Lactation

Distributed into milk; discontinue nursing or the drug.a


Pediatric Use

Use with caution in premature and full-term neonates and infants because of potential for gray syndrome toxicity.a


Gray syndrome can be fatal within a few hours of symptom onset; symptoms include abdominal distension (with or without emesis), progressive pallid cyanosis, and vasomotor collapse (frequently accompanied by irregular respiration).a Syndrome may be reversible if drug discontinued at early evidence of symptoms.a


Immature metabolic processes in neonates and infants may result in excessive chloramphenicol concentrations.a Adjust dosage accordingly and monitor blood concentrations at appropriate intervals.a


Hepatic Impairment

Excessive chloramphenicol concentration may occur in patients with impaired hepatic function.a Decrease dosage accordingly.a Determine chloramphenicol concentrations at appropriate intervals.a


Renal Impairment

Excessive chloramphenicol concentrations may occur in patients with impaired renal function.a Decrease dosage accordingly.a Determine chloramphenicol concentrations at appropriate intervals.a


Common Adverse Effects


Hematologic effects (blood dyscrasias, bone marrow depression); GI effects (nausea, vomiting, glossitis, stomatitis, diarrhea, enterocolitis).a


Interactions for Chloromycetin Sodium Succinate


Specific Drugs
























Drug



Interaction



Comments



Antianemia agents



Possible delayed response to iron preparations, vitamin B12, or folic acidc



Concomitant use of iron preparations, vitamin B12, or folic acid should be avoided if possiblec



Anticoagulants, oral



Possible increased anticoagulant effect;c chloramphenicol may impair utilization of prothrombin or decrease vitamin K production by intestinal bacteriac



β-Lactam antibiotics



In vitro evidence of antagonism with penicillins or cephalosporinsc



Concomitant use with penicillins or cephalosporins not recommendedc



Myelosuppressive agents



Potential additive bone marrow depressiona c



Avoid concomitant use with other drugs that may cause bone marrow depressiona c



Phenobarbital



Possible decreased chloramphenicol concentrationsc



Monitor chloramphenicol concentrations in patients receiving concomitant phenobarbitalc



Rifampin



Possible decreased chloramphenicol concentrations103


Chloromycetin Sodium Succinate Pharmacokinetics


Absorption


Bioavailability


Inactive until chloramphenicol sodium succinate is hydrolyzed in vivo to active chloramphenicol, presumably by esterases in liver, kidneys, and lungs.102 107


Bioavailability following IV administration varies; there is considerable interindividual variation in plasma chloramphenicol concentrations.101 102 107 109 114


Distribution


Extent


Widely distributed into most body tissues and fluids, including saliva, ascitic fluid, pleural fluid, synovial fluid, and aqueous and vitreous humor.c Highest concentrations attained in liver and kidneys.c


CSF concentrations may be 21–50% of concurrent plasma concentrations in patients with uninflamed meninges and 45–89% of concurrent plasma concentrations in patients with inflamed meninges.c


Crosses the placenta and is distributed into milk.a


Plasma Protein Binding


Approximately 60%.c


Elimination


Metabolism


Chloramphenicol sodium succinate hydrolyzed to active chloramphenicol, presumably by esterases in liver, kidneys, and lungs.102 107 Rate and extent of hydrolysis is highly variable.101 102 107 109 114


Chloramphenicol inactivated principally in the liver by glucuronyl transferase.c


Elimination Route


Eliminated in urine by glomerular filtration or active tubular secretion.c Approximately 30% of an IV dose excreted unchanged in urine, but fraction excreted in urine varies considerably and may range from 6–80% in neonates and children.102 107 109


Half-life


Adults with normal renal and hepatic function: plasma half-life 1.5–4.1 hours.101 104 107


Neonates and infants: plasma half-life ≥24 hours in neonates 1–2 days of age and approximately 10 hours in those 10–16 days of age.c Premature infants and neonates have immature mechanisms for glucuronide conjugation and excretion which results in higher and more prolonged chloramphenicol concentrations.c


Special Populations


Patients with impaired hepatic function: plasma half-life prolonged.c


Patients with impaired renal function: plasma half-life not substantially prolonged, but half-lives of the inactive conjugated metabolites may be prolonged.c


Stability


Storage


Parenteral


Powder for Injection

15–25°C.a


Compatibility


For information on systemic interactions resulting from concomitant use, see Interactions.


