Ciprofloxacin Hydrochloride

Ciprofloxacin Lactate

AHFS Class: Quinolones (8:12.18)

VA Class: AM900
Chemical Name: 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7(1-piperazinyl)-3-quinolinecarboxylic acid
Chemical Name: 1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7(1-piperazinyl)-3-quinolinecarboxylic acid monohydrochloride monohydrate

View the associated Essentials monograph.

Introduction

Ciprofloxacin is a fluoroquinolone anti-infective agent.

Uses

Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.

Ciprofloxacin is used orally or IV in adults for the treatment of urinary tract infections (UTIs), ^{1 178 180 205 292 296 297 300 323 326 327 329 332 336 337 338 339 340 341 342 343 344 345 351 352 353 354 359 375 379 380 429 435 466 474 479 481 504 579} chronic bacterial prostatitis,^{1 579} acute sinusitis,^{1 579} lower respiratory tract infections, ^{1 178 205 296 297 300 324 326 333 335 345 346 347 355 356 357 358 359 374 375 380 433 435 466 474 479 481 491 579 59} skin and skin structure infections,^{1 292 178 205 280 296 297 300 326 334 359 362 363 364 372 373 374 376 377 380 433 466 468 474 479 481 579} or bone and joint infections^{1 178 205 296 297 300 326 359 362 365 367 368 369 370 371 374 375 380 433 466 474 479 481 595} 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^{1 579 663 667 678} and also is used for prophylaxis following ingestion of B. anthracis spores†⁶⁶² and for the treatment of inhalational anthrax†, cutaneous anthrax†, or GI and oropharyngeal anthrax†.^{667 670 678} Ciprofloxacin also is used orally for the treatment of acute sinusitis,¹ typhoid fever, and GI infections caused by susceptible bacteria.^{1 178 296 297 466 474 479 481} Ciprofloxacin is used 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.^{1 579} 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.^{296 492 579} IV ciprofloxacin is used in conjunction with IV piperacillin sodium (no longer commercially available in the US as a single-entity preparation) for empiric anti-infective therapy in febrile neutropenic patients.⁵⁷⁹

Ciprofloxacin hydrochloride extended-release tablets (ProQuin^® XR) are used in adults for the treatment of uncomplicated UTIs (acute cystitis).⁷⁷⁶ Ciprofloxacin extended-release tablets containing both the hydrochloride and the base (Cipro^® XR) are used in adults for the treatment of uncomplicated UTIs (acute cystitis), complicated UTIs, or acute uncomplicated pyelonephritis.⁷¹⁵ These extended-release tablet preparations are not interchangeable with each other.⁷⁷⁶ In addition, safety and efficacy of extended-release tablet preparations have been established only for infections involving the urinary tract; these preparations 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 IV ciprofloxacin or with ciprofloxacin conventional tablets or oral suspension.^{715 776}

Although ciprofloxacin has been used orally or IV for the treatment of acute, uncomplicated gonorrhea^{1 314 317 322 428 606 619 631} and disseminated gonococcal infections†,⁶³¹ fluoroquinolones are no longer recommended for the treatment of gonorrhea.^{671 672 673} (See Uses: Gonorrhea and Associated Infections.)

Prior to initiation of ciprofloxacin therapy, appropriate specimens should be obtained for identification of the causative organism(s) and in vitro susceptibility tests.¹ 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.¹ Because resistant strains of Pseudomonas aeruginosa have developed during ciprofloxacin therapy,^{128 137 138 139 140 144 180 205 280 300 302 346 359 361 362 363 370 371 424 435 458 466 479 596} in vitro susceptibility tests probably should be performed periodically when the drug is used in the treatment of infections caused by this organism.¹ Because staphylococci may develop resistance to ciprofloxacin during prolonged therapy with the drug, in vitro susceptibility tests should be repeated during therapy,^{522 586 587} especially when infections are caused by oxacillin-resistant strains of Staphylococcus aureus (previously known as methicillin-resistant S. aureus or MRSA).⁵²²

Bone and Joint Infections

Pending revision, the material in this section should be considered in light of more recently available information in the MEDWATCH notification at the beginning of this monograph.

Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of bone and joint infections, including osteomyelitis,^{205 296 326 362 365 367 368 369 370 371 375 474 479 535 706} caused by susceptible E. aerogenes†,^{369 370 706} E. cloacae,^{1 362 369 370 375 380 474 579 706} E. coli†,^{362 368 369 370 474 535} K. pneumoniae†,^{326 368 371 706} M. morganii†,^{369 370 706} P. mirabilis†,^{368 369 371 380 474 706} Ps. aeruginosa,^{1 205 296 300 326 359 362 368 369 370 371 380 433 474 479 535 579 706} or S. marcescens.^{1 296 362 368 369 370 380 474 579} The drug also has been used in adults for the treatment of bone and joint infections caused by susceptible S. aureus†,^{296 326 370 474 535 706} S. epidermidis†,^{326 474 535} other coagulase-negative staphylococci†,^{326 370} or Enterococcus faecalis† (formerly S. faecalis),^{370 706} but other anti-infectives generally are preferred for these infections.^{522 538} Although resistance to ciprofloxacin has been reported in some strains of oxacillin-resistant S. aureus,^{140 144 362 548 549} oral ciprofloxacin may be a useful alternative to parenteral anti-infectives for the treatment of infections caused by susceptible oxacillin-resistant staphylococci.^{522 538}

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.^{297 362 365 367 369 371 466 479 481 706} Treatment failures have been reported most frequently in patients with an underlying metal appliance at the site of infection^{362 367 474} and in patients with ciprofloxacin-resistant Ps. aeruginosa or S. aureus.^{363 369 371} 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.⁵⁹⁵

Endocarditis

Endocarditis Caused by the HACEK Group

Although only limited experience is available to date, ciprofloxacin is recommended by the American Heart Association (AHA) and Infectious Diseases Society of America (IDSA) as an alternative agent for the treatment of native or prosthetic valve endocarditis† caused by fastidious gram-negative bacilli known as the HACEK group (Actinobacillus actinomycetemcomitans, Cardiobacterium hominis, Eikenella corrodens, Haemophilus aphrophilus, H. influenzae, H. parainfluenzae, H. paraphrophilus, Kingella denitrificans, K. kingae).⁷⁶⁸ The HACEK group accounts for up to 10% of cases of community-acquired native valve endocarditis in patients who are not IV drug abusers and also rarely cause prosthetic valve endocarditis.⁷⁶⁸ These organisms should be considered ampicillin-resistant, but may be susceptible to third or fourth generation cephalosporins, the fixed combination of ampicillin and sulbactam, or fluoroquinolones.⁷⁶⁸

The AHA and IDSA state that the regimen of choice for the treatment of HACEK endocarditis is ceftriaxone or ampicillin-sulbactam.⁷⁶⁸ These experts state that a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) may be considered an alternative when β-lactam anti-infectives cannot be used.⁷⁶⁸ However, because only limited data are available regarding use of fluoroquinolones in these infections, patients with HACEK endocarditis who are hypersensitive to β-lactam anti-infectives should be treated in consultation with an infectious disease specialist.⁷⁶⁸

Staphylococcal Endocarditis in the Absence of Prosthetic Materials

For the treatment of native valve endocarditis caused by staphylococci susceptible to penicillinase-resistant penicillins, the AHA and IDSA recommend IV nafcillin or oxacillin (with or without gentamicin) as the regimen of choice and IV cefazolin (with or without gentamicin) as an alternative; IV vancomycin is recommended for native valve endocarditis caused by oxacillin-resistant staphylococci.⁷⁶⁸ Although clinical experience is limited, the AHA and IDSA suggest that an oral regimen of ciprofloxacin and rifampin can be considered as an alternative for the treatment of uncomplicated right-sided S. aureus endocarditis† in IV drug abusers who will not comply with a parenteral regimen.⁷⁶⁸

