Evaluation of the appropriate use of commonly prescribed fluoroquinolones and the risk of dysglycemia

Figures & data

Table 1 Summary of fluoroquinolone indications encountered in the study

Community-acquired pneumonia

Hospital-acquired pneumonia/ventilator-associated pneumonia

Chronic obstructive pulmonary disease exacerbation

Diabetic foot infection

Skin and soft tissue infection

Intra-abdominal infection

Urinary tract infection

Prophylaxis for transurethral resection of bladder tumor

Prophylaxis for endoscopic retrograde cholangiopancreatography

Table 2 Baseline characteristics of the study population (N=118)

Characteristics	Percentage
Demographic and medical characteristics
Female sex	37.3%
Male sex	62.7%
Mean female age	61 years
Mean male age	64 years
Renal impairment	29.7%
Diabetic	14.0%
Nondiabetic	86.0%
Drug therapy
Steroids	32.2%
Insulin therapy	11.0%
Oral antidiabetic agents	5.1%
Combination
Steroids + oral antidiabetic	4.2%
Steroids + insulin	2.5%
Steroids + insulin + oral antidiabetic	0.8%
Baseline blood glucose level*
Normal	51.8%
Hyperglycemia	47.1%
Hypoglycemia	1.1%

Note:

* Baseline blood glucose level was monitored in only 21.2% of the patients.

Abbreviation: N, total number.

Table 3 Microorganisms isolated in positive cultures during the study

Gram-positive

Staphylococcus spp.

Streptococcus spp.

Enterococcus spp.

Gram-negative

Pseudomonas spp.

Serratia spp.

Escherichia coli

Klebsiella spp.

Extended spectrum beta-lactamase (E. coli, Klebsiella spp.)

Proteus spp.

Acinetobacter spp.

Citrobacter spp.

Morganella spp.

Alcaligenes xylosoxidans

Anaerobes

Candida spp.

Table 4 Summary of the results of fluoroquinolone indications

Fluoroquinolone	Indication
	Appropriate	Inappropriate
Ciprofloxacin	96.6%	3.4%
Levofloxacin	94.0%	6.0%
Moxifloxacin	66.7%	33.3%
Weighted average percentage	93.2%	6.8%

Note: The final weighted average percentage of the appropriate indication for fluoroquinolones is 93.2%.

Table 5 Fluoroquinolone doses in different indications

Fluoroquinolone	Dose
	Appropriate (n)	Inappropriate (n)
Ciprofloxacin
CAP	1	0
HAP/VAP	1	0
Diabetic foot infection	10	2
SSTI	5	1
Prophylaxis for TURBT	10	1
Prophylaxis for ERCP	5	0
IAI	3	0
UTI	2	8
Others	10	0
Levofloxacin
CAP	28	15
COPD exacerbation	4	1
IAI	0	1
Others	0	1
Moxifloxacin
CAP	3	0
HAP/VAP	1	0
COPD exacerbation	2	0
UTI	1	0
Others	2	0

Abbreviations: n, number of patients; CAP, community-acquired pneumonia; COPD, chronic obstructive pulmonary disease; HAP, hospital-acquired pneumonia; VAP, ventilator-associated pneumonia; SSTI, skin and soft tissue infection; TURBT, transurethral resection of bladder tumor; ERCP, endoscopic retrograde cholangiopancreatography; UTI, urinary tract infection; IAI, intra-abdominal infection.

Table 6 Summary of the doses of fluoroquinolone therapy

Fluoroquinolone	Dose
	Appropriate	Inappropriate
Ciprofloxacin	79.7%	20.3%
Levofloxacin	64.0%	36.0%
Moxifloxacin	100.0%	0.0%
Weighted average percentage	74.6%	25.4%

Note: The final weighted average percentage of the appropriate dose of fluoroquinolones is 74.6%.

Table 7 Summary of patients with renal impairment

Fluoroquinolone	Number of patients with renal impairment	Inappropriate dose adjustment (%)
Ciprofloxacin	18	44.4
Levofloxacin	14	85.7
Moxifloxacin	3	No need for dose adjustment

Table 8 Summary of the duration of fluoroquinolone therapy

Fluoroquinolone	Duration
	Appropriate	Inappropriate
Ciprofloxacin	52.5%	47.5%
Levofloxacin	60.0%	40.0%
Moxifloxacin	77.8%	22.2%
Weighted average percentage	57.6%	42.4%

Note: The final weighted average percentage of the appropriate duration of fluoroquinolone therapy is 57.6%.

Table 9 Incidence of dysglycemia in diabetic and nondiabetic patients

Fluoroquinolone	Patients developing dysglycemia	Diabetics
		Yes	No
Ciprofloxacin	50.0%	28.8%	71.2%
Levofloxacin	42.4%	24.0%	76.0%
Moxifloxacin	7.6%	33.3%	66.7%

Table 10 Blood glucose level monitoring

Fluoroquinolone	Glucose monitoring		Baseline
	Yes	No	Yes			No
			Normal	Hyperglycemia	Hypoglycemia
Ciprofloxacin	49.2%	50.8%	13.6%	22.0%	1.7%	62.7%
Levofloxacin	90.0%	10.0%	16.0%	14.0%	0.0%	70.0%
Moxifloxacin	77.8%	22.2%	22.2%	11.1%	0.0%	66.7%

Table 11 Dysglycemia with fluoroquinolone therapy

Fluoroquinolone	Dysglycemia
	Yes		No
	Hyperglycemia	Hypoglycemia
Ciprofloxacin	39.0%	0.0%	61.0%
Levofloxacin	70.0%	6.0%	24.0%
Moxifloxacin	33.3%	11.1%	55.6%

