Uses
Ciprofloxacin is used orally or IV for the treatment of urinary tract infections (UTIs), chronic bacterial prostatitis, acute sinusitis, lower respiratory tract infections (including nosocomial pneumonia and acute exacerbations of chronic bronchitis), GI infections, skin and skin structure infections, or bone and joint infections caused by susceptible gram-negative and gram-positive aerobic bacteria. Ciprofloxacin is used orally or IV for inhalational anthrax (postexposure) following suspected or confirmed exposure to aerosolized Bacillus anthracis spores and also is used for prophylaxis following ingestion of B. anthracis spores and for the treatment of inhalational anthrax, cutaneous anthrax, or GI and oropharyngeal anthrax. Ciprofloxacin is used orally or IV for the treatment or prophylaxis of plague. In addition, ciprofloxacin is used orally or IV in conjunction with metronidazole for the treatment of complicated intra-abdominal infections caused by Escherichia coli, Pseudomonas aeruginosa, Proteus mirabilis, Klebsiella pneumoniae, or Bacteroides fragilis. Because ciprofloxacin is inactive against most anaerobic bacteria, the drug is ineffective in and should not be used alone if a mixed aerobic-anaerobic bacterial infection is suspected. Ciprofloxacin has been used in conjunction with other anti-infectives for empiric anti-infective therapy in febrile neutropenic patients.
Ciprofloxacin extended-release tablets containing both the hydrochloride and the base are used in adults for the treatment of uncomplicated UTIs (acute cystitis), complicated UTIs, or acute uncomplicated pyelonephritis. Safety and efficacy of ciprofloxacin extended-release tablets have been established only for infections involving the urinary tract; the extended-release tablets should not be used for the treatment of infections at other sites (e.g., respiratory tract, skin and skin structure, bone and joint, GI tract, intra-abdominal) that are treated with ciprofloxacin conventional tablets or oral suspension or with IV ciprofloxacin.
Prior to initiation of ciprofloxacin therapy, appropriate specimens should be obtained for identification of the causative organism(s) and in vitro susceptibility tests. Ciprofloxacin therapy may be started pending results of susceptibility tests, but should be discontinued and other appropriate anti-infective therapy substituted if the organism is found to be resistant to ciprofloxacin. Because resistant strains of Pseudomonas aeruginosa have developed during ciprofloxacin therapy, in vitro susceptibility tests should be performed periodically when the drug is used in the treatment of infections caused by this organism. Because staphylococci may develop resistance to ciprofloxacin during prolonged therapy with the drug, in vitro susceptibility tests should be repeated during therapy, especially when infections are caused by oxacillin-resistant strains of Staphylococcus aureus (previously known as methicillin-resistant S. aureus or MRSA).
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Bone and Joint Infections
Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of bone and joint infections, including osteomyelitis, caused by susceptible E. aerogenes,E. cloacae,E. coli,K. pneumoniae,M. morganii,P. mirabilis,Ps. aeruginosa, or S. marcescens. The drug also has been used in adults for the treatment of bone and joint infections caused by susceptible S. aureus,S. epidermidis, other coagulase-negative staphylococci, or Enterococcus faecalis (formerly S. faecalis), but other anti-infectives generally are preferred for these infections. Although resistance to ciprofloxacin has been reported in some strains of oxacillin-resistant S. aureus, oral ciprofloxacin may be a useful alternative to parenteral anti-infectives for the treatment of infections caused by susceptible oxacillin-resistant staphylococci.
Clinical response has been reported in 61-86% and bacteriologic cure has been reported in 75-81% of patients with bone and joint infections (caused principally by gram-negative aerobes) who received oral ciprofloxacin. Treatment failures have been reported most frequently in patients with an underlying metal appliance at the site of infection and in patients with ciprofloxacin-resistant Ps. aeruginosa or S. aureus. However, there is evidence from a randomized, controlled study in patients with culture-proven staphylococcal infections associated with stable orthopedic implants that a long-term regimen (3-6 weeks) of ciprofloxacin and rifampin given after initial debridement and a 2-week IV regimen of flucloxacillin (not commercially available in the US) or vancomycin with rifampin or placebo can result in cure of the infection without removal of the implant.
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Endocarditis
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Endocarditis Caused by the HACEK Group
Ciprofloxacin is used as an alternative for the treatment of endocarditis (native or prosthetic valve or other prosthetic material) caused by fastidious gram-negative bacilli known as the HACEK group (Haemophilus, Aggregatibacter, Cardiobacterium hominis, Eikenella corrodens, Kingella). The HACEK group accounts for up to 10% of cases of community-acquired native valve endocarditis in patients who are not IV drug abusers. These organisms should be considered ampicillin-resistant, but may be susceptible to third or fourth generation cephalosporins or fluoroquinolones.
The American Heart Association (AHA) and Infectious Diseases Society of America (IDSA) recommend ceftriaxone (or other third or fourth generation cephalosporin) for the treatment of endocarditis caused by the HACEK group, but state that a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) may be considered in patients who cannot tolerate cephalosporins. Because only limited data are available regarding use of fluoroquinolones for the treatment of HACEK endocarditis, an infectious disease specialist should be consulted when treating such infections in patients who cannot tolerate cephalosporins.
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GI Infections
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Infectious Diarrhea
Ciprofloxacin (conventional tablets, oral suspension) is used in adults for the treatment of infectious diarrhea caused by susceptible strains of enterotoxigenic E. coli,Campylobacter fetus subsp. jejuni,Salmonella
(see Uses: Typhoid Fever and other Salmonella Infections) ,Shigella (S. flexneri,S. boydii, S. sonnei,S. dysenteriae), or Vibrio(see Uses: Vibrio Infections) . Because ciprofloxacin is active in vitro against many pathogens associated with infectious diarrhea, including E. coli, Shigella, Salmonella, Aeromonas, Vibrio, Yersinia enterocolitica, and some strains of Campylobacter, some clinicians suggest that it may be a drug of choice for empiric treatment of the disease. However, because of concerns about increasing emergence of fluoroquinolone-resistant strains of Campylobacter secondary to widespread use of the drugs, judicious use of fluoroquinolones for the treatment and prevention of enteropathogenic diarrhea is warranted.
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Cyclospora and Cystoisospora Infections
Although co-trimoxazole is the drug of choice for GI infections caused by Cyclospora cayetanensis or Cystoisospora belli (formerly Isospora belli), ciprofloxacin is recommended as an alternative for the treatment of cyclosporiasis and has been used for the treatment of cystoisosporiasis (formerly isosporiasis). Ciprofloxacin may not be as effective as co-trimoxazole, but may be useful for the treatment of these infections in patients who cannot tolerate co-trimoxazole.
