173
DIAG. MICROBIOL. INFECT. DIS. 1990;13:173-176
Intravenous and Oral Ciprofloxacin in the Therapy of Serious Infections Cynthia L. Gibert, Mary Seiler, Linda Joe, Margo A. Smith, and Fred Gordin
INTRODUCTION Ciprofloxacin is a fluorinated quinolone that prevents bacterial replication by inhibiting bacterial DNA gyrase (Wolfson and Hooper, 1985). Oral ciprofloxacin has been shown to have a broad antibacterial spectrum and to be effective therapy against Gramnegative and Gram-positive organisms, including difficult to treat organisms such as Pseudomonas aeruginosa and Staphylococcus aureus (Arcieri et al., 1986). Oral ciprofloxacin is currently licensed and marketed, and reported toxicity in adults has been limited (Ball, 1986). Earlier clinical trials of intravenous (IV) ciprofloxacin have studied the pharmacokinetics, as well as the efficacy and safety, of this agent (Gonzales et al., 1985; Bergan et al., 1987; Scully and Neu, 1987). To evaluate the efficacy and safety of IV ciprofloxacin in the treatment of acutely ill hospitalized patients with suspected serious bacterial infections, we conducted a prospective analysis of ciprofloxacin as initial therapy, which we report here. PATIENTS AND METHODS All patients were hospitalized adults on the medical, surgical, or neurology services of the Veterans Administration Medical Center in Washington, D.C. The study period was from 1987 to 1988. All enrolled patients had a documented or suspected infection with a pathogen presumed to be susceptible to cipFrom the Department of Medicine, Section of Infectious Diseases, Veterans Affairs Medical Center, Washington, D.C. Address reprint requests to: Dr. F. Gordin, Section of Infectious Diseases, Veterans Affairs Medical Center, 50 Irving Street, NW, Washington, DC 20422. Received January 10, 1990, revised and accepted January 12, 1990. © 1990 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010 0732-8893/90/$3.50
rofloxacin. Patients were eligible for enrollment in the study if they were older than 18 years of age, had an infection that warranted the use of parenteral antimicrobial therapy, had not received other effective antibiotic therapy in the previous 72 hr, were not allergic to a carboxyquinolone, and had no presumably fatal underlying disease. Appropriate cultures and diagnostic studies were obtained. Definitive proof of infection was established by the following: growth of cultures with an organism thought to represent the causative pathogen, clinical signs and symptoms of infection, as well as radiographic studies, bone scans, and biopsies as indicated. Intravenous ciprofloxacin was administered at a daily dose of 400 or 600 mg (200 or 300 mg every 12 hr infused over 30 min) for a minimum of 2 days. For those patients who received additional therapy with oral ciprofloxacin, the daily dose was 1000 or 1500 mg (500 or 750 mg orally every 12 hr) after fasting or 2 hr after a meal. The decision to change the patient to oral ciprofloxacin was made by the principal investigator and was based on the patient's general clinical response to therapy and ability to take oral medication. Baseline hematologic studies, blood chemistries, and urinalysis were obtained at entry and repeated every 3-5 days to evaluate toxicity. The study personnel monitored the patients daily to evaluate their clinical course, as well as to look for evidence of any adverse drug reactions. An assessment of the overall response to therapy was based on a combination of the clinical and bacteriologic response. Appropriate cultures, as well as radiographic and laboratory studies, were repeated during the study every 3-5 days to assess the drug's effectiveness. An assessment of the clinical response was made both at the end of IV therapy and at the end of oral therapy. Complete resolution was defined as elim-
174
C.L. Gibert et al.
