J Kyorin Med Soc 50（3）: 131 〜 135, 2019

Neonatal Panton-Valentine leukocidin-positive MRSA (USA300) sepsis translated from dacryocystitis

Introduction

　 Acute dacryocystitis presents as inflammation of the lacrimal sac and is typically caused by bacterial infection. The organisms commonly isolated from lacrimal abscesses include Staphylococcus aureus, Streptococcus pneumoniae, Haemophilus influenzae and coagulase-negative Staphylococcus1-5). Although Staphylococcus is commonly isolated, specific reports on community-

assoc iated (CA) MRSA are rare6,7 ) . Congeni ta l nasolacrimal duct obstruction is the most common cause of neonatal dacryocystitis, which may be accompanied by secondary obstruction caused by infection, trauma, or structural abnormalities such as dacryocystocele1,8). Many cases of congenital nasolacrimal duct obstruction recover spontaneously9); however, some cases may progress to dacryocystitis1,2). Furthermore, cases of sepsis arising from dacryocystitis are rarely reported6). Panton-

Case Report

Tomoko Saijo1), Zentaro Kiuchi1), Daisuke FuKuhara1), Tadamitsu ueSato1), Yuki uehara2,3)

Kunimasa Yan1)

1) Department of Pediatrics, Kyorin University School of Medicine 2) Department of Clinical Laboratory, St. Luke’s International Hospital

3) Department of Microbiology, Juntendo University Faculty of Medicine

（Received: June 20, 2019; Accept: August 16, 2019.）

Abstract

　 Dacryocystitis is a common disease encountered by pediatricians in their daily practice. However, in rare cases, sepsis may develop following methicillin-resistant Staphylococcus aureus (MRSA)-associated dacryocystitis, which requires hospitalization. Herein, we report the case of a neonate who developed sepsis from dacryocystitis. We describe a case of boy who was hospitalized for sepsis from dacryocystitis at 7 days old and was successfully treated with vancomycin. Phylogenetic analysis revealed that the causative agent was a Panton-Valentine leukocidin (PVL)-positive, community-associated USA300 MRSA strain. We suspect that this strain being the causal agent of dacryocystitis was the major factor responsible for progression. This study suggests that even in the absence of immunological or structural abnormalities, fatal complications may arise from dacryocystitis, depending on the causative bacteria.

Abbreviations

PVL–Panton-Valentine leukocidinCA-MRSA–community-associated, methicillin-resistant Staphylococcus aureusHA-MRSA–hospital-associated, methicillin-resistant Staphylococcus aureusACME–arginine catabolic mobile elementSCCmec–staphylococcal cassette chromosome mecMIC–minimum inhibitory concentration

Keywords: Panton-Valentine leucocidin, Community-acquired infection, MRSA, Dacryocystitis, Neonate, sepsis

J Kyorin Med Soc 50（3）132 Tomoko Saijo, et al

Valentine leukocidin (PVL) is a pore-forming toxin that induces polymorphonuclear cell death by necrosis or apoptosis10). Most methicillin-resistant Staphylococcus aureus (MRSA) clonal lineage USA300 strains prevalent in the United States produce PVL11); therefore, these strains can cause severe infections such as necrotizing pneumonia and severe sepsis12). Herein, we report the case o f a neonate who deve loped seps is from dacryocystitis13), which was attributed to a PVL-positive CA-MRSA USA300 strain.

Case Report

　 A 7-day-old Japanese neonate was referred to our pediatric department with a fever of 38℃, signs of toxicity and erythematous swelling in his medial lower eyelid. He was born via spontaneous vaginal delivery at a gestational age of 39 weeks, 1 day in a general obstetrics and gynecology hospital, with a birth weight of 3020 g. His mother did not experience any infection during the perinatal period, and he had not been hospitalized in a neonatal intensive care unit. 　 On admission, the patient had the following clinical measurements: height, 51.8 cm (+1.3 SD); weight, 3190 g (+2.0 SD); body temperature, 38.3℃ ; heart rate, 142 beats per minute and regular; blood pressure, 84/- mmHg; and respiratory rate, 42 breaths per minute. His general condition was poor, with decreased activity and an erythematous mass in his medial lower eyelid with mucopurulent discharge (Figure 1A). Laboratory examinations revealed a white blood cell count of 29,400 cells/mm3 and a slight nuclear shift to the left (1.5% bands, 77% segs, 6% lymphocytes, 14% monocytes, 1% eosinophils), as well as mild C-reactive protein elevation (1.43 mg/dL). 　 A maxillofacial computed tomographic scan revealed