In HIV-infected patients, ciprofloxacin is recommended as an alternative to co-trimoxazole for treatment and chronic maintenance therapy (secondary prophylaxis) of cystoisosporiasis.
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Shigella Infections
Ciprofloxacin (conventional tablets, oral suspension) is used for the treatment of shigellosis caused by susceptible Shigella. Infections caused by Sh. sonnei usually are self-limited (48-72 hours), and mild cases may not require treatment with anti-infectives. However, because there is some evidence that anti-infectives may shorten the duration of diarrhea and the period of fecal excretion of Shigella, anti-infective treatment generally is recommended in addition to fluid and electrolyte replacement in patients with severe shigellosis, dysentery, or underlying immunosuppression. An empiric treatment regimen can be used initially, but in vitro susceptibility testing of clinical isolates is indicated since resistance is common. A fluoroquinolone (preferably ciprofloxacin or, alternatively, levofloxacin or moxifloxacin) generally has been recommended for the treatment of shigellosis. However, fluoroquinolone-resistant Shigella have been reported in the US, especially in international travelers, the homeless, and men who have sex with men (MSM). Depending on in vitro susceptibility, alternatives to fluoroquinolones for the treatment of shigellosis include co-trimoxazole or azithromycin (not recommended in those with bacteremia); ceftriaxone or azithromycin are considered drugs of choice for the treatment of shigellosis when the susceptibility of the isolate is unknown or when ampicillin- or co-trimoxazole-resistant strains are involved.
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Yersinia Infections
Although GI infections caused by Yersinia enterocolitica or Y. pseudotuberculosis usually are self-limited and anti-infective therapy unnecessary, the American Academy of Pediatrics (AAP), US Centers for Disease Control and Prevention (CDC), IDSA, and others recommend use of anti-infectives in immunocompromised individuals or for the treatment of severe infections or when septicemia or other invasive disease occurs. GI infections caused by Y. enterocolitica or Y. pseudotuberculosis can occur as the result of ingesting undercooked pork, unpasteurized milk, or contaminated water; infection has occurred in infants whose caregivers handled contaminated chitterlings (raw pork intestines) or tofu. The incubation period usually is 24-48 hours. Use of co-trimoxazole, an aminoglycoside (e.g., amikacin, gentamicin, tobramycin), a fluoroquinolone (e.g., ciprofloxacin), doxycycline, or cefotaxime has been recommended when treatment is considered necessary; combination therapy may be necessary. Some clinicians suggest that the role of anti-infectives in the management of enterocolitis, pseudoappendicitis syndrome, or mesenteric adenitis caused by Yersinia needs further evaluation.
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Travelers' Diarrhea
Ciprofloxacin (conventional tablets, oral suspension) is used for the short-term treatment of travelers' diarrhea and has been used for the prevention of travelers' diarrhea in adults traveling for relatively short periods of time to high-risk areas.
The most common cause of travelers' diarrhea worldwide is noninvasive enterotoxigenic strains of E. coli (ETEC), but travelers' diarrhea also can be caused by various other bacteria including enteroadherent and other E. coli pathotypes, Campylobacter jejuni, Shigella, Salmonella, A. hydrophila, Plesiomonas shigelloides, Yersinia enterocolitica, or V. parahaemolyticus or non-O-group 1 V. cholerae. In some cases, travelers' diarrhea is caused by parasitic enteric pathogens (e.g., Giardia duodenalis [also known as G. lamblia or G. intestinalis], Cryptosporidium parvum, Cyclospora cayetanensis, Entamoeba histolytica, Dientamoeba fragilis) or viral enteric pathogens (e.g., rotavirus, norovirus, astrovirus).
Countries where travelers are at low risk of travelers' diarrhea include the US, Canada, Australia, New Zealand, Japan, and countries in Northern and Western Europe. Travelers are at intermediate risk for travelers' diarrhea in Eastern Europe, South Africa, and some of the Caribbean islands, but are at high risk in most of Asia, the Middle East, Africa, and Central and South America.
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Treatment
Travelers' diarrhea caused by bacteria may be self-limited and often resolves within 3-7 days without anti-infective treatment. If diarrhea is moderate or severe, associated with high fever or bloody stools, persisting longer than 3 days, or extremely disruptive to travel plans, short-term (1-3 days) treatment with an anti-infective usually is recommended. Since bacteria are the most common cause of travelers' diarrhea (80-90% of cases), an anti-infective directed against enteric bacterial pathogens is used for empiric treatment. CDC and other experts state that a fluoroquinolone (e.g., ciprofloxacin, levofloxacin) generally is considered the anti-infective of choice for empiric treatment, including self-treatment, of travelers' diarrhea in adults. Azithromycin can be used as a treatment alternative for individuals who should not receive fluoroquinolones (e.g., children, pregnant women) and is a drug of choice for travelers in areas with a high prevalence of fluoroquinolone-resistant Campylobacter (e.g., South and Southeast Asia) or those who have not responded after 48 hours of fluoroquinolone treatment. Rifaximin is another alternative for the treatment of travelers' diarrhea caused by noninvasive E. coli. Antimotility agents may be used as an adjunct to anti-infective treatment to provide symptomatic relief; oral rehydration therapy should be used if indicated, especially in young children or geriatric adults.
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Prophylaxis
CDC and most experts do not recommend routine prophylactic use of anti-infectives to prevent travelers' diarrhea in individuals traveling to areas of risk. Because travelers' diarrhea is a relatively nonthreatening illness that usually is mild and self-limiting and can be effectively treated and because of the risks of widespread use of prophylactic anti-infectives (i.e., potential adverse drug reactions, selection of resistant organisms, increased susceptibility to infections caused by these or other organisms), anti-infective prophylaxis for prevention of travelers' diarrhea should be considered only in select individuals. This includes short-term travelers who are high-risk individuals (e.g., HIV-infected or other immunocompromised individuals, travelers with poorly controlled diabetes mellitus or chronic renal failure) and those who are taking critical trips during which even a short period of diarrhea could adversely affect the purpose of the trip.
The use of anti-infective prophylaxis in travelers should be weighed against use of prompt, early self-treatment with anti-infectives, a strategy that can limit the duration of illness to 6-24 hours in most cases. If anti-infective prophylaxis is indicated, a fluoroquinolone (e.g., ciprofloxacin, levofloxacin) usually is recommended for nonpregnant adults, although the increasing incidence of quinolone resistance in pathogens that cause travelers' diarrhea (e.g., Campylobacter) should be considered and may limit their benefit in the future. Azithromycin and rifaximin also have been used for prevention of travelers' diarrhea. Results of controlled studies indicate that the diarrhea attack rate can be reduced by 90% or more by the use of anti-infective prophylaxis; however, efficacy depends on resistance patterns of pathogenic bacteria in each travel area and these patterns have evolved over the last several decades.