ination of all signs and symptoms related to the infection. If there was a marked or moderate reduction in the severity or number of signs and symptoms of infection, the clinical response was judged to be an improvement. A case was defined as a clinical failure if there was insufficient lessening of the signs and symptoms of infection to qualify as an improvement. If, for any reason, a final evaluation was not possible, the outcome was defined as indeterminate. The bacteriologic response was determined by appropriate culture results at the end of therapy and graded as either eradication, persistence, or indeterminate for nonurinary tract infections. For urinary tract infections, cultures were obtained 5-9 days after treatment and again at 28 days. Based on the urine culture results, the bacteriologic outcome was classified as eradication, persistence, or indeterminate. The overall response to therapy was based on a combination of clinical and bacteriological responses and was categorized as a cure, partial cure, failure, or indeterminate. Ciprofloxacin susceptibility for all infecting organisms was determined using the modified KirbyBauer disk procedure (Gonzales et al., 1985). In our microbiology laboratory, the organism was considered susceptible to ciprofloxacin if the zone size was >21 mm, intermediate if 16-20 mm, and resistant if 1.0 but 42.0 ~g/ml, or resistant if the MIC was >2.0 ~g/ml.
TABLE 1.
RESULTS
TABLE 2.
From May 1987 to December 1988, 51 patients received IV ciprofloxacin for presumed serious bacterial infections. Eleven patients were removed from the study within 2 days and were not evaluated. Two of these 11 patients were withdrawn prematurely from the protocol by the house staff, one patient removed himself from the study, and a treatable pathogen was not identified from the remaining eight patients. All of the 40 evaluated patients were men with a median age of 60 (range, 30-86 years). At the time of the initiation of therapy, 24 infections were considered severe and 16 were considered moderate. Sources of infection included eight bacteremias, eight pneumonias, five urinary tract infections, 15 skin and soft-tissue infections, two gastrointestinal infections, one endocarditis, and one osteomyelitis (Table 1). Nine of the 40 evaluable patients received IV therapy only (range, 5-17.5 days; median, 13 days). Thirty-one patients received c o m -
Sources of Infection Sources
No.
Skin and soft Tissue Cellulitis Wound Ulcer Abscess Otitis externa Respiratory tract Pneumonia Pneumonia with empyema Bacteremias Source unknown Intraabdominal source Genitourinary tract Catheter related Urinary tract infections Complicated Uncomplicated Gastrointestinal Enterocolitis Endocarditis Right-sided Bone/joint Osteomyelitis
4 4 4 2 1 6 2 4 2 1 1 3 2 2 1 1
bination IV/oral ciprofloxacin. The duration of IV therapy was 2-14.5 days (mean, 6 days) followed by oral therapy, if indicated, for 2-165 days (mean, 8 days). Fifty-six clinically significant organisms were isolated from the 40 patients evaluated (Table 2). Ciprofloxacin eradicated 42 (75%) of these organisms, including all 19 bacteria of the Enterobacteriaceae Bacteriological Response to Therapy
Organism S. aureus Streptococcus sp.
Other Gram (+)a P. aeruginosa X. maltophilia Escherichia coli Klebsiella sp. Proteus mirabilis Haemophilus sp. Carnpylobacter jejuni
Eradication Persistence Indeterminate 1
5
1
4 2
1 0
0 0
9 0
4 2
0 0
10 3
0 0
0 0
3
0
0
3
0
0
0
0
1
Other Gram (--)b
6
0
0
M. fortuitum
1
0
0
42
12
2
Total
"1 each Staphylococcus epidermidis and Corynebacterium sp. bl each Enterobacter cloacae, Citrobacter diversus, Eikenella corrodens, Serratia marcescens, Branhamella catarrhalis, and Shigella sonnei.
Ciprofloxacin for Serious Infections
TABLE 3.
