scholarly journals Suspected penicillin allergy: risk assessment using an algorithm as an antibiotic stewardship project

2020 ◽  
Vol 29 (6) ◽  
pp. 174-180
Author(s):  
Christiane Querbach ◽  
Tilo Biedermann ◽  
Dirk H. Busch ◽  
Rüdiger Eisenhart-Rothe ◽  
Susanne Feihl ◽  
...  
Keyword(s):  
Risk Stratification ◽  
Bacterial Infections ◽  
University Hospital ◽  
Beta Lactam ◽  
Delayed Reaction ◽  
Allergy Testing ◽  
Beta Lactam Antibiotics ◽  
Patient Reported ◽  
Provocation Testing ◽  
Reliable Solution

Summary Background Beta-lactam antibiotics (BLA) are the treatment of choice for a large number of bacterial infections. Putative BLA allergies are often reported by patients, but rarely confirmed. Many patients do not receive BLA due to suspected allergy. There is no systematic approach to risk stratification in the case of a history of suspected BLA allergy. Methods Using the available stratification programs and taking current guidelines into account, an algorithm for risk stratification, including recommendations on the use of antibiotics in cases of compellingly indicated BLA despite suspected BLA allergy, was formulated by the authors for their maximum care university hospital. Results The hospital is in great need of recommendations on how to deal with BLA allergies. Patient-reported information in the history forms the basis for classifying the reactions into four risk categories: (1) BLA allergy excluded, (2) benign delayed reaction, (3) immediate reaction, and (4) severe cutaneous and extracutaneous drug reaction. Recommendations strictly depend on this classification and range from use of full-dose BLA or use of BLA under certain conditions (e.g., two-stage dose escalation, non-cross-reactive BLA only) to prohibiting all BLA and the use of alternative non-BLA. In case of suspected immediate or delayed allergic reactions, there is an additional recommendation regarding subsequent allergy testing during a symptom-free interval. Conclusion Triage of patients with suspected BLA is urgently required. While allergy testing, including provocation testing, represents the most reliable solution, this is not feasible in all patients due to the high prevalence of BLA allergies. The risk stratification algorithm developed for the authors’ hospital represents a tool suitable to making a contribution to rational antibiotic therapy.

scholarly journals Mycoplasma pneumoniae may cause dyspnoea and hospitalisations in young healthy adults

2021 ◽  
Author(s):  
Riku Metsälä ◽  
Solja Ala-Korpi ◽  
Juha Rannikko ◽  
Merja Helminen ◽  
Marjo Renko
Keyword(s):  
Respiratory Tract ◽  
Mycoplasma Pneumoniae ◽  
Hospital Setting ◽  
Health Condition ◽  
Clinical Findings ◽  
Antimicrobial Treatment ◽  
University Hospital ◽  
Upper Respiratory Tract ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics

AbstractPolymerase chain reaction (PCR)-based diagnostics for Mycoplasma pneumoniae (M. pneumoniae) from the respiratory tract has become widely available, but the interpretation of the results remains unclear. M. pneumoniae has been suggested to cause mainly mild and self-limiting infections or asymptomatic carriage. However, systematic analyses of the association between PCR results and clinical findings are scarce. This study aimed to clarify the clinical features of PCR-positive M. pneumoniae infections in a hospital setting. We reviewed 103 PCR-positive patients cared for in a university hospital during a 3-year period. Data on age, sex, health condition, acute symptoms, other pathogens found, laboratory and X-ray results and treatments were collected. Over 85% of the patients had a triad of typical symptoms: fever, cough and shortness of breath. Symptoms in the upper respiratory tract were rare. In 91% of the cases, M. pneumoniae was the only pathogen found. The highest incidence was found in the age group of 30–40 years, and 68% of the patients did not have any underlying diseases. Most patients were initially empirically treated with beta-lactam antibiotics and needed 2–4 changes in their treatment. Only 6% were discharged without an antibiotic effective against M. pneumoniae. This study shows that M. pneumoniae often led to hospitalisation and that patients needed appropriate antimicrobial treatment to recover. Mixed infections were rare, and situations that could be interpreted as carriage did not occur.

scholarly journals Cross-Reactivity of Drug-Dependent Antibodies in Patients with Immune Thrombocytopenia Induced By Beta-Lactam Antibiotics