Anti-infectives recommended for prophylaxis of travelers' diarrhea may prevent bacterial illness, but are not effective in preventing diarrhea caused by parasitic or viral pathogens, and use of such prophylaxis may give a false sense of security to the traveler about the risk associated with consuming certain local foods and beverages. The principal preventive measures that can be used to prevent travelers' diarrhea are prudent dietary practices (e.g., avoid raw or undercooked meat and seafood, avoid raw fruits and vegetable, avoid foods or drinks purchased from street vendors or establishments where unhygienic conditions are present).
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HIV-Infected Individuals
CDC, National Institutes of Health (NIH), and IDSA state that decisions regarding treatment of travelers' diarrhea in HIV-infected individuals are similar to those in immunocompetent individuals and should be based on diarrhea severity and hydration status. If possible, treatment decisions should be based on results of stool samples and in vitro susceptibility testing. Oral hydration without anti-infective treatment may be sufficient for management of HIV-infected patients with CD4 T-cell counts exceeding 500 cells/mm who have had only 1-2 days of loose stools without blood or fever. Anti-infective treatment may be indicated in those with CD4 T-cell counts of 200-500 cells/mm who have severe diarrhea affecting quality of life or ability to work. Diagnostic evaluation and anti-infective treatment is indicated in those with advanced HIV disease (CD4 T-cell counts less than 200 cells/mm or concomitant AIDS-defining illness) who have clinically severe diarrhea (i.e., 6 or more stools per day or bloody stools and/or accompanied by fever or chills). These experts state that empiric treatment with a fluoroquinolone is reasonable in HIV-infected individuals, and IV ceftriaxone and IV cefotaxime are reasonable alternatives.
CDC, NIH, and IDSA state that, while prophylaxis against travelers' diarrhea is not generally recommended for HIV-infected travelers, such prophylaxis may be considered for some of these individuals, depending on their level of immunosuppression and the region and duration of travel. These clinicians suggest that oral fluoroquinolones (e.g., ciprofloxacin) can be used in HIV-infected adults when prophylaxis of travelers' diarrhea is considered necessary. Rifaximin also can be considered for such prophylaxis. For HIV-infected patients who are pregnant or are already receiving co-trimoxazole for prophylaxis of Pneumocystis jirovecii (formerly Pneumocystis carinii) pneumonia (PCP), co-trimoxazole may provide some degree of protection from travelers' diarrhea; however, co-trimoxazole probably should not be administered solely for prophylaxis of travelers' diarrhea in HIV-infected patients because of the risk of adverse effects.
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Intra-abdominal Infections
Ciprofloxacin (IV, conventional tablets, oral suspension) is used in conjunction with metronidazole for the treatment of complicated intra-abdominal infections caused by E. coli, Ps. aeruginosa, P. mirabilis, K. pneumoniae, or Bacteroides fragilis.
For initial empiric treatment of mild to moderately severe community-acquired, extrabiliary, complicated intra-abdominal infections in adults (e.g., perforated or abscessed appendicitis), IDSA recommends either monotherapy with cefoxitin, ertapenem, moxifloxacin, tigecycline, or the fixed combination of ticarcillin and clavulanic acid, or a combination regimen that includes either a cephalosporin (cefazolin, ceftriaxone, cefotaxime, cefuroxime) or fluoroquinolone (ciprofloxacin, levofloxacin) in conjunction with metronidazole.
For initial empiric treatment of high-risk or severe community-acquired, extrabiliary, complicated intra-abdominal infections in adults (e.g., those with advanced age, immunocompromise, severe physiologic disturbance), IDSA recommends either monotherapy with a carbapenem (doripenem, imipenem, meropenem) or the fixed combination of piperacillin and tazobactam, or a combination regimen that includes either a cephalosporin (cefepime, ceftazidime) or fluoroquinolone (ciprofloxacin, levofloxacin) in conjunction with metronidazole.
For additional information on management of intra-abdominal infections, the current clinical practice guidelines from IDSA available at http://www.idsociety.org should be consulted.
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Meningitis and Other CNS Infections
IV ciprofloxacin has been used with some success for the treatment of meningitis caused by gram-negative bacteria. However, only low concentrations of ciprofloxacin are distributed into CSF, and further study is needed to more fully evaluate efficacy and safety of the drug in the treatment of CNS infections. Some clinicians suggest that fluoroquinolones (including ciprofloxacin) be considered for the treatment of meningitis only when the infection is caused by multidrug-resistant gram-negative bacilli or when the usually recommended anti-infectives cannot be used or have been ineffective.
Ciprofloxacin has been effective when used alone or in conjunction with other drugs (e.g., antipseudomonal aminoglycosides) to treat meningitis and other CNS infections caused by susceptible Ps. aeruginosa. Some clinicians suggest that a regimen of ciprofloxacin with or without an aminoglycoside can be used as an alternative for the treatment of Ps. aeruginosa meningitis when cefepime or ceftazidime cannot be used.
Ciprofloxacin also has been used for the treatment of meningitis and other CNS infections caused by susceptible Salmonella. Some clinicians suggest that ciprofloxacin alone or in conjunction with a third generation cephalosporin (cefotaxime, ceftriaxone) may be a drug of choice for the treatment of Salmonella meningitis in pediatric patients, especially when the causative organism is resistant to other drugs.
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Ophthalmic and Otic Infections
Oral or IV ciprofloxacin is used in the treatment of malignant otitis externa caused by Ps. aeruginosa. Bacterial otitis externa usually is caused by Ps. aeruginosa or S. aureus. Although acute bacterial otitis externa localized in the external auditory canal may be effectively treated using topical anti-infectives (e.g., ciprofloxacin otic suspension, ofloxacin otic solution), malignant otitis externa is an invasive, potentially life-threatening infection, especially in immunocompromised patients such as those with diabetes mellitus or HIV infection, and requires prompt diagnosis and long-term treatment with systemic anti-infectives. The treatment of choice for malignant otitis externa usually is ciprofloxacin or an antipseudomonal β-lactam (e.g., ceftazidime, imipenem). Because ciprofloxacin-resistant Ps. aeruginosa have been reported with increasing frequency in patients with malignant otitis externa and has been associated with treatment failure, clinical isolates should be tested for in vitro susceptibility, especially if there is an inadequate response to treatment.
