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26/10/2015

Tetracyclines

26/10/2015 Tetracyclines Official re <a href=p rint from UpToDate ® www.uptodate.com ©2015 UpToDate ® Tetracyclines Author D Byron May, PharmD, BCPS Section Editor David C Hooper, MD Deputy Editor Jennifer Mitty, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Sep 2015. | This topic last updated: Jul 23, 2014. INTRODUCTION — Chlortetracycline was the first tetracycline discovered, in 1948. Since then five additional tetracyclines have been isolated or derived (oxytetracycline, tetracycline, demeclocycline , doxycycline and minocycline ), but only the last four are available for systemic use in the United States. Of these four agents, doxycycline and minocycline are the most frequently prescribed. Research to find tetracycline analogues lead to the development of the glycylcyclines. Tigecycline is the first of this new class of agents and exhibits broad­ spectrum antibacterial activity similar to the tetracyclines [ 1 ]. Doxycycline is one of the most active tetracyclines and is the most often used clinically since it possesses many advantages over traditional tetracycline and minocycline . Doxycycline can be administered twice daily, has both intravenous (IV) and oral (PO) formulations, achieves reasonable concentrations even if administered with food, and is less likely to cause photosensitivity [ 2 ]. Doxycycline may be an alternative for use in children since it binds calcium to a lesser extent than tetracycline, which can cause tooth discoloration and bony growth retardation. MECHANISM OF ACTION — The tetracyclines enter the bacterial cell wall in two ways: passive diffusion and an energy­dependent active transport system, which is probably mediated in a pH­dependent fashion. Once inside the cell, tetracyclines bind reversibly to the 30S ribosomal subunit at a position that blocks the binding of the aminoacyl­tRNA to the acceptor site on the mRNA­ribosome complex. Protein synthesis is ultimately inhibited, leading to a bacteriostatic effect [ 3 ]. RESISTANCE — In contrast to many other antibiotics, tetracyclines are infrequently inactivated biologically or altered chemically by resistant bacteria. Resistance to these agents develops primarily by preventing accumulation of the drug inside the cell either by decreasing influx or increasing efflux. Once resistance develops to one of the drugs in this class, it is typically conferred to all tetracyclines. However, there are differences in resistance among species of bacteria. Resistance genes to tetracyclines often occur on plasmids or other transferable elements such as transposons [ 4 ]. Bacteria carrying a ribosome protection type of resistance gene produce a cytoplasmic protein that interacts with the ribosomes and allows the ribosomes to proceed with protein synthesis even in the presence of high intracellular levels of the drug [ 4,5 ]. Tigecycline has a reduced potential for resistance, as it is not affected by the two major mechanisms of tetracycline resistance: ribosomal protection proteins and efflux pumps [ 6 ]. Thus, tigecycline may have activity against tetracycline­resistant organisms [ 7,8 ]. SPECTRUM OF ACTIVITY — The antimicrobial activity of all the tetracyclines is essentially the same although some differences in the relative degree of activity against certain pathogens do exist among the various agents ( table 1 ). As an example, minocycline appears to be the most active of the compounds due to its slight increase in lipid solubility. Doxycycline follows closely behind. The tetracyclines are considered broad­spectrum bacteriostatic antibiotics that are used to treat infection caused by many aerobic gram­positive and gram­negative bacteria. However, they also have activity against many atypical pathogens, including Rickettsia spp., Borrelia spp., Coxiella burnetii, Treponema spp., Chlamydia spp., Mycoplasma pneumoniae, Plasmodium spp., Vibrio cholerae, Vibrio vulnificus, Brucella spp., Calymmatobacterium granulomatis, Leptospira, Borrelia burgdorferi, Borrelia recurrentis, Burkholderia pseudomallei, Mycobacterium marinum, and Entamoeba histolytica. These drugs have little activity against fungi and viruses [ 9 ]. http://www.uptodate.com/contents/tetracyclines?topicKey=ID%2F494&elapsedTimeMs=0&source=search_result&searchTerm=tetraciclina&selectedTitle… 1/9 " id="pdf-obj-0-6" src="pdf-obj-0-6.jpg">

