Jurnal Ipd 7
Jurnal Ipd 7
Levofloxacin in the
treatment of community-
acquired pneumonia
Expert Rev. Anti Infect. Ther. 8(5), 505–514 (2010)
Ayman M Noreddin†1 Levofloxacin is a fluoroquinolone that has a broad spectrum of activity against several causative
and Walid F Elkhatib2,3 bacterial pathogens of community-acquired pneumonia (CAP). The efficacy and tolerability of
1
Department of Pharmacy Practice,
levofloxacin 500 mg once daily for 10 days in patients with CAP are well established. Furthermore,
School of Pharmacy, Hampton a high-dose (750 mg), short-course (5 days) of once-daily levofloxacin has been approved for
University, Hampton, VA 23668, USA use in the USA in the treatment of CAP, acute bacterial sinusitis, acute pyelonephritis and
2
Department of Pharmacy Practice and complicated urinary tract infections. Levofloxacin can be used as a monotherapy in patients
Pharmaceutical Sciences, College of
Pharmacy, University of Minnesota with CAP, however, levofloxacin combination therapy with anti-pseudomonal b-lactam (or
Duluth, 1110 Kirby Dr. Life Science aminoglycoside) should be considered if Pseudomonas aeruginosa is the causative pathogen of
232, Duluth, MN 55812, USA the respiratory infection. The high-dose, short-course levofloxacin regimen maximizes its
3
Department of Microbiology and concentration-dependent antibacterial activity, decreases the potential for drug resistance and
Immunology, Faculty of Pharmacy,
Ain-Shams University, African Union has better patient compliance. Oral levofloxacin is rapidly absorbed and is bioequivalent to the
Organization, Abbassia, Cairo intravenous formulation and the patients can switch between these formulations, which results
P.O.B.: 11566, Egypt in more options with respect to the therapeutic regimens. Furthermore, levofloxacin is generally
†
Author for correspondence: well tolerated, has good tissue penetration and adequate concentrations can be maintained at
Tel.: +1 757 728 6690
Fax: +1 757 727 5840 the site of infections.
[email protected]
Keywords : community-acquired pneumonia • fluoroquinolones • levofloxacin • pharmacodynamics
• pharmacokinetics • therapeutic use • tolerability
worldwide for more than a decade [26] . Furthermore, increasing Pharmacodynamic properties
rates of antibiotic resistance (most notably, penicillin, cepha- Spectrum of activity
losporin and macrolide resistance) observed in bacteria that Levofloxacin is the l-isomer of the racemic fluoroquinolone
commonly cause CAP have resulted in increased treatment ofloxacin [39,41] . Topoisomerase IV is the main target for levo-
failures and inferior clinical outcomes for many patients with floxacin in Gram-positive bacteria and DNA gyrase (topoisomer-
CAP [14,15,27–30] . Although there are reports of the emergence of ase II) is the target for Gram-negative bacteria [42] . Levofloxacin
resistance to some fluoroquinolones among S. pneumoniae [26] , has a broad spectrum of antibacterial activity that involves several
the incidence of levofloxacin-resistant organisms has remained Gram-positive and Gram-negative aerobes and atypical bacteria.
