Search

The article discusses a study of four isolates of Klebsiella pneumoniae chosen randomly from the extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae isolates collected during a survey of four medical centers in Bulgaria between 2002 and 2003. ESBL production was detected using the double-disk synergy method and the ESBL disk confirmatory method of the Clinical and Laboratory Standards Institute (CLSI) using ceftazidime and cefotaxime either alone or in combination with clavulanic acid. Disk-diffusion method and the agar-dilution procedure following CLSI guidelines were used to determine antimicrobial susceptibility.

Scope: This European Society of Clinical Microbiology and Infectious Diseases guideline provides evidence-based recommendations to support a selection of appropriate antibiotic use practices for patients seen in the emergency department (ED) and guidance for their implementation. The topics addressed in this guideline are (a) Do biomarkers or rapid pathogen tests improve antibiotic prescribing and/or clinical outcomes? (b) Does taking blood cultures in common infectious syndromes improve antibiotic prescribing and/or clinical outcomes? (c) Does watchful waiting without antibacterial therapy or with delayed antibiotic prescribing reduce antibiotic prescribing without worsening clinical outcomes in patients with specific infectious syndromes? (d) Do structured culture follow-up programs in patients discharged from the ED with cultures pending improve antibiotic prescribing?, Methods: An expert panel was convened by European Society of Clinical Microbiology and Infectious Diseases and the guideline chair. The panel selected in consensus the four most relevant antimicrobial stewardship topics according to pre-defined relevance criteria. For each main question for the four topics, a systematic review was performed, including randomized controlled trials and observational studies. Both clinical outcomes and stewardship process outcomes related to antibiotic use were deemed relevant. The literature searches were conducted between May 2021 and March 2022. In April 2022, the panel members were formally asked to suggest additional studies that were not identified in the initial searches. Data were summarized in a meta-analysis if possible or otherwise summarized narratively. The certainty of the evidence was classified according to the Grading of Recommendations Assessment, Development and Evaluation criteria. The guideline panel reviewed the evidence per topic critically appraising the evidence and formulated recommendations through a consensus-based process. The strength of the recommendations was classified as strong or weak. To substantiate the implementation process, implementation trials or observational studies describing facilitators/barriers for implementation were identified from the same searches and were summarized narratively., Recommendations: The recommendations on the use of biomarkers and rapid pathogen diagnostic tests focus on the initiation of antibiotics in patients admitted through the ED. Their effect on the discontinuation or de-escalation of antibiotics during hospital stay was not reported, neither was their effect on hospital infection prevention and control practices. The recommendations on watchful waiting (i.e. withholding antibiotics with some form of follow-up) focus on specific infectious syndromes for which the primary care literature was also included. The recommendations on blood cultures focus on the indication in three common infectious syndromes in the ED explicitly excluding patients with sepsis or septic shock. Most recommendations are based on very low and low certainty of evidence, leading to weak recommendations or, when no evidence was available, to best practice statements. Implementation of these recommendations needs to be adapted to the specific settings and circumstances of the ED. The scarcity of high-quality studies in the area of antimicrobial stewardship in the ED highlights the need for future research in this field., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The present study aimed to explore the genomic characteristics of eight New Delhi metallo-β-lactamase-1 (NDM-1)-producing carbapenem-resistant Pseudomonas aeruginosa (CRPA) isolates from a Bulgarian tertiary hospital (2021-2023) in comparison to blaNDM-1-positive strains originating from the Balkans. Antimicrobial susceptibility testing, phenotypic assays for carbapenemase activity, PCR screening, whole-genome sequencing (WGS), and phylogenomic analysis were performed. Seven of the CRPA isolates investigated (Minimum inhibitory concentration values of imipenem and meropenem >32 mg L-1) were also resistant to piperacillin-tazobactam, ceftazidime, ceftazidime-avibactam, cefepime, ceftolozane-tazobactam, amikacin, tobramycin, ciprofloxacin, and levofloxacin, but were susceptible to colistin (0.5-2 mg L-1) and cefiderocol (0.25-1 mg L-1). The P. aeruginosa Pae57 isolate (designated Pae57) remained susceptible to aminoglycosides as well. WGS uncovered the co-existence of blaNDM-1 and blaGES-1. The isolates belonged to the ST654 high-risk clone, except for Pae57 (ST611). Alignment against reference sequences revealed the presence of a Tn21 transposon harboring bleMBL-blaNDM-1-ISAba125. It was similar to that found in the P. aeruginosa ST654 NDM1_1 strain (GCA_020404785.1) from Serbia. Phylogenomic analysis of our isolates indicated that seven of them (ST654) differed from each other in no more than 44 single-nucleotide polymorphisms (SNPs). Pae57 (ST611) was strikingly different (>21,700 SNPs) compared to all Balkan strains. In conclusion, to our knowledge this is the first report of blaNDM-1-positive P. aeruginosa ST611 isolation, which indicates the transmission dynamics of this determinant between high-risk and potentially high-risk P. aeruginosa clones. Obtained results unveil the dissemination of clonally related NDM-1-producing P. aeruginosa strains in the monitored hospital for approximately a 2-year period.