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Tetracyclines

26/10/2015 Tetracyclines Official re <a href=p rint from UpToDate ® www.uptodate.com ©2015 UpToDate ® Tetracyclines Author D Byron May, PharmD, BCPS Section Editor David C Hooper, MD Deputy Editor Jennifer Mitty, MD, MPH All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Sep 2015. | This topic last updated: Jul 23, 2014. INTRODUCTION — Chlortetracycline was the first tetracycline discovered, in 1948. Since then five additional tetracyclines have been isolated or derived (oxytetracycline, tetracycline, demeclocycline , doxycycline and minocycline ), but only the last four are available for systemic use in the United States. Of these four agents, doxycycline and minocycline are the most frequently prescribed. Research to find tetracycline analogues lead to the development of the glycylcyclines. Tigecycline is the first of this new class of agents and exhibits broad­ spectrum antibacterial activity similar to the tetracyclines [ 1 ]. Doxycycline is one of the most active tetracyclines and is the most often used clinically since it possesses many advantages over traditional tetracycline and minocycline . Doxycycline can be administered twice daily, has both intravenous (IV) and oral (PO) formulations, achieves reasonable concentrations even if administered with food, and is less likely to cause photosensitivity [ 2 ]. Doxycycline may be an alternative for use in children since it binds calcium to a lesser extent than tetracycline, which can cause tooth discoloration and bony growth retardation. MECHANISM OF ACTION — The tetracyclines enter the bacterial cell wall in two ways: passive diffusion and an energy­dependent active transport system, which is probably mediated in a pH­dependent fashion. Once inside the cell, tetracyclines bind reversibly to the 30S ribosomal subunit at a position that blocks the binding of the aminoacyl­tRNA to the acceptor site on the mRNA­ribosome complex. Protein synthesis is ultimately inhibited, leading to a bacteriostatic effect [ 3 ]. RESISTANCE — In contrast to many other antibiotics, tetracyclines are infrequently inactivated biologically or altered chemically by resistant bacteria. Resistance to these agents develops primarily by preventing accumulation of the drug inside the cell either by decreasing influx or increasing efflux. Once resistance develops to one of the drugs in this class, it is typically conferred to all tetracyclines. However, there are differences in resistance among species of bacteria. Resistance genes to tetracyclines often occur on plasmids or other transferable elements such as transposons [ 4 ]. Bacteria carrying a ribosome protection type of resistance gene produce a cytoplasmic protein that interacts with the ribosomes and allows the ribosomes to proceed with protein synthesis even in the presence of high intracellular levels of the drug [ 4,5 ]. Tigecycline has a reduced potential for resistance, as it is not affected by the two major mechanisms of tetracycline resistance: ribosomal protection proteins and efflux pumps [ 6 ]. Thus, tigecycline may have activity against tetracycline­resistant organisms [ 7,8 ]. SPECTRUM OF ACTIVITY — The antimicrobial activity of all the tetracyclines is essentially the same although some differences in the relative degree of activity against certain pathogens do exist among the various agents ( table 1 ). As an example, minocycline appears to be the most active of the compounds due to its slight increase in lipid solubility. Doxycycline follows closely behind. The tetracyclines are considered broad­spectrum bacteriostatic antibiotics that are used to treat infection caused by many aerobic gram­positive and gram­negative bacteria. However, they also have activity against many atypical pathogens, including Rickettsia spp., Borrelia spp., Coxiella burnetii, Treponema spp., Chlamydia spp., Mycoplasma pneumoniae, Plasmodium spp., Vibrio cholerae, Vibrio vulnificus, Brucella spp., Calymmatobacterium granulomatis, Leptospira, Borrelia burgdorferi, Borrelia recurrentis, Burkholderia pseudomallei, Mycobacterium marinum, and Entamoeba histolytica. These drugs have little activity against fungi and viruses [ 9 ]. http://www.uptodate.com/contents/tetracyclines?topicKey=ID%2F494&elapsedTimeMs=0&source=search_result&searchTerm=tetraciclina&selectedTitle… 1/9 " id="pdf-obj-0-29" src="pdf-obj-0-29.jpg">

All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Sep 2015. | This topic last updated: Jul 23, 2014.