For use of ciprofloxacin hydrochloride in the topical treatment of ophthalmic and otic infections caused by susceptible bacteria,
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Respiratory Tract Infections
Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of respiratory tract infections, including acute sinusitis, acute exacerbations of chronic bronchitis), bronchiectasis, lung abscess, and pneumonia, caused by susceptible E. aerogenes,E. cloacae,E. coli,Haemophilus influenzae,H. parainfluenzae,K. oxytoca,K. pneumoniae,P. mirabilis,Ps. aeruginosa,S. aureus, or S. pneumoniae (penicillin-susceptible strains). The drug also is used for the treatment of respiratory tract infections caused by susceptible Moraxella catarrhalis.
IV ciprofloxacin is used for the treatment of nosocomial pneumonia caused by susceptible H. influenzae or K. pneumoniae and for the treatment of acute bacterial sinusitis caused by H. influenzae, S. pneumoniae (penicillin-susceptible strains), or M. catarrhalis.
Ciprofloxacin should be used for the treatment of acute bacterial sinusitis or acute bacterial exacerbations of chronic bronchitis only when there are no other treatment options.Because systemic fluoroquinolones, including ciprofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient
(see Cautions) and because acute bacterial sinusitis and acute bacterial exacerbations of chronic bronchitis may be self-limiting in some patients,the risks of serious adverse reactions outweigh the benefits of fluoroquinolones for patients with these infections.In controlled studies in adults with respiratory tract infections, oral ciprofloxacin therapy was as effective as therapy with oral amoxicillin, oral ampicillin, IV cefamandole, oral doxycycline, or IV imipenem and cilastatin sodium. Oral ciprofloxacin therapy generally resulted in a bacteriologic cure rate of 80-98% in adults with respiratory tract infections. Oral ciprofloxacin has been most effective in the treatment of respiratory tract infections caused by H. influenzae or M. catarrhalis; treatment failures have occurred when the drug was used in the treatment of infections caused by S. pneumoniae or Ps. aeruginosa. Treatment failure of S. pneumoniae respiratory tract infections may be related to the moderate in vitro susceptibility of this organism to ciprofloxacin. Although ciprofloxacin may be effective, it is not a drug of first choice for the treatment of presumed or confirmed pneumonia secondary to S. pneumoniae, and some clinicians suggest that ciprofloxacin generally not be used for empiric treatment of community-acquired pneumonia when S. pneumoniae is likely or suspected as the causative organism. A β-lactam antibiotic generally is preferred for empiric treatment of these infections and also is preferred in other respiratory tract infections known or suspected to be caused by pneumococci or streptococci. Ciprofloxacin probably should not be used in the treatment of aspiration pneumonia because these infections generally involve anaerobic bacteria.
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Acute Exacerbations of Chronic Bronchitis
Clinical improvement has occurred when oral ciprofloxacin was used alone for the treatment of acute exacerbations of bronchopulmonary Ps. aeruginosa infections in adults with cystic fibrosis. As with other anti-infectives, Ps. aeruginosa may be cleared temporarily from the sputum, but a bacteriologic cure rarely is obtained and should not be expected in these patients.
Resistant strains of Ps. aeruginosa have developed during ciprofloxacin therapy; in one study, up to 45% of cystic fibrosis patients developed resistance after 2 weeks of therapy with the drug. Clinical improvement occurred in some patients despite the emergence of resistant Ps. aeruginosa; in some cases, the resistant organisms reverted to being susceptible after ciprofloxacin therapy was discontinued. Further study is necessary to determine if emergence of resistance will limit use of ciprofloxacin in the treatment of Ps. aeruginosa infections in cystic fibrosis patients. Some clinicians caution against long-term use of ciprofloxacin in these patients and recommend that the drug be used in short courses (e.g., 14 days), alternated with other anti-infectives active against Ps. aeruginosa (e.g., aztreonam, extended-spectrum penicillins, third generation cephalosporins) and/or used in conjunction with one of these agents. If ciprofloxacin is used, it is important that susceptibility of isolates be tested carefully in subsequent exacerbations.
Although many cystic fibrosis patients are children, ciprofloxacin, like other quinolones, generally should not be used in children younger than 18 years of age. Some clinicians suggest that the possible benefits of ciprofloxacin therapy may outweigh the possible risks in certain cystic fibrosis patients 9-18 years of age with infections that were known to be resistant to or failed to respond to other available anti-infectives.
(See Cautions: Pediatric Precautions.)
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Nosocomial Pneumonia
Ciprofloxacin is used IV for the treatment of nosocomial pneumonia, including hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.
Local susceptibility data should be used when selecting initial empiric regimens for the treatment of nosocomial pneumonia, including hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. For empiric treatment of hospital-acquired bacterial pneumonia in patients with risk factors for multidrug-resistant bacteria, the American Thoracic Society (ATS) and IDSA recommend use of anti-infectives that have a broad spectrum of activity against gram-positive, gram-negative, and anaerobic bacteria. An anti-infective active against methicillin-resistant S. aureus (MRSA; also known as oxacillin-resistant S. aureus) (e.g., vancomycin, linezolid) should be included in the initial empiric regimen in hospitals where MRSA is common or if there are other factors that increase the risk for these strains.
For additional information on management of nosocomial pneumonia, the current clinical practice guidelines from IDSA available at http://www.idsociety.org should be consulted.
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Skin and Skin Structure Infections
Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of skin and skin structure infections caused by susceptible C. freundii,E. cloacae,E. coli, K. oxytoca,K. pneumoniae,M. morganii,P. mirabilis,P. vulgaris,P. stuartii,Ps. aeruginosa,Serratia marcescens,S. aureus (oxacillin-susceptible strains),S. epidermidis (oxacillin-susceptible strains), or S. pyogenes (group A β-hemolytic streptococci). The drug has been effective in the treatment of cellulitis, abscesses, folliculitis, furunculosis, pyoderma, postoperative wound infections, and infected ulcers, burns, or wounds.
Ciprofloxacin may be particularly useful as an oral agent for the treatment of skin and skin structure infections caused by susceptible gram-negative bacteria. Because staphylococci, streptococci, and anaerobes are only moderately susceptible to ciprofloxacin, ciprofloxacin generally should not be used alone and other anti-infectives remain the drugs of choice for skin and skin structure infections caused by these bacteria. Treatment failures have been reported in patients with skin or skin structure infections caused by S. aureus and the increasing emergence of strains of staphylococci resistant to quinolones limits the usefulness of the drugs in the treatment of these infections. Some clinicians suggest that ciprofloxacin therapy may be particularly useful for the treatment of hospital-acquired decubitus ulcers when anti-infective therapy is indicated.
In several controlled studies, oral ciprofloxacin was at least as effective as IV cefotaxime in the treatment of skin and skin structure infections caused by susceptible organisms. Oral ciprofloxacin resulted in a bacteriologic cure rate of 80-92% in patients with skin and skin structure infections.