To solve the problem with pan-drug resistant and extensively drug-resistant Gram-negative microbes, newly approved drugs such as ceftazidime/avibactam, cefiderocol, plazomicin, meropenem/vaborbactam, and eravacycline have been introduced in practice. The aim of the present study was to collect carbapenemase-producing clinical Enterobacterales isolates, to characterize their carbapenemase genes and clonal relatedness, and to detect their susceptibility to commonly used antimicrobials and the above-mentioned newly approved antibiotics. Sixty-four carbapenemase producers were collected in a period of one year from four Bulgarian hospitals, mainly including Klebsiella pneumoniae (89% of the isolates) and also single Proteus mirabilis , Providencia stuartii and Citrobacter freundii isolates. The main genotype was bla NDM-1 (in 61%), followed by bla KPC-2 (23%), bla VIM-1 (7.8%) and bla OXA-48 (7.8%). Many isolates showed the presence of ESBL ( bla CTX-M-15/-3 in 76.6%) and AmpC ( bla CMY-4 in 37.5% or bla CMY-99 in 7.8% of isolates). The most common MLST type was K. pneumoniae ST11 (57.8%), followed by ST340 (12.5%), ST258 (6.3%) and ST101 (6.3%). The isolates were highly resistant to standard-group antibiotics, except they were susceptible to tigecycline (83.1%), colistin (79.7%), fosfomycin (32.8%), and aminoglycosides (20.3-35.9%). Among the newly approved compounds, plazomicin (90.6%) and eravacycline (76.3%) showed the best activity. Susceptibility to ceftazidime/avibactam and meropenem/vaborbactam was 34.4% and 27.6%, respectively. For cefiderocol, a large discrepancy was observed between the percentages of susceptible isolates according to EUCAST susceptibility breakpoints (37.5%) and those of CLSI (71.8%), detected by the disk diffusion method. This study is the first report to show patterns of susceptibility to five newly approved antibiotics among molecularly characterized isolates in Bulgaria. The data may contribute to both the improvement of treatment of individual patients and the choice of infection control strategy and antibiotic policy.

Epidemiological and experimental evidence indicated that processed meat consumption is associated with colorectal cancer risks. Several studies suggest the involvement of nitrite or nitrate additives via N-nitroso-compound formation (NOCs). Compared to the reference level (120 mg/kg of ham), sodium nitrite removal and reduction (90 mg/kg) similarly decreased preneoplastic lesions in F344 rats, but only reduction had an inhibitory effect on Listeria monocytogenes growth comparable to that obtained using the reference nitrite level and an effective lipid peroxidation control. Among the three nitrite salt alternatives tested, none of them led to a significant gain when compared to the reference level: vegetable stock, due to nitrate presence, was very similar to this reference nitrite level, yeast extract induced a strong luminal peroxidation and no decrease in preneoplastic lesions in rats despite the absence of NOCs, and polyphenol rich extract induced the clearest downward trend on preneoplastic lesions in rats but the concomitant presence of nitrosyl iron in feces. Except the vegetable stock, other alternatives were less efficient than sodium nitrite in reducing L. monocytogenes growth., (© 2023. Springer Nature Limited.)