INTRODUCTION — Chlortetracycline was the first tetracycline discovered, in 1948. Since then five additional tetracyclines have been isolated or derived (oxytetracycline, tetracycline, demeclocycline, doxycycline and minocycline), but only the last four are available for systemic use in the United States. Of these four agents, doxycycline and minocycline are the most frequently prescribed. Research to find tetracycline analogues lead to the development of the glycylcyclines. Tigecycline is the first of this new class of agents and exhibits broad­ spectrum antibacterial activity similar to the tetracyclines [1].

Doxycycline is one of the most active tetracyclines and is the most often used clinically since it possesses many advantages over traditional tetracycline and minocycline. Doxycycline can be administered twice daily, has both intravenous (IV) and oral (PO) formulations, achieves reasonable concentrations even if administered with food, and is less likely to cause photosensitivity [2]. Doxycycline may be an alternative for use in children since it binds calcium to a lesser extent than tetracycline, which can cause tooth discoloration and bony growth retardation.

MECHANISM OF ACTION — The tetracyclines enter the bacterial cell wall in two ways: passive diffusion and an energy­dependent active transport system, which is probably mediated in a pH­dependent fashion. Once inside the cell, tetracyclines bind reversibly to the 30S ribosomal subunit at a position that blocks the binding of the aminoacyl­tRNA to the acceptor site on the mRNA­ribosome complex. Protein synthesis is ultimately inhibited, leading to a bacteriostatic effect [3].

RESISTANCE — In contrast to many other antibiotics, tetracyclines are infrequently inactivated biologically or altered chemically by resistant bacteria. Resistance to these agents develops primarily by preventing accumulation of the drug inside the cell either by decreasing influx or increasing efflux. Once resistance develops to one of the drugs in this class, it is typically conferred to all tetracyclines.

However, there are differences in resistance among species of bacteria. Resistance genes to tetracyclines often occur on plasmids or other transferable elements such as transposons [4]. Bacteria carrying a ribosome protection type of resistance gene produce a cytoplasmic protein that interacts with the ribosomes and allows the ribosomes to proceed with protein synthesis even in the presence of high intracellular levels of the drug

[4,5].

Tigecycline has a reduced potential for resistance, as it is not affected by the two major mechanisms of tetracycline resistance: ribosomal protection proteins and efflux pumps [6]. Thus, tigecycline may have activity against tetracycline­resistant organisms [7,8].

SPECTRUM OF ACTIVITY — The antimicrobial activity of all the tetracyclines is essentially the same although some differences in the relative degree of activity against certain pathogens do exist among the various agents (table 1). As an example, minocycline appears to be the most active of the compounds due to its slight increase in lipid solubility. Doxycycline follows closely behind.

The tetracyclines are considered broad­spectrum bacteriostatic antibiotics that are used to treat infection caused by many aerobic gram­positive and gram­negative bacteria. However, they also have activity against many atypical pathogens, including Rickettsia spp., Borrelia spp., Coxiella burnetii, Treponema spp., Chlamydia spp., Mycoplasma pneumoniae, Plasmodium spp., Vibrio cholerae, Vibrio vulnificus, Brucella spp., Calymmatobacterium granulomatis, Leptospira, Borrelia burgdorferi, Borrelia recurrentis, Burkholderia pseudomallei, Mycobacterium marinum, and Entamoeba histolytica. These drugs have little activity against fungi and viruses [9].