175
Response to Therapy by Diagnosis Cure
Partial Cure
Failure
Indeterminate
Skin and soft tissue Pneumonia Bacterernia Urinary tract Gastrointestinal Endocarditis Osteomyelitis
10
4
1
0
5 4 4 2 0 0
2 2 1 0 0 1
0 0 0 0 1 0
1 2 0 0 0 0
Total
25
10
2
3
Diagnosis
family. Five of the seven isolates of Staphylococcus aureus and four of nine isolates of Pseudomonas aeruginosa persisted despite therapy. Both isolates of Xanthomonas maltophilia persisted despite therapy. Two of the strains of S. aureus developed stepwise in vitro resistance to ciprofloxacin during treatment. In one of these patients, clinical failure occurred, whereas in another patient the infection resolved on ciprofloxacin despite the development of in vitro resistance. The overall response to ciprofloxacin therapy was highly favorable for infections caused by both Gramnegative and Gram-positive organisms (Table 3): 35 (88%) patients had partial or complete cures, three patients had an indeterminate outcome, and only two patients failed therapy. As noted above, several patients with P. aeruginosa and X. maltophilia had persistence of these organisms; however, these patients had clinical resolution of their infections. Patients showing good responses to therapy included individuals with a wide spectrum of diseases, including skin and soft-tissue infections, pneumonias, bacteremias, urinary tract infections, and gastrointestinal infections. One case of particular interest was an individual with malignant external otitis caused by P. aeruginosa. After 48 days of combined IV and oral ciprofloxacin, the infection resolved without need for surgery. A second case of interest was a 72-year-old man who presented with disseminated skin disease caused by Mycobacterium fortuitum, one of the rapidgrowing nontuberculous mycobacteria. The organism was unusually resistant and sensitive in vitro only to ciprofloxacin, amikacin, and minocycline. The patient was treated initially with IV dprofloxacin and amikacin for 2 weeks and completed an oral regimen of ciprofloxacin and minocycline. After 176 days of combined therapy, the patient had complete resolution of his skin lesions with negative mycobacterial cultures. The two patients who failed to respond to cip-
rofloxacin both had infections caused by S. aureus. One individual was an IV drug user with right-sided endocarditis. Despite in vitro sensitivity to ciprofloxacin, the patient remained febrile and bacteremic after 6 days of therapy. The patient was changed to nafcillin and gentamicin, with rapid resolution of fever and symptoms and clearance of bacteremia. The second patient was a 59-year-old man with sickle cell disease and recurrent leg ulcers. The patient had an acute infection caused by methicillin-resistant S. aureus and P. aeruginosa. On ciprofloxacin, the patient had initial improvement with eradication of the P. aeruginosa; however the S. aureus became increasingly resistant to ciprofloxacin and the patient's infection worsened. The patient was eventually changed to vancomycin with complete resolution of his infection. Only two patients had documented adverse reactions attributable to ciprofloxacin. One patient had mild diarrhea, and a second person had a transient elevation in creatinine.
DISCUSSION In this study of 40 patients treated with IV ciprofloxacin as initial therapy, we have shown ciprofloxacin to be highly effective against a wide range of organisms causing a variety of infections. We found the drug to be well tolerated with a minimum of adverse effects. Patients with infections caused by Gram-negative organisms did especially well, with persistence of bacteria only occurring in the Pseudomonadaceae family. Despite the persistence of these Pseudomonadaceae organisms, clinical outcome was favorable for almost all of the patients. Although the majority of patients with infections caused by Gram-positive organisms responded well to therapy, we did note development of resistance to ciprofloxacin in two individuals with S. aureus infections. The development of resistance to ciprofloxacin by S. aureus has been noted by others and is of concern (Maple et al., 1989; Piercy et al., 1989). Intravenous ciprofloxacin is an attractive drug for treating serious infections in hospitalized patients for w h o m oral therapy is inadequate or not feasible. Ciprofloxacin enables the clinician to avoid the toxicities of the aminoglycosides as well as the potential for allergic reactions associated with the cephalosporins and extended-spectrum penicillins. Intravenous ciprofloxacin may be one of the few antibiotics available to treat life-threatening infections caused by multiply antibiotic-resistant organisms. Intravenous ciprofloxacin should have a clear role as the initial therapy of infections caused by Gramnegative bacteria. The lack of significant toxicity, the 12-hr dosing interval, and the availability of oral cip-
176
rofloxacin as continuation therapy makes it an attractive antibiotic agent. A l t h o u g h ciprofloxacin has been s h o w n to be effective in treating infections caused by Gram-positive organisms, the develop-
C.L. Gibert et al.
m e n t of resistance is of concern, and the use of ciprofloxacin in treating S. aureus infections requires further study.
