Penicillins

A velvet multisubunit complex was recently detected in the filamentous fungus Penicillium chrysogenum , the major industrial producer of the β-lactam antibiotic penicillin. Core components of this complex are P. chrysogenum VelA (PcVelA) and PcLaeA, which regulate secondary metabolite production, hyphal morphology, conidiation, and pellet formation. Here we describe the characterization of PcVelB, PcVelC, and PcVosA as novel subunits of this velvet complex. Using yeast two-hybrid analysis and bimolecular fluorescence complementation (BiFC), we demonstrate that all velvet proteins are part of an interaction network. Functional analyses using single- and double-knockout strains clearly indicate that velvet subunits have opposing roles in the regulation of penicillin biosynthesis and light-dependent conidiation. PcVelC, together with PcVelA and PcLaeA, activates penicillin biosynthesis, while PcVelB represses this process. In contrast, PcVelB and PcVosA promote conidiation, while PcVel...

Betalactams are the most frequent cause of hypersensitivity reactions to drugs mediated by a specific immune mechanism. Immediate reactions occur within 1 to 6 hours after betalactam administration, and are generally IgE-mediated. They clinically translate into urticaria, angioedema and anaphylaxis. Non-immediate or delayed reactions occur after 1 hour of administration. These are the most common reactions and are usually mediated by T cells. The most frequent type is the maculopapular or morbilliform exanthematous eruption. Most individuals who report allergies to penicillin and betalactams can tolerate this group of antibiotics. To make diagnosis, a detailed medical history is essential to verify whether it was an immediate or non-immediate reaction. Thereafter, in vivo and/or in vitro tests for investigation may be performed. The challenging test is considered the gold standard method for diagnosis of betalactam hypersensitivity. The first approach when suspecting a reaction to b...

Patients and Methods. Forty-six consecutive patients who presented with upper gastrointestinal symptoms and tested positive for H. pylori infection were included in the study. In every patient, after performance of upper gastrointestinal endoscopy, antral biopsies were ...

PURPOSE The purpose of this study was to: (1) evaluate the prevalence of mutans streptococci (MS) and dental caries in sickle cell anemia (SCA) patients receiving long-term prophylactic penicillin therapy; and (2) determine changes in MS colonization and dental caries upon discontinuing the antibiotic. METHODS Sixty subjects with SCA and 60 age- and race-matched control subjects participated in this study. The SCA subjects were divided into 2 separate age groups: (1) group 1 subjects were under 6 years of age and received penicillin twice a day; and (2) group 2 subjects were 6 to 12 years old and received no daily prophylactic antibiotics, although up to age 6 they had received daily penicillin before it was discontinued. DMFS/dmfs scores for all subjects were obtained through a comprehensive dental examination including bitewing radiographs. Stimulated salivary samples to assess MS levels were obtained on all subjects. Data on medical, dental, fluoride, and dietary history were obt...

Antibiotic overuse is driving the emergence of antibiotic resistance worldwide. Good data on prescribing behaviours of healthcare providers are needed to support antimicrobial stewardship initiatives. This study examined the differences in antibiotic prescribing rates of public and private primary care clinics in Malaysia. We used data from the National Medical Care Survey (NMCS), a nationwide cluster sample of Malaysian public and private primary care clinics in 2014. NMCS contained demographic, diagnoses and prescribing from 129 public clinics and 416 private clinics. We identified all encounters who were prescribed antibiotic and analyse the prescribing rate, types of antibiotics, and diagnoses that resulted in antibiotic. Five thousand eight hundred ten encounters were prescribed antibiotics; antibiotic prescribing rate was 21.1 % (public clinics 6.8 %, private clinics 30.8 %). Antibiotic prescribing was higher in private clinics where they contributed almost 87 % of antibiotics...

Background Penicillin acylases (PACs) are enzymes of industrial relevance in the manufacture of β-lactam antibiotics. Development of a PAC with a longer half-life under the reaction conditions used is essential for the improvement of the operational stability of the process. A gene encoding a homologue to Escherichia coli PAC was found in the genome of the thermophilic bacterium Thermus thermophilus (Tth) HB27. Because of the nature of this PAC and its complex maturation that is crucial to reach its functional heterodimeric final conformation, the overexpression of this enzyme in a heterologous mesophilic host was a challenge. Here we describe the purification and characterization of the PAC protein from Tth HB27 overexpressed in Escherichia coli. Results Fusions to a superfolder green fluorescent protein and differential membrane solubilization assays indicated that the native enzyme remains attached through its amino-terminal end to the outer side of the cytoplasmic membrane of Tt...

