Wydanie 1/2013
str. 22

Ocena skuteczności lewofloksacyny w leczeniu bakteryjnego zapalenia spojówek u niemowląt

Effectiveness of Levofloxacin Therapy in Bacterial Conjunctivitis in Infants

Szumiński Michał, Bakunowicz-Łazarczyk Alina, Sielicka Danuta

Department of Paediatric Ophthalmology with Strabismus Treatment Center of Medical University of Białystok,
Childrens University Hospital in Białystok
Head: Professor Alina Bakunowicz-Łazarczyk, M.D., Ph.D.

Summary: Aim: To evaluate bacteriology of mucopurulent discharge and response to monotherapy with 0.5% levofloxacin in conjunctivitis and congenital nasolacrimal duct obstruction in infants.
Patients and Methods: 154 samples from the conjunctival sac were obtained from 92 children with bacterial conjunctivitis, of which 35 also had nasolacrimal duct obstruction. The cultures were incubated and the infectious agents isolated. Children with simple conjunctivitis were treated with 0.5% levofloxacin Q2h for 2 days (except night hours) and then QID for 7 days. Control samples were taken 10 days after treatment initiation.
Results: Cultures were positive for bacteria from 140 samples (90.9%). 158 isolates of 9 different organisms were found. 140 Gram- -positive isolates were recovered, representing 88.6% of all isolates. The most common bacterial species was Streptococcus pneumonia, which accounted for 20.3% of all isolates. Gram-negative bacteria were recovered from 18 samples (11.4%). The predominant Gram- -negative bacterium was Hemophilus influenza. Monotherapy with levofloxacin was successful in 93.5%.
Conclusions: Bacterial conjunctivis, even associated with nasolacrimal duct obstruction can be managed with highest effectiveness with 0.5% levofloxacin.

Słowa kluczowe: bakteryjne zapalenie spojówek, lewofloksacyna, niemowlęta.

Keywords: bacterial conjunctivitis, levofloxacin, infants.


Conjunctivitis in small children is the most frequently caused by bacterial infection. Typically it presents with moderate to severe conjunctivitis and thick mucous-purulent discharge, which often is the most copious in the morning. Bacterial conjunctivitis in children the most frequently is caused by staphylococcal, streptococcal and Gram-negative bacilli (1). Conjunctivitis course can be acute, supraacute or chronic. Acute conjunctivitis at the begining is characterized by unilateral hyperaemia, epiphora, conjunctival oedema oraz muco-purulent discharge. When the infection is caused especially by streptococcus pseudo-membranes can be also present. Supra-acute conjunctivitis (e.g. neisserhia gonorrhoe infection in infants) is present with significant hemosis, and also palpebral oedema, and accumulation of copious, green-yellowish discharge in conjunctival sac. Frequently, coexisting periauricular lymph nodes enlargement is observed. Chronic conjunctivitis is often of recurrent characteristics with periodical exaccerbations. In newborns it can be associated with Chlamydia trachomatis infection, in adolescents and adults more often is coexisting with blepharitis of staphylococcal etiology.

Purpose
The aim of the paper is to evaluate etiology of the bacterial conjunctivitis in infants and efficacy of the treatment with 0.5% levofloxacin eyedrops.
Material and Methods
In 92 infants (females: males = 50: 42) with bacterial conjunctivitis (in 35 newborns with coexisting nasolactrimal duct obstruction) 154 samples from conjunctival sac were collected (after eyelid eversion) using thin, sterile swab with transportation medium. Material was referred to the laboratory within 15 minutes from samples collection. After 1–2 days long incubation bacterial isolates were cultured and then determined. Following samples collection 0.5% levofloxacine eyedrops treatment was reccommended. Dosage regimen consisted of 1 antibiotic drop administration to the conjunctival sac every 2 hours with night break for the first two days, and then QID for the following 7 days. Control samples were collected after 10 days from the treatment initiation.

Results
Positive cultures results were obtained in 140 (90.9%) of conjunctival sac samples. Among 158 isolates 6 different microorganisms were selected. In majority of cases conjunctivitis in infants were caused by Gram-positive bacteria (140 isolates – 88.6%), among which the most frequently isolated bacteria was Streptococcus pneumoniae, which consituted 58 of all isolates (36.7%). Gram-negative bacteria was detected in 18 isolates (11.4%). The most common bacteria in that group of pathogens was Hemophilus influenzae, which dominated in bacterial population red staining according to Gram’s method and constituted of 9.5% of all isolates. Bacterial conjunctivitis etiology in infants was shown on diagram (Fig. 1). Monotherapy using 0.5% levofloxacin was efficient in 86 children (93.5%).

Conclusions
Monotherapy with 0.5% levofloxacin in infants is highly effective in case of bacterial conjunctivitis – simple or associated with nasolacrimal duct obstruction.