REFERENCES Arcieri G, Griffith E, Gruenwald G, et al. (1987) Ciprofloxacin: an update on clinical experience. Am J Med 82(suppl 4A):381-386. Ball P (1986) Ciprofloxacin: an overview of adverse experiences. J Antimicrob Chemother 18(suppl D): 187-193. Bergan T, Thorsteinsson S, Solberg R, et al. (1987) Pharmacokinetics of ciprofloxacin: intravenous and increasing oral doses. Am J Med 82:(suppl 4A):97-102. Gonzales MA, Moranchel A, Duran S, et al. (1985) Multiple dose pharmacokinetics of ciprofloxacin administered intravenously to normal volunteers. Antimicrob Agents Chemother 28:235-239.
Maple P, Hamilton-Miller J, Brumfitt W (1989) World-wide antibiotic resistance in methicillin-resistant Staphylococcus aureus. Lancet 1:537-540. Piercy E, Barbaro D, Luby J, Mackowiak P (1989) Ciprofloxacin for methicillin-resistant Staphylococcus aureus infections. Antimicrob Agents Chemother 33:128-130. Scully B, Neu H (1987) Treatment of serious infections with intravenous ciprofloxacin. Am J Med 82:(suppl 4A):369-375. Wolfson J, Hooper D (1985) The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrob Agents Chemother 28:581586.
DIAG. MICROBIOL. INFECT. DIS. 1990;13:173-176
Intravenous and Oral Ciprofloxacin in the Therapy of Serious Infections Cynthia L. Gibert, Mary Seiler, Linda Joe, Margo A. Smith, and Fred Gordin
INTRODUCTION Ciprofloxacin is a fluorinated quinolone that prevents bacterial replication by inhibiting bacterial DNA gyrase (Wolfson and Hooper, 1985). Oral ciprofloxacin has been shown to have a broad antibacterial spectrum and to be effective therapy against Gramnegative and Gram-positive organisms, including difficult to treat organisms such as Pseudomonas aeruginosa and Staphylococcus aureus (Arcieri et al., 1986). Oral ciprofloxacin is currently licensed and marketed, and reported toxicity in adults has been limited (Ball, 1986). Earlier clinical trials of intravenous (IV) ciprofloxacin have studied the pharmacokinetics, as well as the efficacy and safety, of this agent (Gonzales et al., 1985; Bergan et al., 1987; Scully and Neu, 1987). To evaluate the efficacy and safety of IV ciprofloxacin in the treatment of acutely ill hospitalized patients with suspected serious bacterial infections, we conducted a prospective analysis of ciprofloxacin as initial therapy, which we report here. PATIENTS AND METHODS All patients were hospitalized adults on the medical, surgical, or neurology services of the Veterans Administration Medical Center in Washington, D.C. The study period was from 1987 to 1988. All enrolled patients had a documented or suspected infection with a pathogen presumed to be susceptible to cipFrom the Department of Medicine, Section of Infectious Diseases, Veterans Affairs Medical Center, Washington, D.C. Address reprint requests to: Dr. F. Gordin, Section of Infectious Diseases, Veterans Affairs Medical Center, 50 Irving Street, NW, Washington, DC 20422. Received January 10, 1990, revised and accepted January 12, 1990. © 1990 Elsevier Science Publishing Co., Inc. 655 Avenue of the Americas, New York, NY 10010 0732-8893/90/$3.50
rofloxacin. Patients were eligible for enrollment in the study if they were older than 18 years of age, had an infection that warranted the use of parenteral antimicrobial therapy, had not received other effective antibiotic therapy in the previous 72 hr, were not allergic to a carboxyquinolone, and had no presumably fatal underlying disease. Appropriate cultures and diagnostic studies were obtained. Definitive proof of infection was established by the following: growth of cultures with an organism thought to represent the causative pathogen, clinical signs and symptoms of infection, as well as radiographic studies, bone