The present study aimed to explore the genotypic and phenotypic characteristics of biofilm formation in Bulgarian nosocomial Stenotrophomonas maltophilia isolates (n = 221) during the period 2011-2022, by screening for the presence of biofilm-associated genes (BAG) (spgM, rmlA and rpfF), their mutational variability, and assessment of the adherent growth on a polystyrene surface. The methodology included: PCR amplification, whole-genome sequencing (WGS) and crystal violet microtiter plate assay for biofilm quantification. The overall incidence of BAG was: spgM 98.6%, rmlA 86%, and rpfF 66.5%. The most prevalent genotype was spgM+/rmlA+/rpfF+ (56.1%), followed by spgM+/rmlA+/rpfF- (28.5%), and spgM+/rmlA-/rpfF+ (9.5%), with their significant predominance in lower respiratory tract isolates compared to those with other origin (P < 0.001). All strains examined were characterized as strong biofilm producers (OD550 from 0.224 ± 0.049 to 2.065 ± 0.023) with a single exception that showed a weak biofilm-forming ability (0.177 ± 0.024). No significant differences were observed in the biofilm formation according to the isolation source, as well as among COVID-19 and non-COVID-19 isolates (1.256 ± 0.028 vs. 1.348 ± 0.128, respectively). Also, no correlation was found between the biofilm amounts and the corresponding genotypes. WGS showed that the rmlA accumulated a larger number of variants (0.0086 per base) compared to the other BAG, suggesting no critical role of its product to the biofilm formation. Additionally, two of the isolates were found to harbour class 1 integrons (7-kb and 2.6-kb sized, respectively) containing sul1 in their 3' conservative ends, which confers sulfonamide resistance. To the best of our knowledge, this is the first study on S. maltophilia biofilm formation in Bulgaria, which also identifies novel sequence types (ST819, ST820 and ST826). It demonstrates the complex nature of this adaptive mechanism in the multifactorial pathogenesis of biofilm-associated infections.

In vitro digestions of dry-cured sausages formulated with four different rates of added sodium nitrite and sodium nitrate (NaNO 2 / NaNO 3 , in ppm: 0/0; 80/80; 120/120; 0/200) were performed with a dynamic gastrointestinal digester (DIDGI®). The chemical reactivity of the potentially toxic nitroso-compounds (NOCs), oxidation reactions products and different iron types were evaluated over time. No nitrite nor nitrate dose effect was observed on NOCs' chemical reactivity. Nitrosothiols were scarce, and nitrosylheme was destabilized for every conditions, possibly leading to free iron release in the digestive tract. Total no N- volatile N- nitrosamines concentrations increased in the gastric compartment while residual nitrites and nitrates remained stable. The minimal rate of 80/80 ppm nitrite/nitrate was enough to protect against lipid oxidation in the digestive tract. The present results provide new insights into the digestive chemistry of dry sausages, and into new reasonable arguments to reduce the load of additives in formulations., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

Processed meats' nutritional quality may be enhanced by bioactive vegetable molecules, by preventing the synthesis of nitrosamines from N-nitrosation, and harmful aldehydes from lipid oxidation, through their reformulation. Both reactions occur during digestion. The precise effect of these molecules during processed meats' digestion must be deepened to wisely select the most efficient vegetable compounds. The aim of this study was to design an in vitro experimental method, allowing to foresee polyphenols and vitamins' effects on the chemical reactivity linked to processed meats' digestion. The method measured the modulation of end products formation (specific nitroso-tryptophan and thiobarbituric acid reactive substances (TBARS)), by differential UV-visible spectrophotometry, according to the presence or not of phenolic compounds (chlorogenic acid, rutin, naringin, naringenin) or vitamins (ascorbic acid and trolox). The reactional medium was supported by an oil in water emulsion mimicking the physico-chemical environment of the gastric compartment. The model was optimized to uphold the reactions in a stable and simplified model featuring processed meat composition. Rutin, chlorogenic acid, naringin, and naringenin significantly inhibited lipid oxidation. N-nitrosation was inhibited by the presence of lipids and ascorbate. This methodology paves the way for an accurate selection of molecules within the framework of processed meat products reformulation.