In a small study in hospitalized adult IV drug abusers with right-sided staphylococcal endocarditis (about 68% were infected with human immunodeficiency virus [HIV]), an oral regimen of ciprofloxacin and rifampin appeared to be as effective as a parenteral regimen of oxacillin or vancomycin given with gentamicin; cure rates were similar (95% for the oral regimen or 88% for the parenteral regimen).⁷⁶⁹ However, the possibility that staphylococci in such patients may be resistant to both ciprofloxacin and rifampin should be considered.⁷⁶⁹

Staphylococcal Endocarditis in the Presence of Prosthetic Valves or Materials

For the treatment of coagulase-negative staphylococcal prosthetic valve endocarditis, the AHA and IDSA recommend a regimen of IV nafcillin or oxacillin with oral or IV rifampin and parenteral gentamicin (if the causative organism is oxacillin-susceptible) or a regimen of IV vancomycin with oral or IV rifampin and parenteral gentamicin (if the causative organism is oxacillin-resistant).⁷⁶⁸ If the causative organism is resistant to gentamicin and other aminoglycosides, the AHA and IDSA suggest that use of a fluoroquinolone instead of the aminoglycoside can be considered in these regimens for the treatment of staphylococcal prosthetic valve endocarditis†, provided in vitro susceptibility tests indicate the organism is susceptible to the fluoroquinolone.⁷⁶⁸ However, this recommendation is based on animal studies and only limited clinical data are available.⁷⁶⁸

Culture-negative Endocarditis

Ciprofloxacin is recommended for use in a multiple-drug regimen for the empiric treatment of culture-negative endocarditis†.⁷⁶⁸ Blood cultures are negative in up to 20% of patients with infective endocarditis because of inadequate microbiologic technique, infection with highly fastidious bacteria or nonbacterial pathogens, or administration of anti-infective agents prior to obtaining blood cultures.⁷⁶⁸ Selection of the most appropriate anti-infective regimen for the treatment of culture-negative endocarditis is difficult and should be guided by epidemiologic features and the clinical course of the infection.⁷⁶⁸ Consultation with an infectious diseases specialist is recommended.⁷⁶⁸ For empiric treatment of native valve culture-negative endocarditis, the AHA and IDSA recommend a regimen that includes the fixed combination of ampicillin and sulbactam and gentamicin or a regimen that includes vancomycin, gentamicin, and ciprofloxacin.⁷⁶⁸

GI Infections

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,^{1 293 297 474 477} Campylobacter fetus subsp. jejuni,^{1 293 297 350 474 538} Salmonella (see Uses: Typhoid Fever and other Salmonella Infections), Shigella^{297 477 538 612} (S. flexneri,^{1 612} S. boydii, S. sonnei,^{1 474} S. dysenteriae),^{1 612} or Vibrio (see Uses: Vibrio Infections).^{538 664 756 757 758 759} Because ciprofloxacin is active in vitro against most pathogens associated with infectious diarrhea, including E. coli, Shigella, Salmonella, Aeromonas, Vibrio, Yersinia enterocolitica, and some strains of Campylobacter, it may be a drug of choice for the empiric treatment of the disease.^{296 350 378 420 493 522 610 611} 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.^{588 589}

Cyclospora and Isospora Infections

Although co-trimoxazole generally is the drug of choice for GI infections caused by Cyclospora† or Isospora†,^{477 557 667} ciprofloxacin is recommended as an alternative.^{533 667} Ciprofloxacin may not be as effective, but may be useful for the treatment of these infections in patients who cannot tolerate co-trimoxazole.⁵³³