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Against N. gonorrhoeae, the 2006 Gonococcal Isolate Surveillance Project (GISP) report shows that 25.6 percent of isolates collected in 2006 were resistant to penicillin, tetracycline, ciprofloxacin, or some combination of those antibiotics [10]. Therefore, use of tetracyclines for the treatment of N. gonorrhoeae in the US is NOT recommended by the CDC.

Doxycycline is effective for patients with nongonococcal urethritis caused by Chlamydia trachomatis; however, recurrent urethritis in patients previously treated with doxycycline may be the result of tetracycline­resistant U. urealyticum. Doxycycline is an alternative agent in the treatment of genital Chlamydial infections [11].

Tigecycline has a broader spectrum of activity when compared to the tetracyclines. Tigecycline has activity against gram­positive pathogens including: Enterococcus spp., vancomycin­resistant enterococci (VRE), Listeria, Streptococcus spp., both methicillin­susceptible and ­resistant S. aureus, and S. epidermidis. Its gram­negative activity includes: Acinetobacter baumannii, Citrobacter spp., Enterobacter spp., Escherichia coli, Klebsiella spp., Pasteurella multocida, Serratia marcescens, and Stenotrophomonas maltophilia [6,7].

PHARMACODYNAMICS/PHARMACOKINETICS — In animal studies, the pharmacokinetic/pharmacodynamic parameter that most closely correlates with the efficacy of tetracyclines is the 24 hour ratio of the area under the concentration­versus­time curve (AUC) to the minimum inhibitory concentration (MIC). After exposure of Staphylococcus aureus to the tetracyclines at five times the MIC for two hours, a post­antibiotic effect lasting for three hours has been observed [12].

Combination of tetracyclines and penicillins — A deleterious effect was observed for the combination of a static and cidal antibiotic when chlortetracycline and penicillin were used together for the treatment of pneumococcal meningitis. The combination of the two drugs was inferior to penicillin alone. Tetracycline administered with ampicillin or amoxicillin may result in diminished bactericidal activity of the penicillin. Thus, combinations of tetracyclines and penicillins should be avoided, if possible.

Absorption of the tetracyclines — Absorption of tetracyclines occurs primarily in the proximal small intestine and the stomach. The bioavailability of oral doxycycline approaches 95 percent (with or without food), with peak serum concentrations seen one to three hours after the dose. By contrast, the bioavailability of oral tetracycline is reduced by 50 percent if it is taken with food. The absorption of all tetracyclines can be decreased with the concomitant administration of multivalent cations (ie, aluminum, calcium, iron, magnesium). These cations chelate with the tetracyclines impairing their absorption. Concurrent administration of products containing divalent or trivalent cations should be avoided with all tetracyclines with the possible exception of doxycycline [13].

Serum concentrations — The maximum serum concentration after an intravenous dose of doxycycline occurs within 30 minutes; after tigecycline, within one hour. Peak concentrations of doxycycline range from 1.5 to 2.5 mcg/mL after a dose of 200 mg orally and 4 to 10 mcg/mL for the same dose administered intravenously. Doxycycline has an apparent volume of distribution of 50 liters and is 90 percent protein bound.

Distribution — In general, tetracyclines penetrate into tissues and body fluids fairly well. Among the following agents, the degree of tissue penetration correlates to lipid solubility: minocycline > doxycycline > tetracycline [14].

For doxycycline, therapeutic concentrations have been found in the aqueous humour, CSF (11 to 56 percent of serum concentrations), peritoneal fluid, tears, lungs, sinuses, digestive and biliary tracts, kidney, liver, and prostate [14­16]. Doxycycline also distributes into the bone, fat, and muscle at concentrations below plasma levels [15].

Tetracycline distributes well into ascitic fluid, bile, CNS (10 to 26 percent), sinuses, pleural and synovial fluid

[14].

Minocycline has been found in therapeutic concentrations in the aqueous humor, bile, duodenum, fallopian tubes/ovaries, liver, lung, sinuses, saliva, sputum, tears, and thyroid gland. Minocycline distributes in lower concentrations to the bladder, breast, lymph nodes, prostate, and skin [14,15].

