Materials Express

Clinical efﬁcacy and safety of silver nanoparticle- based disinfectant combined with piperacillin sodium and sulbactam sodium in the treatment of lower respiratory tract infection

Xiaofei Li, Lina Sheng, Juncai Tu, and Lianqing Lou∗ Department of Infectious Diseases, Yiwu Central Hospita, Yiwu 322000, Zhejiang, PR China

ABSTRACT This study evaluated the clinical efficacy and safety of piperacillin sulbactam in the treatment of lower respiratory tract infections, asIP: well 192.168.39.211 as the efficacy On: of Wed,silver 29 nanoparticle-basedSep 2021 02:32:18 disinfectant in equipment disinfection to reduce exogenous infection.Copyright: From American May Scientific 2018 to Publishers November 2018, 100 patients that had been Delivered by Ingenta diagnosed with a lower respiratory tract infection and hospitalized were divided into an experimental group and a control group. The experimental group was given piperacillin/sulbactam, and the control group was given mezlocillin/sulbactam, where 5.0 g was added to 100 mL of normal saline and administered via intravenous Article drip twice a day over a treatment course of 14 days. The cure rate of the experimental and control groups were 65.22% and 56.52% respectively. The efficacy rate was 91.30% and 91.30% respectively, with no significant difference between the two groups (P>0.05). The results indicated that piperacillin/sulbactam is a safe, effective treatment for lower respiratory tract infections in elderly patients, the equipment was sterilized with silver nanoparticle-based disinfectant to reduce the incidence of adverse reactions and exogenous infections. Keywords: Piperacillin/Sulbactam, Mezlocillin/Sulbactam, Lower Respiratory Tract Infection, Elderly Patients, Silver Material.

1. INTRODUCTION Lower respiratory tract infections (LRTIs) are signiﬁ- Cefoperazone/sulbactam is a type of compound prepara- cant contributors to death of the elderly due to low immune tion. The third generation of cefoperazone can effectively function [1–3]. With the extensive application of anti- block the synthesis of bacterial cell walls and has signif- microbial drugs, the selective pressure on microorganisms icant antibacterial effects. Sulbactam, another component has increased, and the number of drug-resistant strains of the drug, is a -lactamase inhibitor that can irreversibly is increasing. This brings challenges to the treatment bind a variety of -lactamases produced by drug-resistant of pulmonary infection, particularly in elderly patients. strains and has signiﬁcant bactericidal effects. In addi- Piperacillin is a broad-spectrum semi-synthetic acrylamide tion, it can prevent cefoperazone from being hydrolyzed penicillin, which has a wide antibacterial spectrum and by -lactamase. The combination of sulbactam and cef- strong antibacterial effects [4–7]. It has good antibacterial operazone can enhance the degradation ability of the drug effects on most Gram-negative and positive bacteria, but against a variety of -lactamases, and the combination of drug resistance is increasing. Sulbactam is a strong broad- the two has a clear synergistic effect. spectrum -lactamase inhibitor, and can protect antibiotics from -lactamase damage. Piperacillin/sulbactam ∗Author to whom correspondence should be addressed. is a compound preparation of piperacillin sodium and

756 Mater. Express, Vol. 10, No. 5, 2020 Clinical efﬁcacy and safety of silver nanoparticle-based disinfectant Materials Express Li et al. sulbactam sodium [8–10], and it is hoped that the com- experimental group, piperacillin/sulbactam produced by bined preparation can protect against piperacillin sodium Shenyang Huatai Pharmaceutical Research Co., Ltd. was -lactamase damage and enhance the anti-enzyme and used. The batch number of the control drug was 030730, bactericidal ability of piperacillin sodium [11–13]. and was produced by Hainan General Sanyang Pharma- At present, intravenous piperacillin sodium/sulbactam ceutical Co., Ltd. and the batch number was 030306. For sodium is commonly used to treat patients with LRTIs. participants that had a negative skin test, the usage was Removal of intravenous drips, dosing, and contact with 5.0 g added to 100–250 mL of physiological salt water patients and nurses often introduce exogenous viruses, pre- given by intravenous drip twice a day. The course of treat- senting challenges to the disinfection of intravenous drip ment was 5–14 d, and both treatments were the same. The equipment. Common disinfection methods can only inac- observation indexes, including the rate of hypothermia, the tivate bacteria or viruses attached to the surface of the improvement of symptoms (sputum volume, color, cough device and the human body, but lack long-lasting antibac- frequency), the disappearance time of signs (lung moist terial properties. By interfering with the formation of the rale, dry rale), the length of use of antibiotics, a labora- cell wall, the silver nanoparticle material can damage the tory examination (blood routine, liver and kidney function, cell membrane and inhibit the formation of protein and chest X-ray ﬁlm, sputum bacteriology culture, drug sensi- nucleic acid. The material also has good functionality with tivity test), and the evaluation standard of the pulmonary biological metabolism and very low biological toxicity, infection score (CPIS) 2, are shown in Table I. The highest therefore it is harmless and quickly metabolized out of score was 12 points. When a score drops below six points, the body. Moreover, the silver nanoparticle material can antibiotics can be stopped. be applied to the surface of equipment to achieve long- term and sustained antibacterial and sterilization effects. 2.3. Assessment of Therapeutic Effects At present, silver nanoparticle material is often used for According to the Guidance Standard for Clinical Research clinical disinfection in hospitals because of its excellent of Scandium Bacteria issued by the Ministry of Health antibacterial and adhesion properties.

