Drug Triggers and Clinic of Acute Generalized Exanthematous Pustulosis (AGEP): A Literature Case Series of 297 Patients

Acute generalized exanthematous pustulosis (AGEP) is a rare skin reaction, commonly caused by drugs. Available evidence mostly relies on small studies or case reports. We collected published AGEP case reports and, subsequently, described the patient characteristics, suspect and concomitant drugs, time to onset, disease management, and clinical prognosis. This study included 297 AGEP patients (64.3% women) obtained from 250 published case reports or case series with individual patient data. AGEP affected patients of all ages, but the majority of patients (88.2%) were ≥25 years old. The most frequently reported suspect drugs were anti-infectives for systemic use (36.5%), particularly antibacterials for systemic use (31.0%), and especially beta-lactam antibacterials (18.3%) and macrolides (4.3%). Other frequent suspect drugs were antineoplastics (12.2%), and anti-inflammatory/anti-rheumatic products (5.2%) plus hydroxychloroquine (12.8%). Mean time to onset was 9.1 days (standard deviation SD 13.94). Some patients developed fever (64.3%) and systemic involvement (18.9%), and most patients (76.4%) received pharmacological treatment for AGEP. Seven patients died, although five of them were already critically ill prior to AGEP. In conclusion, antibiotics remain the most common suspected cause of AGEP. While case mortality rate may be up to 2.5%, disentangling the role of AGEP on the fatal outcome from the role of the preexisting health conditions remains challenging.

Comprehensive analysis of imipenemase (IMP)-type metallo-Beta-lactamase showing global distribution threating Asia

Antibiotic resistance, particularly beta-lactam resistance, is a major problem worldwide. Imipenemase or IMP-type metallo-beta-lactamase (MBL) has become a more prominent enzyme, especially in Asia, since it was discovered in the 1990s in Japan. There are currently more than 91 variants of IMP-type enzymes. The most commonly identified variant of IMP-type enzymes is IMP-1 variant. IMP-type MBLs have been identified in more than 10 species in Enterobacterales. Pseudomonas aeruginosa is the most frequent carrier of IMP-type enzymes worldwide. In Asia, IMP-type MBLs have been distributed in many countries in the region. This work investigated a variety of currently available IMP-type MBLs in both global level and regional level. Out of 88 variants of IMP-type MBLs reported worldwide, only 32 variants were found to have susceptibility profiles. Most of the IMP-type MBLs were resistant to Carbapenems, especially Imipenem and Meropenem, followed by the 3rd generation cephalosporins, and interestingly, monobactams. Our results comprehensively indicated the distribution of IMP-type MBLs in Asia and raised the awareness of the situation of antimicrobial resistance in the region.