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 2350-2350
Author(s):  
Matthew John Slaught ◽  
Daniel W. Bougie ◽  
Richard H. Aster
Keyword(s):  
Bacterial Infections ◽  
Immune Thrombocytopenia ◽  
Conflicts Of Interest ◽  
Cross Reactivity ◽  
Beta Lactam ◽  
Cross Reactions ◽  
Beta Lactam Antibiotics ◽  
Wide Range ◽  
Group 2 ◽  
Group 1

More than 50 beta lactam (BL) antibiotics are now in active use for treatment of a wide range of bacterial infections. BL antibiotics are among the most common drugs capable of inducing antibodies (DDAbs) that cause drug-induced immune thrombocytopenia (DITP). Most DDAbs are highly specific for the sensitizing drug but beta lactams all have a common core structure and many similarities among side groups that are added to augment potency and modify specificity, raising the possibility that a DDAb specific for one BL may cross-react with another. We studied DDAbs from 33 patients with DITP induced by 9 commonly used BL drugs to determine whether patterns of cross-reactivity exist that might influence the choice of an alternative antibiotic in a patient with BL-induced DITP. DDAbs were demonstrated in a flow cytometric assay considered to be "positive" when immunoglobulins in patient serum but not normal serum react with normal platelets in the presence, but not in the absence of drug (Blood 2018;131:1486). DDAbs detected in the 33 patients were specific for 9 different BL drugs that were divided into two groups, "penicillins" (Group 1) and cephalosporins (Group 2) on the basis of structural similarities (Figure 1). In Group 1 were 19 DDAbs specific for amoxicillin (2), nafcillin (4) and piperacillin (13). Structurally similar ampicillin and penicillin were also tested with these abs. In Group 2 were 14 DDAbs specific for cefadroxil (1), cefepime (2), ceftazidime (2), ceftizoxime (1), ceftriaxone (7) and cephalexin 1). Cross-reactions identified within these groups of DDAbs are shown in Tables 1 and 2. Cross-reactions, many quite strong (S) were observed among DDAbs specific for drugs in both structural groups (Tables 1 and 2). Particularly noteworthy were cross-reactions of the 19 Group 1 DDAbs with ampicillin (6) and penicillin (6) (Table 1) and of the 14 Group 2 DDAbs with cefepime (6), ceftizoxazole (6) and ceftriaxone (3) (Table 2). The findings show that platelet-specific DDAbs induced by beta lactam antibiotics, in contrast with those induced by medications like quinine, sulfamethoxazole and vancomycin, commonly cross-react with other antibiotics of this class. In patients with immune thrombocytopenia induced by a beta lactam antibiotic, it may be prudent to avoid switching to another beta lactam or, if this is necessary, to monitor platelet counts carefully. Disclosures No relevant conflicts of interest to declare.

scholarly journals Species-Specific Sensitivity of Coagulase-Negative Staphylococci to Single Antibiotics and Their Combinations

2011 ◽  
Vol 60 (2) ◽  
pp. 155-161 ◽  
Author(s):  
GRAŻYNA SZYMAŃSKA ◽  
MAGDALENA SZEMRAJ ◽  
ELIGIA M. SZEWCZYK
Keyword(s):  
University Hospital ◽  
Hospital Environment ◽  
Beta Lactam ◽  
Coagulase Negative Staphylococci ◽  
Methicillin Resistant ◽  
Beta Lactam Antibiotics ◽  
Resistant Strains ◽  
Staphylococcus Hominis ◽  
Species Specific

The activity of beta-lactam antibiotics (oxacillin, cloxacillin, cephalotin), vancomycin, gentamicin and rifampicin applied in vitro individually and in combination against 37 nosocomial methicillin-resistant strains of coagulase-negative staphylococci (CNS) was assessed to demonstrate the heterogeneity of this group of bacteria and estimate the chance of the efficacy of such therapy. The strains belonged to four species: Staphylococcus epidermidis, Staphylococcus haemolyticus, Staphylococcus cohnii, Staphylococcus hominis. They originated from a hospital environment and from the skin of medical staff of the intensive care unit of a paediatric ward at a university hospital. All strains were methicillin-resistant, according to CLSI standards, but individual strains differed in MIC(ox) values. Susceptibility to other tested antibiotics was also characteristic for the species. The increased susceptibility to antibiotics in combinations, tested by calculating the fractional inhibitory concentration (FIC) index, concerned 26 out of 37 investigated strains and it was a feature of a particular species. Combinations of vancomycin and cephalotin against S. epidermidis and oxacillin with vancomycin were significant, as well as cephalotin and rifampicin in growth inhibition of multiresistant S. haemolyticus strains.