steady with levofloxacin resistance rates in S. pneumoniae of The MIC of levofloxacin required to inhibit the growth of 90%
approximately less than 1% worldwide [31–35] . of clinical isolates (MIC90) is used to assess the in vitro activity of
The chemical name of levofloxacin is S-9-fluoro-2,3-dihydro- levofloxacin. The levofloxacin MIC breakpoints for S. pneumoniae
3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1, 2, tested were obtained from the Clinical and Laboratory Standards
3-de]-1, 4-benzoxazine-6-carboxylic acid hemihydrate with the Institute and they were 2 mg/l or less (susceptible), 4 mg/l (inter-
empirical formula C18H20FN3O4 ·½ H2O (Figure 1) . Levofloxacin mediate) and 8 mg/l or more (resistant) [41,43] . It generally also has
is a light yellowish-white crystal or crystalline powder and its high in vitro activity against S. pneumoniae (including penicillin-
molecular weight is 370.38. It interferes with critical processes susceptible, -intermediate and -resistant strains), which are com-
in the bacterial cell, such as DNA replication, transcription, monly causative in CAP. However, the activity of levofloxacin
repair and recombination, by inhibiting type II topoisomerases. is variable against S. aureus and Enterococcus faecalis [41] . The
Human cells lack these topoisomerases, but they are essential for levofloxacin MIC90 for penicillin-susceptible, -intermediate and
bacterial DNA replication, thereby allowing these agents to be -resistant isolates of S. pneumoniae was 1 mg/l in different studies
specific for bacterial cells. DNA topoisomerases are responsible and greater than 97% of the tested isolates were susceptible to the
for separating the strands of duplex bacterial DNA, inserting drug [31–34,38,44] . Furthermore, levofloxacin generally appears to
another strand of DNA through the break, and then resealing the retain its activity against strains of S. pneumoniae that are resistant
originally separated strands [36,37] . Levofloxacin is active against to penicillin plus macrolides [32] .
a broad range of Gram-positive, Gram-negative and atypical Levofloxacin has variable activity against S. aureus. Depending
bacteria that may be causative pathogens in community-acquired on methicillin susceptibility, levofloxacin had MIC90 values of
and nosocomial infections. Levofloxacin is a well-established 0.25–4.0 mg/l against methicillin-susceptible S. aureus (MSSA)
treatment option for respiratory and urinary tract infections isolates, whereas methicillin-resistant S. aureus isolates exhibited
(UTIs), particularly since levofloxacin is active against some levofloxacin resistance with MIC90 values of greater than 4 to
penicillin- and macrolide-resistant species, such as S. pneumoniae 64 mg/l or more [38,44–46] . The in vitro activity of levofloxacin
(the most common causative pathogen for community-acquired against E. faecalis was limited (MIC90 of 8 to 32 mg/l or more in
respiratory infections) [31–34,38,39] , and the incidence of penicil- vancomycin-susceptible and -resistant strains). Although levo-
lin- and macrolide-resistance in many species is both high and floxacin has limited activity against coagulase-negative staphy-
widespread [40] . In the USA, a high-dose, short-course regimen lococci (>4 mg/l; 54.1%) [45] , it has demonstrated good in vitro
of levofloxacin (750 mg once daily for 5 days) is approved for the activity against a range of other Gram-positive bacteria, such as
treatment of adults with CAP, acute bacterial sinusitis (ABS), Streptococcus pyogenes (1 mg/l; 99.9%) [32,33] and b-hemolytic
complicated UTI and acute pyelonephritis (AP). The use of levo- streptococci (0.5–1 mg/l; 99.1–100%) [47] .
floxacin, including some data on the high-dose, short-course Generally, levofloxacin has good in vitro activity against
treatment regimen, has been reviewed previously [39] . This review Gram-negative bacteria including the common respiratory tract
focuses on the pharmacology of levofloxacin in the treatment pathogens H. influenzae [31–35,38,44,48–50] , H. parainfluenzae [50]
of CAP. and M. catarrhalis [31,35,44,48–50] , as well as different urinary
tract pathogens (K. pneumoniae [38,44,51] , Enterobacter cloacae
O [38,44,51–53] and Proteus mirabilis [38,45,48]). The MIC90 values for
levofloxacin against isolates of H. influenzae, H. parainfluenzae
F COOH and M. catarrhalis were 0.06 mg/l or less and it had approximately
100% susceptibility rates. Levofloxacin was also highly active
• ½H2O against b-lactamase-negative and -positive isolates of H. influ
N N enzae [31–34,38] and M. catarrhalis [31,44,48–50,54,55] . On the other
hand, the activity of levofloxacin is variable against the urinary
N O CH3 tract pathogen Escherichia coli and P. aeruginosa. The MIC90 of
H3C
levofloxacin against E. coli ranged from 0.06 mg/l or less (suscep-
H tible) to greater than 8 mg/l (resistant) [38,44,45,51,56] . Levofloxacin
showed a lower level of activity against isolates of P. aeruginosa,
with MIC90 values ranging from 0.5 to 64 mg/l and the suscepti-
Figure 1. Levofloxacin.