in 1993, the criteria for efficacy evaluation are divided Article The purpose of this study was to evaluate the clini- into four levels: recovery, significant effect, progress, and cal efficacy and safety of intravenous piperacillin sodium/ IP: 192.168.39.211 On: Wed, ineffectiveness.29 Sep 2021 02:32:18 Recovery indicates that after treatment, sulbactam sodium injection in the treatment of LRTIs Copyright: American Scientificsymptoms, Publishers signs, laboratory tests, and etiology tests were in elderly Chinese patients after silver materialDelivered disinfec- by Ingenta tion, and to provide evidence that it overcomes clinical completely restored to normal. Significant effect indicates resistance and is a reasonable and effective disinfection that after treatment, the above four items were significantly procedure. improved, but one of them was not completely restored to normal. Progress indicates that after treatment, the four items were improved, but did not reach the significant 2. MATERIALS AND METHODS effect standard. Ineffectiveness indicates that after 72 hours 2.1. General Data of treatment, the symptoms were not improved or were Patients in our hospital from May to November 2018 aggravated. The effective rate is calculated according to with LRTIs were selected in accordance with diagnosis the combination of cure and significant effect [14–16]. standards from 2004 internal medicine and 2004 practical geriatrics. The inclusion criteria required a minimum age 2.4. Adverse Reaction Observation 60 years old, an unlimited number of men and women, The relationship between adverse reactions and drugs no serious liver or kidney dysfunction, and no history of can be divided into five grades: positively related, likely drug allergies. The exclusion criteria excluded those who related, possibly related, positively unrelated, and difficult were expected to fail to complete the course of treatment to judge. The first three are considered adverse reactions, due to various reasons, had a history of central nervous and the incidence of adverse reactions is counted. diseases or epilepsy, or refused to participate in the trial. A total of 44 cases were included, including seven cases of acute attack of chronic obstructive pulmonary disease Table I. Clinical pulmonary infection score. (AECOPD) and 27 cases of pneumonia. Project 0 point 1 point 2 point

Body temperature 36–38 38–39 >39 or <36 2.2. Trial Design (12 hour average) Clinical control trials (CCT) were used in the study Leukocyte count 4–11 11–17 <4or>17 design. The selected 44 patients with LRTIs were divided (109/L) into two groups: the piperacillin/sulbactam experimen- Secretion No sputum Medium sputum Lots of sputum > < tal group (n = 24), and the mezlocillin/sulbactam control Oxygenation index 23 23 n = X-ray inﬁltrating No Plaque like Fusion sheet group ( 20). The experimental group was treated with shadow an intravenous drip device sterilized with silver. In the

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2.5. Statistical Analysis The Statistical Package for the Social Sciences (SPSS) software was used for the statistical analysis. The Group t test was used for the measurement data, the test was used for the counting data, and the exact probability method was used for some data.

3. RESULTS AND DISCUSSION 3.1. Characterization of Silver-Based Disinfection Materials As shown in Figure 1(A), the shape of the silver disinfection particle is regular and round with differing particle sizes. After magniﬁcation, as shown in Figure 2, the silver material with a large particle size is attached to the outer wall of the tube, while the silver material with a small particle size is attached to the inner wall.

