Showing papers on "Penicillin published in 2001"

Antimicrobial Resistance among Clinical Isolates of Streptococcus pneumoniae in the United States during 1999–2000, Including a Comparison of Resistance Rates since 1994–1995

Abstract: A total of 1,531 recent clinical isolates of Streptococcus pneumoniae were collected from 33 medical centers nationwide during the winter of 1999–2000 and characterized at a central laboratory. Of these isolates, 34.2% were penicillin nonsusceptible (MIC ≥ 0.12 μg/ml) and 21.5% were high-level resistant (MIC ≥ 2 μg/ml). MICs to all beta-lactam antimicrobials increased as penicillin MICs increased. Resistance rates among non-beta-lactam agents were the following: macrolides, 25.2 to 25.7%; clindamycin, 8.9%; tetracycline, 16.3%; chloramphenicol, 8.3%; and trimethoprim-sulfamethoxazole (TMP-SMX), 30.3%. Resistance to non-beta-lactam agents was higher among penicillin-resistant strains than penicillin-susceptible strains; 22.4% of S. pneumoniae were multiresistant. Resistance to vancomycin and quinupristin-dalfopristin was not detected. Resistance to rifampin was 0.1%. Testing of seven fluoroquinolones resulted in the following rank order of in vitro activity: gemifloxacin > sitafloxacin > moxifloxacin > gatifloxacin > levofloxacin = ciprofloxacin > ofloxacin. For 1.4% of strains, ciprofloxacin MICs were ≥4 μg/ml. The MIC90s (MICs at which 90% of isolates were inhibited) of two ketolides were 0.06 μg/ml (ABT773) and 0.12 μg/ml (telithromycin). The MIC90 of linezolid was 2 μg/ml. Overall, antimicrobial resistance was highest among middle ear fluid and sinus isolates of S. pneumoniae; lowest resistance rates were noted with isolates from cerebrospinal fluid and blood. Resistant isolates were most often recovered from children 0 to 5 years of age and from patients in the southeastern United States. This study represents a continuation of two previous national studies, one in 1994–1995 and the other in 1997–1998. Resistance rates with S. pneumoniae have increased markedly in the United States during the past 5 years. Increases in resistance from 1994–1995 to 1999–2000 for selected antimicrobial agents were as follows: penicillin, 10.6%; erythromycin, 16.1%; tetracycline, 9.0%; TMP-SMX, 9.1%; and chloramphenicol, 4.0%, the increase in multiresistance was 13.3%. Despite awareness and prevention efforts, antimicrobial resistance with S. pneumoniae continues to increase in the United States.

On the antibacterial action of cultures of a penicillium, with special reference to their use in the isolation of B. influenzæ

Abstract: 1. A certain type of penicillium produces in culture a powerful antibacterial substance. The antibacterial power of the culture reaches its maximum in about 7 days at 20o C. and after 10 days diminishes until it has almost disappeared in 4 weeks. 2. The best medium found for the production of the antibacterial substance has been ordinary nutrient broth. 3. The active agent is readily filterable and the name "penicillin" has been given to filtrates of broth cultures of the mould. 4. Penicillin loses most of its power after 10 to 14 days at room temperature but can be preserved longer by neutralization. 5. The active agent is not destroyed by boiling for a few minutes but in alkaline solution boiling for 1 hour markedly reduces the power. Autoclaving for 20 minutes at 115o C. practically destroys it. It is soluble in alcohol but insoluble in ether or chloroform. 6. The action is very marked on the pyogenic cocci and the diphtheria group of bacilli. Many bacteria are quite insensitive, e.g. the coli-typhoid group, the influenza-bacillus group, and the enterococcus. 7. Penicillin is non-toxic to animals in enormous doses and is non-irritant. It doses not interfere with leucocytic function to a greater degree than does ordinary broth. 8. It is suggested that it may be an efficient antiseptic for application to, or injection into, areas infected with penicillin-sensitive microbes. 9. The use of penicillin on culture plates renders obvious many bacterial inhibitions which are not very evident in ordinary cultures. 10. Its value as an aid to the isolation of B. influenzae has been demonstrated.