bility rates were 71–94% [38,44,45,48,51] . It also had limited activity
www.expert-reviews.com 507
Drug Profile Noreddin & Elkhatib
8.6 mg/l for oral administration [41,76] , and levofloxacin steady- in patients with impaired renal function (creatinine clearance
state conditions were reached within 48 h of initiating once-daily [CLCR] 50 ml/min), therefore dosage adjustment is required to
intravenous or oral 750 mg doses [41] . After oral administration, avoid drug accumulation as shown in Table 1 [41] . Furthermore,
the Tmax of levofloxacin is reached within 1–2 h, and the absolute levofloxacin is not cleared effectively by hemodialysis or con-
bioavailability of oral levofloxacin 500 and 750 mg is approximately tinuous ambulatory peritoneal dialysis [39,41] . The pharmacoki-
99% [41,75,76] . Systemic exposure to levofloxacin was similar for the netic properties of levofloxacin are not influenced by age, gender
intravenous and oral formulations upon administering equal doses or race, and they do not show noticeable differences between
of levofloxacin [41] and the AUC24 was 103 [75] and 90.7 mg/h/l healthy adults and patients with HIV [39] , or patients with seri-
[76] at steady state after intravenous or oral administ ration of ous community-acquired bacterial infections [41] . Levofloxacin
levofloxacin 750 mg once daily, respectively. pharmacokinetics in hepatically impaired patients have not been
The in vitro studies revealed that 24–38% of levofloxacin was investigated; however, because of the limited hepatic metabolism
bound to plasma proteins (mainly to serum albumin in humans) of levofloxacin, hepatic impairment may not have a prominent
and the binding was independent of levofloxacin concentration effect on the drug pharmacokinetics [41] .
[41] . The volumes of distribution obtained in the pharmacokinetic
studies are within the range of 74–112 l after single or multiple Clinical efficacy
doses of levofloxacin 500 or 750 mg [75,76] . Levofloxacin is dis- The efficacy of levofloxacin 750 mg once daily (intravenous and
tributed extensively in tissues and fluids throughout the body oral) for 5 days in adults with CAP [66] , ABS [85] and compli
and accumulates in phagoc ytic cells [39] . Furthermore, the mean cated UTI [86,87] has been assessed in a number of randomized,
concentrations of levofloxacin in tissues and fluids in the lungs, double-blind, multicentre, noninferiority trials [66,85–87] . The end
ELF, alveolar macrophages, polymorphonuclear leukocytes, points were the clinical success rate (proportion of patients show-
paranasal sinus mucosa and urine surpass the concentration of ing either a clinical cure or improvement with no need for further
levofloxacin in the plasma [39,77–83] . It has been reported that the antimicrobial therapies in both situations) 1–2 weeks after the end
paranasal sinuses mucosa:plasma concentration ratio was 2.56 of treatment [66] or at 2–3 weeks of the study [85] , or the micro-
at Tmax after a single 500 mg oral dose of levofloxacin and the biological eradication rate (all pathogens identified in samples at
concentration of levofloxacin in the paranasal sinuses mucosa the study entry were eradicated) at 2–3 weeks of the study [86,87] .
was generally higher than the MIC90 of the common causative Levofloxacin indications and dosing for patients with normal
pathogens for upper respiratory tract infections (0.008–2.0 mg/l), renal function are summarized in Table 2 .
including penicillin-susceptible, -intermediate and -resistant iso- Patients enrolled in the noninferiority trial in CAP were aged
lates of S. pneumoniae [82] . In healthy volunteers, oral levofloxacin 18 years or over and were diagnosed with mild-to-severe CAP.