Fig. 2. Comparison of cure rate between the two groups (1. experi- 3.2. Comparison of Baseline Between Test Group and mental group; 2. control group). Control Group The baseline level was essentially the same, and the two groups were comparable (see Tables II and III) with no Table II. Baseline characteristics of observe group, control group (cases). statistically significant difference between the two groups (P>0.05). Index Observe group Control group Average age 76.05 ± 8.72 75.73 ± 8.70 3.3. Comparison of ClinicalIP: Efficacy 192.168.39.211 Between On: Wed, Gender29 Sep (male/female) 2021 02:32:18 18/6 17/3 Piperacillin/Sulbactam and Mezlocillin/SulbactamCopyright: American Scientific Publishers Clinical observation and study showed that 46Delivered strains of by Ingenta pathogenic bacteria were isolated from the experimental 3.4. Evaluation of Adverse Events and control groups, of which, 23 strains were isolated The mood and satisfaction of the experimental group were Article from the experimental group and 23 from the control higher than that of the control group (Figs. 4–6). In the group. In the analysis of the pathogenic bacteria and clin- experimental group, there was one case of an adverse ical efficacy, the cure rate of the experimental and con- event, which may have been related to the drug. The pri- trol groups were 65.22% and 56.52% respectively, and mary manifestation was erythema, and the incidence of the the efficacy rate was 91.30% and 91.30% respectively. adverse event was 3.23%. In the control group, there were With no difference in the efficacy rates, the cure rate two cases of adverse events that included one case of facial is statistically significant (P = 0.546, 1.000 respectively) redness and one case of elevated transaminase (ALT), (Figs. 2–3). which may have been related to drugs. The incidence of

Fig. 1. SEM characterization of silver nanometer disinfection materials.

758 Mater. Express, Vol. 10, 2020 Clinical efﬁcacy and safety of silver nanoparticle-based disinfectant Materials Express Li et al.

Table III. CIPS score of observe group, control group (cases).

Index Observe group Control group

CIPS score Light 7 5 Medium 12 10 Severe 5 5 adverse events was 6.67%. and there was no statistically signiﬁcant difference between the two groups (Fig. 7).

3.5. Discussion Cephalosporins are widely used in the treatment of LRTIs. They can inhibit the infectious inﬂammation caused by various bacteria and fungi. However, traditional

Fig. 5. Patient social status score.

cephalosporins are likely to make bacteria produce -lactamase, which leads to the emergence of resistant strains, increases the probability of bacterial resistance, and leads to poor efﬁcacy. Cefotaxime sodium and sulbac- Article tam sodium are new generation cephalosporins. Sulbactam IP: 192.168.39.211 On: Wed, sodium29 Sep is2021 a semi 02:32:18 synthetic -lactamase inhibitor, which Copyright: American Scientificcan antagonize Publishers the -lactamase produced by bacteria, Delivered by Ingentaenhance the antibacterial effect of cefotaxime sodium, and effectively improve the bacterial clearance rate [17–20]. At present, there are major problems in the ﬁeld of anti- infection. To overcome some of these problems, clinicians should focus on minimizing the production and spread of drug-resistant strains [21], especially in the elderly. Due to the unreasonable application of piperacillin in Fig. 3. Comparison of effective rate between the two groups. thebed,theissueofdrugresistant bacteria is becoming

Fig. 4. Patient emotional status score. Fig. 6. Patient satisfaction score.