Although ciprofloxacin is active in vitro against most common aerobic pathogens isolated from animal and human bite wounds, including Flavobacterium and Eikenella corrodens, the in vitro activity of the drug against streptococci, which frequently are isolated from such wounds (usually in mixed cultures), and against anaerobes generally is poor. Therefore, use of the drug as monotherapy in these infections is not recommended pending accumulation of additional efficacy data.
For additional information on management of skin and skin structure infections, the current clinical practice guidelines from IDSA available at http://www.idsociety.org should be consulted.
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Urinary Tract Infections and Prostatitis
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Uncomplicated and Complicated Urinary Tract Infections
Ciprofloxacin extended-release tablets containing both the hydrochloride and the base are used only for the treatment of uncomplicated UTIs (acute cystitis) caused by susceptible E. faecalis, E. coli, P. mirabilis, or S. saprophyticus, complicated UTIs caused by susceptible E. coli, K. pneumoniae, P. mirabilis, Ps. aeruginosa, or E. faecalis, or acute uncomplicated pyelonephritis caused by E. coli in adults.
Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of complicated or uncomplicated UTIs caused by susceptible Citrobacter koseri (formerly C. diversus),C. freundii,Enterobacter cloacae,E. aerogenes,E. coli,Klebsiella oxytoca,K. pneumoniae,Morganella morganii,Proteus mirabilis,Providenciarettgeri,P. stuartii,Pseudomonas aeruginosa, or Serratia marcescens. The drug also is used in adults for the treatment of UTIs caused by susceptible gram-positive bacteria, including Staphylococcus aureus,S. epidermidis (oxacillin-susceptible strains),S. saprophyticus, or E. faecalis.
Ciprofloxacin (IV, conventional tablets, oral suspension) is used in pediatric patients 1 year of age or older for the treatment of complicated UTIs and pyelonephritis caused by susceptible E. coli. Although effective in UTIs, ciprofloxacin is not a drug of first choice for these infections in pediatric patients because of the risk of adverse effects (e.g., musculoskeletal effects) reported in this patient population.
(See Cautions: Pediatric Precautions.) Ciprofloxacin should be used for the treatment of uncomplicated UTIs only when there are no other treatment options.Because systemic fluoroquinolones, including ciprofloxacin, have been associated with disabling and potentially irreversible serious adverse reactions (e.g., tendinitis and tendon rupture, peripheral neuropathy, CNS effects) that can occur together in the same patient
(see Cautions) and because uncomplicated UTIs may be self-limiting in some patients,the risk of serious adverse reactions outweigh the benefits of fluoroquinolones for patients with uncomplicated UTIs.Some clinicians suggest that ciprofloxacin be reserved for the treatment of complicated UTIs, especially those caused by multidrug-resistant bacteria. IDSA and other experts state that fluoroquinolones (ciprofloxacin, levofloxacin, ofloxacin) generally should be considered alternatives for the treatment of uncomplicated UTIs (e.g., acute cystitis) and should be used in these infections only when other urinary anti-infectives are likely to be ineffective or are contraindicated or not tolerated.
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Clinical Experience
In controlled studies in men and women, oral ciprofloxacin therapy was as effective as therapy with oral co-trimoxazole in the treatment of uncomplicated UTIs; bacteriologic cure rates and rate of relapse and/or reinfection were similar with both drugs. Oral ciprofloxacin therapy generally results in a bacteriologic cure in 80-100% of patients with UTIs. Oral ciprofloxacin is more effective in the treatment of uncomplicated UTIs than in complicated infections, and most treatment failures occur in patients with underlying structural abnormalities of the urinary tract (e.g., obstructions, neurogenic bladder) or indwelling catheters.
Oral ciprofloxacin has been as effective as oral co-trimoxazole in the treatment of complicated UTIs, and has been effective in the treatment of UTIs caused by organisms resistant to co-trimoxazole. Prolonged, high-dose oral ciprofloxacin therapy (500-750 mg every 12 hours) has been effective in the treatment of complicated UTIs caused by multidrug-resistant Ps. aeruginosa.
A 3-day regimen of oral ciprofloxacin (conventional tablets) generally is effective for the treatment of acute, uncomplicated cystitis caused by susceptible strains of E. coli, E. faecalis, P. mirabilis, or S. saprophyticus (bacteriologic eradication rate 81-100%). Oral ciprofloxacin (conventional tablets) has been effective in women for the treatment of uncomplicated UTIs when given as a single 100- or 250-mg dose. However, efficacy of a single dose of the drug for the treatment of these infections has not been clearly established; single-dose therapy was less effective in the treatment of UTIs caused by gram-positive bacteria than in those caused by gram-negative bacteria.
Safety and efficacy of ciprofloxacin extended-release tablets for the treatment of uncomplicated UTIs (acute cystitis) have been evaluated in a randomized, double-blind, controlled study in adults. In this study, adults were randomized to receive ciprofloxacin extended-release tablets (500 mg once daily for 3 days) or conventional ciprofloxacin tablets (250 mg twice daily for 3 days). The bacteriologic eradication rate with no new infections or superinfections at the time of test of cure (post-therapy day 4-11) was 94.5% in those who received the extended-release tablets and 93.7% in those who received conventional tablets. Safety and efficacy of ciprofloxacin extended-release tablets for the treatment of complicated UTIs or acute uncomplicated pyelonephritis also have been evaluated in a randomized, double-blind study. In this study, adults were randomized to receive ciprofloxacin extended-release tablets (1 g once daily for 7-14 days) or conventional ciprofloxacin tablets (500 mg twice daily for 7-14 days). In the per-protocol population, the bacteriologic eradication rate with no new infections or superinfections at the time of test of cure (post-therapy day 5-11) in those who received the extended-release tablets was 89.2 or 87.5% in those with complicated UTIs or uncomplicated pyelonephritis, respectively; in those who received the conventional tablets, the rates were 81.4 or 98.1%, respectively.
In clinical studies evaluating IV or oral ciprofloxacin for the treatment of complicated UTIs and pyelonephritis in pediatric patients 1-17 years of age, the bacteriologic eradication rate was about 84% in those receiving ciprofloxacin compared with about 78% in those receiving a cephalosporin.
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Prostatitis
Ciprofloxacin (IV, conventional tablets, oral suspension) is used in men for the treatment of recurrent UTIs and chronic prostatitis caused by E. coli or P. mirabilis. Ciprofloxacin has been most effective in the treatment of prostatitis caused by E. coli or other Enterobacteriaceae, and has been effective in infections that did not respond to co-trimoxazole therapy. Prostatitis caused by Ps. aeruginosa, enterococci, or staphylococci may respond poorly to the drug. Because high concentrations of ciprofloxacin are attained in prostatic tissues, the drug may become a drug of choice for the treatment of recurrent UTIs associated with prostatitis; however, further study is needed to compare efficacy of ciprofloxacin with that of other anti-infectives used in the treatment of these infections.