(500 or 750 mg) had a mean ELF:plasma concentration ratio at Other inclusion criteria involved one or more signs or symp-
steady state of 1.16 using population pharmacokinetic modeling toms including fever, a white blood cell count of greater than
and 3.18 using Monte Carlo simulation [82] . With a lower dosage 10,000 cells/mm3, or hypothermia. The exclusion criteria involved
of levofloxacin (500 mg once daily for 3 days), Cmax and AUC24 patients without a confirmed diagnosis of CAP, patients who had
values for the drug were significantly higher (p < 0.01) in the no follow-up visit, patients who increased (>120%) or reduced
polymorphonuclear leukocytes than in plasma [84] . On the other
hand, the concentrations of levofloxacin in the ELFs and alveolar Table 1. Dosing in patients with diminished
macrophages were 1.5–6-fold higher than that in the plasma at renal function.
steady state after receiving levofloxacin 500 mg once daily for
5 days in older patients undergoing diagnostic bronchoscopy with Renal status Initial dose (mg) Subsequent
dose
a mean age of 62 years [80] .
Levofloxacin is mainly eliminated through the kidneys, with CLCR ≥50 ml/min 500 500 mg q24h
75–87% of the dose excreted unchanged in the urine within CLCR 20–49 ml/min 500 250 mg q24h
48–72 h of administering oral levofloxacin 500 or 750 mg,
CLCR 10–19 ml/min 500 250 mg q48h
and less than 4% is excreted in the feces [41,75,76] . After a sin-
gle dose of levofloxacin 750 mg, the mean drug concentration Hemodialysis 500 250 mg q48h
in the urine was 475 mg/l at 4 h and 186 mg/l at 24 h [77] , CAPD 500 250 mg q48h
and less than 5% of the dose is excreted in the urine as inactive
CLCR ≥50 ml/min 750 750 mg q24h
metabolites of levofloxacin [41] . The mean total body clearance
(CL) of levofloxacin in healthy volunteers was 8–9.4 l/h [75,76] CLCR 20–49 ml/min 750 750 mg q48h
and approximately 8.6–13.6 l/h [41] . Levofloxacin also appears CLCR 10–19 ml/min 750 500 mg q48h
to undergo glomerular filtration as well as tubular secretion [41] .
Hemodialysis 750 500 mg q48h
After single or multiple doses of oral or intravenous levofloxacin
750 mg, the mean terminal plasma elimination half-life (t1/2b) CAPD 750 500 mg q48h
is 7.5–8.8 h in the pharmacokinetic studies [75,76] . On the other CAPD: Chronic ambulatory peritoneal dialysis; CLCR : Creatinine clearance;
q24h: Every 24 h; q48h: Every 48 h.
hand, the t1/2b of levofloxacin is increased and the CL reduced
(<80%) the scheduled doses, and patients who had combination versus 85.7% and 100 versus 90%, respectively [66] . Retrospective
therapy with levofloxacin [66] . Patients with mild-to-severe CAP
analysis revealed that the clinical success rates in the patients with
received levofloxacin 750 mg (intravenous or oral) once daily for
CAP caused by the typical pathogens H. influenzae, H. parainflu
5 days or 500 mg once daily for 10 days and those receiving the enzae or S. pneumoniae were also similar between the levofloxacin
higher dosage of levofloxacin were given a placebo for the last 750 and 500 mg treatment groups (92.3 vs 92.9%, 100 vs 90%
5 days of the 10-day treatment regimen [66] . Susceptibility test-
and 90.9 vs 90%, respectively) [66] .