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RSV-induced lower respiratory tract infection over four consecutive epidemics. European Journal of Pediatrics, 166(12), pp.1267–1272. 4. McKinney, J.D., Höner zu Bentrup, K., Muñoz-Elías, E., Miczak, A., Chen, B., Chan, W.T., Swenson, D., Sacchettini, J.C., Jacobs Jr., W.R. and Russell, D.G., 2000. Persistence of Mycobacterium tuber- culosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase. Nature, 406(6797), pp.735–738. 5. Bont, L., Steijn, M., Van Aalderen, W.M., Brus, F., Th Draaisma, J.M., Van Diemen-Steenvoorde, R.A., Pekelharing-Berghuis, M. and Kimpen, J.L., 2004. Seasonality of long term wheezing following respiratory syncytial virus lower respiratory tract infection. Thorax, 59(6), pp.512–516. 6. Bont, L., Heijnen, C.J., Kavelaars, A., van Aalderen, W.M., Brus, F., Draaisma, J.M., Pekelharing-Berghuis, M., van Diemen- Steenvoorde, R.A. and Kimpen, J.L., 2001. Local interferon-gamma levels during respiratory syncytial virus lower respiratory tract infection are associated with disease severity. Journal of Infectious Dis- eases, 184(3), pp.355–358. 7. Huchon, G.J., Gialdroni-Grassi, G., Léophonte, P., Manresa, F., Schaberg, T. and Woodhead, M., 1996. Initial antibiotic therapy for Fig. 7. Adverse reactions after treatment (1. cough; 2. abdominal pain; lower respiratory tract infection in the community: A European sur- 3. headache; 4. vertigo). vey. European Respiratory Journal, 9(8), pp.1590–1595. 8. van der Steen, J.T., Mehr, D.R., Kruse, R.L., Ribbe, M.W. and van der Wal, G., 2007. Dementia, lower respiratory tract infection, increasingly serious. It easily hydrolyzed by -lactamase, and long-term mortality. Journal of the American Medical Directors so the drug resistance rate of piperacillin sodium is Association, 8(6), pp.396–403. gradually increasing [22–23]. Sulbactam is a competi- 9. Hiatt, P.W., Grace, S.C., Kozinetz, C.A., Raboudi, S.H., Treece, tive and irreversible broad-spectrum -lactamase inhibitor, D.G., Taber, L.H. and Piedra, P.A., 1999. Effects of viral lower respi- which also has a certain effect on the ultra-wide-spectrum ratory tract infection on lung function in infants with cystic fibrosis. Pediatrics, 103(3), pp.619–626. enzyme [24–30]. IP: 192.168.39.211 On: Wed, 2910. SepLi, T., 2021 Yang, 02:32:18 J., Ali, Z., Wang, Z., Mou, X., He, N. and Wang, Z., Copyright: American Scientific2017 Publishers. Synthesis of aptamer-functionalized Ag nanoclusters for MCF- Delivered by Ingenta7 breast cancer cells imaging. Science China Chemistry, 60(3), 4. CONCLUSION pp.370–376. The concentration of 2 mL -lactamase has a strong inhi- 11. Prat, C., Domínguez, J., Rodrigo, C., Giménez, M., Azuara, M., bition effect, but it has a chromosomal mediated effect Jiménez, O., Galí, N. and Ausina, V., 2003. Procalcitonin, C-reactive Article on type I -lactamase. The compound preparation of protein and leukocyte count in children with lower respiratory tract infection. The Pediatric Infectious Disease Journal, 22(11), piperacillin and sulbactam has a broad antibacterial spec- pp.963–967. trum and strong antibacterial effects. It can destroy the 12. Yang, G., Lai, Y., Xiao, Z., Tang, C. and Deng, Y., 2018. Ultrasen- rabbit by -lactamase and has a good synergistic effect. sitive electrochemical immunosensor of carcinoembryonic antigen Results showed no difference in the effective rate, fine based on gold-label silver-stain signal amplification. Chinese Chem- rate, or bacterial clearance rate after treatment. The adverse ical Letters, 29(12), pp.1857–1860. 13. Qiu, L., Zhao, L., Xing, C. and Zhan, Y., 2018. Redox-responsive reaction rate was statistically significant. Moreover, silver polymer prodrug/AgNPs hybrid nanoparticles for drug delivery. Chi- disinfectant can effectively sterilize the equipment and can nese Chemical Letters, 29(2), pp.301–304. be adsorbed on the surface of the equipment to enable 14. Yang, G., Xiao, Z., Tang, C., Deng, Y., Huang, H. and He, Z., 2019. continuous sterilization. Recent advances in biosensor for detection of lung cancer biomark- ers. Biosensors and Bioelectronics, 141, pp.111416(1)–111416(11). 15. Li, T., He, N., Wang, J., Li, S., Deng, Y. and Wang, Z., 2016. Effects Acknowledgment: 2017 Anhui Public Welfare of the i-motif DNA loop on the fluorescence of silver nanoclusters. Technology Application Research Linkage Project RSC Advances, 6(27), pp.22839–22844. (1704f0804042). 16. Albazzaz, M.K., Pal, C., Berman, P. and Shale, D.J., 1994.Inflam- matory markers of lower respiratory tract infection in elderly people. Age and Ageing, 23(4), pp.299–302. References and Notes 17. Zong, Z., Lü, X., Liu, Y., Yang, Y., Yu, R., Fu, X., Huang, W., 1. Finegold, S.M. and Johnson, C.C., 1985. Lower respiratory Cai, S., Yu, Z., Zeng, X., Duan, M., Xia, P., Zhu, W., Ji, X., tract infection. The American Journal of Medicine, 79(5), Zhao, H., Chen, Y., Yin, F. and Ni, Z., 2005. Piperacillin-sulbactam pp.73–77. versus piperacillin-tazobactam: A multicentre, randomised, single- 2. Mehr, D.R., Binder, E.F., Kruse, R.L., Zweig, S.C., Madsen, R., blind, controlled clinical trial. International Journal of Antimicrobial Popejoy, L. and D’Agostino, R.B., 2001. Predicting mortality in Agents, 26(1), pp.22–27. nursing home residents with lower respiratory tract infection. JAMA, 18. Biswas, A.R., Ramaswamy, S. and Bapna, J.S., 1991. Analgesic 286(19), pp.2427–2436. effect of Momordica charantia seed extract in mice and rats. Journal 3. Rossi, G.A., Medici, M.C., Arcangeletti, M.C., Lanari, M., of Ethnopharmacology, 31(1), pp.115–118. Merolla, R., Paparatti, U.D., Silvestri, M., Pistorio, A., Chezzi, C. 19. Coccolini, F., Catena, F., Ansaloni, L., Ercolani, G., Di Saverio, S., and Osservatorio RSV Study Group, 2007. Risk factors for severe Gazzotti, F., Lazzareschi, D. and Pinna, A.D., 2011. A prospective,