Shigella Infections

Ciprofloxacin (conventional tablets, oral suspension) is used for the treatment of shigellosis caused by susceptible Shigella.⁴⁷⁷ Anti-infective therapy generally is indicated in addition to fluid and electrolyte replacement for the treatment of severe cases of shigellosis since anti-infectives appear to shorten the duration of diarrhea and period of fecal excretion of Shigella.⁶⁶⁷ A fluoroquinolone (e.g., ciprofloxacin, norfloxacin, ofloxacin) or ceftriaxone are considered drugs of choice for the treatment of shigellosis when the susceptibility of the isolate is unknown; azithromycin also has been recommended and co-trimoxazole or ampicillin may be effective if the strain is known to be susceptible to these drugs.^{477 538 667}

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.^{477 667 681} 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.⁶⁸¹ The incubation period usually is 24–48 hours.⁶⁸¹ 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;^{477 538 681} combination therapy may be necessary.⁴⁷⁷ 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.⁶⁷⁷

Travelers’ Diarrhea

Ciprofloxacin (conventional tablets, oral suspension) has been used for the short-term treatment of travelers’ diarrhea† or for the prevention of travelers’ diarrhea† in adults traveling for relatively short periods of time to high-risk areas.^{378 399 420 525 610 611 648 650 651 677 679}

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 enteroaggregative E. coli (EAEC), Campylobacter jejuni, Shigella, Salmonella, A. hydrophila, Plesiomonas shigelloides, Yersinia enterocolitica, or V. parahaemolyticus or non-O-group 1 V. cholerae.^{420 525 610 611 612 648 650 651 677} In some cases, travelers’ diarrhea is caused by a parasitic enteric pathogen (e.g., Giardia duodenalis [also known as G. lamblia or G. intestinalis], Cryptosporidium parvum, Cyclospora cayetanensis, Entamoeba histolytica, Dientamoeba fragilis) or a viral enteric pathogen (e.g., rotavirus, norovirus).^{420 525 648}

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.⁵²⁵ 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 Asia, the Middle East, Africa, and Central and South America.⁵²⁵

Treatment. Although travelers’ diarrhea usually is self-limited and often resolves within 3–4 days without anti-infective treatment, symptoms may persist in some individuals.^{420 525 648 650 651 677 679} If diarrhea is moderate or severe, persists for longer than 3 days, or is associated with fever or bloody stools, short-term treatment (1–3 days) with an anti-infective may be indicated.^{420 525 650 651 677 679} A fluoroquinolone (e.g., ciprofloxacin, levofloxacin, norfloxacin, ofloxacin) generally is recommended when treatment, including self-treatment, of travelers’ diarrhea is indicated in adults.^{420 525 611 612 648 650 677 679} Azithromycin can be used as a treatment alternative for individuals who should not receive fluoroquinolones (e.g., children, pregnant women) and may be a drug of choice for travelers in areas with a high prevalence of fluoroquinolone-resistant Campylobacter (e.g., Thailand, India) or those who have not responded after 48 hours of fluoroquinolone treatment.^{420 525} Rifaximin is another alternative for the treatment of travelers’ diarrhea caused by noninvasive E. coli.^{420 525} Bismuth subsalicylate or an antimotility agent may be used as an adjunct to anti-infective treatment to provide symptomatic relief;^{420 525 648} oral rehydration therapy should be used if indicated, especially in young children or geriatric adults.^{420 525} Travelers should consult a clinician if diarrhea persists despite treatment.^{420 525 648}

Prophylaxis. The CDC and most experts do not recommend routine prophylactic use of anti-infectives to prevent travelers’ diarrhea in individuals traveling to areas of risk.^{420 525 611 648} 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), these experts state that anti-infectives should be used for prophylaxis only in select individuals.^{420 525 611 648} This includes short-term travelers who are high-risk individuals (e.g., travelers with immunosuppression or immunodeficiency such as HIV-infected individuals) and other individuals taking critical trips during which even a short episode of diarrhea could impact the purpose of the trip.^{420 525 611}