ing of the causative pathogens to levofloxacin was carried out but The efficacy of the high-dose, short-course of levofloxacin in
initial treatment was empirical. The noninferiority of levofloxacin
achieving early resolution of symptoms has been studied [90] ,
750 mg once daily for 5 days to levofloxacin 500 mg once daily and the results revealed that the resolution of purulent sputum,
for 10 days was established if the upper limit of the two-sided shortness of breath, chills and cough were 40.6 versus 30.7%,
95% confidence interval for the between-group difference in the 35.1 versus 27.7%, 54.8 versus 54.2% and 10 versus 10.1% of
clinical success rate was less than 15% (if both treatment groups
patients who received the levofloxacin 750 or 500 mg regimen,
had a clinical success rate of 80–90%) or less than 10% (if bothrespectively. Furthermore, 99.4% of the 158 pathogens isolated
treatment groups had a clinical success rate of ≥90%) [66] . Theat study entry were susceptible to levofloxacin and there was no
results revealed that levofloxacin 750 mg once daily for 5 days significant difference between treatment groups in the time of
was at least as effective as 500 mg once daily for 10 days in the
switching from the intravenous administration of levofloxacin
treatment of mild-to-severe CAP in the overall patient population
to the oral administration of the drug [90] . The high-dose, short-
[66] , as well as in patients with CAP caused by atypical organ-course of levofloxacin (750 mg once daily for 5 days) also had
isms (C. pneumoniae and/or M. pneumoniae) [88] , and for elderlygood efficacy in the subgroup of patients with severe CAP with
patients aged 65 years or older [89] . high clinical success rates of more than 85%. Moreover, high
In patients receiving either the levofloxacin 750 or 500 mg regi-
microbiological response rates (≥87.5%) were observed in the
men, the baseline characteristics were similar overall microbio
subgroup of microbiologically evaluable patients receiving lev-
logical eradication rates in both groups receiving levofloxacin [66] .
ofloxacin regardless of the treatment regimen [91] . In the same
The eradication rates were high in subgroups of microbiologically
study, the microbiological eradication was observed in 88.2% of
evaluable patients infected with aerobic Gram-positive (82.8 vs typical pathogens identified from respiratory cultures and 90% of
85.3%) and Gram-negative (96.2 vs 90.7%) pathogens, as well atypical pathogens identified by serological methods [91] .
as other pathogens (93.8 vs 96.2%), when patients received levo- It has been reported that levofloxacin 750 mg once daily for
floxacin 750 mg once daily for 5 days or levofloxacin 500 mg 5 days had good efficacy in patients with CAP caused by atypical
once daily for 10 days. Similar results were obtained with atypi
organisms [88] . The overall clinical success rate 1–2 weeks after
cal pathogens and typical pathogens, where eradication rates treating patients with CAP caused by only one atypical path
for S. pneumoniae, H. influenzae and H. parainfluenzae in the ogen with levofloxacin was more than 95% and the noninferiority
corresponding post-therapy visit were 86.4 versus 85%, 92.3 of levofloxacin 750 mg once daily for 5 days as compared with
the 10‑day regimen was also established in
Table 2. Levofloxacin indications and dosing for patients with normal this study. The overall clinical success rate
renal function†. was 94.8% for patients with CAP caused
Type of infection Dose (mg) Duration (days) by atypical pathogens receiving the levo-
floxacin 750 mg regimen as compared with
Community-acquired pneumonia 500 7–14
96.5% for those receiving the levofloxacin
Community-acquired pneumonia 750 5 500 mg regimen [88] . Furthermore, the
Nosocomial pneumonia 750 7–14 clinical success rates at 1–2 weeks post-
treatment for patients with C. pneumoniae,
Acute bacterial exacerbation of chronic bronchitis 500 7–14
L. pneumophila and M. pneumoniae were
Acute bacterial sinusitis 500 10–14 comparable between the groups receiving
Acute bacterial sinusitis 750 5 the levofloxacin 750 and 500 mg dosing
regimen (90.9 vs 100%, 100 vs 100% and
Complicated skin and skin-structure infection 750 7–14
95.3 vs 94.4%, respectively) [88] .