scans, and biopsies as indicated. Intravenous ciprofloxacin was administered at a daily dose of 400 or 600 mg (200 or 300 mg every 12 hr infused over 30 min) for a minimum of 2 days. For those patients who received additional therapy with oral ciprofloxacin, the daily dose was 1000 or 1500 mg (500 or 750 mg orally every 12 hr) after fasting or 2 hr after a meal. The decision to change the patient to oral ciprofloxacin was made by the principal investigator and was based on the patient's general clinical response to therapy and ability to take oral medication. Baseline hematologic studies, blood chemistries, and urinalysis were obtained at entry and repeated every 3-5 days to evaluate toxicity. The study personnel monitored the patients daily to evaluate their clinical course, as well as to look for evidence of any adverse drug reactions. An assessment of the overall response to therapy was based on a combination of the clinical and bacteriologic response. Appropriate cultures, as well as radiographic and laboratory studies, were repeated during the study every 3-5 days to assess the drug's effectiveness. An assessment of the clinical response was made both at the end of IV therapy and at the end of oral therapy. Complete resolution was defined as elim-
174
C.L. Gibert et al.
ination of all signs and symptoms related to the infection. If there was a marked or moderate reduction in the severity or number of signs and symptoms of infection, the clinical response was judged to be an improvement. A case was defined as a clinical failure if there was insufficient lessening of the signs and symptoms of infection to qualify as an improvement. If, for any reason, a final evaluation was not possible, the outcome was defined as indeterminate. The bacteriologic response was determined by appropriate culture results at the end of therapy and graded as either eradication, persistence, or indeterminate for nonurinary tract infections. For urinary tract infections, cultures were obtained 5-9 days after treatment and again at 28 days. Based on the urine culture results, the bacteriologic outcome was classified as eradication, persistence, or indeterminate. The overall response to therapy was based on a combination of clinical and bacteriological responses and was categorized as a cure, partial cure, failure, or indeterminate. Ciprofloxacin susceptibility for all infecting organisms was determined using the modified KirbyBauer disk procedure (Gonzales et al., 1985). In our microbiology laboratory, the organism was considered susceptible to ciprofloxacin if the zone size was >21 mm, intermediate if 16-20 mm, and resistant if 1.0 but 42.0 ~g/ml, or resistant if the MIC was >2.0 ~g/ml.
TABLE 1.
RESULTS
TABLE 2.
From May 1987 to December 1988, 51 patients received IV ciprofloxacin for presumed serious bacterial infections. Eleven patients were removed from the study within 2 days and were not evaluated. Two of these 11 patients were withdrawn prematurely from the protocol by the house staff, one patient removed himself from the study, and a treatable pathogen was not identified from the remaining eight patients. All of the 40 evaluated patients were men with a median age of 60 (range, 30-86 years). At the time of the initiation of therapy, 24 infections were considered severe and 16 were considered moderate. Sources of infection included eight bacteremias, eight pneumonias, five urinary tract infections, 15 skin and soft-tissue infections, two gastrointestinal infections, one endocarditis, and one osteomyelitis (Table 1). Nine of the 40 evaluable patients received IV therapy only (range, 5-17.5 days; median, 13 days). Thirty-one patients received c o m -
Sources of Infection Sources
No.