scholarly journals Biochemical profile and resistance phenotype of bacteria isolated from the operating site departments of the National Reference University Hospital of N’Djamena

2021 ◽  
Vol 10 (1) ◽  
pp. 381-396
Author(s):  
Bessimbaye Nadlaou ◽  
Djimadoum Mbanga ◽  
Issakou Bakarnga-Via ◽  
Claude Oualé ◽  
Nicolas Barro ◽  
...  
Keyword(s):  
Average Rate ◽  
University Hospital ◽  
Beta Lactam ◽  
Beta Lactams ◽  
Surgical Services ◽  
National Reference ◽  
Beta Lactam Antibiotics ◽  
Medical Microbiology ◽  
Normal Period ◽  
Staphylococcus Spp

The aim is to assess the level of contamination of wound bacteria in operated patients in the surgical departments of the National Reference University Hospital (CHURN) of N’Djamena. From August 1, 2018 to August 1, 2019, an observational culture study on wound pus was carried out in patients operated on from the surgical services of the N’Djamena CHURN according to standard methods of medical microbiology. Of the 1092 patients operated on, 565 patients were released within a normal period of hospitalization and 527 in contact with the pathogens were maintained. Significant differences were observed between the proportions of positive (86%) and sterile (14%) cultures; female (30.36%) and male (69.63%) operated subjects with probabilities of 0.02 and 0.001 respectively. Escherichia coli were the most common germs (32.7%), followed by Staphylococcus spp (20.9%). The bacteria isolated were resistant to beta-lactam antibiotics at an average rate of 40%, only imipenem, a last-resort antibiotic, was very sensitive (99.5%). In view of these results, we recommend that prescribers avoid prescribing antibiotics without laboratory evidence for fear of losing the beta-lactams permanently.

Beta-lactam Resistance Mechanisms in Pathogens Isolated from Patients Admitted to Intensive Care Unit

2017 ◽  
Vol 68 (6) ◽  
pp. 1225-1228
Author(s):  
Carmen Axente ◽  
Delia Muntean ◽  
Luminita Baditoiu ◽  
Roxana Moldovan ◽  
Elena Hogea ◽  
...  
Keyword(s):  
Intensive Care Unit ◽  
Intensive Care ◽  
Antimicrobial Resistance ◽  
Resistance Mechanisms ◽  
University Hospital ◽  
Beta Lactam ◽  
Extended Spectrum Beta Lactamase ◽  
Beta Lactam Antibiotics ◽  
Current Context ◽  
A Prospective Study

Intensive care units (ICUs) are often referred to as the epicentre of infection diseases in a hospital. Many studies highlighted the importance of using local antimicrobial resistance data, to guide empirical antibiotic therapy. As a consequence, the present study is particularly important, especially in the current context, when we are witnessing an ascending trend of antimicrobial resistance. Beta-lactams are the most frequently used class of antibiotics for treating patients infected with various germs. The aim of this study is to analyse the modalities by which microorganisms become resistant to antibiotics of this class, in an intensive care unit of a Romanian university hospital. During the period between January, the 1st 2012 and December the 31st 2013, a prospective study was conducted in the largest ICU from the Western part of Romania. Various resistance mechanisms to beta-lactam antibiotics were detected. Among these, there is great concern regarding the high number of extended-spectrum beta-lactamase producing microorganisms, as in most cases they determine the use of carbapenems, thus increasing the risk of occurrence and dissemination of carbapenemase-producing bacteria.

scholarly journals Implementation of Antibiotic Stewardship in a University Hospital Setting

Antibiotics ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 93
Author(s):  
Milan Kolar ◽  
Miroslava Htoutou Sedlakova ◽  
Karel Urbanek ◽  
Patrik Mlynarcik ◽  
Magdalena Roderova ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Pseudomonas Aeruginosa ◽  
Klebsiella Pneumoniae ◽  
Antibiotic Stewardship ◽  
Bacterial Infections ◽  
Hospital Setting ◽  
University Hospital ◽  
Beta Lactam ◽  
Stewardship Program ◽  
Clonal Spread