If anti-infective prophylaxis is indicated, a fluoroquinolone (ciprofloxacin, levofloxacin, norfloxacin, ofloxacin) usually is recommended for nonpregnant adults,^{420 525 648} although the increasing incidence of quinolone resistance in pathogens that cause travelers’ diarrhea (e.g., Campylobacter) should be considered.^{420 525} Results of controlled studies indicate that various anti-infectives when taken prophylactically can reduce the diarrhea attack rate from 40% to 4%; however, efficacy depends on resistance patterns of pathogenic bacteria in each travel area and these patterns have evolved over the last several decades.⁵²⁵

Anti-infectives that have been used for prophylaxis of travelers’ diarrhea 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.^{420 525 648} 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).^{420 525 330 334 648}

HIV-Infected Individuals. The Prevention of Opportunistic Infections Working Group of the US Public Health Service and the Infectious Diseases Society of America (USPHS/IDSA) states that, while prophylaxis against travelers’ diarrhea is not generally recommended for travelers, such prophylaxis may be considered for some HIV-infected travelers, depending on the individual’s level of immunosuppression and the region and duration of travel.⁶⁶¹ These clinicians suggest that oral fluoroquinolones (e.g., ciprofloxacin) can be used in HIV-infected adults when prophylaxis of travelers’ diarrhea is considered necessary (e.g., in those at high risk of infection when the period of travel is brief).⁶⁶¹ HIV-infected individuals receiving co-trimoxazole for prophylaxis of Pneumocystis jiroveci (formerly Pneumocystis carinii) pneumonia (PCP) may be protected to some degree 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 and because use of the drug should be reserved for future prophylaxis of PCP.⁶⁶¹

The USPHS/IDSA also suggests that all HIV-infected individuals traveling to developing countries be provided with an appropriate anti-infective regimen (e.g., ciprofloxacin [500 mg twice daily for 3–7 days] or co-trimoxazole [for children, pregnant women]) to carry with them to use empirically if they develop travelers’ diarrhea.⁶⁶¹ However, these individuals should be instructed to consult a physician of their diarrhea is severe and does not respond to the empiric regimen, if their stools contain blood, if fever is accompanied by shaking or chills, or if dehydration develops.⁶⁶¹

Intra-abdominal Infections

Ciprofloxacin (IV initially followed by oral therapy with conventional tablets or oral suspension) is used in conjunction with oral metronidazole for the treatment of complicated intra-abdominal infections caused by E. coli, Ps. aeruginosa, P. mirabilis, K. pneumoniae, or Bacteroides fragilis.^{1 579}

The IDSA states that patients with community-acquired intra-abdominal infections of mild to moderate severity may receive initial treatment with an empiric regimen that has a narrower spectrum of activity because unnecessary use of broad spectrum agents in such infections may contribute to emergence of resistance.⁷⁷³ Therefore, IDSA recommends use of the fixed combination of ampicillin and sulbactam, cefazolin or cefuroxime in conjunction with metronidazole, the fixed combination of ticarcillin and clavulanate, ertapenem monotherapy, or a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin) in conjunction with metronidazole for treatment of mild to moderate community-acquired intra-abdominal infections.⁷⁷³

Patients who are immunosuppressed or have more severe community-acquired intra-abdominal infections, however, should receive a regimen that has a broader spectrum of activity.⁷⁷³ Regimens recommended by IDSA for such individuals include meropenem monotherapy; imipenem and cilastatin monotherapy; a third or fourth generation cephalosporin (cefepime, cefotaxime, ceftazidime, ceftriaxone) in conjunction with metronidazole; ciprofloxacin in conjunction with metronidazole; the fixed combination of piperacillin and tazobactam; or aztreonam in conjunction with metronidazole.⁷⁷³ Other clinicians suggest that severely ill patients and those with prolonged hospitalization should receive an initial regimen that includes an antipseudomonal agent such as an antipseudomonal penicillin (ticarcillin and clavulanate, piperacillin and tazobactam), a carbapenem (imipenem or meropenem), ceftazidime, or cefepime used in conjunction with metronidazole.⁵³⁸ These clinicians state that an aminoglycoside also could be included in the empiric regimen;⁵³⁸ however, IDSA states that aminoglycosides should not be used routinely in patients with community-acquired intra-abdominal infections but may be included in empiric regimens for treatment of nosocomial intra-abdominal infections, depending on local patterns of in vitro susceptibility of nosocomial isolates.⁷⁷³