THỰC TRẠNG SỬ DỤNG KHÁNG SINH TRONG ĐIỀU TRỊ NỘI TRÚ TẠI TRUNG TÂM Y TẾ HUYỆN YÊN DŨNG, TỈNH BẮC GIANG NĂM 2020

Mục tiêu: Mô tả thực trạng sử dụng kháng sinh trong điều trị nội trú tại Trung tâm y tế (TTYT) huyện Yên Dũng, tỉnh Bắc Giang năm 2020. Phương pháp nghiên cứu: Nghiên cứu áp dụng thiết kế nghiên cứu mô tả cắt ngang. Số liệu được hồi cứu từ dữ liệu trong phần mềm của khoa Dược và khảo sát 300 bệnh án được rút ngẫu nhiên từ các bệnh án nội trú từ 01/01/2020-31/12/2020 tại TTYT huyện Yên Dũng, tỉnh Bắc Giang. Các chỉ số chính của nghiên cứu bao gồm: Số lượng kháng sinh được sử dụng trong năm (tính theo DDD); phân loại KS theo cấu trúc hóa học; số ngày dùng kháng sinh; tỷ lệ bệnh án có phối hợp kháng sinh; kết quả điều trị sau khi dùng kháng sinh. Kết quả chính: Kháng sinh (KS) nội chiếm 54,54% tính theo giá trị DDD (DDD – Defined Dose Daily - là liều trung bình duy trì hằng ngày với chỉ định chính của một thuốc KS); KS nhóm beta-lactam chiếm trên 80%; 65,33% số bệnh án được kê 1 loại KS; 30,33% số bệnh án có kê 2 loại KS; đáng lưu ý là một tỷ lệ nhỏ (4,33%) số bệnh án phối hợp 3 loại KS trong điều trị; 54,33% số bệnh án có chỉ định KS từ 5-7 ngày; 43,33% bệnh án có kê KS từ 7-10 ngày; đặc biệt có 2,34% bệnh nhân phải điều trị KS trên 10 ngày (chủ yếu ở khoa ngoại); 66,0% bệnh nhân khỏi bệnh hoàn toàn và 31,3% bệnh nhân tiến triển tốt sau khi được chỉ định điều trị bằng KS và các thuốc phối hợp. Kết luận: Nhìn chung TTYT Yên Dũng đã tuân thủ tốt các khuyến cáo của Bộ Y tế trong sử dụng KS về số lượng; chủng loại và thời gian sử dụng. Tuy nhiên, còn tồn tại một số vấn đề cần cải thiện, đó là: tỷ lệ KS nội được sử dụng trong bệnh viện thấp hơn so với khuyến cáo của Bộ Y tế (54,54% so với khuyến cáo là 75%); có 4,33% bệnh án phối hợp tới 3 loại KS trong điều trị; có một tỷ lệ nhỏ bệnh án (2,34%) dùng KS dài ngày (trên 10 ngày, chủ yếu ở khoa ngoại).

Penicillinase plasmid Australia type in Neisseria gonorrhoeae isolated in Poland

Purpose Neisseria gonorrhoeae is an etiological agent of gonorrhea which remains a major public health problem the mechanisms that determine resistance to drugs of the beta-lactam class, which are recommended for the treatment of gonorrhea, are currently the most important problem in its treatment. Chromosomal mutations are responsible for resistance to ceftriaxone and cefepime. The possibility of mutations in the gene encoding beta-lactamase (blaTEM) in the penicillinase plasmid may also turn out to be a serious threat. Methods The occurrence of resistance encoded on penicillinase plasmid has been investigated. For this purpose, the susceptibility of bacteria was determined and the gene for resistance to beta-lactams as well as the plasmids themselves was typed. Results Of the 333 strains tested, 21 (6.3%) had the beta-lactamase gene and produced penicillinase. Two of the beta-lactamase: TEM-1 and TEM-135 occurred among the tested strains of N. gonorrhoeae. Most of the known penicillinase plasmid types of N. gonorrhoeae were demonstrated: the Asian, the African, the Toronto/Rio plasmids and Australian variants. Conclusions In the first 3 years, TEM-1 beta-lactamases dominated in N. gonorrhoeae, which were replaced by TEM-135 in the following years of the study. Not all molecular methods are capable of varying the types of penicillinase plasmids. A particularly noteworthy observation is the fact that the Australia-type of penicillinase plasmid (3270 bp) was identified for the first time in Europe, and the second time in the world.

Role of AmpC-Inducing Genes in Modulating Other Serine Beta-Lactamases in Escherichia coli

The consistently mutating bacterial genotypes appear to have accelerated the global challenge with antimicrobial resistance (AMR); it is therefore timely to investigate certain less-explored fields of targeting AMR mechanisms in bacterial pathogens. One of such areas is beta-lactamase (BLA) induction that can provide us with a collection of prospective therapeutic targets. The key genes (ampD, ampE and ampG) to which the AmpC induction mechanism is linked are also involved in regulating the production of fragmented muropeptides generated during cell-wall peptidoglycan recycling. Although the involvement of these genes in inducing class C BLAs is apparent, their effect on serine beta-lactamase (serine-BLA) induction is little known. Here, by using ∆ampD and ∆ampE mutants of E. coli, we attempted to elucidate the effects of ampD and ampE on the expression of serine-BLAs originating from Enterobacteriaceae, viz., CTX-M-15, TEM-1 and OXA-2. Results show that cefotaxime is the preferred inducer for CTX-M-15 and amoxicillin for TEM-1, whereas oxacillin for OXA-2. Surprisingly, exogenous BLA expressions are elevated in ∆ampD and ∆ampE mutants but do not always alter their beta-lactam susceptibility. Moreover, the beta-lactam resistance is increased upon in trans expression of ampD, whereas the same is decreased upon ampE expression, indicating a differential effect of ampD and ampE overexpression. In a nutshell, depending on the BLA, AmpD amidase moderately facilitates a varying level of serine-BLA expression whereas AmpE transporter acts likely as a negative regulator of serine-BLA.