The article describes activities of an antibiotic center at a university hospital in the Czech Republic and presents the results of antibiotic stewardship program implementation over a period of 10 years. It provides data on the development of resistance of Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Staphylococcus aureus to selected antibiotic agents as well as consumption data for various antibiotic classes. The genetic basis of resistance to beta-lactam antibiotics and its clonal spread were also assessed. The study showed significant correlations between aminoglycoside consumption and resistance of Escherichia coli and Klebsiella pneumoniae to gentamicin (r = 0.712, r = 0.869), fluoroquinolone consumption and resistance of Klebsiella pneumoniae to ciprofloxacin (r = 0.896), aminoglycoside consumption and resistance of Pseudomonas aeruginosa to amikacin (r = 0.716), as well as carbapenem consumption and resistance of Pseudomonas aeruginosa to meropenem (r = 0.855). Genotyping of ESBL- positive isolates of Klebsiella pneumoniae and Escherichia coli showed a predominance of CTX-M-type; in AmpC-positive strains, DHA, EBC and CIT enzymes prevailed. Of 19 meropenem-resistant strains of Klebsiella pneumoniae, two were identified as NDM-positive. Clonal spread of these strains was not detected. The results suggest that comprehensive antibiotic stewardship implementation in a healthcare facility may help to maintain the effectiveness of antibiotics against bacterial pathogens. Particularly beneficial is the work of clinical microbiologists who, among other things, approve administration of antibiotics to patients with bacterial infections and directly participate in their antibiotic therapy.

scholarly journals Prevalence and Impact of Reported Drug Allergies among Rheumatology Patients

Diagnostics ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 918
Author(s):  
Shirley Chiu Wai Chan ◽  
Winnie Wan Yin Yeung ◽  
Jane Chi Yan Wong ◽  
Ernest Sing Hong Chui ◽  
Matthew Shing Him Lee ◽  
...  
Keyword(s):  
Lupus Erythematosus ◽  
Patient Specific ◽  
Beta Lactam ◽  
Tertiary Referral Hospital ◽  
Allergy Testing ◽  
Antibiotic Allergy ◽  
Lactam Antibiotic ◽  
Inflammatory Drugs ◽  
Provocation Testing ◽  
Rheumatological Diseases

Background: Drug allergies (DA) are immunologically mediated adverse drug reactions and their manifestations depend on a variety of drug- and patient-specific factors. The dysregulated immune system underpinning rheumatological diseases may also lead to an increase in hypersensitivity reactions, including DA. The higher prevalence of reported DA, especially anti-microbials, also restricts the medication repertoire for these already immunocompromised patients. However, few studies have examined the prevalence and impact of reported DA in this group of patients. Methods: Patients with a diagnosis of rheumatoid arthritis (RA), spondyloarthritis (SpA), or systemic lupus erythematosus (SLE) were recruited from the rheumatology clinics in a tertiary referral hospital between 2018 and 2019. Prevalence and clinical outcomes of reported DA among different rheumatological diseases were calculated and compared to a cohort of hospitalized non-rheumatology patients within the same period. Results: A total of 6081 patients (2541 rheumatology patients: 1286 RA, 759 SpA, and 496 SLE; and 3540 controls) were included. DA was more frequently reported among rheumatology patients compared to controls (23.8% vs. 13.8%, p < 0.01). Antibiotics and non-steroidal anti-inflammatory drugs (NSAIDs) were the two most commonly reported categories of DA with a prevalence of 12.0% and 5.1%, respectively. Reported antibiotics allergies were more frequent in patients with RA (OR = 1.20, 95% CI = 1.02–1.62, p = 0.03) and SLE (OR = 4.69, 95% CI = 3.69–5.95, p < 0.01); and associated with increased infection-related admissions among rheumatology patients (OR = 1.79, 95% CI = 1.09–2.95, p = 0.02). Among the subgroup of patients referred for allergy testing, 85.7% of beta-lactam antibiotic allergy labels were found to be inaccurate and de-labelled after negative drug provocation testing. Conclusion: The prevalence of reported DA was significantly higher in rheumatology patients. Reported antibiotic allergy was associated with increased rate of infection-related admissions. However, the rate of genuine antibiotic allergy was low. Further studies are needed to guide proper assessment of reported DA and impact of comprehensive allergy testing in this group of patients.

scholarly journals Diversity And Antibiograms of Secondary Bacterial Isolates From Cutaneous Leishmaniasis Wounds