760 Mater. Express, Vol. 10, 2020 Clinical efﬁcacy and safety of silver nanoparticle-based disinfectant Materials Express Li et al.

multi centre, randomized clinical study to compare the efficacy and 25. Roberts, J.A., Roberts, M.S., Robertson, T.A., Dalley, A.J. and safety of Ertapenem 3 days versus ampicillin-sulbactam 3 days in the Lipman, J., 2009. Piperacillin penetration into tissue of critically ill treatment of localized community acquired intra-abdominal infec- patients with sepsis—Bolus versus continuous administration? Crit- tion. (T.E.A. study: Three days ertapenem vs. three days ampicillin- ical Care Medicine, 37(3), pp.926–933. sulbactam). BMC Gastroenterology, 11(1), pp.1–5. 26. Bryson, H.M. and Brogden, R.N., 1994. Piperacillin/tazobactam. 20. Saito, A., Ishikawa, K., Nakayama, I., Tomizawa, M., Abe, M., A review of its antibacterial activity, pharmacokinetic properties and Shibaki, H., Chimoto, T., Tanaka, M., Ito, C. and Takeuchi, K., 1985. therapeutic potential. Drugs, 47(3), pp.506–535. A double-blind comparative study of aspoxicillin and piperacillin in 27. Harris, A.D., Perencevich, E., Roghmann, M.C., Morris, G., the treatment of respiratory tract infections. Journal of the Japanese Kaye, K.S. and Johnson, J.A., 2002. Risk factors for piperacillin- Association for Infectious Diseases, 59(2), pp.164–200. tazobactam-resistant Pseudomonas aeruginosa among hospital- 21. Gutman, J.A., Peck, A.J., Kuypers, J. and Boeckh, M., 2007.Rhi- ized patients. Antimicrobial Agents and Chemotherapy, 46(3), novirus as a cause of fatal lower respiratory tract infection in adult pp.854–858. stem cell transplantation patients: A report of two cases. Bone Mar- 28. Mouton, Y., Leroy, O., Beuscart, C., Chidiac, C., Senneville, E., row Transplantation, 40(8), pp.809–811. Ajana, F. and Lecocq, P., 1993. Efficacy, safety and tolerance 22. Lin, J.H., Chiu, S.C., Lin, Y.C., Chen, H.L., Lin, K.H., Shan, K.H., of parenteral piperacillin/tazobactam in the treatment of patients Wu,H.S.andLiu,H.F.,2009. Clinical and genetic analysis of human with lower respiratory tract infections. Journal of Antimicrobial bocavirus in children with lower respiratory tract infection in Taiwan. Chemotherapy, 31(SA), pp.87–95. Journal of Clinical Virology, 44(3), pp.219–224. 29. Sanders Jr., C.V., 1994. Piperacillin/tazobactam in the treatment of 23. Chen,G.,Hu,Z.,Lu,J.andMiao,P.,2010. Distribution and antibi- community-acquired and nosocomial respiratory tract infections: A otic resistance of pathogens isolated from nosocomial lower res- review. Intensive Care Medicine, 20(S3), pp.21–26. piratory tract infection. Chinese Journal of Nosocomiology, 20(4), 30. Manncke, K., Springsklee, M., Heizmann, W.R. and Sonntag, H.G., pp.564–566. 1996. Sulbactam in combination with mezlocillin, piperacillin or 24. Lode, H., 2001. Role of sultamicillin and ampicillin/sulbactam in the cefotaxime: Clinical and bacteriological findings in the treatment of treatment of upper and lower bacterial respiratory tract infections. serious bacterial infections. International Journal of Antimicrobial International Journal of Antimicrobial Agents, 18(3), pp.199–209. Agents, 6(S), pp.47–54.

Received: 13 January 2020. Accepted: 12 February 2020. Article

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