Postoperative (nosocomial) intra-abdominal infections usually require treatment with multiple-drug regimens and, because these infections often involve resistant organisms, IDSA recommends that empiric regimens be selected based on local nosocomial susceptibility patterns.⁷⁷³

Meningitis and Other CNS Infections

IV ciprofloxacin has been used with some success for the treatment of meningitis† caused by gram-negative bacteria.^{360 707 762 763 764 765 774 818} However, only low concentrations of ciprofloxacin are distributed into CSF,^{1 436} and further study is needed to more fully evaluate efficacy and safety of the drug in the treatment of CNS infections.^{293 481} 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.^{774 818}

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.^{360 818} 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.⁷⁷⁴

Ciprofloxacin also has been used for the treatment of meningitis and other CNS infections caused by susceptible Salmonella.^{762 763 764 765} 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.^{762 763}

Ophthalmic and Otic Infections

Oral or IV ciprofloxacin is used in the treatment of malignant otitis externa† caused by Ps. aeruginosa.^{781 782 783 784 785 816} Bacterial otitis externa usually is caused by Ps. aeruginosa or S. aureus.^{782 783 784 785 816} 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.^{781 782 783 784} The treatment of choice for malignant otitis externa usually is ciprofloxacin or an antipseudomonal β-lactam (e.g., ceftazidime, imipenem).^{781 782 783 784} Because ciprofloxacin-resistant Ps. aeruginosa have been reported with increasing frequency in patients with malignant otitis externa and has been associated with treatment failure,^{783 784 785} clinical isolates should be tested for in vitro susceptibility, especially if there is an inadequate response to treatment.⁷⁸⁵

For use of ciprofloxacin hydrochloride in the topical treatment of ophthalmic and otic infections caused by susceptible bacteria, see Ciprofloxacin 52:04.12.

Respiratory Tract Infections

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.⁵⁷⁹ Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of respiratory tract infections, including bronchiectasis,^{333 374 474 479 596} bronchitis,^{205 297 301 333 335 345 346 347 356 374 435 466 474 479} lung abscess,^{474 596} and pneumonia,^{205 326 333 346 347 356 357 435 466 474 479 491 596} caused by susceptible E. aerogenes†,⁴⁷⁴ E. cloacae,^{1 333 474 579} E. coli,^{1 333 345 355 474 491 579} Haemophilus influenzae,^{1 297 301 324 333 346 351 380 427 474 491 596 579} H. parainfluenzae,^{1 297 474 579} K. oxytoca†,⁴⁷⁴ K. pneumoniae,^{1 297 301 333 345 351 380 474 579} P. mirabilis,^{1 380 474 579} Ps. aeruginosa,^{1 300 301 324 333 346 359 374 380 427 433 474 579} S. aureus†,^{333 345 380 491} or S. pneumoniae (penicillin-susceptible strains).^{1 324 326 333 345 346 355 356 357 425 427 474 491} The drug also is used for the treatment of respiratory tract infections caused by susceptible Moraxella catarrhalis;^{1 324 333 346 356 395 427 474 491 579} however, ciprofloxacin, like other quinolones, generally should not be used in children.^{1 205 479 522} (See Cautions: Pediatric Precautions.)

