"The U.S. Food and Drug Administration today approved Zerbaxa (ceftolozane/tazobactam), a new antibacterial drug product, to treat adults with complicated intra-abdominal infections (cIAI) and complicated urinary tract infections (cUTI).
Mechanism Of Action
Ciprofloxacin is a member of the fluoroquinolone class of antibacterial agents [see Microbiology].
CIPRO XR tablets are formulated to release drug at a slower rate compared to immediate-release tablets. Approximately 35% of the dose is contained within an immediate-release component, while the remaining 65% is contained in a slow-release matrix.
Maximum plasma ciprofloxacin concentrations are attained between 1 and 4 hours after dosing with CIPRO XR. In comparisontothe 250 mg and 500 mg ciprofloxacinimmediate-releasetwice a day (BID) treatment,the Cmax of CIPRO XR 500 mg and 1000 mg once daily are higher than the corresponding BID doses, while the AUCs over 24 hours are equivalent.
The following table compares the pharmacokinetic parameters obtained at steady state for these four treatment regimens (500 mg once a day (QD) CIPRO XR versus 250 mg BID ciprofloxacin immediate-release tablets and 1000 mg QD CIPRO XR versus 500 mg BID ciprofloxacin immediate-release).
Table 5: Ciprofloxacin Pharmacokinetics (Mean ± SD)
Following CIPRO and CIPRO XR Administration
|Cmax (mg/L)||AUC0-24h (mg•h/L)||T½(hr)||Tmax (hr) 1|
|CIPRO XR 500 mg QD||1.59 ± 0.43||7.97 ± 1.87||6.6 ± 1.4||1.5 (1 - 2.5)|
|CIPRO 250 mg BID||1.14 ± 0.23||8.25 ± 2.15||4.8 ± 0.6||1 (0.5 - 2.5)|
|CIPRO XR 1000 mg QD||3.11 ± 1.08||16.83 ± 5.65||6.31 ± 0.72||2 (1 - 4)|
|CIPRO 500 mg BID||2.06 ± 0.41||17.04 ± 4.79||5.66 ± 0.89||2 (0.5 - 3.5)|
|1 median (range)|
Results of the pharmacokinetic studies demonstrate that CIPRO XR may be administered with or without food (for example, high-fat and low-fat meals or under fasted conditions).
The volume of distribution calculated for intravenous ciprofloxacin is approximately 2.1–2.7 L/kg. Studies with the oral and intravenous forms of ciprofloxacin have demonstrated penetration of ciprofloxacin into a variety of tissues. The binding of ciprofloxacin to serum proteins is 20% to 40%, which is not likely to be high enough to cause significant protein binding interactions with other drugs. Following administration of a single dose of CIPRO XR, ciprofloxacin concentrations in urine collected up to 4 hours after dosing averaged over 300 mg/L for both the 500 mg and 1000 mg tablets; in urine excreted from 12 to 24 hours after dosing, ciprofloxacin concentration averaged 27 mg/L for the 500 mg tablet, and 58 mg/L for the 1000 mg tablet.
Four metabolites of ciprofloxacin were identified in human urine. The metabolites have antimicrobial activity, but are less active than unchanged ciprofloxacin. The primary metabolites are oxociprofloxacin (M3) and sulfociprofloxacin (M2), each accounting for roughly 3% to 8% of the total dose. Other minor metabolites are desethylene ciprofloxacin (M1), and formylciprofloxacin (M4). The relative proportion of drug and metabolite in serum corresponds to the composition found in urine. Excretion of these metabolites was essentially complete by 24 hours after dosing. Ciprofloxacin is an inhibitor of CYP1A2 mediated metabolism. Co-administration of ciprofloxacin with other drugs primarily metabolized by CYP1A2 results in increased plasma concentrations of these drugs and could lead to clinically significant adverse events of the co-administered drug [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS and DRUG INTERACTIONS].