Discussion
Our study proved, that local monotherapy with levofloxacin is highly effective, thus study results entitles us to ask the question, if that wideprofile antibiotic can be used as a treatment of choice in cases of bacterial conjunctivitis in infants?
Levofloxacin is fluoroquinolone antibiotic, L-isomer ofloxacin racemate. Its’ mechanism of action is associated with influence of DNA/ DNA gyraze complex. DNA gyraze inhibition (encoded by gyrA and gyrB genes) of Gram-negative bacteria and IV topoisomeraze (encoded by parC and parE genes) of Gram-positive bacteria cause DNA threads separation, which than makes replication, transcription and recombination of bacterial genetic material impossible
(2–4). Efficiency of general and local levofloxacin use in infections due Gram-positive and Gram-negative bacteria was confirmed in numerous clinical trials (5–7). The problem of levofloxacin resistance development possibility remains, mainly due to 2 main mechanisms. First resistance development mechanism is associated with mutations in resistance to quinolones region as a result of replication errors or gene transfer errors, detected in Streptoccocus pneumoniae and Streptoccocus viridans. Second mechanism consists of intra­cellular medicine concentration reduction, concerning mainly Gram-negative bacteria (8, 9).

What’s important, after many years of using that antibiotic in clinical practice, no significant changes in bacterial susceptibility responsible for conjuntivitis in children and adults were noted. Levofloxacin eyedrops are characterized by good solubility, which ensures high antibiotic concentration in the tear film (following 1 antibiotic drop administration medicine concentration in tear film is above 2 mg/l for the next at least 6 hours) and in anterior chamber. It was additionaly shown, that levofloxacin is characterized by low cytotoxicity to corneal cells and the least potent among fluoroquinolones inhibiting wound healing process. Levofloxacin properties listed and its’ high efficiency ensures good clinical effect of bacterial conjunctivitis treatment in infants. No resistance development of the bacteria the most commonly responsible for conjunctivitis entitles using levofloxacin as the first line treatment. Levofloxain therapy limitation is such an issue, that it requires frequent administration and systematic approach from parents. Szaflik et al. study on levofloxacin efficiency administered TID and its’ safety in conjunctivitis treatment in adults showed good clinical response and no differences comparing standard therapy (10). However, to give the answer to the question: whether levofloxacin administration frequency reduction to 3 eyedrops daily influence bacterial resistance development and efficiency of the treatment in infants, further clinical studies should be implemented.

Literature:
1. Turno-Kręcicka A., Barć A., Kański J.: Choroby oczu u dzieci. Górnicki Wydawnictwo Medyczne, Wrocław 2002.
2. Drlica K.: Control of bacterial DNA supercoiling. Mol. Microbiol. 1992; 6(4): 425–433.
3. Hooper D.C.: Quinolone mode of action. Drugs 1995; 49(2): 10–15.
4. Zhanel G.G., Ennis K., Vercaigne L., Walkty A., Gin A.S., Embil J., Smith H., Hoban D.J.: A critical review of the fluoroquinolones: focus on respiratory infections. Drugs 2002; 62(1): 13–59.
5. Janoir C., Podglajen I., Kitzis M.D., Poyart C., Gutmann L.: In vitro exchange of fluoroquinolone resistance determinants between Streptococcus pneumoniae and viridans streptococci and genomic organization of the parE-parC region in S. mitis. J. Infect. Dis. 1999; 180(2): 555–558.
6. Asbell P.A., Colby K.A., Deng S., McDonnell P., Meis­ler D.M., Raizman M.B., Sheppard J.D. Jr., Sahm D.F.: Ocular TRUST: nationwide antimicrobial susceptibility patterns in ocular isolates. Am. J. Ophthalmol. 2008; 145(6): 951–958.
7. Kresken M., Becker K., Seifert H., Leitner E., Körber-Irrgang B., von Eiff C., Löschmann P.A.; Study Group: Resistance trends and in vitro activity of tigecycline and 17 other antimicrobial agents against Gram-positive and Gram-negative organisms, including multidrug-resistant pathogens, in Germany. Eur. J. Clin. Microbiol. Infect. Dis. 2011; 30(9): 1095–1103.
8. Van Bambeke F., Michot J.M., Van Eldere J., Tulkens P.M.: Quinolones in 2005: an update. Clin. Microbiol. Infect. 2005; 11(4): 256–280.
9. Robicsek A., Jacoby G.A., Hooper D.C.: The worldwide emergence of plasmid-mediated quinolone resistance. Lancet. Infect. Dis. 2006; 6(10): 629–640.
10. Szaflik J., Szaflik J.P., Kaminska A.: Levofloxacin Bacterial Conjunctivitis Dosage Study Group. Clinical and microbiological efficacy of levofloxacin administered three times a day for the treatment of bacterial conjunctivitis. Eur. J. Ophthalmol. 2009; 19(1): 1–9.

Adres do korespondencji (Reprint requests to):
dr n. med. Michał Szumiński
Klinika Okulistyki Dziecięcej z Ośrodkiem Leczenia Zeza UM w Białymstoku
ul. Waszyngtona 17
15-274 Białystok
e-mail: mike-sz@mp.pl

Fig. 1. Percentage of bacterial isolates responsible for infant conjunctivitis.
Ryc. 1. Odsetek izolatów bakterii wywołujących zapalenie spojówek u niemowląt.

 


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