2021 ◽  
Author(s):  
Comfort Yeboaa ◽  
Vivian Etsiapa Boamah ◽  
Hayford Odoi ◽  
Rhoda Owusu-Ntim ◽  
Yaw Duah Boakye ◽  
...  
Keyword(s):  
Cutaneous Leishmaniasis ◽  
Bacterial Infections ◽  
Pathogenic Bacteria ◽  
Bacterial Species ◽  
Healing Process ◽  
Diffusion Method ◽  
Beta Lactam ◽  
Providencia Rettgeri ◽  
Beta Lactam Antibiotics ◽  
Agar Disc

Abstract Background: Leishmaniasis is a vector borne disease caused by an intracellular protozoan parasite. The presence of secondary bacterial infections in cutaneous leishmaniasis wounds exacerbate lesion development and could lead to delay in the healing process. Little is also known about the different bacteria species co-infecting leishmaniasis wounds and their sensitivity patterns in Ghana. This study sought to determine the resistance patterns of bacteria co-infecting cutaneous leishmaniasis wounds from selected communities in the Nkwanta district.Methods: Various bacteria were isolated and characterized from exudates obtained from wound swabs collected with sterile cotton tipped applicators. Confirmation of bacterial identity was done using the analytical profile index and the matrix-assisted laser desorption/ionization time of flight mass spectrometry. Antibiotic susceptibility tests were performed using agar disc diffusion method according to the Clinical and Laboratory Standards Institute breakpoint values.Results: A total of 42 secondary bacteria were isolated from the wounds among which S. aureus was the most predominant (31%). Other pathogenic bacteria that colonized the wounds included Bacillus subtilis (23.8%), Pantoea spp(11.9%), Klebsiella pneumoniea (7.1%), Enterobacter cloacae (7.1%), Aeromonas spp (4.8%), Serratia marcescens (4.8%),Serratia liquefacien (2.4%), Serratia plymutheca (2.4%), Providencia rettgeri (2.4%) and Cronobacter spp (2.4%). Majority of the isolates were obtained from Agoufie (21.4%), Baasare (19%), and Gekrong (16.7%). Most of the isolates were resistant to beta-lactam antibiotics and the third generation cephalosporin. Notably, 84.6% of the S. aureus isolates were methicillin and ciprofloxacin resistant whilst 92.3% were resistant to ampicllin. About sixty-nine percent (69.2%) showed intermediate susceptibility to Erythromycin. Additionally, S. plymutheca was resistant to all the test antibiotics. All the K. pneumoniae and E. cloacae isolates showed resistance to ampicillin, cefotaxime, ceftriaxone, ciprofloxacin, amikacin, aztreonam and meropenem but only 66.7% of these isolates were resistant to piperacillin. All isolates of Providencia rettgeri, Cronobacter spp, S. marcescen, S. liquefacien were resistant to all the beta-lactam antibiotics.Conclusion: This study suggests colonization of cutaneous leishmaniasis wounds with varied bacterial species that are mostly resistant to beta-lactam group of antibiotics.

Clinical relevance, Speciation, and Antibiogram of Non -Diphtherial Corynebacteria isolated from various clinical samples in a tertiary care hospital in Zagazig, Egypt

2021 ◽  
Vol 30 (2) ◽  
pp. 43-49
Author(s):  
Shymaa Yahia ◽  
May M. Sami
Keyword(s):  
Tertiary Care ◽  
Resistance Rate ◽  
University Hospital ◽  
British Society ◽  
Diffusion Method ◽  
Clinical Samples ◽  
Care Hospital ◽  
Beta Lactam ◽  
Beta Lactam Antibiotics ◽  
Isolated Species