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Anthrax
Ciprofloxacin (conventional tablets, oral suspension) is used for inhalational anthrax (postexposure) to reduce the incidence or progression of disease following suspected or confirmed exposure to aerosolized Bacillus anthracis spores in adults and children. Ciprofloxacin (IV, conventional tablets, oral suspension) is used for the treatment of clinically apparent inhalational anthrax, cutaneous anthrax, or GI and oropharyngeal anthrax, and for prophylaxis following ingestion of B. anthracis spores in contaminated meat.
Naturally occurring or endemic cutaneous anthrax in humans can occur after exposure to B. anthracis spores following contact with contaminated soil or infected animals (e.g., goats, sheep, cattle, swine, horses, buffalo, deer) or animal by-products (e.g., hides, hair, wool, carcasses, bone meal); GI or oropharyngeal anthrax can occur after ingestion of anthrax spores (e.g., in contaminated, raw or undercooked meat); and inhalational anthrax can occur after exposure to B. anthracis spores aerosolized during industrial processing of contaminated animal by-products or in the laboratory. Inhalational or cutaneous anthrax also may occur as the result of exposure to aerosolized B. anthracis spores in the context of biologic warfare or bioterrorism, including exposure to mail or other fomites contaminated with anthrax spores.
Following exposure to aerosolized B. anthracis spores, inhalational anthrax may develop if spore-containing particles are deposited into alveolar spaces. Macrophages ingest the spores and some undergo lysis and destruction. Surviving spores are transported via the lymph system to mediastinal lymph nodes where germination and vegetative growth may occur after a period of spore dormancy. Monkey studies have demonstrated that viable spores can persist in a dormant state in alveolar surface epithelium and mediastinal lymph nodes for up to 100 days after inhalation. The process responsible for the delayed transformation of spores to vegetative cells remains to be elucidated. Once germination occurs, disease follows rapidly. Replicating B. anthracis release toxins that can result in hemorrhage, edema, and necrosis. Cutaneous anthrax may occur if B. anthracis spores are introduced into a cut or abrasion (e.g., on the face, neck, or arms). Septicemia and meningeal anthrax result from hematogenous spread of the organism from the primary cutaneous, GI, or inhalation site. Although discharge from cutaneous lesions might be infectious, the risk for person-to-person transmission of cutaneous anthrax is low. Person-to-person transmission and secondary cases of anthrax (e.g., in medical personnel) have not been documented to date.
For the treatment of clinically apparent inhalational, GI, or meningeal anthrax and anthrax septicemia that occurs as the result of natural or endemic exposures to B. anthracis, parenteral penicillin historically has been considered the drug of choice and IV ciprofloxacin or IV doxycycline have been suggested as alternatives. However, it has been postulated that exposures to B. anthracis that occur in the context of biologic warfare or bioterrorism may involve bioengineered resistant strains and this concern should be considered when selecting initial anti-infective regimens for treatment of anthrax that occurs as the result of bioterrorism-related exposures or when selecting anti-infectives for postexposure prophylaxis following such exposures.B. anthracis with natural resistance to penicillins have been reported and there are published reports of B. anthracis strains that have been engineered to have tetracycline and penicillin resistance as well as resistance to other anti-infectives (e.g., macrolides, chloramphenicol, rifampin). In addition, reduced susceptibility to ofloxacin (4-fold increase in MICs from baseline) has been produced in vitro following sequential subculture of the Sterne strain of B. anthracis in subinhibitory concentrations of the fluoroquinolone.
Recommendations for the treatment and prophylaxis of anthrax have evolved based on experience gained in treating US patients who developed inhalational or cutaneous anthrax during September and October 2001 following bioterrorism-related exposures to B. anthracis spores as well results of animal studies and concerns related to treating large numbers of individuals in a mass casualty setting.
In addition to the information contained in the following sections, infectious disease and public health experts should be consulted for the most recent information on public health ramifications of bioterrorism-related exposures to anthrax spores and possible changes in recommendations for the treatment or prophylaxis of anthrax following such exposures. Information on ongoing developments also can be obtained at http://www.bt.cdc.gov.
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Postexposure Prophylaxis of Anthrax
Ciprofloxacin is used for inhalational anthrax (postexposure) to reduce the incidence or progression of disease following suspected or confirmed exposure to aerosolized B. anthracis spores in adults or children. CDC, US Public Health Service Advisory Committee on Immunization Practices (ACIP), US Working Group on Civilian Biodefense, and US Army Medical Research Institute of Infectious Diseases (USAMRIID) recommend oral ciprofloxacin and oral doxycycline as the initial drugs of choice for postexposure prophylaxis following exposure to aerosolized anthrax spores, including exposures that occur in the context of biologic warfare or bioterrorism. Some of these experts (e.g., ACIP, US Working Group on Civilian Biodefense) state that levofloxacin or other oral fluoroquinolones (moxifloxacin, ofloxacin) are alternatives for postexposure prophylaxis when ciprofloxacin or doxycycline cannot be used.
Ciprofloxacin and doxycycline are considered equally effective for postexposure prophylaxis following exposure to aerosolized B. anthracis spores. During the bioterrorism-related exposures to B. anthracis spores in September and October 2001, CDC initially recommended postexposure prophylaxis with either ciprofloxacin or doxycycline; however, CDC subsequently revised these recommendations because of the large number of individuals exposed to B. anthracis who required postexposure prophylaxis. Widespread use of any anti-infective agent can promote resistance to that drug and because many common pathogens already are resistant to tetracycline but fluoroquinolone resistance is not yet common among these same organisms, CDC suggested that use of doxycycline for postexposure prophylaxis was preferable for this event since it would preserve effectiveness of ciprofloxacin against other organisms. Ultimately, however, selection of an anti-infective agent for postexposure prophylaxis should be based on the clinical setting, susceptibility, and reported adverse effects associated with the drugs and either doxycycline or ciprofloxacin (or another fluoroquinolone) may be preferable for an individual patient.
Following natural, occupational, or bioterrorism-related exposures to aerosolized B. anthracis spores, anti-infective postexposure prophylaxis should be initiated immediately or as soon as possible. Postexposure vaccination with anthrax vaccine (if available) may be indicated in conjunction with anti-infective postexposure prophylaxis in some individuals. Vaccine-induced immunity provides protection if there are issues related to the anti-infective postexposure prophylaxis regimen (e.g., poor adherence, early discontinuance because of adverse effects) or if there are residual spores that germinate after the anti-infective regimen has been completed. When indicated and available, vaccination with anthrax vaccine should be initiated as soon as possible, preferably within 10 days of the exposure.