Evolution, incidence, and susceptibility of bacterial bloodstream isolates from 519 bone marrow transplant patients.

Abstract: Bacteria remain an important cause of infection in bone marrow transplants. To examine shifts in the etiology and susceptibility of bacterial isolates from transplants, we reviewed the incidence and susceptibility of blood isolates during a 7-year period. The infection rate fell dramatically during this time. Gram-positive organisms were isolated more often than gram-negative organisms, but the trend is reversing. Streptococci surpassed staphylococci for 5 years as the leading pathogen. Increasing resistance to penicillin, ciprofloxacin, and imipenem was noted in Streptococcus species. With the exception of type 1 beta-lactamase-producing bacteria and Pseudomonas aeruginosa, gram-negative isolates remained overall susceptible to ceftazidime. Increased antibiotic prophylaxis coincided with the reduction in percentage of infected patients and increase in resistance to beta-lactam antibiotics. Mortality attributed to bacteremia was low except for infections caused by P. aeruginosa and the Enterobacter, Serratia, Citrobacter group. There was no mortality attributable to gram-positive organisms such as Staphylococcus aureus and viridans streptococci.

Is This Patient Allergic to Penicillin?: An Evidence-Based Analysis of the Likelihood of Penicillin Allergy

Abstract: Data Synthesis Patients’ self-reported history has low accuracy for diagnosis of true penicillin allergy. By evaluating studies comparing clinical history to the skin test for penicillin allergy among patients with and without a positive history for penicillin allergy, positive and negative likelihood ratios were calculated. History of penicillin allergy had a positive likelihood ratio of 1.9 (95% confidence interval [CI], 1.5-2.5), while absence of history of penicillin allergy had a negative likelihood ratio of 0.5 (95% CI, 0.4-0.6).

Antimicrobial susceptibilities of 1,684 Streptococcus pneumoniae and 2,039 Streptococcus pyogenes isolates and their ecological relationships: results of a 1-year (1998-1999) multicenter surveillance study in Spain.

Abstract: A nationwide multicenter susceptibility surveillance study which included 1,684 Streptococcus pneumoniae and 2,039 S. pyogenes isolates was carried out over 1 year in order to assess the current resistance patterns for the two most important gram-positive microorganisms responsible for community-acquired infections in Spain. Susceptibility testing was done by a broth microdilution method according to National Committee for Clinical Laboratory Standards M100-S10 interpretative criteria. For S. pneumoniae, the prevalences of highly resistant strains were 5% for amoxicillin and amoxicillin-clavulanic acid; 7% for cefotaxime; 22% for penicillin; 31% for cefuroxime; 35% for erythromycin, clarithromycin, and azithromycin; and 42% for cefaclor. For S. pyogenes, the prevalence of erythromycin resistance was 20%. Efflux was encountered in 90% of S. pyogenes and 5% of S. pneumoniae isolates that exhibited erythromycin resistance. Erythromycin resistance was associated with clarithromycin and azithromycin in both species, regardless of phenotype. Despite the different nature of the mechanisms of resistance, a positive correlation (r = 0.612) between the two species in the prevalence of erythromycin resistance was found in site-by-site comparisons, suggesting some kind of link with antibiotic consumption. Regarding ciprofloxacin, the MIC was ≥4 μg/ml for 7% of S. pneumoniae and 3.5% of S. pyogenes isolates. Ciprofloxacin resistance (MIC, ≥4 μg/ml) was significantly (P < 0.05) associated with macrolide resistance in both S. pyogenes and S. pneumoniae and with penicillin nonsusceptibility in S. pneumoniae.

Diagnostic evaluation of a large group of patients with immediate allergy to penicillins: the role of skin testing.