The elimination kinetics of ciprofloxacin are similar for the immediate-release and the CIPRO XR tablet. In studies comparing the CIPRO XR and immediate-release ciprofloxacin, approximately 35% of an orally administered dose was excreted in the urine as unchanged drug for both formulations. The urinary excretion of ciprofloxacin is virtually complete within 24 hours after dosing. The renal clearance of ciprofloxacin, which is approximately 300 mL/minute, exceeds the normal glomerular filtration rate of 120 mL/minute. Thus, active tubular secretion would seem to play a significant role in its elimination. Co-administration of probenecid with immediate-release ciprofloxacin results in about a 50% reduction in the ciprofloxacin renal clearance and a 50% increase in its concentration in the systemic circulation. Although bile concentrations of ciprofloxacin are several fold higher than serum concentrations after oral dosing with the immediate-release tablet, only a small amount of the dose administered is recovered from the bile as unchanged drug. An additional 1 to 2% of the dose is recovered from the bile in the form of metabolites. Approximately 20 to 35% of an oral dose of immediate-release ciprofloxacin is recovered from the feces within 5 days after dosing. This may arise from either biliary clearance or transintestinal elimination.
Pharmacokinetic studies of the immediate-release oral tablet (single dose) and intravenous (single and multiple dose) forms of ciprofloxacin indicate that plasma concentrations of ciprofloxacin are higher in elderly subjects ( > 65 years) ascomparedtoyoungadults. Cmax is increased16 to 40%, andmeanAUCisincreasedapproximately 30%, which can be at least partially attributed to decreased renal clearance in the elderly. Elimination half-life is only slightly (~20%) prolonged in the elderly. These differences are not considered clinically significant [see Use in Specific Populations].
In patients with reduced renal function, the half-life of ciprofloxacin is slightly prolonged. No dose adjustment is required for patients with uncomplicated UTIs receiving 500 mg CIPRO XR. For cUTI and AUP, where 1000 mg is the appropriate dose, the dosage of CIPRO XR should be reduced to CIPRO XR 500 mg q24h in patients with creatinine clearance equal to or below 30 mL/min [see DOSAGE AND ADMINISTRATION].
In preliminary studies in patients with stable chronic cirrhosis, no significant changes in ciprofloxacin pharmacokinetics have been observed. The kinetics of ciprofloxacin in patients with acute hepatic insufficiency, however, have not been fully elucidated [see Use in Specific Populations].
Concurrent administration of antacids containing magnesium hydroxide or aluminum hydroxide may reduce the bioavailability of CIPRO by as much as 90% [see DOSAGE AND ADMINISTRATION and DRUG INTERACTIONS].
Histamine H2-receptor Antagonists
Histamine H2-receptor antagonists appear to have no significant effect on the bioavailability of CIPRO.
The serum concentrations of CIPRO and metronidazole were not altered when these two drugs were given concomitantly.
In a pharmacokinetic study, systemic exposure of tizanidine (4 mg single dose) was significantly increased (Cmax 7-fold, AUC 10-fold) when the drug was given concomitantly with CIPRO (500 mg twice a day for 3 days). Concomitant administration of tizanidine and CIPRO XR is contraindicated due to the potentiation of hypotensive and sedative effects of tizanidine [see CONTRAINDICATIONS].
In a study conducted in 12 patients with Parkinson's disease who were administered 6 mg ropinirole once daily with 500 mg CIPRO twice-daily, the mean Cmax and mean AUC of ropinirole were increased by 60% and 84%, respectively. Monitoring for ropinirole-related adverse reactions and appropriate dose adjustment of ropinirole is recommended during and shortly after co-administration with CIPRO XR [see WARNINGS AND PRECAUTIONS].
Following concomitant administration of 250 mg CIPRO with 304 mg clozapine for 7 days, serum concentrations of clozapine and N-desmethylclozapine were increased by 29% and 31%, respectively. Careful monitoring of clozapine associated adverse reactions and appropriate adjustment of clozapine dosage during and shortly after co-administration with CIPRO XR are advised.
Following concomitant administration of a single oral dose of 50 mg sildenafil with 500 mg CIPRO to healthy subjects, the mean Cmax and mean AUC of sildenafil were both increased approximately two-fold. Use sildenafil with caution when co-administered with CIPRO XR due to the expected two-fold increase in the exposure of sildenafil upon co-administration of CIPRO [see DRUG INTERACTIONS].
In clinical studies it was demonstrated that concomitant use of duloxetine with strong inhibitors of the CYP450 1A2 isozyme such as fluvoxamine, may result in a 5-fold increase in mean AUC and a 2.5-fold increase in mean Cmax of duloxetine.