dilation of the lacrimal sac, as well as right eye bulbar conjunctiva and subcutaneous edema. Inflammation did not spread to the orbit (Figure 1B).　 We diagnosed the patient with dacryocystitis accompanied by preseptal cellulitis. Blood cultures were obtained before the initiation of antimicrobial therapy. He was empirically treated with intravenous sulbactam/ampicillin (150 mg q8h) and moxifloxacin eye drops. On day 2 of hospitalization, his fever persisted and the inflammatory reaction worsened (WBC count, 25,200 cells/mm3; CRP level, 8.9 mg/dL), resulting in a decline in overall condition. Therefore, we performed a lumbar puncture to exclude purulent meningitis. Cerebrospinal f lu id f indings of 13 white blood cel ls/µL (97% mononuclear cells), protein concentration 50.1 mg/dL and glucose 83 mg/dL were within normal ranges14,15). Additionally, staphylococci were found in the blood culture carried out at the time of admission. Therefore, antibiotic therapy was changed to a combination of vancomycin (50 mg q8h) and cefotaxime (150 mg q6h), because we could not completely eliminate MRSA meningitis. On the same day, a significant amount of pus spontaneously drained from the nasal cavity. The patient’s fever subsided on day 3 of hospitalization, and his erythema, swelling, and induration were alleviated. On day 3 of hospitalization, a definitive blood culture report of MRSA infection was returned. Cerebrospinal fluid culture was reported as negat ive on day 5 of hospitalization; therefore, vancomycin monotherapy was initiated and continued for 2 weeks. 　 Additionally, we performed an immunity test, because he was re-hospitalized with Escherichia coli-associated urinary tract infection 1 month after discharge. Immunoglobulin (IgG 962 mg/dL, IgA <3 mg/dL, IgM 30 mg/dL) , complement levels (CH50 ≧60.1 U/mL, C3 124

Figure 1.　 (A) Arrows indicate diffuse erythema and swelling of the medial lower eyelid on admission. (B) A maxillofacial computed tomographic scan revealed dilation of the lacrimal sac (arrowhead) in addition to bulbar conjunctiva and subcutaneous edema (arrows) of the right eye. Inflammation did not spread to the orbit.

September, 2019 133Neonatal Panton-Valentine leukocidin-positive MRSA (USA300) sepsis translated from dacryocystitis

mg/dL, C4 24 mg/dL), neutrophil phagocytic function and neutrophil sterilizing function were within normal ranges. He completed a 10-day course of antibiotic therapy and recovered without any problems.　 An assessment performed 9 months after onset confirmed that the patient’s growth and development were normal and that dacryocystitis had not recurred.

Antimicrobial Susceptibility and Genotype

Characterization of MRSA Strain

　 Chromosomal DNA was extracted from the MRSA strain by using the small-scale phenol extraction method. The staphylococcal cassette chromosome (SCC) mec type was determined as IVa by six multiplex PCRs (M-PCRs), which identify the ccr gene complex (ccr), the mec gene complex (mec) and specific structures in the junkyard regions16). In addition, PCR analysis of the Panton-Valentine leukocidin (PVL) gene was performed with the reported primers17). The arginine catabolic mobile element (ACME) was determined by detection of the arcA gene by PCR18). These PCRs of the MRSA strain were positive for PVL and ACME, respectively.

Discussion

　 This report is the first to identify the PVL in the causative agent, MRSA, of sepsis from dacryocystitis. The genotype analysis of the present case suggests that the presence of PVL may have caused early progression of sepsis from dacryocystitis.　 Dacryocystitis often requires treatment via probing, because anatomical abnormalities are present in many cases1,2). However, the current case did not require prob ing because a s ign i f i cant amount o f pus spontaneously drained from the nasal cavity on day 2 of hospitalization.　The patient responded favorably to antibiotic therapy, with the infection resolving without relapse. It suggested that he had no structural abnormalities.　 Meanwhile, he was re-hospitalized with Escherichia coli-associated urinary tract infection 1 month after discharge. Because bacterial infection recurred, an immunity test was conducted. Based on these results, we concluded that the patient had no immune disorder. An immature immune system, a narrow nasal canal structure, and the presence of highly virulent pathogens all contribute to the progression of sepsis from dacryocystitis. Accordingly, we speculate that the