In controlled studies in adults with respiratory tract infections, oral ciprofloxacin therapy was as effective as therapy with oral amoxicillin,³⁵⁶ oral ampicillin,³³⁵ IV cefamandole,⁴⁹¹ oral doxycycline,³⁴⁷ or IV imipenem and cilastatin sodium.³⁶¹ Oral ciprofloxacin therapy generally resulted in a bacteriologic cure rate of 80–98% in adults with respiratory tract infections.^{297 355 356 466 479 481} Oral ciprofloxacin has been most effective in the treatment of respiratory tract infections caused by H. influenzae or M. catarrhalis;^{178 296 298 479 596} treatment failures have occurred when the drug was used in the treatment of infections caused by S. pneumoniae^{178 324 358 425 427 479} or Ps. aeruginosa.^{178 324 346 358 427 479 596} Treatment failure of S. pneumoniae respiratory tract infections may be related to the moderate in vitro susceptibility of this organism to ciprofloxacin.^{324 355 427} Although ciprofloxacin may be effective, it is not a drug of first choice for the treatment of pneumonia secondary to S. pneumoniae,¹ 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.^{5 178 296 356 427 479 522 621} 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.^{293 294 296 522 538} Ciprofloxacin probably should not be used in the treatment of aspiration pneumonia because these infections generally involve anaerobic bacteria.^{293 296 621}

Nosocomial Pneumonia

Ciprofloxacin is used for the treatment of nosocomial pneumonia, including hospital-acquired, ventilator-associated, and healthcare-associated pneumonia.⁷⁸⁰

IDSA and the American Thoracic Society (ATS) state that monotherapy with a fluoroquinolone (ciprofloxacin, levofloxacin, moxifloxacin), ceftriaxone, ampicillin and sulbactam, or ertapenem may be used for initial empiric therapy of nosocomial pneumonia in patients with early onset of pneumonia and no known risk factors for multidrug-resistant bacteria.⁷⁸⁰ In severely ill patients or those with late-onset disease or risk factors for multidrug-resistant bacteria, these and other experts recommend use of an antipseudomonal cephalosporin (cefepime, ceftazidime), antipseudomonal penicillin (piperacillin and tazobactam, ticarcillin and clavulanate), or antipseudomonal carbapenem (imipenem or meropenem) in conjunction an aminoglycoside (amikacin, gentamicin, tobramycin) or antipseudomonal fluoroquinolone (ciprofloxacin, levofloxacin).^{538 780} Local susceptibility data should be used when selecting the empiric regimen.^{779 780} Levofloxacin or moxifloxacin may be preferred to ciprofloxacin if multidrug-resistant S. pneumoniae are suspected.^{779 780} In hospitals where oxacillin-resistant (methicillin-resistant) Staphylococcus are common or if there are risk factors for these strains, the initial regimen also should include vancomycin or linezolid.^{538 779 780}

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.^{178 205 296 299 301 302 304 305 307 308 309 310 311 359 424 474 479} 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.^{205 306 307 309 310 312 424 425 466 474 479}

Resistant strains of Ps. aeruginosa have developed during ciprofloxacin therapy;^{137 138 139 178 180 296 299 302 424 435 479 481 596} in one study, up to 45% of cystic fibrosis patients developed resistance after 2 weeks of therapy with the drug.^{180 308} Clinical improvement occurred in some patients despite the emergence of resistant Ps. aeruginosa;^{178 296 308 309 312 479} in some cases, the resistant organisms reverted to being susceptible after ciprofloxacin therapy was discontinued.⁴⁷⁹ 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.^{137 293 296 299 302 305 307 308 309 310 311 312 324 358 359 424 481} 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)^{293 294 296 479} and/or used in conjunction with one of these agents.^{293 296 479 522} If ciprofloxacin is used, it is important that susceptibility of isolates be tested carefully in subsequent exacerbations.⁴⁸¹

Although many cystic fibrosis patients are children,^{308 424} ciprofloxacin, like other quinolones, generally should not be used in children younger than 18 years of age†.^{1 205 479 522} 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.⁵²² (See Cautions: Pediatric Precautions.)

