Blayney Marc P, Al Madani Mahmud
Division of Newborn Care, Department of Obstetrics, Ottawa Hospital - General Campus, University of Ottawa, Ottawa, Ontario.
Paediatr Child Health. 2006 Dec;11(10):659-63.
Following the introduction of cloxacillin and gentamicin as the first line of treatment for possible late-onset sepsis (LOS) in the authors' neonatal intensive care unit (NICU), it was subsequently noted that very low birth weight (VLBW) infants improved clinically, despite subsequently positive blood cultures for oxacillin-resistant, coagulase-negative Staphylococcus (CONS). The results of the management of VLBW infants with CONS sepsis during one calendar year, based on clinical rather than laboratory findings, are presented.
VLBW infants with LOS were identified through the neonatal database, and the charts of those with CONS were reviewed for antibiotic usage, antibiotic resistance pattern, clearance of CONS from the blood and NICU discharge status. Oxacillin sensitivity was determined by the presence of the mecA gene.
From January 1 to December 31, 2002, 27 VLBW infants, treated in the authors' NICU for LOS due to CONS, were identified. The mean age of LOS infants with CONS was 15 days (median 12 days; range three to 54 days), the mean birth weight (+/- SD) was 904+/-247 g, and the mean gestational age at birth (+/- SD) was 27+/-2 weeks. All infants were started on cloxacillin and gentamicin, and improved clinically over the first 48 h. Six isolates were sensitive to cloxacillin. Twenty-three infants grew oxacillin-resistant CONS, eight of whom had persistence of CONS on repeat culture secondary to central lines. Two infants grew two strains of CONS. Eighteen of 22 infants (82%) with in vitro oxacillin-resistant CONS had clearance of bacteremia with cloxacillin and gentamicin. Ten infants (37%) received vancomycin, based on the authors' guidelines. There were no cases of prolonged bacteremia requiring rifampicin. Three infants died, but none of the deaths could be attributed to CONS.
The authors describe clinical improvement with clearance of CONS using cloxacillin and gentamicin, despite laboratory results suggesting oxacillin resistance. The authors' unit policy was based on clinical response and permitted the continuation of cloxacillin, provided that a repeat blood culture was negative. Vancomycin use was suggested for clinical deterioration or persistence of CONS. These results question the in vitro tests of resistance. Clearance of oxacillin-resistant CONS from the blood points to in vivo sensitivity, while the laboratory testing suggests in vitro resistance. The absence of subsequent positive blood cultures for CONS confirms clearance of this organism.
It was demonstrated that cloxacillin (150 mg/kg/day dose), along with gentamicin, can clear CONS from the blood within 48 h. The relationship between in vivo and in vitro sensitivities also needs to be further studied both in the laboratory and in a prospective trial.
在作者所在的新生儿重症监护病房（NICU）将氯唑西林和庆大霉素作为可能的晚发性败血症（LOS）的一线治疗药物引入后，随后注意到极低出生体重（VLBW）婴儿临床症状有所改善，尽管随后血培养结果显示对苯唑西林耐药的凝固酶阴性葡萄球菌（CONS）呈阳性。本文呈现了基于临床而非实验室检查结果，对VLBW婴儿CONS败血症进行为期一年管理的结果。
通过新生儿数据库识别患有LOS的VLBW婴儿，并查阅CONS患儿的病历，以了解抗生素使用情况、抗生素耐药模式、CONS从血液中的清除情况以及NICU出院状态。通过mecA基因的存在来确定苯唑西林敏感性。
2002年1月1日至12月31日，在作者所在的NICU中，有27名因CONS导致LOS的VLBW婴儿被识别出来。CONS导致LOS的婴儿的平均年龄为15天（中位数12天；范围3至54天），平均出生体重（±标准差）为904±247克，平均出生胎龄（±标准差）为27±2周。所有婴儿均开始使用氯唑西林和庆大霉素治疗，且在最初48小时内临床症状有所改善。6株分离菌对氯唑西林敏感。23名婴儿培养出苯唑西林耐药的CONS，其中8名因中心静脉导管导致再次培养时CONS持续存在。2名婴儿培养出两种CONS菌株。22名体外苯唑西林耐药的CONS婴儿中有18名（82%）使用氯唑西林和庆大霉素后菌血症得以清除。根据作者的指南，10名婴儿（37%）接受了万古霉素治疗。没有出现需要利福平治疗的长时间菌血症病例。3名婴儿死亡，但均非CONS所致。
作者描述了尽管实验室结果显示对苯唑西林耐药，但使用氯唑西林和庆大霉素后CONS清除且临床症状改善的情况。作者所在科室的政策基于临床反应，只要重复血培养为阴性，就允许继续使用氯唑西林。对于临床病情恶化或CONS持续存在的情况，建议使用万古霉素。这些结果对体外耐药性检测提出了质疑。血中苯唑西林耐药CONS的清除表明体内敏感，而实验室检测显示体外耐药。随后未出现CONS血培养阳性结果证实了该菌已被清除。
结果表明，氯唑西林（剂量为150毫克/千克/天）与庆大霉素联合使用可在（用药后）48小时内清除血液中的CONS。体内和体外敏感性之间的关系还需要在实验室和前瞻性试验中进一步研究。