In a study conducted in 9 healthy volunteers, concomitant use of 1.5 mg/kg IV lidocaine with 500 mg ciprofloxacin twice daily resulted in an increase of lidocaine Cmax and AUC by 12% and 26%, respectively. Although lidocaine treatment was well tolerated at this elevated exposure, a possible interaction with CIPRO XR and an increase in adverse reactions related to lidocaine may occur upon concomitant administration.
Metoclopramide significantly accelerates the absorption of oral ciprofloxacin resulting in a shorter time to reach maximum plasma concentrations. No significant effect was observed on the bioavailability of ciprofloxacin.
When CIPRO XR was administered as a single 1000 mg dose concomitantly with omeprazole (40 mg once daily for three days) to 18 healthy volunteers, the mean AUC and Cmax of ciprofloxacin were reduced by 20% and 23%, respectively. The clinical significance of this interaction has not been determined.
Mechanism Of Action
The bactericidal action of ciprofloxacin results from inhibition of the enzymes topoisomerase II (DNA gyrase) and topoisomerase IV (both Type II topoisomerases), which are required for bacterial DNA replication, transcription, repair, and recombination.
Mechanism Of Resistance
The mechanism of action of fluoroquinolones, including ciprofloxacin, is different from that of other antimicrobial agents such as beta-lactams, macrolides, tetracyclines, or aminoglycosides; therefore, microorganisms resistant to these classes of drugs may be susceptible to ciprofloxacin. Resistance to fluoroquinolones occurs primarily by either mutations in the DNA gyrases, decreased outer membrane permeability, or drug efflux. In vitro resistance to ciprofloxacin develops slowly by multiple step mutations. Resistance to ciprofloxacin due to spontaneous mutations occurs at a general frequency of between < 10-9 to 1x10-6.
There is no known cross-resistance between ciprofloxacin and other classes of antimicrobials.
Ciprofloxacin has been shown to be active against most isolates of the following bacteria, both in vitro and in clinical infections ciprofloxacin [see INDICATIONS AND USAGE].
The following in vitro data are available, but their clinical significance is unknown. At least 90 percent of the following bacteria exhibit an in vitro minimum inhibitory concentration (MIC) less than or equal to the susceptible breakpoint for ciprofloxacin ( ≤ 1 mcg/mL). However, the efficacy of ciprofloxacin in treating clinical infections due to these bacteria has not been established in adequate and well-controlled clinical trials.
Gram-Negative BacteriaCitrobacter koseri
Susceptibility Test Methods
When available, the clinical microbiology laboratory should provide the results of in vitro susceptibility test results for antimicrobial drug products used in resident hospitals to the physician as periodic reports that describe the susceptibility profile of nosocomial and community-acquired pathogens. These reports should aid the physician in selecting an antibacterial drug product for treatment.
Quantitative methods are used to determine antimicrobial minimum inhibitory concentrations (MICs). These MICs provide estimates of the susceptibility of bacteria to antimicrobial compounds. The MICs should be determined using a standardized test method (broth and/or agar).1,3 The MIC values should be interpreted according to criteria provided in Table 5.
Quantitative methods that require measurement of zone diameters can also provide reproducible estimates of the susceptibility of bacteria to antimicrobial compounds. The zone size provides an estimate of the susceptibility of bacteria to antimicrobial compounds. The zone size should be determined using a standardized test method.2,3 This procedure uses paper disks impregnated with 5 mcg ciprofloxacin to test the susceptibility of bacteria to ciprofloxacin. The disc diffusion interpretive criteria are provided in Table 6.
Table 6: Susceptibility Test Interpretive Criteria for
|Enterobacteriaceae||≤ 1||2||≥ 4||≥ 21||16-20||≤ 15|
|Enterococcus faecalis||≤ 1||2||≥ 4||≥ 21||16-20||≤ 15|
|Pseudomonas aeruginosa||≤ 1||2||≥ 4||≥ 21||16-20||≤ 15|
|Staphylococcus saprophyticus||≤ 1||2||≥ 4||≥ 21||16-20||≤ 15|
|S=Susceptible, I=Intermediate, and R=Resistant.|
A report of “Susceptible” indicates that the antimicrobial is likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations at the site of infection necessary to inhibit growth of the pathogen. A report of “Intermediate” indicates that the result should be considered equivocal, and, if the microorganism is not fully susceptible to alternative, clinically feasible drugs, the test should be repeated. This category implies possible clinical applicability in body sites where the drug is physiologically concentrated or in situations where high dosage of drug can be used. This category also provides a buffer zone that prevents small uncontrolled technical factors from causing major discrepancies in interpretation. A report of “Resistant” indicates that the antimicrobial is not likely to inhibit growth of the pathogen if the antimicrobial compound reaches the concentrations usually achievable at the infection site; other therapy should be selected.