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,^{1 372 474 579} E. cloacae,^{1 362 474 579} E. coli,^{1 326 372 374 375 376 377 380 474 579} K. oxytoca,⁴⁷⁴ K. pneumoniae,^{1 362 372 376 377 380 474 579} M. morganii,^{1 474 579} P. mirabilis,^{1 362 364 372 376 377 380 474 579} P. vulgaris,^{1 372 474 579} P. stuartii,^{1 374 377 474 579} Ps. aeruginosa,^{1 280 300 326 359 362 372 374 375 376 377 382 433 474 579} Serratia marcescens†,^{362 380} S. aureus (oxacillin-susceptible strains),^{1 326 362 364 372 373 374 375 376 377 382 466 474 579} S. epidermidis (oxacillin-susceptible strains),^{1 364 372 375 376 377 382 474 579} or S. pyogenes (group A β-hemolytic streptococci).^{1 362 373 374 579} The drug has been effective in the treatment of cellulitis,^{297 326 334 372 373 376 381 382 466 474} abscesses,^{205 297 334 364 372 373 474} folliculitis,^{364 374} furunculosis,^{205 364} pyoderma,²⁰⁵ postoperative wound infections,^{326 334 372 373 374 375 376 382 474} and infected ulcers,^{297 326 334 372 376 377 382 466 474} burns,^{297 373 474} or wounds.^{205 297 364 376 466 474}

Ciprofloxacin may be particularly useful as an oral agent for the treatment of skin and skin structure infections caused by susceptible gram-negative bacteria.^{334 363 372 479 481} 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.^{293 468 481 492 522 538} Treatment failures have been reported in patients with skin or skin structure infections caused by S. aureus.⁴⁴⁰ In addition, the increasing emergence of strains of staphylococci resistant to quinolones limits the usefulness of the drugs in the treatment of these infections.^{140 144 362 548 549} Some clinicians suggest that ciprofloxacin therapy may be particularly useful for the treatment of hospital-acquired decubitus ulcers when anti-infective therapy is indicated.^{293 296 334 479 522}

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.^{334 372 373} Oral ciprofloxacin resulted in a bacteriologic cure rate of 80–92% in patients with skin and skin structure infections.^{297 466 468 474}

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.⁴⁹² Therefore, use of the drug as monotherapy in these infections is not recommended pending accumulation of additional efficacy data.^{492 522}

Urinary Tract Infections and Prostatitis

Uncomplicated and Complicated Urinary Tract Infections

Ciprofloxacin extended-release tablets containing ciprofloxacin hydrochloride (ProQuin^® XR) are used only for the treatment of uncomplicated UTIs (acute cystitis) caused by susceptible E. coli or K. pneumoniae in adults.⁷⁷⁶

Ciprofloxacin extended-release tablets containing both the hydrochloride and the base (Cipro^® XR) 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.⁷¹⁵

Ciprofloxacin (IV, conventional tablets, oral suspension) is used in adults for the treatment of complicated or uncomplicated UTIs caused by susceptible Citrobacter diversus,^{1 474 579} C. freundii,^{1 339 340 341 375 380 474 579} Enterobacter cloacae,^{1 327 332 380 474 579} E. aerogenes†,⁴⁷⁴ E. coli,^{1 297 326 327 329 332 336 338 339 340 351 352 353 375 380 474 504 579} Klebsiella oxytoca†,⁴⁷⁴ K. pneumoniae,^{1 297 327 329 336 338 340 341 353 375 474 504 579} Morganella morganii,^{1 340 341 474 579} Proteus mirabilis,^{1 327 332 336 340 352 353 474 504 579} Providencia rettgeri,^{1 474 579} P. stuartii†,^{326 474} Pseudomonas aeruginosa,^{1 297 300 326 327 336 338 339 340 341 351}