Antibiotics are frequently prescribed in the older person, the dosification needs special care, since the pharmacokinetic parameters changes with aging and the side effects can be different in the older person. The creatinine clearance changes and we must modify the way we prescribe such antibiotics to the elderly, calculating. The variety of antibiotics now available led us to consider this paper in which we have presented the antimicrobial agents that can be considered in the treatment of the older person. We present several groups: the penicillins, cephalosporins, monobactams, carbapenems and betalactamase inhibitors or the great betalactam group. Other trimetroprin-sulfame-thoxazole, the newer macrolides (azithromycin and clarithromycin) as well as the aminoglycosides, vancomycin, clindamycin, metroridazole. The indications and contraindications are presented and reviewed.

An outbreak of pseudobacteremia due to Streptococcus pyogenes (group A streptococci [GAS]) and methicillin-susceptible Staphylococcus aureus (MSSA) was traced to the venting procedure for aerobic bottles prior to their loading into the incubator of the BacT/Alert analyzer (Organon Teknika). Bacteria shed by a laboratory worker suffering from impetigo and cellulitis contaminated the aerobic bottles of 10 patients. All blood culture isolates, in addition to the isolates from the laboratory worker, were of the same GAS M and T types. All MSSA isolates from blood cultures and the index case's hands had the same lytic phage profile. Procedural breakdowns were identified in the laboratory. Bottles were vented outside the biological safety cabinet, gloves were not worn, and unprotected needles were used for the venting procedure. The source of the aspirated bacteria that contaminated the bottles was identified and the index case was treated promptly.

Gonorrhea is the second most commonly reported notifiable disease in the United States; 350,062 gonorrhea cases were reported in 2014. Sexually transmitted infections caused by Neisseria gonorrhoeae are a cause of pelvic inflammatory disease in women, which can lead to serious reproductive complications including tubal infertility, ectopic pregnancy, and chronic pelvic pain. Prevention of sequelae and of transmission to sexual partners relies largely on prompt detection and effective antimicrobial treatment. However, treatment has been compromised by the absence of routine antimicrobial susceptibility testing in clinical care and evolution of antimicrobial resistance to the antibiotics used to treat gonorrhea. 2014. The Gonococcal Isolate Surveillance Project (GISP) was established in 1986 as a sentinel surveillance system to monitor trends in antimicrobial susceptibilities of N. gonorrhoeae strains in the United States. Each month, N. gonorrhoeae isolates are collected from up to t...

Granuloma inguinale (donovanosis) is seen predominantly in adults (it rarely occurs in children) and mainly affects genital skin and mucosa. Infection occurs at other skin and mucosal sites, and hematogenous dissemination to bone also has been described. The infection responds dramatically to appropriate antibiotic treatment. We present two cases of granuloma inguinale occurring in children (8 months and 5 months of age) causing mastoiditis and external ear discharges. A temporal lobe abscess also developed in the 8-month-old child. Subsequent computed tomography scans showed marked improvement in the brain lesion after treatment. The second child had a polypoid mass in the middle ear that on biopsy showed the features of granuloma inguinale. The mother of this child had biopsy-proven granuloma inguinale of the uterine cervix. These cases indicate that granuloma inguinale can be transmitted during vaginal delivery, and careful cleansing of neonates born to infected mothers is recomm...

Staphylococcus lugdunensis is an atypically virulent coagulase-negative staphylococcal species associated with acute and destructive infections that often resemble Staphylococcus aureus infections. Several types of infection caused by S. lugdunensis (e.g., native valve endocarditis, prosthetic joint infection, and intravascular catheter infection) are associated with biofilm formation, which may lead to an inability to eradicate the infection due to the intrinsic nature of biofilms to resist high levels of antibiotics. In this study, planktonic MICs and MBCs and biofilm bactericidal concentrations of 10 antistaphylococcal antimicrobial agents were measured for 15 S. lugdunensis isolates collected from patients with endocarditis, medical device infections, or skin and soft tissue infections. Planktonic isolates were susceptible to all agents studied, but biofilms were resistant to high concentrations of most of the drugs. However, moxifloxacin was able to kill 73% of isolates growing...