The optimum duration of postexposure prophylaxis after an inhalation exposure to B. anthracis spores is unclear. Because of the possible persistence of anthrax spores in lung tissue following an aerosol exposure, prolonged postexposure prophylaxis usually is required. Based on a competing-risks model, some clinicians suggest that the optimum duration of prophylaxis depends on the dose of inhaled spores. These clinicians state that a duration of 60 days may be adequate for a low-dose exposure, but that a duration exceeding 4 months may be necessary to reduce the risk following a high-dose exposure. ACIP, CDC, US Working Group on Civilian Biodefense, and USAMRIID recommend that postexposure prophylaxis following a confirmed exposure (including in laboratory workers with confirmed exposures to B. anthracis cultures) should be continued for at least 60 days in previously unvaccinated individuals. If anthrax vaccine is used in conjunction with anti-infective prophylaxis for postexposure prophylaxis in exposed individuals, ACIP and USAMRIID recommend continuing anti-infective prophylaxis until 14 days after the third dose of the vaccine series (even if this results in more than 60 days of anti-infective prophylaxis).
Postexposure anti-infective prophylaxis may be indicated in laboratory workers and other individuals who work in occupations that result in exposure to B. anthracis and may also be considered following a naturally occurring GI exposure to B. anthracis (e.g., ingestion of meat from an undercooked carcass of an anthrax-infected animal).
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Infants and Children
Although ciprofloxacin generally is not recommended for use in infants and children
(see Cautions: Pediatric Precautions) , the benefits of ciprofloxacin prophylaxis outweigh the risks for inhalational anthrax (postexposure) and the drug may be used in children to reduce the incidence or progression of disease following exposure to aerosolized B. anthracis spores. ACIP, CDC, and other experts recommend that infants and children receive ciprofloxacin or doxycycline for initial anti-infective prophylaxis following suspected bioterrorism-related exposures to B. anthracis spores; however, if exposure has been confirmed and in vitro tests indicate that the organism is susceptible to penicillin, the postexposure prophylaxis regimen in children may be switched to oral amoxicillin . Although monotherapy with a penicillin is not recommended for treatment of inhalational anthrax when high concentrations of the organism are likely to be present, penicillins (e.g., amoxicillin, amoxicillin and clavulanate potassium, penicillin G procaine) may be considered an option for anti-infective prophylaxis, including when ciprofloxacin or doxycycline are contraindicated. The likelihood of β-lactamase induction resulting in an increase in penicillin MICs is lower when only a small number of vegetative cells are present and, therefore, penicillin monotherapy can be considered for postexposure prophylaxis.
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Pregnant and Breast-feeding Women
The possible benefits of postexposure prophylaxis against anthrax should be weighed against the possible risks to the fetus when choosing an anti-infective for postexposure prophylaxis in pregnant women. ACIP, CDC, and other experts state that ciprofloxacin should be considered the drug of choice for initial postexposure prophylaxis in pregnant women exposed to B. anthracis spores and that, if in vitro studies indicate that the organism is susceptible to penicillin, then consideration can be given to changing the postexposure regimen to amoxicillin. Women who become pregnant while receiving anti-infective prophylaxis should continue the existing regimen and consult with a healthcare provider or public health official to discuss whether an alternative regimen might be more appropriate.
AAP considers ciprofloxacin to be usually compatible with breast-feeding since the amount of the quinolone potentially absorbed by nursing infants would be small and no observable change in infants associated with such exposure has been reported to date. Because the long-term safety of prolonged exposure of nursing infants (e.g., during a 60-day regimen for anthrax) to breast milk from ciprofloxacin-treated women currently is not known, CDC recommends that lactating women who are concerned about the use of ciprofloxacin during anthrax prophylaxis consider expressing and then discarding their breast milk so that breast-feeding can be resumed once anti-infective prophylaxis is complete.
(See Cautions: Pregnancy, Fertility, and Lactation.) ACIP states that amoxicillin is an option for postexposure prophylaxis in nursing women if in vitro studies indicate that the organism is susceptible to penicillin. If the infant has been exposed to B. anthracis and is receiving postexposure prophylaxis, the anti-infective used in the woman should be the same as that used in the nursing infant, whenever possible.
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Individuals at Contaminated Sites
For the bioterrorism-related exposures to B. anthracis spores that occurred in the US during the fall of 2001, CDC recommended that anti-infective prophylaxis be initiated (pending additional information) in individuals exposed to an air space where a suspicious material may have been aerosolized (e.g., near a suspicious powder-containing letter during opening) and in individuals who shared the air spaces likely to be the source of an inhalational anthrax case. While culture of nasal swabs can occasionally document exposure and provide clues to help assess the exposure circumstances, these nasal swabs are investigative tools only and results cannot be used to rule out exposure to B. anthracis. Following confirmation of the presence of B. anthracis spores, CDC recommended that a full 60-day postexposure regimen be completed in individuals exposed to an air space known to be contaminated with aerosolized B. anthracis, in individuals exposed to an air space known to be the source of an inhalational anthrax case, and in individuals along the transit path of an envelope or other vehicle containing B. anthracis that may have been aerosolized (e.g., a postal sorting facility in which an envelope containing B. anthracis was processed).
Remediation workers with repeated entries into contaminated sites over a prolonged period of time may require anti-infective prophylaxis for considerably longer than the 60 days recommended for individuals with a single exposure. Some remediation workers exposed during the bioterrorism-related events that occurred in the US during the fall of 2001 received anti-infective prophylaxis for more than 6 months. At that time, CDC recommended that anti-infective prophylaxis be continued throughout the period of risk and for 60 days after the risk of exposure ended, unless a 6-dose series of anthrax vaccine had been completed and annual boosters were up to date.
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Laboratory Workers and Other Individuals
Laboratory workers and other individuals who work in occupations that might result in repeated exposure to aerosolized B. anthracis spores should receive preexposure vaccination with anthrax vaccine adsorbed. ACIP states that anti-infective postexposure prophylaxis is not necessary in fully vaccinated workers who wear appropriate personal protective equipment (PPE) while working in environments contaminated with B. anthracis spores, unless PPE is disrupted. If there is any type of disruption of PPE in a worker who is fully or partially vaccinated against anthrax, ACIP recommends that anti-infective postexposure prophylaxis be given for at least 30 days in conjunction with any remaining indicated doses of anthrax vaccine. Following an occupational exposure to B. anthracis spores in previously unvaccinated workers, ACIP recommends that anti-infective postexposure prophylaxis be given for 60 days in conjunction with postexposure vaccination and states that the anti-infective prophylaxis regimen should be continued for 14 days after the third vaccine dose (even if this results in more than 60 days of anti-infective prophylaxis).