Table S1 Ciprofloxacin oral dosage

Ciprofloxacin (FDA-approved indication)	Severity	PO dose (adult)	Frequency	Duration
UTI	Acute uncomplicated	250 mg	q 12 h	3 days
	Mild/moderate	250 mg	q 12 h	7–14 days
	Severe/complicated	500 mg	q 12 h	7–14 days
Chronic prostatitis	Mild/moderate	500 mg	q 12 h	28 days
Acute sinusitis	Mild/moderate	500 mg	q 12 h	10 days
Lower RTI	Mild/moderate	500 mg	q 12 h	7–14 days
	Severe/complicated	750 mg	q 12 h	7–14 days
SSTI	Mild/moderate	500 mg	q 12 h	7–14 days
	Severe/complicated	750 mg	q 12 h	7–14 days
Bone and joints	Mild/moderate	500 mg	q 12 h	4–6 weeks
	Severe/complicated	750 mg	q 12 h	4–6 weeks
Infectious diarrhea	Mild/moderate/severe	500 mg	q 12 h	5–7 days
Typhoid fever	Mild/moderate	500 mg	q 12 h	10 days
Intra-abdominal	Complicated	500 mg	q 12 h	7–14 days
Neisseria gonorrhoeae	Uncomplicated	250 mg	Single dose	Single dose

Notes: Ciprofloxacin should be used as 400 mg IV q 8 h or 750 mg PO q 12 h for febrile neutropenia and nosocomial pneumonia for patients with normal kidney function.

Abbreviations: FDA, United States Food and Drug Administration; PO, per os; UTI, urinary tract infection; q 12 h, every 12 hours; RTI, respiratory tract infection; SSTI, skin and soft tissue infection; IV, intravenous; q 8 h, every 8 hours.

Table S2 Ciprofloxacin equivalent AUC dosing regimen

Ciprofloxacin oral dosage	Equivalent ciprofloxacin IV dosage
250 mg tablet q 12 h	200 mg IV q 12 h
500 mg tablet q 12 h	400 mg IV q 12 h
750 mg tablet q 12 h	400 mg IV q 8 h

Abbreviations: AUC, area under the curve; IV, intravenous; q 12 h, every 12 hours; q 8 h, every 8 hours.

Table S3 Adjustment of ciprofloxacin dose in renal impairment

CrCl 25–49 mL/minute	200–400 mg IV q 12 h
	250–500 mg PO q 12 h
CrCl <25 mL/minute	200 mg IV q 12 h
	250–500 mg PO q 24 h
Hemodialysis	250–500 mg PO q 24 h (after dialysis)

Abbreviations: CrCl, creatinine clearance; IV, intravenous; q 12 h, every 12 hours; PO, per os; q 24 h, every 24 hours.

Table S4 Levofloxacin oral/IV dosage

Levofloxacin (FDA-approved indication)	PO/IV dose (adult)	Frequency	Duration
AECB	500 mg	q 24 h	7 days
	750 mg	q 24 h	5 days
CAP	500 mg	q 24 h	7–14 days
	750 mg	q 24 h	5 days
Sinusitis	500 mg	q 24 h	10–14 days
	750 mg	q 24 h	5 days
HAP	750 mg	q 24 h	7–14 days
Uncomplicated SSTI	500 mg	q 24 h	7–10 days
Complicated SSTI	750 mg	q 24 h	7–14 days
Chronic prostatitis	500 mg	q 24 h	28 days
Complicated UTI	250 mg	q 24 h	10 days
	750 mg	q 24 h	5 days
Acute pyelonephritis	250 mg	q 24 h	10 days
	750 mg	q 24 h	5 days
Uncomplicated UTI	250 mg	q 24 h	3 days

Abbreviations: FDA, United states Food and Drug administration; PO, per os; IV, intravenous; AECB, acute exacerbations of chronic bronchitis; q 24 h, every 24 hours; CAP, community-acquired pneumonia; HAP, hospital-acquired pneumonia; SSTI, skin and soft tissue infection; UTI, urinary tract infection.

Table S5 Adjustment of levofloxacin dose in renal impairment

Acute sinusitis, AECB, CAP, uncomplicated SSTI, chronic bacterial prostatitis
CrCl >50 mL/minute	No dosage adjustment required
CrCl 20–49 mL/minute	500 mg then 250 mg q 24 h
CrCl 10–19 mL/minute	500 mg then 250 mg q 48 h
hemodialysis	500 mg then 250 mg q 48 h
Complicated SSTI, nosocomial pneumonia
CrCl 20–49 mL/minute	750 mg q 48 h
CrCl 10–19 mL/minute	500 mg q 48 h

Abbreviations: AECB, acute exacerbations of chronic bronchitis; CAP, community-acquired pneumonia; SSTI, skin and soft tissue infection; CrCl, creatinine clearance; q 24 h, every 24 hours; q 48 h, every 48 hours.

Table S6 Moxifloxacin oral/IV dosage

Moxifloxacin (FDA-approved indication)	PO/IV dose (adult)	Frequency	Duration
Acute bacterial sinusitis	400 mg	q 24 h	10 days
AECB	400 mg	q 24 h	5 days
CAP	400 mg	q 24 h	10 days
Uncomplicated SSTI	400 mg	q 24 h	7 days
Complicated SSTI	400 mg	q 24 h	7–21 days
Complicated intra-abdominal infections	400 mg	q 24 h	5–14 days

Abbreviations: FDA, United States Food and Drug Administration; AECB, acute exacerbations of chronic bronchitis; CAP, community-acquired pneumonia; SSTI, skin and soft tissue infection; q 24 h, every 24 hours.