Biodegradable dental films containing a combination of amoxycillin and metronidazole were prepared by a dispersion method. The aim of the present study was to determine the antimicrobial activity of this formulation against the pathogens which are commonly implicated in periodontal infections. Films showed sustained release in vitro for a period of 16 days. In situ release studies carried out using fresh bovine buccal mucosa in a flow through cell, showed that drug concentrations were maintained above MIC values for the entire period of the release studies. Samples from these studies were capable of inhibiting the growth of most of the test strains. The combination of amoxycillin and metronidazole using carrier polymer poly-L (lactide co-glycolide) not only showed an extended spectrum of antimicrobial activity but also showed a synergistic effect against Eubacterium limosum, which had earlier been reported resistant to metronidazole.

ABSTRACTThe prevalence ofStaphylococcus aureuscausing prosthetic joint infection (PJI) supports investigation of higher doses of daptomycin in the management of PJI. This was a prospective, randomized controlled trial studying safety and efficacy of daptomycin (6 and 8 mg/kg of body weight) compared with standard-of-care therapy for PJI. This open-label study randomized 75 patients undergoing 2-stage revision arthroplasty to daptomycin at 6 or 8 mg/kg or a comparator (vancomycin, teicoplanin, or semisynthetic penicillin). After prosthesis removal, patients received 6 weeks of antibiotic treatment and a 2- to 6-week antibiotic-free period before implantation of a new prosthesis. Test of cure (TOC) was within 1 to 2 weeks after reimplantation. The primary objective was evaluation of creatine phosphokinase (CPK) levels. Secondary objectives were clinical efficacy and microbiological assessments. Of 73 CPK safety population patients, CPK elevation of >500 U/liter occurred in 4 of 25 ...

Metallo-beta-lactamases (MBLs) are broad spectrum, Zn(II) dependent lactamases able to confer resistance to virtually every β-lactam antibiotic currently available. The large diversity of active site structures and metal content among MBLs from different sources has limited the design of a pan-MBL inhibitor. GOB-18 is a divergent MBL from subclass B3, expressed by the opportunistic Gram-negative pathogen Elizabethkingia meningoseptica This MBL is atypical since several residues conserved in B3 enzymes (such as a metal ligand His) are substituted in GOB enzymes. Here we report the crystal structure of the periplasmic di-Zn(II) form of GOB-18. This enzyme displays a unique active site structure, with residue Gln116 coordinating the Zn1 ion through its terminal amide moiety, replacing a ubiquitous His residue. This situation contrasts with that of B2 MBLs, where an equivalent His116Asn substitution leads to a di-Zn(II) inactive species. Instead, both the mono- and di-Zn(II) forms of GO...

Actinomycosis of the anterior abdominal wall is a rare infection caused by different Actinomyces species. We report a case of primary actinomycosis localized on the anterior abdominal wall, diagnosed by computed tomography (CT) scan, postoperatively confirmed by histopathological examination and treated by surgical resection combined with postoperative antibiotic therapy. The patient has been free of recurrence after 1 year. A review of the available literature is also presented.

The surface coverage of certain dry fermented sausages such as Italian salami by some species of Penicillium provides their characteristic flavor and other beneficial properties. One of them is the protective effect by means of a uniform film of white mold against undesirable microorganisms. The aim of this work was to identify and to isolate the fungal species present in mature Italian type of salami and to evaluate if it is possible to obtain some of them as starters. In addition, the effects of temperature (14 °C and 25 °C), water activity (a w) (0.90, 0.95 and 0.995) and 2.5 % sodium chloride (NaCl) on fungal growth were determined. Similarly, the proteolytic and lipolytic activity and the ability to produce toxic secondary metabolites were evaluated in order to characterize some possible starter strain. All species found belong to the genus Penicillium, including a performing starter as Penicillium nalgiovense and some potentially toxicogenic species. All the strains showed a h...

SUMMARYA total of 160 consecutive isolates of Neisseria gonorrhoeae was collected over a 3-month period. They were tested for their susceptibility to penicillin, erythromycin and spectinomycin and the auxotype and the serotype determined. We have evaluated two sampling methods, the collection of every fifth isolate and the first 20 isolates (10 male and 10 female) each month, to determine whether either is representative of the total population. There was no significant difference between either method of sampling and the total for detecting the predominant auxotypes and serovars or the distributions in antibiotic susceptibility. It is possible to monitor major changes in a gonococcal population, particularly susceptibility to antibiotics, using a sample of the total population.