Skin and soft Tissue Cellulitis Wound Ulcer Abscess Otitis externa Respiratory tract Pneumonia Pneumonia with empyema Bacteremias Source unknown Intraabdominal source Genitourinary tract Catheter related Urinary tract infections Complicated Uncomplicated Gastrointestinal Enterocolitis Endocarditis Right-sided Bone/joint Osteomyelitis
4 4 4 2 1 6 2 4 2 1 1 3 2 2 1 1
bination IV/oral ciprofloxacin. The duration of IV therapy was 2-14.5 days (mean, 6 days) followed by oral therapy, if indicated, for 2-165 days (mean, 8 days). Fifty-six clinically significant organisms were isolated from the 40 patients evaluated (Table 2). Ciprofloxacin eradicated 42 (75%) of these organisms, including all 19 bacteria of the Enterobacteriaceae Bacteriological Response to Therapy
Organism S. aureus Streptococcus sp.
Other Gram (+)a P. aeruginosa X. maltophilia Escherichia coli Klebsiella sp. Proteus mirabilis Haemophilus sp. Carnpylobacter jejuni
Eradication Persistence Indeterminate 1
5
1
4 2
1 0
0 0
9 0
4 2
0 0
10 3
0 0
0 0
3
0
0
3
0
0
0
0
1
Other Gram (--)b
6
0
0
M. fortuitum
1
0
0
42
12
2
Total
"1 each Staphylococcus epidermidis and Corynebacterium sp. bl each Enterobacter cloacae, Citrobacter diversus, Eikenella corrodens, Serratia marcescens, Branhamella catarrhalis, and Shigella sonnei.
Ciprofloxacin for Serious Infections
TABLE 3.
175
Response to Therapy by Diagnosis Cure
Partial Cure
Failure
Indeterminate
Skin and soft tissue Pneumonia Bacterernia Urinary tract Gastrointestinal Endocarditis Osteomyelitis
10
4
1
0
5 4 4 2 0 0
2 2 1 0 0 1
0 0 0 0 1 0
1 2 0 0 0 0
Total
25
10
2
3
Diagnosis
family. Five of the seven isolates of Staphylococcus aureus and four of nine isolates of Pseudomonas aeruginosa persisted despite therapy. Both isolates of Xanthomonas maltophilia persisted despite therapy. Two of the strains of S. aureus developed stepwise in vitro resistance to ciprofloxacin during treatment. In one of these patients, clinical failure occurred, whereas in another patient the infection resolved on ciprofloxacin despite the development of in vitro resistance. The overall response to ciprofloxacin therapy was highly favorable for infections caused by both Gramnegative and Gram-positive organisms (Table 3): 35 (88%) patients had partial or complete cures, three patients had an indeterminate outcome, and only two patients failed therapy. As noted above, several patients with P. aeruginosa and X. maltophilia had persistence of these organisms; however, these patients had clinical resolution of their infections. Patients showing good responses to therapy included individuals with a wide spectrum of diseases, including skin and soft-tissue infections, pneumonias, bacteremias, urinary tract infections, and gastrointestinal infections. One case of particular interest was an individual with malignant external otitis caused by P. aeruginosa. After 48 days of combined IV and oral ciprofloxacin, the infection resolved without need for surgery. A second case of interest was a 72-year-old man who presented with disseminated skin disease caused by Mycobacterium fortuitum, one of the rapidgrowing nontuberculous mycobacteria. The organism was unusually resistant and sensitive in vitro only to ciprofloxacin, amikacin, and minocycline. The patient was treated initially with IV dprofloxacin and amikacin for 2 weeks and completed an oral regimen of ciprofloxacin and minocycline. After 176 days of combined therapy, the patient had complete resolution of his skin lesions with negative mycobacterial cultures. The two patients who failed to respond to cip-
rofloxacin both had infections caused by S. aureus. One individual was an IV drug user with right-sided endocarditis. Despite in vitro sensitivity to ciprofloxacin, the patient remained febrile and bacteremic after 6 days of therapy. The patient was changed to nafcillin and gentamicin, with rapid resolution of fever and symptoms and clearance of bacteremia. The second patient was a 59-year-old man with sickle cell disease and recurrent leg ulcers. The patient had an acute infection caused by methicillin-resistant S. aureus and P. aeruginosa. On ciprofloxacin, the patient had initial improvement with eradication of the P. aeruginosa; however the S. aureus became increasingly resistant to ciprofloxacin and the patient's infection worsened. The patient was eventually changed to vancomycin with complete resolution of his infection. Only two patients had documented adverse reactions attributable to ciprofloxacin. One patient had mild diarrhea, and a second person had a transient elevation in creatinine.