Aim: The aim of this study was to investigate the mechanisms of beta-lactam-resistance and the clonal relatedness of carbapenem-nonsusceptible Klebsiella pneumoniae and Escherichia coli isolates, collected consecutively in eight centers in five Bulgarian cities from November 2014 to March 2018. Carbapenemase-producing enterobacteria were detected in all but one centers. Overall, 104 K. pneumoniae and one E. coli were analysed., Materials and Methods: Antimicrobial susceptibility and beta-lactamases were analysed. Conjugation experiments, plasmid fingerprinting and replicon typing, as well as MLST and ERIC-PCR were carried out., Results: KPC-2 (51%) and NDM-1 (47%) were the main carbapenemases identified. KPC-2 producing K. pneumoniae were classified into 10 MLST-types. The four dominating MLST-types ST29, ST15, ST336 and ST902 comprised 79% of the KPC-2 producers. All but one of the NDM-1 producing isolates belonged to the MLST-type ST11 and were found in seven centers. Furthermore, single K. pneumoniae isolates producing VIM-1 (ST147) and OXA-48 (ST15) were identified. In addition to the carbapenemases, the ESBLs CTX-M-15, CTX-M-3, and SHV-12 as well as AmpC enzyme CMY-4 were found. The FIIAs-replicon-type was found in all KPC-2 producers while the A/C-replicons dominated in NDM-1 producing isolates. The single NDM-1 producing E. coli was determined as MLST-Type ST10 (Warwick scheme)., Conclusion: The interregional clonal expansion of NDM-1 producing ST11 K. pneumoniae and the dissemination of bla KPC-2 carrying plasmids were responsible for the spread of carbapenemase-producing K. pneumoniae in Bulgaria. Our findings highlight the urgency to prevent dissemination of these highly transmissible and dangerous lineages., (Copyright © 2019 Elsevier B.V. All rights reserved.)

A total of 82 extended spectrum beta-lactamase (ESBL) producing Klebsiella pneumoniae and 4 Klebsiella oxytoca isolates were collected in 2014 from four geographical areas in Bulgaria and their multilocus sequence type (MLST) and transferability of the ESBL encoding genes were investigated. The predominant type was CTX-M-15 (87%), followed by CTX-M-3 (9%), SHV-12 or SHV-2 (2%) and CTX-M-14 (1%). The CTX-M-15 producers belonged to ST15 (34.1%) and to a lesser extent to CC17 (ST16, ST17, ST336). The CTX-M-15 transconjugants showed a presence of R, A/C 2 and F replicons. The CTX-M-3 producers were assigned to ST29, ST70, ST432, ST542 and ST15 types and the transconjugants carried M 2 replicons. To the best of our knowledge, this is the first report that fully describes the MLST types among Bulgarian ESBL producing K. pneumoniae and the first report of the detection of IncR plasmid replicon type in our country., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim of this study was to analyze the beta-lactamases and the molecular epidemiology of 19 clinically significant isolates of Proteus mirabilis with decreased susceptibility to imipenem, which have been collected from seven hospitals, located in different Bulgarian towns (Sofia, Varna, and Pleven). The isolates were obtained from blood, urine, tracheal and wound specimens. One additional isolate from hospital environment was included. Susceptibility testing, conjugation experiments, and plasmid replicon typing were carried out. Beta-lactamases were characterized by isoelectric focusing, PCR, and sequencing. Clonal relatedness was investigated by RAPD and PFGE. Integron mapping was performed by PCR and sequencing. All isolates showed a multidrug-resistance profile, but remained susceptible to piperacillin/tazobactam, cefepime, meropenem, and fosfomycin. They produced identical beta-lactamases, namely: TEM-1, VIM-1, and CMY-99. PCR mapping revealed that the bla VIM-1 gene was part of a class 1 integron that additionally included the aac(6')-I, dhfrA1, and ant(3″)-Ia genes. In addition, 17 of the isolates carried the armA gene. Conjugation experiments and plasmid replicon typing were unsuccessful. The isolates were clonally related according to RAPD and PFGE typing. This study reveals the nationwide distribution of a multidrug-resistant P. mirabilis clone producing VIM-1 and CMY-99 along with the presence of different aminoglycoside resistance mechanisms.