Uncomplicated skin and skin-structure infection 500 7–10
Chronic bacterial prostatitis 500 28 Post-marketing surveillance
Acute pyelonephritis 250 10
Post-marketing data have demonstrated
that simultaneous levofloxacin admin-
Complicated urinary tract infection 250 10 istration with warfarin may increase the
Uncomplicated urinary tract infection 250 3 prothrombin time. Therefore, anticoagu-
Inhalation anthrax (postexposure) 500 60 lation and bleeding should be monitored
in patients receiving the two drugs con-
†
Frequency of dose: every 24 h.
comitantly [41] . Owing to the incidence of
www.expert-reviews.com 509
Drug Profile Noreddin & Elkhatib
musculoskeletal disorders, levofloxacin should not be adminis- Levofloxacin 750 mg once daily for 5 days is a well tolerated
tered to pediatric patients aged less than 18 years [41] . Like other fluoroquinolone for patients with CAP or UTIs [86,87,92] . In a
fluoroquinolones, levofloxacin decreases theophylline metabo- pooled analysis of patients with respiratory infections receiving
lism and dosage adjustment for theophylline may be essential for the levofloxacin 750 or 500 mg regimen, the results revealed that
concurrent administration of both drugs. On the other hand, 45.5 and 49% of patients, respectively, had adverse effects during
concomitant fluoroquinolone administration with ciclosporin has the therapy. The adverse effects in both dosage regimens included
shown elevated serum concentrations of ciclosporin but these nausea, vomiting, diarrhea, dyspepsia, constipation, abdomi-
alterations were not clinically significant [41] . nal pain, headache, insomnia and dizziness. The incidence of
levofloxacin-associated adverse effects was similar between both
Safety & tolerability treatment regimens (8 vs 7.6%) [92] .
Levofloxacin 750 mg once daily (intravenous and/or oral) for Photosensitivity reactions might be associated with the use
5 days is currently approved for the treatment of different infec- of fluoroquinolones after exposure to the sun or UV light [41] .
tions including CAP (caused by S. pneumoniae, H. influenzae, Fluoroquinolones can potentially prolong the QT interval but
H. parainfluenzae, M. pneumoniae and C. pneumoniae), ABS there were no cases of torsade de pointes in any clinical or post-
(caused by S. pneumoniae, H. influenzae and M. catarrhalis), marketing trials [41,92] . As with most other antibacterial agents,
complicated UTI (caused by E. coli, K. pneumoniae and Proteus levofloxacin was associated in some cases with C. difficile-related
mirabilis) and AP (caused by E. coli) in patients with normal diarrhea, which varied in severity from mild diarrhea to pseudo
renal function (CLCR : ≥50 ml/min) [41] . Depending on the membranous colitis [41] . Patients receiving levofloxacin and other
dose, intravenous levofloxacin must be administered slowly as quinolones may undergo tendon effects, including ruptures of
an infusion over a minimum period of 60–90 min. Levoflox the hand, Achilles tendon and shoulder [41] . The incidence of
acin tablets or oral solution are generally prescribed at a dosage drug-related adverse effects in patients with CAP or ABS was
of 250, 500 or 750 mg once daily and the tablet formulation of also similar between the levofloxacin 750 and 500 mg dosing
levofloxacin can be taken with or without food; however, the regimens [92] .
oral solution should be taken 1 h prior to or 2 h after meals.