Parenteral


Solution CompatibilityHID
























Compatible



Dextran 40,000



Dextran 6% in dextrose 5%



Dextran 6% in sodium chloride 0.9%



Dextrose–Ringer’s injection combinations



Dextrose–Ringer’s injection, lactated, combinations



Dextrose 5% in Ringer’s injection, lactated



Dextrose–saline combinations



Dextrose 5% in sodium chloride 0.9%



Dextrose 2½, 5, or 10% in water



Fat emulsion 10%, intravenous



Fructose 10% in sodium chloride 0.9%



Fructose 10% in water



Invert sugar 5 and 10% in sodium chloride 0.9%



Invert sugar 5 and 10% in water



Ionosol products



Normosol M in dextrose 5% in water



Normosol R



Ringer’s injection



Ringer's injection, lactated



Sodium chloride 0.45 or 0.9%



Sodium lactate (1/6) M


Drug Compatibility

















































Admixture CompatibilityHID

Compatible



Amikacin sulfate



Aminophylline



Ascorbic acid injection



Calcium chloride



Calcium gluconate



Colistimethate sodium



Cyanocobalamin



Dimenhydrinate



Dopamine HCl



Ephedrine sulfate



Heparin sodium



Hydrocortisone sodium succinate



Kanamycin



Lidocaine HCl



Magnesium sulfate



Metaraminol bitartrate



Methyldopate HCl



Methylprednisolone sodium succinate



Metronidazole



Metronidazole HCl with sodium bicarbonate



Nafcillin sodium



Oxacillin sodium



Oxytocin



Penicillin G potassium



Penicillin G sodium



Pentobarbial sodium



Phenylephrine HCl



Phenlephrine HCl with sodium bicarbonate



Phytonadione



Plasma protein fraction



Potassium chloride



Promazine HCl



Ranitidine HCl



Sodium bicarbonate



Sodium bicarbonate with phenylephrine HCl



Thiopental sodium



Verapamil HCl



Vitamin B complex with C



Incompatible



Chlorpromazine HCl



Hydroxyzine HCl



Polymyxin B sulfate



Prochlorperazine edisylate



Prochlorperazine mesylate



Promethazine HCl



Vancomycin



















Y-Site CompatibilityHID

Compatible



Acyclovir sodium



Cyclophosphamide



Enalaprilat



Esmolol HCl



Foscarnet sodium



Hydromorphone HCl



Labetalol HCl



Magnesium sulfate



Meperidine HCl



Morphine sulfate



Nicardipine HCl



Perphenazine



Tacrolimus



Incompatible



Fluconazole


Actions and SpectrumActions



  • Usually bacteriostatic in action, but may be bactericidal in high concentrations or against highly susceptible organisms.c




  • Inhibits protein synthesis in susceptible organisms by binding to 50S ribosomal subunits.c Also inhibits protein synthesis in rapidly proliferating mammalian cells; reversible bone marrow depression reported during chloramphenicol therapy may occur because of inhibition of protein synthesis in mitochondria of bone marrow cells.c




  • Inactive until chloramphenicol sodium succinate is hydrolyzed in vivo to active chloramphenicol.102 107




  • Spectrum of activity includes many gram-positive and -negative aerobic bacteria, many anaerobic bacteria, and some other organisms (e.g., Rickettsia, Chlamydia, and Mycoplasma).c Inactive against fungi and viruses.c




  • Gram-positive aerobes: active against Streptococcus pneumoniae and other streptococci.104 110 c Also active in vitro against Bacillus anthracis.161 167




  • Gram-negative aerobes: active against some strains of Brucella, Burkholderia mallei, B. cepacia, Francisella tularensis, Haemophilus influenzae, Neisseria meningitidis, Proteus mirabilis, Salmonella, and Shigella,104 110 Vibrio cholerae, and Yersinia pestis,171 172




  • Anaerobes: active against Bacteroides fragilis, Clostridium, Fusobacterium, Prevotella melaninogenica, and Veillonella.104 110




  • Resistance has been reported in staphylococci, S. pneumoniae,126 131 Escherichia coli, H. influenzae,104 110 125 Neisseria meningitidis, Salmonella, and Shigella.142



Advice to Patients



  • Advise patients that antibacterials (including chloramphenicol) should only be used to treat bacterial infections and not used to treat viral infections (e.g., the common cold).a




  • Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.a




  • Importance of women informing clinician if they are or plan to become pregnant or plan to breast-feed.a




  • Importance of advising patients of other important precautionary information.a (See Cautions.)