Tigecycline distributes well into the bile, CSF, and lung. Animal data demonstrate that tigecycline distributes well into bone, bone marrow, spleen, and thyroid [15,17].

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In addition, all the tetracyclines cross the placenta and accumulate in the bone and teeth of the fetus. The tetracyclines are also excreted in breast milk, although complexation with calcium in breast milk limits availability to the breast­fed infant [14].

Routes of elimination — The routes of elimination differ among the tetracyclines. The primary route of elimination for tetracycline is the kidney via glomerular filtration. Doxycycline is primarily eliminated in the intestinal tract, with up to 90 percent of the dose excreted in the feces. Approximately 20 percent of a doxycycline dose is eliminated by glomerular filtration. Tigecycline is eliminated through the feces as unchanged drug.

Dose adjustment is not necessary for doxycycline or tigecycline in patients with renal dysfunction, and thus, these are the preferred tetracyclines in this population [13]. Dose adjustment is only required in severe hepatic dysfunction for doxycycline and tigecycline (maintenance dose 25 mg IV every 12 hours) [6]. Minocycline is metabolized in the liver to at least six inactive metabolites. Only 4 to 9 percent of minocycline is excreted via the kidneys, and fecal concentrations are also minimal. No accumulation of minocycline is seen with hepatic failure. Similar to doxycycline, food has little effect on the absorption of minocycline. The tetracyclines are minimally removed by hemodialysis, peritoneal dialysis, or hemofiltration; therefore, dose adjustments are not necessary in these situations [13].

SPECIAL POPULATIONS

Pregnant or breastfeeding women — Tetracyclines can cause fetal toxicity when given to pregnant women. For certain infections, the potential risks may be offset by the benefits. However, tetracyclines should generally not be used in pregnant women or children under the age of eight years unless other appropriate drugs are ineffective or contraindicated.

Tetracyclines cross the placenta and achieve concentrations in umbilical­cord plasma and amniotic fluid of 60 and 20 percent, respectively, of levels in the maternal circulation. This can cause accumulation in fetal bone and teeth. Tetracyclines are found in high concentrations in human breast milk, but concentrations are very low in breast­fed infants, which is probably a reflection of chelation by calcium in breast milk [13].

Renal failure — These agents, with the possible exception of doxycycline and tigecycline, should generally not be used in patients with end­stage renal disease (table 2) [2].

ADVERSE REACTIONS — Tetracyclines are generally safe drugs, but some adverse effects can occur.

The following provides a brief summary of some of the major adverse effects associated with tetracyclines. These issues are discussed in detail separately. See Tetracycline drug information, Doxycycline drug information, Minocycline drug information, Tigecycline drug information, and Demeclocycline drug information.

Gastrointestinal — Dose­related gastrointestinal side effects are the most common complaint in patients taking oral tetracyclines and intravenous tigecycline [1]. These include abdominal discomfort, epigastric pain, nausea, vomiting and anorexia. Food may decrease these symptoms but also may decrease the absorption of tetracycline by 50 percent. Food does not affect the absorption of doxycycline.

Tetracyclines may alter gut flora to cause large bulky stools and diarrhea. Diarrhea usually subsides once the agent is stopped. A patient with continued diarrhea, fever, and a rising white blood count should be evaluated for antibiotic associated diarrhea caused by Clostridium difficile. Esophageal ulcerations and strictures have been reported with tetracyclines but can be prevented by taking the drugs with plenty of water and not before bedtime. (See "Clostridium difficile infection in adults: Clinical manifestations and diagnosis".)

Allergic and skin reactions — Hypersensitivity reactions can occur with tetracyclines but are uncommon. If a patient is allergic to one tetracycline, they should be considered allergic to all. Photosensitivity reactions can occur, ranging from a red rash to blistering on areas exposed to the sun. These reactions are most common with demeclocycline but can occur with all analogues. Photosensitivity can be decreased by avoiding direct sunlight or wearing protective clothing with sunscreen [2].