According to the European Antimicrobial Resistance Surveillance System project results, Bulgaria has become one of the European countries with dramatically increasing rates of extended-spectrum beta-lactamase (ESBL) producers. The aim of this work was to investigate the epidemiology of ESBL-producing Escherichia coli clinical isolates in Bulgaria, collected from seven clinical centers in three towns, during two study periods: 2002-2003 and 2006-2009. For 193 ESBL-producing E. coli isolates random amplified polymorphic DNA (RAPD) analyses, phylogenetic typing, and screening for O25b-ST131 isolates were carried out. Antimicrobial susceptibility, ESBL-type and transferability of resistance determinants were analyzed. Four different ESBL-types, namely TEM-139, SHV-12, CTX-M-3, and CTX-M-15 were found. CTX-M-15 dominated, being found in 88% of the isolates. RAPD-typing revealed 35 types, among which type A dominated, comprising 65% of the isolates. Sixty-eight percent of the 193 isolates belonged to the O25b-ST131 clone, to the phylogenetic group B2, mostly showed RAPD-type A (92%) and were found in all participating hospitals. O25b-ST131 isolates predominantly produced CTX-M-15 (96%), and less SHV-12 (n=3) or TEM-139 (n=2). In conclusion, this study demonstrated for the first time the country-wide dissemination of a highly resistant B2 O25b-ST131 CTX-M-15 producing E. coli clone in Bulgaria.

Humanity entered the twenty-first century with revolutionary achievements in biomedical research. At the same time multiple "dual-use" results have been published. The battle against infectious diseases is meeting new challenges, with newly emerging and re-emerging infections. Both natural disaster epidemics, such as SARS, avian influenza, haemorrhagic fevers, XDR and MDR tuberculosis and many others, and the possibility of intentional mis-use, such as letters containing anthrax spores in USA, 2001, have raised awareness of the real threats. Many great men, including Goethe, Spinoza, J.B. Shaw, Fr. Engels, J.F. Kennedy and others, have recognized that liberty is also a responsibility. That is why the liberty to decide now represents an acknowledged necessity: biomedical research should be supported, conducted and published with appropriate measures to prevent potential "dual use". Biomedical scientists should work according to the ethical principles of their Code of Conduct, an analogue of Hippocrates Oath of doctors; and they should inform government, society and their juniors about the problem. National science consulting boards of experts should be created to prepare guidelines and control the problem at state level. An international board should develop minimum standards to be applicable by each country. Bio-preparedness is considered another key-measure.

Abdominal gunshot injury is a life-threatening condition that requires urgent and complex measures: control of hemorrhage and source of infection through a surgical intervention; prophylaxis and antibiotic therapy of the infectious complications; intensive care for cardiology and pulmonary support. First phase in infection process (diffuse peritonitis and bacteremia), is governed by Escherichia coli, Enterococcus spp, Bacteroides fragilis group, while the second (development of abscess)--by anaerobes. Application of antibiotic prophylaxis or therapy depends on the time since the incidence together with the score evaluating severity of patient'status. Empiric antibiotic therapy should be broad-spectrum and rapidly bactericidal.

A single Klebsiella pneumoniae strain isolated in a Bulgarian hospital was found to produce CTX-M-71, a new CTX-M variant characterized by one amino acid substitution from glycine to cysteine at position 238 in comparison to CTX-M-15. This exchange decreased the hydrolytic activity of the beta-lactamase for cefotaxime, ceftazidime, and cefepime.

Two Pseudomonas aeruginosa urine isolates from Bulgaria and Germany produced two new VIM-2 variants. VIM-15 had one amino acid substitution (Tyr218Phe) which caused a significant increase in hydrolytic efficiency. The substitution Ser54Leu, characterizing VIM-16, showed no influence on enzyme activity. Both genes were part of class I integrons located in the chromosome.

The aim of the study was to describe the emergence, the spread, and the prevalence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae in Bulgaria. Over eight years (1996-2003), 442 ESBL-screen-positive isolates were collected in nine medical institutions in four Bulgarian towns. Class A ESBLs of the SHV, TEM, and CTX-M groups were identified in seven species. SHV-type enzymes persisted during the whole study period, TEM-ESBLs appeared first in 1999, and CTX-M-types appeared first in 2001. The rate of CTX-M enzyme producers increased rapidly between 2001 and 2003, while the rate of SHV producers decreased. Six different ESBL-types were identified, namely, SHV-2, -5, and -12, CTX-M-3 and -15, and a new TEM-3-like variant (TEM-139). The most widespread enzymes were SHV-12, CTX-M-15, and CTX-M-3 found in seven centers. TEM-139 was identified mainly in one center. A trend for strains harboring more than one ESBL gene, for example, CTX-M + SHV, was observed since 2002. Plasmid fingerprinting and random amplified polymorphic DNA analysis typing revealed wide dissemination of identical plasmids among different bacterial species and hospitals, as well as clonal spread of ESBL producers. Our data contribute to clarify the dynamics in the prevalence of ESBLs in Bulgaria and demonstrate the importance of molecular procedures for their analysis.

