Neonatal Bacterial Conjunctivitis in Korea in the 21St Century

CLINICAL SCIENCE

Neonatal Bacterial Conjunctivitis in Korea in the 21st Century

Kang Yeun Pak, MD,* Sung Il Kim, MD,†‡ and Jong Soo Lee, MD, PhD†‡

surface lubrication and bacterial clearance by tearing, abun- Purpose: To investigate the microbial cause and antibiotic dance mucosal immune cells in the conjunctiva, and antibac- susceptibility of neonatal bacterial conjunctivitis in Korean patients terial effect of tears.2 These mechanisms are immature in in the 21st century. neonates, and consequently, bacterial conjunctivitis is one of Methods: We retrospectively reviewed the medical records of the most common neonatal infections. patients diagnosed with neonatal bacterial conjunctivitis between Neisseria gonorrhoeae and Chlamydia trachomatis in January 2000 and December 2015. We recorded the organism, the maternal birth canal cause neonatal inclusion conjuncti- antibiotic susceptibility, and antibiotics used. vitis and were major causes of microbial neonatal conjunctivitis before the 21st century. But the incidence of neonatal Results: A total of 82 neonates were included in the study (53 conjunctivitis has decreased because of development of males and 29 females), with a mean age of 17.5 6 7.1 days. The antibiotics, more widespread use of prepartum examination, most commonly isolated organisms were Staphylococcus aureus (43 and increased use of cesarean section.3 cases, 52.4%), coagulase-negative staphylococci (11 cases, 13.4%), Methicillin-resistant Staphylococcus aureus (MRSA) is Staphylococcus epidermidis (11 cases, 13.4%), Serratia marcescens increasingly recognized as a significant pathogen. Becerra (4 cases, 4.9%), Pseudomonas aeruginosa (4 cases, 4.9%), and et al4 reported that 1 in 5 children in intensive care units had Enterobacter cloacae (3 cases, 3.7%). We found no cases of acquired an MRSA infection. A large-scale study of ocular Neisseria gonorrhoeae or Chlamydia trachomatis infection. Resis- MRSA5 has reported an increase in the incidence and tance to methicillin (83.7%), macrolide (81.4%), and aminoglyco- resistance of this pathogen. Conjunctivitis was reported as side (23.3%) was observed in patients with S. aureus infection. the predominant presentation, and it was very common in Conjunctivitis that did not improve with erythromycin or tobramycin neonates. However, reports on the incidence of MRSA in generally improved with the additional use of tosufloxacin. neonatal conjunctivitis in Korea are limited. The purpose of this study was to investigate the Conclusions: The prevalence of neonatal gonococcal or chlamyd- microbial causes and antibiotic sensitivity of neonatal bacte- ial conjunctivitis has decreased in the 21st century. However, rial conjunctivitis with review of the literature. methicillin-resistant S. aureus has been increasing, but these cases are responsive to tosufloxacin. Key Words: bacteria, culture, neonatal conjunctivitis MATERIALS AND METHODS (Cornea 2017;36:415–418) This study is a retrospective review of the medical records of patients who were diagnosed with neonatal bacterial conjunctivitis between January 2000 and December acterial conjunctivitis, an inflammation of the conjunctiva 2015 in Pusan National University Hospital. The institutional Bdue to abnormal proliferation of bacteria, requires accu- review board of Pusan National University Hospital approved rate diagnosis and treatment because it can cause severe the study protocol, and the protocol complied with the tenets complications, although the prognosis is good in most cases.1 of the Declaration of Helsinki. The outer eye has several defense mechanisms to maintain The inclusion criteria were as follows: the patient was homeostasis such as the blinking action of the eyelids, ocular less than 4 weeks old, a positive culture result was obtained from conjunctival discharge, and antibiotic sensitivity results were available for the culture. We recorded age, sex, place of Received for publication August 10, 2016; revision received October 26, birth, type of delivery, type of prophylactic antibiotics used, 2016; accepted November 13, 2016. Published online ahead of print organisms cultured, and the antibiotic susceptibility of the December 20, 2016. infectious organism. The patients were classified into 4 From the *Department of Ophthalmology, Haeundae Paik Hospital, Inje University, Busan, Korea; †Department of Ophthalmology, School of groups by age interval of a week and most common organism, Medicine, Pusan National University, Busan, Korea; and ‡Medical and incidence of MRSA was investigated in each group. Research Institute, Pusan National University Hospital, Busan, Korea. Bacterial culture was performed on the lower conjunctival sac The authors have no funding or conflicts of interest to disclose. using a smear of conjunctival discharge. The lower eyelid was Reprints: Jong Soo Lee, MD, PhD, Department of Ophthalmology, Pusan National University Hospital, 179 Gudeok-ro, Seo-gu, Busan KS012, pulled to expose the lower conjunctival sac, and a sterile Korea (e-mail: [email protected]). cotton-tipped swab was used to collect the smear. The swab Copyright © 2016 Wolters Kluwer Health, Inc. All rights reserved. was then put into a transport medium tube and sent to the