Abstract: Background: Penicillin is no longer the most commonly prescribed β-lactam, and the pattern of reactions has changed. We studied the diagnostic value of skin testing in penicillin-allergic subjects from a population where benzylpenicillin is not now the most frequently used β-lactam. Methods: Patients with a history of immediate allergic reactions to penicillins were studied with: skin tests with major and minor determinants of benzylpenicillin (BPO/MDM), amoxicillin, and ampicillin; in vitro determination of specific IgE; and controlled administration for those with a positive history but negative skin and in vitro tests. A reaction was considered immediate when symptoms appeared within a maximum of 1 h after drug intake. Results: After testing, 290 patients (71% having anaphylaxis and 29% having urticaria) proved to be allergic. Amoxicillin was involved in 64.8% and benzylpenicillin in 2.8% of the patients. Skin test positivity to at least one determinant appeared in 70% of cases, amoxicillin being the most frequent. The overall sensitivity decreased markedly when only BPO and MDM were considered. In 13.1% of patients, the diagnosis was established by in vitro test and in 16.9% by controlled administration. Of the 290 patients, 42.1% were positive to determinants generated from benzylpenicillin and 57.9% were selective responders. Conclusions: Sensitivity of skin tests to BPO was lower than reported, being partly replaced by minor determinants, mostly amoxicillin. The incorporation of additional reagents and the development of new tests are required, and these will probably change as the patterns of consumption vary.

Cross-linked aggregates of penicillin acylase: robust catalysts for the synthesis of β-lactam antibiotics

Abstract: A novel method for the immobilization of penicillin G acylase (penicillin amidohydrolase, EC 35111) is reported It involves the physical aggregation of the enzyme, followed by chemical cross-linking to form insoluble cross-linked enzyme aggregates (CLEAs) Compared with conventionally immobilized penicillin G acylases, these CLEAs possess a high specific activity as well as a high productivity and synthesis/hydrolysis (S/H) ratio in the synthesis of semi-synthetic antibiotics in aqueous media Moreover, they are active in a broad range of polar and apolar organic solvents

Plasmid-Encoded Metallo-β-Lactamase (IMP-6) Conferring Resistance to Carbapenems, Especially Meropenem

Abstract: In 1996, Serratia marcescens KU3838 was isolated from the urine of a patient with a urinary tract infection at a hospital in northern Japan and was found to contain the plasmid pKU501. Previously, we determined that pKU501 carries bla(IMP) and the genes for TEM-1-type beta-lactamases as well as producing both types of beta-lactamases (H. Yano, A. Kuga, K. Irinoda, R. Okamoto, T. Kobayashi, and M. Inoue, J. Antibiot. 52:1135-1139, 1999). pKU502 is a recombinant plasmid that contains a 1.5-kb DNA fragment, including the metallo-beta-lactamase gene, and is obtained by PCR amplification of pKU501. The sequence of the metallo-beta-lactamase gene in pKU502 was determined and revealed that this metallo-beta-lactamase gene differed from the gene encoding IMP-1 by one point mutation, leading to one amino acid substitution: 640-A in the base sequence of the IMP-1 gene was replaced by G, and Ser-196 was replaced by Gly in the mature enzyme. This enzyme was designated IMP-6. The strains that produced IMP-6 were resistant to carbapenems. The MICs of panipenem and especially meropenem were higher than the MIC of imipenem for these strains. The k(cat)/K(m) value of IMP-6 was about sevenfold higher against meropenem than against imipenem, although the MIC of meropenem for KU1917, which produced IMP-1, was lower than that of imipenem, and the MIC of panipenem was equal to that of imipenem. These results support the hypothesis that IMP-6 has extended substrate profiles against carbapenems. However, the activity of IMP-6 was very low against penicillin G and piperacillin. These results suggest that IMP-6 acquired high activity against carbapenems, especially meropenem, via the point mutation but in the process lost activity against penicillins. Although IMP-6 has reduced activity against penicillins due to this point mutation, pKU501 confers resistance to a variety of antimicrobial agents because it also produces TEM-1-type enzyme.