Preparations


Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.


* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name


















Chloramphenicol Sodium Succinate

Routes



Dosage Forms



Strengths



Brand Names



Manufacturer



Parenteral



For injection



1 g (of chloramphenicol)*



Chloramphenicol Sodium Succinate Sterile



American Pharmaceutical Partners



Chloromycetin Sodium Succinate



Monarch



Disclaimer

This report on medications is for your information only, and is not considered individual patient advice. Because of the changing nature of drug information, please consult your physician or pharmacist about specific clinical use.


The American Society of Health-System Pharmacists, Inc. and Drugs.com represent that the information provided hereunder was formulated with a reasonable standard of care, and in conformity with professional standards in the field. The American Society of Health-System Pharmacists, Inc. and Drugs.com make no representations or warranties, express or implied, including, but not limited to, any implied warranty of merchantability and/or fitness for a particular purpose, with respect to such information and specifically disclaims all such warranties. Users are advised that decisions regarding drug therapy are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and the information is provided for informational purposes only. The entire monograph for a drug should be reviewed for a thorough understanding of the drug's actions, uses and side effects. The American Society of Health-System Pharmacists, Inc. and Drugs.com do not endorse or recommend the use of any drug. The information is not a substitute for medical care.

AHFS Drug Information. © Copyright, 1959-2011, Selected Revisions August 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.


† Use is not currently included in the labeling approved by the US Food and Drug Administration.




References


Only references cited for selected revisions after 1984 are available electronically.



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113. Shann F, Linnemann V, Mackenzie A et al. Absorption of chloramphenicol sodium succinate after intramuscular administration in children. N Engl J Med. 1985; 313:410-4. [IDIS 203367] [PubMed 4022068]



114. Sack CM, Koup JR, Smith AL. Chloramphenicol pharmacokinetics in infants and young children. Pediatrics. 1980; 66:579-84. [IDIS 123431] [PubMed 7432844]



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120. Dance DA, Wuthiekanun V, Chaowagul W et al. Interactions in vitro between agents used to treat melioidosis. J Antimicrob Chemother. 1989; 24:311-6. [PubMed 2681117]



121. French GL, Ling TKW, Davies DP et al. Antagonism of ceftazidime by chloramphenicol in vitro and in vivo during treatment of gram negative meningitis. BMJ. 1985; 291:636-7. [IDIS 205179] [PubMed 3928061]



122. Cephalosporins interactions: chloramphenicol. In: Hansten PD, Horn JR. Drug interactions: clinical significance of drug-drug interactions. 6th ed. Philadelphia: Lea & Febiger; 1989:213-4.



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124. Flegg P, Cheong I, Welsby PD. Chloramphenicol: are concerns about aplastic anemia justified? Drug Safety. 1992; 7:167-9.



125. Jorgensen JH. Update on mechanisms and prevalence of antimicrobial resistance in Haemophilus influenzae. Clin Infect Dis. 1992; 14:1119-23. [PubMed 1600014]



126. Friedland IR, Klugman KP. Failure of chloramphenicol therapy in penicillin-resistant pneumococcal meningitis. Lancet. 1992; 339:405-8. [IDIS 291433] [PubMed 1346668]



127. Islam A, Butler T, Nath SK et al. Randomized treatment of patients with typhoid fever by using ceftriaxone or chloramphenicol. J Infect Dis. 1988; 158:742-7. [IDIS 263618] [PubMed 3171225]



128. Saraswathi K, Deodhar LP. A study of V. cholerae strains isolated in Bombay. J Postgrad Med. 1990; 36:128-30. [PubMed 2102910]



129. Willke A, Arman D, Tolunay C. [Susceptibility of Vibrio cholerae El-Tor strains to various antibiotics]. Mikrobiyol Bul. 1988; 22:101-4. [PubMed 3273600]



130. Khan MM, Ara F, Yousuf MO et al. Outbreak of gastroenteritis in different areas of Pakistan. J Pak Med Assoc. 1989; 39:151-4. [PubMed 2504955]



131. Syrogiannopoulos GA, Grivea IN, Beratis NG et al. Resistance patterns of Streptococcus pneumoniae from carriers attendng day-dare centers in Southwestern Greece. Clin Infect Dis. 1997; 25:188-94. [IDIS 392202] [PubMed 9332508]



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