DISCUSSION In this study of 40 patients treated with IV ciprofloxacin as initial therapy, we have shown ciprofloxacin to be highly effective against a wide range of organisms causing a variety of infections. We found the drug to be well tolerated with a minimum of adverse effects. Patients with infections caused by Gram-negative organisms did especially well, with persistence of bacteria only occurring in the Pseudomonadaceae family. Despite the persistence of these Pseudomonadaceae organisms, clinical outcome was favorable for almost all of the patients. Although the majority of patients with infections caused by Gram-positive organisms responded well to therapy, we did note development of resistance to ciprofloxacin in two individuals with S. aureus infections. The development of resistance to ciprofloxacin by S. aureus has been noted by others and is of concern (Maple et al., 1989; Piercy et al., 1989). Intravenous ciprofloxacin is an attractive drug for treating serious infections in hospitalized patients for w h o m oral therapy is inadequate or not feasible. Ciprofloxacin enables the clinician to avoid the toxicities of the aminoglycosides as well as the potential for allergic reactions associated with the cephalosporins and extended-spectrum penicillins. Intravenous ciprofloxacin may be one of the few antibiotics available to treat life-threatening infections caused by multiply antibiotic-resistant organisms. Intravenous ciprofloxacin should have a clear role as the initial therapy of infections caused by Gramnegative bacteria. The lack of significant toxicity, the 12-hr dosing interval, and the availability of oral cip-
176
rofloxacin as continuation therapy makes it an attractive antibiotic agent. A l t h o u g h ciprofloxacin has been s h o w n to be effective in treating infections caused by Gram-positive organisms, the develop-
C.L. Gibert et al.
m e n t of resistance is of concern, and the use of ciprofloxacin in treating S. aureus infections requires further study.
REFERENCES Arcieri G, Griffith E, Gruenwald G, et al. (1987) Ciprofloxacin: an update on clinical experience. Am J Med 82(suppl 4A):381-386. Ball P (1986) Ciprofloxacin: an overview of adverse experiences. J Antimicrob Chemother 18(suppl D): 187-193. Bergan T, Thorsteinsson S, Solberg R, et al. (1987) Pharmacokinetics of ciprofloxacin: intravenous and increasing oral doses. Am J Med 82:(suppl 4A):97-102. Gonzales MA, Moranchel A, Duran S, et al. (1985) Multiple dose pharmacokinetics of ciprofloxacin administered intravenously to normal volunteers. Antimicrob Agents Chemother 28:235-239.
Maple P, Hamilton-Miller J, Brumfitt W (1989) World-wide antibiotic resistance in methicillin-resistant Staphylococcus aureus. Lancet 1:537-540. Piercy E, Barbaro D, Luby J, Mackowiak P (1989) Ciprofloxacin for methicillin-resistant Staphylococcus aureus infections. Antimicrob Agents Chemother 33:128-130. Scully B, Neu H (1987) Treatment of serious infections with intravenous ciprofloxacin. Am J Med 82:(suppl 4A):369-375. Wolfson J, Hooper D (1985) The fluoroquinolones: structures, mechanisms of action and resistance, and spectra of activity in vitro. Antimicrob Agents Chemother 28:581586.