increased pathogenicity of the PVL-positive CA-MRSA USA300 clone isolated in the current case was responsible for the development of sepsis in this patient. 　 MRSA strains are classified as either hospital-associated (HA)-MRSA or CA-MRSA. Risk factors for HA-MRSA infection include long-term facility stay and catheter placement, and mainly affect immunodeficient patients19). Conversely, CA-MRSA often affects healthy children and adults, with the majority of infections located in the skin and soft tissues20). Neonates may acquire CA-MRSA vertically from their mother’s vagina and contaminated breast milk, or by skin-to-skin contact21-23). However, in this case, MRSA was not detected from maternal vaginal culture, and the infection situation in the family or maternity hospital cannot be confirmed.　 CA-MRSA was first reported in the United States in 198124), but has attracted attention in the last 10 years for the rise in highly pathogenic CA-MRSA strains. USA300 isolates carry a type-IV SCCmec element, which confers resistance to β-lactam antibiotics, and a putative pathogenicity island, ACME25). ACME-SCCmecIV linkage is thought to play a key role in the persistence of USA300 in the community26). ACME most l ikely originated in Staphylococcus epidermidis, and enhances fitness and abil ity to colonize skin and mucous membranes25,27). In addition, because PVL is a leukocyte-destroying toxin, PVL-positive CA-MRSA strains can cause severe infections. In recent years, MRSA infections, particularly those caused by CA-MRSA, have increased in frequency among children28). However, cases of CA-MRSA-associated sepsis arising from dacryocystitis are rarely reported6). Therefore, we predict that the presence of PVL, which was confirmed by molecular analysis, by the CA-MRSA isolate with SCCmec IVa-ACME (clone USA300) was likely responsible for the development of sepsis in our patient. 　 Even though dacryocystitis is local infection, systemic administration of antibiotics may be necessary in neonates1,2,6). Furthermore, the possibility of resistant bacteria is taken into consideration in the selection of antibiotics.

Acknowledgements

　 We thank Ikuyo Yamaguchi, MD, PhD, for editing a draft of this manuscript.

J Kyorin Med Soc 50（3）134 Tomoko Saijo, et al

References

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9) Nelson LB, Calhoun JH, Menduke H. Medical management of congenital nasolacrimal duct obstruction. Ophthalmology 92: 1187-90, 1985.

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18) Diep BA, Gill SR, Chang RF, Phan TH, Chen JH, Davidson MG, Lin F, Lin J, Carleton HA, Mongodin EF, Sensabaugh GF, Perdreau-Remington F. Complete genome sequence of USA300, an epidemic clone of community-acquired methicillin-resistant Staphylococcus aureus. Lancet 367: 731-9, 2006.

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September, 2019 135Neonatal Panton-Valentine leukocidin-positive MRSA (USA300) sepsis translated from dacryocystitis

涙嚢炎からMRSA（USA300）敗血症をきたした新生児の１例

　涙嚢炎は小児科医が日常診療の中でしばしば経験する疾患である。症例は日齢７の男児，涙嚢炎の診断で入院し，血 液 培 養 検 査 か ら メ チ シ リ ン 耐 性 黄 色 ブ ド ウ 球 菌

（Methicillin-resistant Staphylococcus aureus：MRSA）が検出され，MRSA敗血症としてバンコマイシンによる治療を行った。後に，菌株解析を施行し，PVL（Panton-Valentine leukocidin）陽性の市中型メチシリン耐性黄色

ブ ド ウ 球 菌（community-associated Methicillin-resistant Staphylococcus aureus：CA-MRSA）（USA300）と同定された。今回，敗血症にまで至った最大の原因は起因菌がPVL陽性のCA-MRSAであったためと考えられ，近年その高病原性について注目されている。涙嚢炎からも起因菌の病原性によっては敗血症や髄膜炎などの重症感染症を引き起こし致死的になりうるため，注意が必要である。

西　條　智　子1） 木　内　善太郎1） 福　原　大　介1） 上　里　忠　光1）

上　原　由　紀2,3） 楊　　　國　昌1）

1）杏林大学医学部小児科学 2）聖路加国際病院臨床検査科

3）順天堂大学医学部微生物学／感染制御科学／総合診療科

J Kyorin Med Soc 50（3）: 0 〜 00, 2019

Keywords: Panton-Valentine leucocidin, Community-acquired infection, MRSA, Dacryocystitis, Neonate, sepsis