Following a bioterrorism-related event, use of anti-infective prophylaxis in asymptomatic individuals in the general population is not indicated unless appropriate public health or law-enforcement agencies have ascertained that a risk of exposure to B. anthracis spores exists. In addition, CDC states that postexposure prophylaxis is not indicated for the prevention of cutaneous anthrax, for autopsy personnel examining bodies infected with anthrax when appropriate isolation precautions and procedures are followed, for hospital personnel caring for patients with anthrax, or for individuals who routinely open or handle mail in the absence of a suspicious letter or credible threat.
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Clinical Experience
Although controlled studies evaluating ciprofloxacin for aerosolized anthrax exposure in humans have not been conducted for ethical reasons, the indication for use of ciprofloxacin is based on serum concentrations of the drug achieved in humans, a surrogate end point reasonably likely to predict clinical benefit. Efficacy of ciprofloxacin has been evaluated in a rhesus monkey model of inhalational anthrax. In this study, rhesus monkeys were exposed to an inhaled mean dose of 11 LD50 (approximately 5.5 x 10) spores (range: 5-30 LD50) of B. anthracis and then received a 30-day regimen of placebo or oral ciprofloxacin beginning 24 hours after exposure. Mortality due to anthrax was significantly lower in monkeys that received ciprofloxacin (1/9) compared with those that received placebo (9/10); the one ciprofloxacin-treated monkey that died of anthrax did so following the 30-day drug administration period. In the monkeys studied, mean serum concentrations of ciprofloxacin 1 hour after dosing (at the expected time of peak serum concentrations) following oral dosing to steady state ranged from 0.98-1.69 mcg/mL; mean steady-state trough concentrations at 12 hours after dosing ranged from 0.12-0.19 mcg/mL. The mean serum concentrations of ciprofloxacin associated with a statistically significant improvement in survival in this rhesus monkey model of inhalational anthrax are reached or exceeded in adult and pediatric patients receiving oral or IV ciprofloxacin.
Some data regarding efficacy of ciprofloxacin for postexposure prophylaxis in humans following exposure to aerosolized B. anthracis spores is available since the drug was used for postexposure prophylaxis in individuals in the US who were exposed to B. anthracis spores in bioterrorism-related incidences that occurred during September and October 2001. Approximately 300 postal or other facilities were tested for B. anthracis spores and anti-infective prophylaxis with ciprofloxacin or other anti-infectives was initiated in approximately 32,000 individuals in Florida, New Jersey, New York, and the District of Columbia who had potential exposures. A full 60-day postexposure prophylaxis regimen was recommended for approximately 8424 of these individuals. To date, no individual who received anti-infective prophylaxis following these bioterrorism-related exposures developed microbiologically confirmed anthrax. Although ciprofloxacin postexposure prophylaxis generally was well tolerated, the incidence of adverse effects was higher than that reported previously in controlled clinical trials evaluating the drug for other indications.
(See Cautions.)
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Treatment of Inhalational Anthrax
The rapid course of symptomatic inhalational anthrax and high mortality rate make early initiation of anti-infective therapy essential. Because of the difficulty in making a rapid microbiologic diagnosis of anthrax, high-risk individuals who develop fever or other evidence of systemic infection should promptly receive therapy for possible anthrax infection while waiting for results of laboratory studies.
Based on clinical experience from the bioterrorism-related anthrax exposures of 2001 and the possibility that a B. anthracis strain resistant to one or more anti-infectives might be used in a future bioterrorism event, CDC and other experts (e.g., US Working Group on Civilian Biodefense, USAMRIID) recommend that treatment of clinically apparent inhalational anthrax in adults, adolescents, or children that occurs as the result of exposure to anthrax spores in the context of biologic warfare or bioterrorism be initiated with a multiple-drug parenteral regimen that includes ciprofloxacin or doxycycline and 1 or 2 additional anti-infectives predicted to be effective. Other drugs to be included in the initial treatment regimen with ciprofloxacin or doxycycline should be selected based on in vitro susceptibility, possibility of efficacy, adverse effects, and cost. Based on in vitro data, other drugs that have been suggested as possibilities to augment ciprofloxacin or doxycycline in such multiple-drug regimens include chloramphenicol, clindamycin, rifampin, vancomycin, macrolides (azithromycin, clarithromycin, erythromycin), imipenem, meropenem, penicillin, ampicillin, daptomycin, quinupristin and dalfopristin, linezolid, and aminoglycosides (gentamicin).
Optimum regimens for treatment of anthrax meningitis are unknown. However, if meningitis is established or suspected, early and aggressive anti-infective treatment is critical. Some clinicians suggest a multiple-drug regimen that includes a fluoroquinolone (e.g., ciprofloxacin) and 1 or 2 additional agents with good CSF penetration (e.g., ampicillin or penicillin, meropenem, rifampin, vancomycin, chloramphenicol).
Results of in vitro susceptibility testing of strains of B. anthracis that were associated with cases of inhalational or cutaneous anthrax that occurred in the US (Florida, New York, District of Columbia) during September and October 2001 in the context of bioterrorism-related exposures to anthrax spores indicate that these strains were susceptible to ciprofloxacin, doxycycline, tetracycline, rifampin, clindamycin, vancomycin, and chloramphenicol. However, only limited or no clinical data are available regarding use of these drugs in the treatment of anthrax. A multiple-drug parenteral regimen that was used in 2 patients who survived inhalational anthrax following the bioterrorism-related exposures in 2001 was a 3-drug regimen of ciprofloxacin (400 mg every 8 hours), rifampin (300 mg every 12 hours), and clindamycin (900 mg every 8 hours). Other multiple-drug regimens that were used for the initial treatment of patients who survived inhalational anthrax following these bioterrorism-related anthrax exposures were ciprofloxacin/cefotaxime/azithromycin (1 patient); levofloxacin/rifampin initially then ciprofloxacin rifampin/vancomycin (1 patient); and oral levofloxacin (prior to diagnosis), then ciprofloxacin/azithromycin, then clindamycin/ceftriaxone/azithromycin, then doxycycline (1 patient). Although it is unclear whether the deaths were related to ineffective regimens and/or delays in initiation of therapy, the regimens used in patients who died of inhalational anthrax following these exposures were levofloxacin/clindamycin/penicillin G (1 patient, initiated on the second day of hospitalization after various anti-infectives, died 3 days after admission); levofloxacin monotherapy (1 patient, died day of admission); levofloxacin/rifampin/penicillin G/ceftriaxone (1 patient, died day of admission); levofloxacin monotherapy, then levofloxacin/rifampin/gentamicin/nafcillin, then ciprofloxacin
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