Tohamy Sally Tohamy, Aboshanab Khaled Mohamed, El-Mahallawy Hadir Ahmed, El-Ansary Mona R, Afifi Salwa Selim
Department of Microbiology and Immunology, Faculty of Pharmacy For Girls, Al-Azhar University, Cairo, Egypt.
Department of Microbiology and Immunology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Infect Drug Resist. 2018 May 25;11:791-803. doi: 10.2147/IDR.S163293. eCollection 2018.
Bloodstream infections with multidrug-resistant (MDR) Gram-negative bacteria (GNB) are among the most frequent complications in immunocompromised cancer patients because of their considerable morbidity and mortality. Several guidelines on antimicrobial therapy have addressed empirical treatment for such serious infections; however, the emergence of microbial resistance has become a significant problem worldwide.
In this study, starting from November 2015 to October 2016, a total of 529 blood specimens were collected from febrile neutropenic cancer patients at a tertiary care cancer hospital in Egypt.
On examination for positive bacterial growth, it was found that 334 specimens showed no growth, while 195 were positive. Out of the 195 positive culture specimens, 102 (102/195, 52.3%) were Gram-negative and 93 (93/195, 47.7%) were Gram-positive. Out of the 102 GNB, 70 (70/102, 68.6%) were MDR, including (27/70, 38.6%), (24/70, 34.3%), (9/70, 12.8%), (4/70, 5.7%), (2/70, 2.8%), (2/70, 2.8%), and (2/70, 2.8%). All MDR GNB showed high resistance to ampicillin, cefepime, ceftriaxone, and cephradine (minimum inhibitory concentration at which 50% of the isolates were inhibited [MIC] >512 μg/mL for each). However, they showed good susceptibility to colistin (MIC <1 μg/mL). The most common extended-spectrum β-lactamases (ESBLs) genes detected were (39/70, 55.7%), (31/70, 44.3%), and (22/70, 31.4%). The most common aminoglycoside-resistant gene detected was ' (42/70, 60%) followed by the plasmid-mediated quinolone resistance determinants; (2/70, 2.8%), (9/70, 12.8%), and (19/70, 27.1%). ESBL determinants were significantly associated with resistance to ciprofloxacin, levofloxacin, amikacin, and carbapenems (-value <0.005). The fractional inhibitory concentration index for ampicillin/sulbactam plus ceftriaxone, ampicillin/sulbactam plus amikacin, and amikacin plus levofloxacin showed synergism against 29 (29/70, 41.4%), 19 (19/70, 27.1%), and 11 (11/70, 15.7%) isolates of the tested MDR GNB isolates, respectively.
Accordingly, new empirical antibiotics should be administered including the use of colistin or meropenem alone or both against the MDR GNB in neutropenic cancer patients.
耐多药（MDR）革兰氏阴性菌（GNB）引起的血流感染是免疫功能低下癌症患者最常见的并发症之一，因其具有相当高的发病率和死亡率。多项抗菌治疗指南已涉及此类严重感染的经验性治疗；然而，微生物耐药性的出现已成为全球范围内的一个重大问题。
在本研究中，从2015年11月至2016年10月，在埃及一家三级癌症专科医院共收集了529份发热性中性粒细胞减少癌症患者的血液标本。
在检查细菌生长阳性情况时，发现334份标本无生长，而195份为阳性。在195份阳性培养标本中，102份（102/195，52.3%）为革兰氏阴性菌，93份（93/195，47.7%）为革兰氏阳性菌。在102株革兰氏阴性菌中，70株（70/102，68.6%）为耐多药菌，包括（27/70，38.6%）、（24/70，34.3%）、（9/70，12.8%）、（4/70，5.7%）、（2/70，2.8%）、（2/70，2.8%）和（2/70，2.8%）。所有耐多药革兰氏阴性菌对氨苄西林、头孢吡肟、头孢曲松和头孢拉定均表现出高度耐药（每种药物使50%分离株受到抑制的最低抑菌浓度[MIC]>512μg/mL）。然而，它们对黏菌素表现出良好的敏感性（MIC<1μg/mL）。检测到的最常见的超广谱β-内酰胺酶（ESBLs）基因是（39/70，55.7%）、（31/70，44.3%）和（22/70，31.4%）。检测到最常见的氨基糖苷类耐药基因是“（42/70，60%），其次是质粒介导的喹诺酮类耐药决定簇；（2/70，2.8%）、（9/70，12.8%）和（19/70，27.1%）。ESBL决定簇与对环丙沙星、左氧氟沙星、阿米卡星和碳青霉烯类药物的耐药性显著相关（P值<0.005）。氨苄西林/舒巴坦加头孢曲松、氨苄西林/舒巴坦加阿米卡星以及阿米卡星加左氧氟沙星的部分抑菌浓度指数分别对29株（29/70，41.4%）、19株（19/70，27.1%）和11株（11/70，15.7%）受试耐多药革兰氏阴性菌分离株表现出协同作用。
因此，应使用新的经验性抗生素治疗，包括单独使用黏菌素或美罗培南或两者联合使用，以治疗中性粒细胞减少癌症患者的耐多药革兰氏阴性菌感染。