In patients receiving levofloxacin, sufficient hydration should Regulatory affairs
be maintained to prevent highly concentrated urine from being Levofloxacin is approved for use in the USA, Canada and world-
formed. Levofloxacin should be administered at least 2 h apart wide in the treatment of CAP, ABS, complicated UTIs and AP.
from agents such as magnesium- or aluminium-containing ant- Surveillance programs undertaken in the USA, Canada and
acids, sucralfate, metal cations, zinc-containing multivitamins worldwide reveal that the rates of S. pneumoniae resistance to
or didanosine. Levofloxacin dosing of 750 mg once daily for levofloxacin was 1% or less. On the other hand, the rate of resist-
5 days in patients with impaired renal function requires the fol- ance to levofloxacin was 2.7% or less in penicillin-resistant iso-
lowing dosage adjustments: CLCR : 20–49 ml/min, 750 mg every lates of S. pneumoniae. Some reports have shown that the rate of
48 h; CLCR: 10–19 ml/min or patients on hemodialysis or chronic levofloxacin resistance in S. pneumoniae in the USA has decreased
ambulatory peritoneal dialysis, 750 mg initial dose then 500 mg between 2000 and 2006 [31,33,35,38,49] .
every 48 h. Owing to the limited metabolism of levofloxacin,
dosage adjustment is expected to be unnecessary in patients with Conclusion
reduced hepatic function [41] . The respiratory fluoroquinolones are considered as a substantial
Data from patients aged 65 years or over (Phase III clinical component of the anti-infective armamentarium for the man-
trials) demonstrated no difference between elderly and younger agement of respiratory infections. Levofloxacin is active against
patients with regard to the safety or effectiveness of levofloxacin, most respiratory pathogens and has a good clinical success rate.
although elderly patients may be more sensitive to levofloxacin, The favorable pharmacodynamic, safety, efficacy and tolerability
mainly due to the effect of the drug on the QT interval. Thus, profile, in addition to in vitro activity against the common respira-
caution is required with the simultaneous administration of levo- tory pathogens, make levofloxacin among the first-line agents for
floxacin with drugs that prolong the QT interval such as class IA the treatment of CAP.
or class III antiarrhythmics in this particular group. Furthermore,
caution is necessary with the use of levofloxacin in the elderly Expert commentary
due to the increased risk of severe tendon disorders in this group The guidelines from the Infectious Diseases Society of America/
of patients, particularly if they are receiving corticosteroids [41] . Americ an Thoracic Society recommend a respiratory fluo-
Blood glucose monitoring is recommended in patients with roquinolone (e.g., levofloxacin 750 mg) or a b-lactam plus a
diabetes mellitus receiving simultaneous hypoglycemic agents macrolide for the treatment of CAP. The use of fluoroquino
and/or insulin because symptomatic hyperglycemia and hypogly- lones is considered to be the primary therapy in the infections
cemia have been reported with levofloxacin administration [41] . caused by penicillin-susceptible S. pneumoniae, penicillin-resis
Concomitant administration of fluoroquinolones (including levo- tant S. pneumoniae, Legionella, H. influenzae, M. pneumoniae
floxacin) with NSAID may increase the risk of CNS stimulation and C. pneumoniae. Levofloxacin combination therapy with
and convulsive seizures [41] . anti-pseudomonal b-lact am (or aminoglycoside) should be
Key issues
• Community-acquired pneumonia (CAP) is one of the leading causes of death and ranks sixth in the overall cause of deaths in the USA.
• Levofloxacin is a valuable antimicrobial agent that has activity against a wide range of bacterial pathogens causing CAP.
• The efficacy of the high-dose (750 mg), short-course (once daily for 5 days) of levofloxacin in achieving early resolution of CAP
symptoms has been shown.
• The levels of levofloxacin-resistant organisms has remained steady with resistance rates less than 1% worldwide for
Streptococcus pneumoniae.
• Levofloxacin activity is concentration dependent and the common predictor of microbiological and clinical outcome is the
AUC:MIC ratio.
• Levofloxacin is distributed throughout the body and the concentration in other tissues can exceed that in the plasma from 2–4 h after
administration and its pharmacokinetics are not affected by age, gender or race.
• Levofloxacin is generally well tolerated in patients with respiratory or urinary tract infections and no clinically significant adverse events
that occurred were deemed to be drug related.
3 Loh LC, Khoo SK, Quah SY et al. 5 Gutierrez F, Masia M, Mirete C et al. The
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