Antibiotic resistance among Listeria, including Listeria monocytogenes, in retail foods

Abstract: Aims: In the past eight to 10 years, reports of antibiotic resistance in food-borne isolates in many countries have increased, and this work examined the susceptibility of 1001 food isolates of Listeria species. Methods and Results: Susceptibility/resistance to eight antibiotics was determined using the Bauer–Kirby disc diffusion assay, and 10·9% of the isolates examined displayed resistance to one or more antibiotics. Resistance to one or more antibiotics was exhibited in 0·6% of Listeria monocytogenes isolates compared with 19·5% of Listeria innocua isolates. Resistance was not observed in Listeria seeligeri or Listeria welshimeri. Resistance to tetracycline (6·7%) and penicillin (3·7%) was the most frequently observed, and while resistance to one antibiotic was most common (9·1%), isolates resistant to two or more antibiotics (1·8%) were also observed. Conclusions: While resistance to the antibiotics most commonly used to treat human listeriosis was not observed in L. monocytogenes, the presence of such resistance in other Listeria species raises the possibility of future acquisition of resistance by L. monocytogenes. Significance and Impact of the Study: The higher level of resistance in L. innocua compared with L. monocytogenes suggests that a species-related ability to acquire resistance to antibiotics exists.

Lack of allergic cross-reactivity to cephalosporins among patients allergic to penicillins.

Abstract: There are some contradicting data about clinical allergic cross-reactivity to cephalosporins among patients who have had a previous allergic reaction to penicillins. The purpose of this study was to assess the safety of administering cephalosporins to penicillin-allergic patients. The diagnosis of penicillin allergy was made by positive skin tests to penicillin reagents and/or provocation tests with the penicillin suspected of causing the allergic reaction. To assess the clinical tolerance to cephalosporins, 41 well-characterized penicillin allergic patients diagnosed by positive skin tests and/or provocation tests were challenged with three cephalosporins that do not share the same side chain to the penicillin that induced the reactions: cephazoline, cefuroxime and ceftriaxone. Skin prick and intradermal tests with all cephalosporins tested were negative. All penicillin-allergic patients tolerated therapeutic doses of the three cephalosporins tested (cephazoline, cefuroxime and ceftriaxone) without any ill effect. These results indicate that the risk of suffering from an allergic reaction on administering cephalosporins to penicillin-allergic patients seems to be very low, provided that cephalosporins with a different side chain to the penicillin responsible for the allergic reaction are used.

Evolution of Streptococcus pneumoniae serotypes and penicillin susceptibility in Latin America., Sireva-Vigia group. 1993 to 1999

Abstract: Background. Since 1993 the Pan American Health Organization has coordinated a surveillance network with the National Reference Laboratories of Argentina, Brazil, Chile, Colombia, Mexico and Uruguay aimed at monitoring capsular types and antimicrobial susceptibility of Streptococcus pneumoniae causing invasive disease in children <6 years of age. Methods. The surveillance system included children 6 years of age and younger with invasive disease caused by S. pneumoniae. The identification, capsular typing and susceptibility to penicillin of the isolates were conducted using a common protocol, based on standard methodologies. Results. By June, 1999, 4105 invasive pneumococcal isolates had been collected mainly from pneumonia (44.1%) and meningitis (41.1%) cases. Thirteen capsular types accounting for 86.1% of the isolates (14, 6A/6B, 5, 1, 23F, 19F, 18C, 19A, 9V, 7F, 3, 9N and 4) remained the most common types during the surveillance period. Diminished susceptibility to penicillin was detected in 28.6% of the isolates, 17.3% with intermediate and 11.3% with high level resistance. Resistance varied among countries and increased during this period in Argentina, Colombia and Uruguay. Serotypes 14 and 23F accounted for 66.6% of the resistance. Conclusion. These surveillance data clearly demonstrate the potential impact of the introduction of a conjugate vaccine on pneumococcal disease and the need for more judicious use of antibiotics to slow or reverse the development of antimicrobial resistance.