Background: The non-diphtherial Corynebacteria, also called “Coryneforms” bacteria are a diversified group of gram positive non sporing bacilli belonging to the genus Corynebacteria. Such bacteria are considered members of human microbiota (skin, respiratory and genital mucus membranes). Coryneform bacteria's pathogenic capacity has been undervalued until recently. Despite of frequently deemed as contaminants, these bacteria have been correlated to diverse clinical infections recently. Objectives: To isolate, speciate, and determine antimicrobial susceptibility pattern of clinically relevant non-diphtherial Corynebacteria from various clinical samples. Methodology: Different clinical samples (blood, urine, sputum, wound swabs, pus) collected from hospitalized patients attending at Zagazig University Hospital. The samples were processed and cultured as per conventional bacteriological methods. A total of 75 clinically relevant corynebacterial isolates exhibited speciation utilizing matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) analysis and their antibiogram was done by disc diffusion method by means of combined guidelines of Clinical and Laboratory Standards Institute (CLSI) as well as British Society for Antimicrobial Chemotherapy (BSAC) because of lack of definite CLSI guidelines. Results: The mean age of the studied patients was 64.6 ± 14.9 years, 60% were male and 40% female. A total 75 clinically relevant Corynebacteria species were obtained from different clinical samples, including wound swabs and pus (53%), sputum (20%), and blood (17%). Forty two percent were isolated from ICUs. The most prevalent isolated species was C.amycolatum (27%), C. striatum (20%), and C.jeikieum (16%). Beta lactam antibiotics showed least activity against Corynebacteria species with resistance rate against penicillin 76% and ceftriaxone 72%, while all isolates exhibited uniform sensitivity (100%) against vancomycin as well as linezolid. Conclusion: This study showed isolation of different clinically relevant non-diaphterial Corynebacteria from different clinical samples with pus and wound swabs as the most common samples from which Corynebacteria were isolated. In particular, C.amycolatum was the most common isolated species. Beta lactam antibiotics (penicillin, ceftriaxone) showed the least activity while vancomycin and linezolid were the most active agents against nondiapdhterial Corynebacteria isolates. Herein, we confirm diphtheroids’ clinical importance among different infections that necessitate evaluating their susceptibility patterns to some common antibacterial agents for guide the best antibiotic to treat infections caused by these species.

scholarly journals Evolution of TEM-Type Enzymes: Biochemical and Genetic Characterization of Two New Complex Mutant TEM Enzymes, TEM-151 and TEM-152, from a Single Patient

2007 ◽  
Vol 51 (4) ◽  
pp. 1304-1309 ◽  
Author(s):  
Frédéric Robin ◽  
Julien Delmas ◽  
Cédric Schweitzer ◽  
Olivier Tournilhac ◽  
Olivier Lesens ◽  
...  
Keyword(s):  
Hydrolytic Activity ◽  
University Hospital ◽  
Sequencing Analysis ◽  
Beta Lactam ◽  
Beta Lactamases ◽  
Beta Lactam Antibiotics ◽  
Extended Spectrum ◽  
Genes Encoding ◽  
Extended Spectrum Beta Lactamases ◽  
Molecular Comparison

ABSTRACT Two clinical isolates of Escherichia coli, CF1179 and CF1295, were isolated from a patient hospitalized in the hematology unit of the University Hospital of Clermont-Ferrand, Clermont-Ferrand, France. They were resistant to penicillin-clavulanate combinations and to ceftazidime. The double-disk synergy test was positive only for isolate CF1179. Molecular comparison of the isolates showed that they were clonally related. E. coli recombinant strains exhibiting the resistance phenotype of the clinical strains were obtained by cloning. The clones corresponding to strains CF1179 and CF1295 produced TEM-type beta-lactamases with pI values of 5.7 and 5.3, respectively. Sequencing analysis revealed two novel bla TEM genes encoding closely related complex mutant TEM enzymes, designated TEM-151 (pI 5.3) and TEM-152 (pI 5.7). These two genes also harbored a new promoter region which presented a 9-bp deletion. The two novel β-lactamases differed from the parental enzyme, TEM-1, by the substitution Arg164His, previously observed in extended-spectrum beta-lactamases (ESBLs), and by the substitutions Met69Val and Asn276Asp, previously observed in the inhibitor-resistant penicillinase TEM-36/IRT-7. They differed by two amino acid substitutions: TEM-152 harbored a Glu240Lys ESBL-type substitution and TEM-151 had an Ala284Gly substitution. Functional analysis of TEM-151 and TEM-152 showed that both enzymes had hydrolytic activity against ceftazidime (k cat, 5 and 16 s−1, respectively). TEM-152 was more resistant than TEM-151 to the inhibitor clavulanic acid (50% inhibitory concentrations, 1 versus 0.17 μM). These results confirm the evolution of TEM-type enzymes toward complex enzymes harboring the two kinds of substitutions which confer an extended spectrum of action against beta-lactam antibiotics and resistance to inhibitors.

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