During a survey of extended-spectrum beta-lactamases (ESBLs) in Bulgaria from 1996 to 2003, a TEM-3-like ESBL was detected in strains of Klebsiella pneumoniae, Escherichia coli, Citrobacter freundii and Klebsiella oxytoca from three centres in three different towns. The nucleotide sequence of the cloned gene was identical to that of TEM-3, except for one substitution (C347A) causing an amino acid exchange at position 49 from leucine to methionine. This TEM-3 variant with both a unique nucleotide and amino acid sequence was designated TEM-139. Transformants producing TEM-3 or TEM-139 expressed identical beta-lactam resistance phenotypes. TEM-139 was the only TEM-type ESBL detected in the surveyed hospitals (seven centres in three towns). TEM-139 is a natural variant of TEM-3 with an amino acid exchange without informational content, detectable only by molecular procedures, e.g. a nucleotide-specific polymerase chain reaction.

To assess the antibiotic policies in Central Eastern European (CEE) countries, a questionnaire on the prevalence of resistance, antibiotic consumption data for ambulatory and hospital care and antibiotic policies, was mailed to national representatives. Data on antibiotic resistance and consumption of antibiotics at national levels are limited and vary considerably among countries. The importance of surveillance data in altering perceptions of the prevalence of resistance is shown by the comparison of surveillance data and interview data. Interview data without surveillance data produced the widest range of estimates of the prevalence of resistance in streptococcus pneumonia -5% in Lithuania and 82% in Belarus. The average consumption of antibiotics in ambulatory care in eight CEE countries in 2001 was 19.35 defined daily doses (DDD)/1000 inhabitants per day, (range 13.1 - 24.8 DDD) and in hospitals in six CEE countries was 2.2 DDD/1000 inhabitants per day (range 1.3-4.5). Over the counter sales of antibiotics are available in some countries. Antibiotic policy interventions do not exist or only apply to specific problems or interventions. Better implementation of antibiotic interventions and education on antibiotic use should be a high priority in this region. An effective strategy requires close co-operation, consultations and partnership at national and international level in particular, via existing international organisations.

A series of seven new cephalosporins was prepared for preliminary microbiological evaluation by N-acylation of 7-aminocephalosporanic acid with substituted N-pyrrolylcarboxylic acids via mixed anhydrides. The chemical structure of the compounds were confirmed by IR, 1H-NMR and mass spectral data. The 7-(N-pyrrolyl) cephalosporin derivatives were tested in vitro by the disc diffusion method upon 3 strains and subsequent determination of the minimal inhibitory concentration (MIC) of the most active ones upon 29 strains. The products of the series exhibited antibacterial activity. They showed selective potency against gram-positive and were practically inactive against gram-negative microorganisms. The compound 3-[(acetyloxy)methyl]-7-([2-[3-(ethoxycarbonyl)-2-methyl-5-phenyl-1H-1-pyrrolyl]acetyl]amino)-6-oxo-7,7a-dihydro-2H,6H-aceto[2,1-b][1,3]thiazine-4-carboxylic acid (4a) was outlined as more active than the reference cefazolin (CAS 23325-78-2) in regard to S. pyogenes and some strains of S. aureus, the MIC of 4a against S. pyogenes were at least 4-fold lower. The toxicological evaluations of the starting N-pyrrolylcarboxylic acids showed no acute toxicity.

New 6beta-cysteinesulfonamidopenicillanic acids and their sulfoxides were synthesized by sulfonylation of 6beta-aminopenicillanic acid or its (S)-sulfoxide with (R)-N-benzyloxycarbonylcysteinesulfonyl chloride ethyl ester (2a, 1b) and (R)-N-benzyloxycarbonylcysteinesulfonyl chloride benzyl ester (2a, 2b). The corresponding 6beta-cysteinesulfonamidopenicillanic acids sulfones 1c and 2c were prepared by oxidation of the sulfoxides 1b and 2b with potassium permanganate in aqueous medium. When combined with ampicillin some of the compounds reduced the minimal inhibitory concentrations of ampicillin against beta-lactamase producing strains.