Prevalence and Antimicrobial Resistance of Paeniclostridium sordellii in Hospital Settings

(1) Background: The purpose of this study was to determine the prevalence of clostridia strains in a hospital environment in Algeria and to evaluate their antimicrobial susceptibility to antibiotics and biocides. (2) Methods: Five hundred surface samples were collected from surfaces in the intensive care unit and surgical wards in the University Hospital of Tlemcen, Algeria. Bacterial identification was carried out using MALDI-TOF-MS, and then the minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined by the E-test method. P. sordellii toxins were searched by enzymatic and PCR assays. Seven products intended for daily disinfection in the hospitals were tested against Clostridium spp. spore collections. (3) Results: Among 100 isolates, 90 P. sordellii were identified, and all strains were devoid of lethal and hemorrhagic toxin genes. Beta-lactam, linezolid, vancomycin, tigecycline, rifampicin, and chloramphenicol all proved effective against isolated strains. Among all strains tested, the spores of P. sordellii exhibited remarkable resistance to the tested biocides compared to other Clostridium species. The (chlorine-based 0.6%, 30 min), (glutaraldehyde solution 2.5%, 30 min), and (hydrogen peroxide/peracetic acid 3%, 15 min) products achieved the required reduction in spores. (4) Conclusions: Our hospital’s current cleaning and disinfection methods need to be optimized to effectively remove spores from caregivers’ hands, equipment, and surfaces.

Investigation of Beta-Lactam and Tetracycline Group Antibiotic Residues in Bovine Liver, Kidney and Muscle Tissue

In this study, beta-lactam and tetracycline antibiotic residues were investigated in cattle liver, kidney and muscle samples. For this purpose, a total of 75 bovine tissue samples (each of 25 from liver, kidney, muscle) taken from 25 cattle slaughtered in a local slaughterhouse in Sivas were used as materials. ELISA method was applied in the analysis and it was studied with commercial test kits. According to the results of the analysis; beta-lactam and tetracycline residues were detected in all bovine tissue samples. Beta-lactam level was determined between 0.75-1.07 ppb (mean 0.94 ± 0.01) in liver samples, 0.67-1.05 ppb (mean 0.81 ± 0.01) in kidney samples and 0.70-2.57 ppb (mean 0.97 ± 0.07) in muscle samples. Tetracycline level was detected in the range of 4.48-8.50 ppb (mean 6.14 ± 0.17) in liver samples, 1.73-6.39 ppb (mean 4.90 ± 0.24) in kidney samples and 3.31-7.45 ppb (mean 5.67 ± 0.25) in muscle samples. The residue levels determined in the examples complied with the legal limits reported in the European Commission and the Turkish Food Codex Communiqué.

An Evidence-Based Multidisciplinary Approach Focused on Creating Algorithms for Targeted Therapy of Infection-Related Ventilator-Associated Complications (IVACs) Caused by Pseudomonas aeruginosa and Acinetobacter baumannii in Critically Ill Adult Patients