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TABLE 1. Organisms Cultured From Patients With Neonatal Bacterial Conjunctivitis Organism No. Eyes (%) S. aureus 43 (52.4) MRSA 36 (43.9) Non-MRSA 7 (8.5) Coagulase-negative Staphylococcus 11 (13.4) S. epidermidis 11 (13.4) S. marcescens 4 (4.9) P. aeruginosa 4 (4.9) Enterobacter 3 (3.7) K. pneunoniae 2 (2.4) C. striatum 1 (1.2) S. mitis 1 (1.2) A. baumannii 1 (1.2) FIGURE 1. Incidence of S. aureus and MRSA in neonatal E. faecalis 1 (1.2) conjunctivitis according to age groups.

week, 55.6% (15/27) in age ,2 weeks, 44.1% (15/34) in microbiological laboratory. The specimen was inoculated age ,3 weeks, and 69.2% (9/13) in age .3 weeks. The onto blood, chocolate, and MacConkey agar media at 37°C incidence of MRSA was higher in age ,3 weeks (14/15, for 48 hours. The organisms were identified using the Vitek II 93.3%), but there was no significant difference between the system (bioMérieux, France). groups (P = 0.206, Fig. 1). Antibiotic susceptibility testing was performed by the Of the 43 cases of S. aureus infection, 26 of the patients broth microdilution method against clindamycin, erythromycin, were born in the Pusan National University hospital. Eryth- gentamicin, oxacillin, penicillin, bactrim, and vancomycin. We romycin was used in 23 neonates and tobramycin in 3 also reviewed all cases in which eye drops for ocular pro- neonates as a prophylactic treatment. One from 23 patients phylaxis were used in the infantile unit between January 2010 treated with erythromycin and 1 from 3 patients treated with and December 2015. Cases that required additional eye drops tobramycin were found to be resistant to treatment. All these were identified by a computerized search. patients improved after the use of tosufloxacin, a third- Statistical analysis was performed using SPSS 12.0 generation fluoroquinolone. (IBM Corporation, New York, NY). Differences were The rate of MRSA was found to be much higher in the assessed using the Fisher exact test and the x2 test. P , Pusan National University Hospital (26/26, 100%) than other 0.05 was considered statistically significant. hospitals (10/17, 58.8%, P , 0.001, Fisher exact test). Of 71 cases in which the type of delivery was known, 43 cases were delivered by cesarean section and 28 cases by RESULTS normal vaginal delivery. S. aureus was the most common A total of 82 neonates (53 males and 29 females) who infectious organism in both groups. The second most common met the eligibility criteria were included in the study. The mean infectious organism was coagulase-negative Staphylococcus in age was 17.5 6 7.1 days. There were 3 cases of coinfection. the cesarean section group and S. epidermidis in the normal ThemostcommonlyisolatedorganismswereS. aureus (n = vaginal delivery group (Table 2). There was no statistical 43, 52.4%), followed by coagulase-negative staphylococci (n = difference in MRSA according to the type of delivery. 11, 13.4%), Staphylococcus epidermidis (n = 11, 13.4%), Between January 2010 and December 2015, erythro- Serratia marcescens (n = 4, 4.9%), Pseudomonas aeruginosa mycin was used in 659 neonates and tobramycin was used in (n = 4, 4.9%), Enterobacter cloacae (n = 3, 3.7%). Klebsiella 728 neonates to provide ocular prophylaxis. A total of 90 pneumonia (2 cases, 2.4%), and one case each of Corynebac- cases (13.7%) from the erythromycin group and 35 cases terium striatum, Streptococcus mitis, Acinetobacter baumannii, (4.8%) from the tobramycin group required additional and Enterococcus faecalis. We found no cases of N. gonor- antibiotic treatment. The tobramycin group showed a signif- rhoeae or C. trachomatis infection (Table 1). icantly lower incidence of purulent eye (P , 0.001, x2 test). Most cases (n = 36, 83.7%) of S. aureus were associated with MRSA that were resistant to oxacillin. S. aureus showed a high rate of resistance to some of the most commonly used DISCUSSION active ingredients of eye drops, including penicillin (n = 39, Historically, neonatal gonococcal conjunctivitis has been 90.7%), clindamycin (n = 29, 67.4%), and erythromycin (n = one of the major causes of blindness in newborns, but the 35, 81.4%), as well as a low rate of resistance to gentamicin introduction of Crede prophylaxis using silver nitrate in 1881 led (n = 10, 23.3%). Only one case was resistant to bactrim and to significant reduction in the incidence of blindness.6–8 vancomycin, but it was sensitive to gentamicin. However, gonococcal conjunctivitis is still a disease that causes The most common organism was S. aureus in all age blindness in approximately 10,000 newborns per year world- groups. The incidence of S. aureus was 50% (4/8) in age ,1 wide, so it is clearly still a serious and important condition.9 In