Standardized susceptibility test procedures require the use of laboratory controls to monitor the accuracy and precision of supplies and reagents used in the assay, and the techniques of the individuals performing the test.1, 2 Standard ciprofloxacin powder should provide the following range of MIC values noted in Table 7. For the diffusion technique using the ciprofloxacin 5 mcg disk the criteria in Table 7 should be achieved.
Table 7: Acceptable Quality
Control Ranges for Ciprofloxacin
|Bacteria||MIC range (mcg/mL)||Zone Diameter (mm)|
|Enterococcus faecalis ATCC 29212||0.25-2||-|
|Escherichia coli ATCC 25922||0.004-0.015||30-40|
|Pseudomonas aeruginosa ATCC 27853||0.25-1||25-33|
|Staphylococcus aureus ATCC 29213||0.12-0.5||-|
|Staphylococcus aureus ATCC 25923||-||22-30|
Animal Toxicology And/Or Pharmacology
Ciprofloxacin and other quinolones have been shown to cause arthropathy in immature animals of most species tested [see WARNINGS AND PRECAUTIONS]. Damage of weight bearing joints was observed in juvenile dogs and rats. In young beagles, 100 mg/kg ciprofloxacin, given daily for 4 weeks, caused degenerative articular changes of the knee joint. At 30 mg/kg, the effect on the joint was minimal. In a subsequent study in young beagle dogs, oral ciprofloxacin doses of 30 mg/kg and 90 mg/kg given daily for 2 weeks caused articular changes which were still observed by histopathology after a treatment-free period of 5 months. At 10 mg/kg no effects on joints were observed. This dose was also not associated with arthrotoxicity after an additional treatment-free period of 5 months. In another study, removal of weight bearing from the joint reduced the lesions but did not totally prevent them.
Crystalluria, sometimes associated with secondary nephropathy, occurs in laboratory animals dosed with ciprofloxacin. This is primarily related to the reduced solubility of ciprofloxacin under alkaline conditions, which predominate in the urine of test animals; in man, crystalluria is rare since human urine is typically acidic. In rhesus monkeys, crystalluria without nephropathy has been noted after single oral doses as low as 5 mg/kg (approximately 0.1-times the highest recommended therapeutic dose based upon body surface area. After 6 months of intravenous dosing at 10 mg/kg/day, no nephropathological changes were noted; however, nephropathy was observed after dosing at 20 mg/kg/day for the same duration (approximately 0.4 times the highest recommended therapeutic dose based upon body surface area).
In dogs, ciprof1oxacin administered at 3 and 10 mg/kg by rapid infusion injection (15 sec.) produces hypotensive effects. These effects are considered to be related to histamine release because they are partially antagonized by pyrilamine, an antihistamine. In rhesus monkeys, rapid infusion injection also produces hypotension. but the effect in this species is inconsistent and less pronounced.
In mice, concomitant administration of nonsteroidal anti-inflammatory drugs such as phenylbutazone and indomethacin with quinolones has been reported to enhance the CNS stimulatory effect of quinolones.
Ocular toxicity seen with some related drugs has not been observed in ciprofloxacin-treated animals.
Uncomplicated Urinary Tract Infections (acute cystitis)
CIPRO XR was evaluated for the treatment of uncomplicated UTIs (acute cystitis) in a randomized, double-blind, controlled clinical trial conducted in the US. This study compared CIPRO XR (500 mg once daily for three days) with ciprofloxacin immediate-release tablets (CIPRO® 250 mg two times a day (BID) for three days). Of the 905 patients enrolled, 452 were randomly assigned to the CIPRO XR treatment group and 453 were randomly assigned to the control group. The primary efficacy variable was bacteriologic eradication of the baseline organism(s) with no new infection or superinfection at test-of-cure (Day 4–11 Post-therapy).