(1) Background: To develop evidence-based algorithms for targeted antibiotic therapy of infection-related ventilator-associated complications (IVACs) caused by non-fermenting Gram-negative pathogens. (2) Methods: A multidisciplinary team of four experts had several rounds of assessments for developing algorithms devoted to targeted antimicrobial therapy of IVACs caused by two non-fermenting Gram-negative pathogens. A literature search was performed on PubMed-MEDLINE (until September 2021) to provide evidence for supporting therapeutic choices. Quality and strength of evidence was established according to a hierarchical scale of the study design. Six different algorithms with associated recommendations in terms of therapeutic choice and dosing optimization were suggested according to the susceptibility pattern of two non-fermenting Gram-negative pathogens: multi-susceptible Pseudomonas aeruginosa (PA), multidrug-resistant (MDR) metallo-beta-lactamase (MBL)-negative-PA, MBL-positive-PA, carbapenem-susceptible Acinetobacter baumannii (AB), and carbapenem-resistant AB. (3) Results: Piperacillin–tazobactam or fourth-generation cephalosporins represent the first therapeutic choice in IVACs caused by multi-susceptible PA. A carbapenem-sparing approach favouring the administration of novel beta-lactam/beta-lactamase inhibitors should be pursued in the management of MDR-MBL-negative PA infections. Cefiderocol should be used as first-line therapy for the management of IVACs caused by MBL-producing-PA or carbapenem-resistant AB. Fosfomycin-based combination therapy, as well as inhaled colistin, could be considered as a reasonable alternative for the management of IVACs due to MDR-PA and carbapenem-resistant AB. (4) Conclusions: The implementation of algorithms focused on prompt revision of antibiotic regimens guided by results of conventional and rapid diagnostic methodologies, appropriate place in therapy of novel beta-lactams, implementation of strategies for sparing the broadest-spectrum antibiotics, and pharmacokinetic/pharmacodynamic optimization of antibiotic dosing regimens is strongly suggested.

Whole Genome Sequencing and Beta-Lactam Resistant Genes in Klebsiella pneumoniae Strains Clinically Isolated from CU Shah Hospital, Gujarat, India

A simple explanation for antimicrobial-resistant opportunistic infections in immunocompromised patients is Klebsiella pneumoniae which gradually being associated in insidious infections globally with high mortality rate. Eight hundred fifty-six antibiotic resistant K. pneumoniae isolates were collected over 3 years period (from different wards and different specimens) from the Microbiology department of C.U. Shah hospital, whose AST checked by Kirby Bauer disk diffusion method. To study AMR genes, virulome, interference of virulence gene with resistance gene, phylogenomic; 6 clinical isolates were proceeded for whole genome sequencing and bio informatics analysis. Klebsiella pneumoniae is a multidrug-resistant (MDR) opportunistic and one of delegate of ESKAPE pathogens groups. This pathogen causes nosocomial infections, urinary tract infections, liver abscesses, wound infections, meningitis. These strains obtain a multidrug resistant phenotype by way of horizontal transfer of ARG transported by either transposons or plasmids. This transfer is generally facilitated by Integrons. In this study antibiotic resistance profile and antibiotic resistance genes analysis as well as virulence gene of K. pneumoniae strains were investigated. The study was carried out using 853 clinical isolates collected during 3 years from C.U. Shah hospital of Surendranagar. Antibiotic resistance profile test was carried out by the VITEK 2 against 21 antibiotics. Out of that 6 samples were proceed for DNA extraction, WGS illumina sequencer and analysis of those raw sequences by TORMES pipeline. In this study antibiotic resistance profile included 13 beta lactam antibiotics which classified under 3 class (Penicillin, Cephalosporin, Carbapenem) of beta lactam and in AMR gene study got total 15 different ESBL resistance genes from 6 different klebsiella pneumoniae strain. All these genes detected with more than 90% identity by CARD. (TORMES Pipeline) CTX-M-15, NDM-5, OKP-B-6, PDC-2, OXA-1, OXA-181, OXA-362, OXA-50, OXA-9, SHV-1, SHV-11, SHV-187, TEM-1, TEM-150. In this study, we’ve analyzed the pattern of antibiotic resistance pattern as a phenotypic characteristic and antibiotic resistance genes as genotypic characteristic and co related the results. As multidrug resistance is a worrying matter, constant observation and regular clinical recognition of resistant bacteria are essential to avoid terrible public health incidents. So, our data should be inferred as a warning for need for prevention and control of the MDR K. pneumoniae in hospital settings.