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5 TABLE 2. et al reported that 95% of cultures from neonates were Organisms Cultured From the Cesarean Section resistant to erythromycin and topical sulfa agents and Group and the Normal Vaginal Delivery Group suggested that gentamicin should be considered as the first- Cesarean Normal Vaginal line therapy. Daum16 found that staphylococci rapidly Organism Section Delivery developed resistance and that most strains were resistant to S. aureus 26 11 erythromycin and thus recommended that topical fluoroqui- Non-MRSA 3 1 nolones should be avoided. Although the number of MRSA MRSA 23 10 strains resistant to quinolones is increasing,17 MRSA patients Coagulase-negative 64in this study were responsive to tosufloxacin. The authors Staphylococcus speculated that antibiotic susceptibility for tosufloxacin varies S. epidermidis 26geographically because it has only recently been released S. marcescens 13in Korea. P. aeruginosa 12 Chlamydia has recently been reported as a common Enterobacter 12cause of neonatal conjunctivitis,18,19 but this study tested only K. pneunoniae 11for bacterial conjunctivitis, and identification of nonbacterial C. striatum 10chlamydia was not possible. Another limitation of this study S. mitis 10is that it was conducted at a tertiary medical institution where A. baumannii 10the newborn subjects could have had a higher incidence of E. faecalis 10congenital diseases or deformities when compared with typical newborns, and preterm birth and low birth weights were likely to be high. These factors result in differences in 1976 in South Korea, gonorrhea infection was reported in 65.2% the frequency of pathogenic strains in neonatal conjunctivitis of newborns with conjunctivitis. The number of reported cases because of effects on the neonatal immune system. In steadily declined to 25% in 1982, 9% in 1991, and 0.9% in addition, longer hospital stays may increase the risk of 1997.10–13 Our data are consistent with this trend, and we did not bacterial conjunctivitis caused by nosocomial infections. identify a case of gonorrhea in our patient group. In developed countries, thanks to the availability of In a previous study conducted on 53 mothers and prenatal care, development of antibiotics, and high standards newborns, examinations of cultures of the mother’s vaginal of hygiene, neonatal conjunctivitis is no longer a major cause bacterial flora and the newborn’s conjunctival sac bacterial flora of blindness in newborns. However, the frequency of non- demonstrated that the bacterial flora of the newborn originated gonococcal bacterial conjunctivitis has increased. With most from the vaginal bacterial flora of the mother. The most common deliveries being performed in hospitals and the length of stay type of bacteria was S. aureus.14 S. aureus was also the most for treatment continuing to increase, nosocomial infections frequently identified bacterium in our patients, but with most with multidrug-resistant bacteria are becoming the leading (83.7%) being MRSA and most of the newborn subjects having cause of neonatal conjunctivitis among newborns. It is been born by cesarean section, it is likely that the conjunctivitis believed that these infections occur postnatally, which infections in these newborns were not caused during labor but suggests that careful attention to hygiene, including thorough were nosocomial infections occurring after birth. The prevalence hand washing, will be effective in decreasing the incidence of of MRSA in neonatal conjunctivitis has been increasing during these infections. We suggest that the preventive effects of the 21st century. Kim et al13 reported in 1997 that 70% of S. antibiotics could be increased by substituting tobramycin, aureus infections were not resistant to oxacillin. This is markedly which has a lower rate of resistance, for erythromycin. different from the figure of 83.7% found in this study. The prevalence of neonatal gonococcal or chlamydial In our study, erythromycin and tobramycin were admin- conjunctivitis has been decreasing in Korea. The most istered immediately after birth as prophylactic antibiotics. common microbial cause in this study was S. aureus and Silver nitrate is highly effective in the prevention of conjunc- most were MRSA. Treatment-resistant MRSA was respon- tivitis caused by gonorrhea, but can itself cause conjunctivitis sive to tosufloxacin. The main route of infection in recent by chemical irritation and is less effective in the prevention of times is likely to be hospital-acquired infection, whereas it chlamydial or nongonococcal inflections.15 Erythromycin has was birth canal infection in the past. Thus, the prevalence of been used as a prophylactic antibiotic, but the production of the neonatal conjunctivitis should be decreased by thorough hand drug was discontinued in late 2011, and it has been recently washing before contact with neonates. Using tobramycin replaced by tobramycin. After the change of drugs, frequency instead of erythromycin would be expected to increase the of the need to administer additional antibiotics has decreased prophylactic effect. from 13.7% to 4.8%. This is likely because although S. aureus showed higher resistance to erythromycin at 81.4%, it showed REFERENCES lower resistance to the gentamicin family of aminoglycosides at 1. Sheikh A, Hurwitz B. 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