Teeth and bone — Tetracyclines can cause a brown to yellow discoloration of the teeth in children under the age of eight that is sometimes associated with hypoplasia of the enamel. The darkening effect on the

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permanent teeth appears to be dose related and does not occur in adults. These agents generally should be avoided in children under the age of eight; however if they must be used, doxycycline may be the preferred agent. Tetracyclines may also deposit in the bone likely due to chelate formation with calcium, thus adding another reason to avoid these agents in children with developing bone formation [2].

Liver and renal — Hepatotoxicity with tetracyclines is rare but can be fatal. This occurs more commonly with tetracycline and minocycline and less often with doxycycline [18].

Tetracyclines inhibit protein synthesis and may exacerbate preexisting renal failure by increasing the azotemia from amino acid metabolism. Demeclocycline can cause a nephrogenic diabetes insipidus, a side effect that is used therapeutically to treat the syndrome of inappropriate antidiuretic hormone secretion (SIADH). The use of outdated tetracyclines has been associated with a reversible Fanconi­like syndrome and renal tubular acidosis; however, current formulations, which do not contain citric acid as an excipient, have virtually eliminated this possibility [2]. (See "Treatment of hyponatremia: Syndrome of inappropriate antidiuretic hormone secretion (SIADH) and reset osmostat".)

Mortality Tigecycline has been associated with increased mortality when compared with other antibacterial drugs. In September 2010, the US Food and Drug Administration (FDA) issued a safety announcement regarding increased mortality with the use of tigecycline in patients with hospital­acquired pneumonia (HAP) [19]. A 2013 analysis of 10 clinical trials showed an increased risk of death in patients receiving tigecycline for FDA­approved uses, including community­acquired bacterial pneumonia, complicated skin and skin structure infections, and complicated intraabdominal infections (2.5 versus 1.8 percent, adjusted risk difference 0.6 percent) [2]. The FDA has subsequently added a boxed warning stating that tigecycline should be reserved for use in situations when alternative agents are not suitable [20]. (See "Treatment of community­acquired pneumonia in adults who require hospitalization", section on 'Tigecycline' and "Treatment of hospital­acquired, ventilator­associated, and healthcare­associated pneumonia in adults", section on 'Other agents'.)

Miscellaneous — A Jarisch­Herxheimer type reaction (JHR) has occurred in patients being treated for spirochetal infections. Effects include fever, chills, headache, malaise, muscle aches, leukocytosis, and exacerbation of cutaneous lesions. The JHR occurs in 75 to 80 percent of those treated for syphilis, 54 percent of those treated for tick­borne relapsing fever, and 82 percent of those treated for louse­borne relapsing fever. Prevention of the JHR in patients is of limited value; the best results are with the use of tumor necrosis factor (TNF) antibodies and steroids. Pretreatment with acetaminophen or meptazinol may reduce the symptoms and duration [21].

Vertigo has been associated with minocycline and appears to be dose­related. More common in women than men, this may appear during the second or third day of therapy and usually resolves in one to two days after discontinuing the drug. Complaints consist of dizziness, ataxia, nausea, vomiting, and tinnitus.

Hematologic effects are very uncommon but may include hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia. Other, less common reactions, include minocycline­induced lupus [22­24] and pericardial effusions [25].

Nausea and vomiting have been reported with increased frequency with tigecycline (30 and 20 percent) compared to tetracyclines [6].

DRUG INTERACTIONS — The absorption of tetracyclines can be impaired by co­administered minerals and antacids (eg, calcium, magnesium, iron), lanthanum, and dairy including milk. Tetracyclines can interact with oral isotretinoin, beta­lactams, and a variety of other drugs. Specific drug interactions of the tetracyclines and management suggestions may be determined by using Lexi­Interact, the drug interactions program included with UpToDate.