The bacteriologic eradication and clinical success rates were similar between CIPRO XR and the control group. The eradication and clinical success rates and their corresponding 95% confidence intervals for the differences between rates (CIPRO XR minus control group) are given in Table 8:
Table 8: Bacteriological Eradication and Clinical Cure
Rates at the Test-of-Cure (TOC) Visit
|CIPRO XR 500 mg QD x 3 Days||CIPRO 250 mg BID x 3 Days|
|Per Protocol Patients4||199||223|
|Bacteriologic Eradication at TOC (n/N)1||188/199 (94.5%)||209/223 (93.7%)|
|CI [-3.5%, 5.1%]|
|Bacteriologic Eradication (by organism) at TOC (n/N)2|
|E. coli||156/160 (97.5%)||176/181 (97.2%)|
|E. faecalis||10/11 (90.9%)||17/21 (81%)|
|P. mirabilis||11/12 (91.7%)||7/7 (100%)|
|S. saprophyticus||6/7 (85.7%)||9/9 (100%)|
|Clinical Response at TOC (n/N)3||189/199 (95%)||204/223 (91.5%)|
|CI [-1.1%, 8.1%]|
|1 n/N = patients with baseline organism(s) eradicated and no
new infections or superinfections/ total number of patients
2 n/N = patients with specified baseline organism eradicated/patients with specified baseline organism
3 n/N = patients with clinical success /total number of patients
4 The presence of a pathogen at a level of ≥ 105 CFU/mL was required for microbiological evaluability criteria, except for S. saprophyticus ( ≥ 104 CFU/mL).
Complicated Urinary Tract Infections And Acute Uncomplicated Pyelonephritis
CIPRO XR was evaluated for the treatment of cUTI and acute uncomplicated pyelonephritis (AUP) in a randomized, double-blind, controlled clinical trial conducted in the US and Canada. The study enrolled 1,042 patients (521 patients per treatment arm) and compared CIPRO XR (1000 mg once daily for 7 to 14 days) with immediate-release ciprofloxacin (500 mg BID for 7 to 14 days). The primary efficacy endpoint for this trial was bacteriologic eradication of the baseline organism(s) with no new infection or superinfection at 5 to 11 days post-therapy (test-of-cure or TOC) for the Per Protocol and Modified Intent-To-Treat (MITT) populations.
The Per Protocol population was defined as patients with a diagnosis of cUTI or AUP, a causative organism(s) at baseline present at ≥ 105 CFU/mL, no inclusion criteria violation, a valid test-of-cure urine culture within the TOC window, an organism susceptible to study drug, no premature discontinuation or loss to follow-up, and compliance with the dosage regimen (among other criteria). More patients in the CIPRO XR arm than in the control arm were excluded from the Per Protocol population and this should be considered in the interpretation of the study results. Reasons for exclusion with the greatest discrepancy between the two arms were no valid test-of-cure urine culture, an organism resistant to the study drug, and premature discontinuation due to adverse events.
An analysi of all patients with a causative organism(s) isolated at baseline and who received study medication, defined as the MITT population, included 342 patients in the CIPRO XR arm and 324 patients in the control arm. Patients with missing responses were counted as failures in this analysis. In the MITT analysisofcUTIpatients,bacteriologic eradicationwas 160/271 (59%) versus 156/248 (62.9%) in CIPRO XR and control arm, respectively [97.5% CI* (-13.5%, 5.7%)]. Clinical cure was 184/271 (67.9%) for CIPRO XR and 182/248 (73.4%) for control arm, respectively [97.5% CI* (-14.4%, 3.5%)]. Bacterial eradication in the MITT analysis of patients with AUP at TOC was 47/71 (66.2%) and 58/76 (76.3%) for CIPRO XR and control arm, respectively [97.5% CI* (-26.8%, 6.5%)]. Clinical cure at TOC was 50/71 (70.4%) for CIPRO XR and 58/76 (76.3%) for the control arm [97.5% CI* (-22.0%, 10.4%)].
* confidence interval of the difference in rates (CIPRO XR minus control).
In the Per Protocol population, the differences between CIPRO XR and the control arm in bacteriologic eradication rates at the TOC visit were not consistent between AUP and cUTI patients. The bacteriologic eradication rate for cUTI patients was higher in the CIPRO XR arm than in the control arm. For AUP patients, the bacteriologic eradication rate was lower in the CIPRO XR arm than in the control arm. This inconsistency was not observed between the two treatment groups for clinical cure rates. Clinical cure rates were 96.1% (198/206) and 92.1% (211/229) for CIPRO XR and the control arm, respectively [difference: 4.0% with a two-sided 97.5% CI (-1.3%, 9.4%)].
The bacterial eradication and clinical cure rates by infection type for CIPRO XR and the control arm at the TOC visit and their corresponding 97.5% confidence intervals for the differences between rates (CIPRO XR minus control arm) are given in Table 9 for the Per Protocol population analysis.
Table 9: Bacteriological
Eradication and Clinical Cure Rates at the Test-of-Cure (TOC) Visit
|CIPRO XR 1000 mg QD||CIPRO 500 mg BID|
|Per Protocol Patients1||206||229|
|Bacteriologic Eradication at TOC (n/N)2||148/166 (89.2%)||144/177 (81.4%)|
|CI [-0.7%, 16.3%]|
|Bacteriologic Eradication (by organism) at TOC (n/N)3|
|E. coli||91/94 (96.8%)||90/92 (97.8%)|
|K. pneumoniae||20/21 (95.2%)||19/23 (82.6%)|
|E. faecalis||17/17 (100%)||14/21 (66.7%)|
|P. mirabilis||11/12 (91.6%)||10/10 (100%)|
|P. aeruginosa||3/3 (100%)||3/3 (100%)|
|Clinical Cure at TOC (n/N)4||159/166 (95.8%)||161/177 (91.0%)|
|CI [-1.1%, 10.8%]|
|Bacteriologic Eradication at TOC (n/N)2||35/40 (87.5%)||51/52 (98.1%)|
|CI [-34.8%, 6.2%]|
|Bacteriologic Eradication of E. coli||35/36 (97.2%)||41/41 (100%)|
|Clinical Cure at TOC (n/N) 4||39/40 (97.5%)||50/52 (96.2%)|
|CI [-15.3%, 21.1%]|
|1 Patients excluded from the Per Protocol population
were primarily those with no causative organism(s) at baseline or no organism
present at ≥ 105 CFU/mL at baseline, inclusion criteria violation, no
valid test-of-cure urine culture within the TOC window, an organism resistant
to study drug, premature discontinuation due to an adverse event, lost to
follow-up, or noncompliance with dosage regimen (among other criteria).
2 n/N = patients with baseline organism(s) eradicated and no new infections or superinfections/total number of patients
3 n/N = patients with specified baseline organism eradicated/patients with specified baseline organism
4 n/N = patients with clinical success /total number of patients
Of the 166 cUTI patients treated with CIPRO XR, 148 (89%) had the causative organism(s) eradicated, 8 (5%) had persistence, 5 (3%) patients developed superinfections and 5 (3%) developed new infections. Of the 177 cUTI patients treated in the control arm, 144 (81%) had the causative organism(s) eradicated, 16 (9%) patients had persistence, 3 (2%) developed superinfections and 14 (8%) developed new infections. Of the 40 patients with AUP treated with CIPRO XR, 35 (87.5%) had the causative organism(s) eradicated, 2 (5%) patients had persistence and 3 (7.5%) developed new infections. Of the 5 CIPRO XR AUP patients without eradication at TOC, 4 were considered clinical cures and did not receive alternative antibiotic therapy. Of the 52 patients with AUP treated in the control arm, 51 (98%) had the causative organism(s) eradicated. One patient (2%) had persistence.
1. Clinical and Laboratory Standards Institute, Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard–9th Edition. CLSI Document M7-A9 . Clinical and Laboratory Standards Institute , 950 West Valley Rd., Suite 2500, Wayne, PA. PA. 19087-1898
2. Clinical and Laboratory Standards Institute (CLSI), Performance Standards for Antimicrobial Disk Susceptibility Tests; Approved Standard–11th Edition. CLSI Document M2-A11. Clinical and Laboratory Standards Institute, 950 West Valley Rd., Suite 2500, Wayne, PA. 19087-1898.
3. Clinical and Laboratory Standards Institute (CLSI). Performance Standards for Antimicrobial Susceptibility Testing; 24th Informational Supplement. CLSI Document M100 S24 . Clinical and Laboratory Standards Institute, 950 West Valley Rd., Suite 2500, Wayne, PA. 19087-1898.
Last reviewed on RxList: 1/31/2017
This monograph has been modified to include the generic and brand name in many instances.
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