SUMMARY AND RECOMMENDATIONS

● Tetracyclines inhibit bacterial protein synthesis by binding reversibly to the 30S ribosomal subunit. (See 'Mechanism of action' above.)

● Decreased accumulation of drug within bacteria leads to resistance; drug uptake is affected by decreasing influx or increasing efflux. (See 'Resistance' above.)

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● The tetracyclines are considered broad­spectrum bacteriostatic antibiotics with activity against many aerobic gram­positive and gram­negative bacteria and atypical pathogens, such as mycoplasma and chlamydia. (See 'Spectrum of activity' above.)

Absorption of tetracyclines occurs primarily in the proximal small intestine and the stomach with good distribution into tissues and body fluids. (See 'Pharmacodynamics/pharmacokinetics' above.)

Tetracyclines should generally not be used in pregnant women or children under the age of eight years unless other appropriate drugs are ineffective or contraindicated. (See 'Special populations' above.)

● Tetracyclines are generally safe; the most common adverse events are related to gastrointestinal symptoms (eg, epigastric discomfort and nausea). (See 'Adverse reactions' above.)

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REFERENCES

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GRAPHICS

Tetracyclines

Spectrum of activity of the tetracyclines

 
 

Pathogens/syndromes

 

Rickettsial infections (doxycycline)

Chlamydial infections (doxycycline)

Traveler's diarrhea (doxycycline)

Early Lyme disease (doxycycline)

Chloroquine­resistant malaria (doxycycline)

Acne

Amebiasis

Actinomycosis

Brucellosis

Borrelia recurrentis

Legionnaire's disease

Leptospirosis

Mycobacterium marinum

Melioidosis

Mycoplasma pneumoniae

Meningococcal prophylaxis (minocycline)

MRSA (minocycline or tigecycline)

Nocardiosis

Pelvic inflammatory disease

Staphylococcus aureus (minocycline or tigecycline)

Syphilis

Tularemia

Vibrio vulnificus

VRE (susceptible strains)

Whipple's disease

Graphic 58190 Version 2.0

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Tetracyclines

Dosing and administration of tetracyclines

 
   

Drug

 

Doxycycline

100 mg IV/PO every 12 hours; No adjustment in renal dysfunction

Tetracycline

250­500 mg PO every 6 hours with normal renal function.

250­500 mg PO every 12 to 24 hours with CrCl 10­50 mL/min.

Not recommended when CrCl <10 mL/min

Minocycline

100 mg PO every 12 hours; No adjustment in renal dysfunction

Demeclocycline 150­300 mg PO every 12 to 24 hours; Avoid use in renal dysfunction

Tigecycline

100 mg initial dose then 50 mg IV every 12 hours; No adjustment in renal dysfunction

Graphic 80309 Version 2.0

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Disclosures

Tetracyclines

Disclosures: D Byron May, PharmD, BCPS Nothing to disclose. David C Hooper, MD Consultant/Advisory Boards: Bacterioscan [Antimicrobials (Urine diagnostic under development)]; Cubist [Antimicrobials (Daptomycin, fidaxomycin, tedizolid, ceftolozane­ tazobactam)]; Shionogi [Antimicrobials (Anti­gram­negative beta­lactam under development)]; Melinta [Antimicrobials (Antimicrobials under development)]; Cepheid [Antimicrobials (rapid genetic diagnostics)]; FabPharma [Antimicrobials (Antimicrobial under development)]. Jennifer Mitty, MD, MPH Nothing to disclose.

Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi­level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.

26/10/2015 Disclosures Tetracyclines Disclosures: D Byron May, PharmD, BCPS Nothing to disclose. David C Hooper, MDConflict of interest policy http://www.uptodate.com/contents/tetracyclines?topicKey=ID%2F494&elapsedTimeMs=0&source=search_result&searchTerm=tetraciclina&selectedTitle… 9/9 " id="pdf-obj-8-20" src="pdf-obj-8-20.jpg">