Alexander Fleming and the discovery of penicillin.

Abstract: Publisher Summary Penicillin permanently changed infectious disease research and therapeutic medicine, it transformed patient expectations and the structures of drug companies, contributed new insights in microbiology and molecular biology, and captured the public imagination and scientific breakthroughs. Alexander Fleming is the scientist who discovered an antibacterial activity in a Penicillium growth medium. To avoid repetition of the phrase “mold broth filtrate,” he coined the term “penicillin,” a substance that eventually became known as a “miracle drug.” Fleming's story has been told many times with enough elaboration that it is sometimes called the “Fleming myth.” This chapter elaborates Fleming's story which is quite fascinating. It is now known than penicillin controls bacteria by inhibiting their cell division. Hence, the phenomenon observed by Fleming—lysis—was extremely unusual. Penicillin was something new: a natural product of unknown structure with strong antibacterial activity. A major interdisciplinary effort was required to develop penicillin. Penicillin is the paradigm for natural products drug discovery; Fleming himself is an enduring role model not only for success in clinical research but also for how to project a positive popular image for the scientific profession.

Need for Annual Surveillance of Antimicrobial Resistance in Streptococcus pneumoniae in the United States: 2-Year Longitudinal Analysis

Abstract: Although changing patterns in antimicrobial resistance in Streptococcus pneumoniae have prompted several surveillance initiatives in recent years, the frequency with which these studies are needed has not been addressed. To approach this issue, the extent to which resistance patterns change over a 1-year period was examined. In this study we analyzed S. pneumoniae antimicrobial susceptibility results produced in our laboratory with isolates obtained over 2 consecutive years (1997-1998 and 1998-1999) from the same 96 institutions distributed throughout the United States. Comparison of results revealed increases in resistant percentages for all antimicrobial agents studied except vancomycin. For four of the agents tested (penicillin, cefuroxime, trimethoprim-sulfamethoxazole, and levofloxacin), the increases were statistically significant (P < 0.05). Resistance to the fluoroquinolone remained low in both years (0.1 and 0.6%, respectively); in contrast, resistance to macrolides was consistently greater than 20%, and resistance to trimethoprim-sulfamethoxazole increased from 13.3 to 27.3%. Multidrug resistance, concurrent resistance to three or more antimicrobials of different chemical classes, also increased significantly between years, from 5.9 to 11%. The most prevalent phenotype was resistance to penicillin, azithromycin (representative macrolide), and trimethoprim-sulfamethoxazole. Multidrug-resistant phenotypes that included fluoroquinolone resistance were uncommon; however, two phenotypes that included fluoroquinolone resistance not found in 1997-1998 were encountered in 1998-1999. This longitudinal surveillance study of resistance in S. pneumoniae revealed that significant changes do occur in just a single year and supports the need for surveillance at least on an annual basis, if not continuously.

Evaluation of PCR primers to screen for Streptococcus pneumoniae isolates and β-lactam resistance, and to detect common macrolide resistance determinants

Abstract: Pneumococcal isolates (n = 148) from various countries (mostly from the USA) were tested by a primer set for PCR. Thirty-eight (86.4%) of the 44 penicillin G-susceptible isolates (MIC or = 2 mg/L), 41 isolates (87.2%) had all three pbps altered, six isolates (12.8%) had altered pbp1a + 2x. Various combinations of altered pbp were seen in penicillin G-intermediate isolates. Prevalence of macrolide resistance genes mef(A) and erm(B) in isolates was clearly reflected by their MICs. All isolates were positive for lytA. The primers were useful for screening for Streptococcus pneumoniae and beta-lactam resistance, and for detection of common macrolide resistance determinants.

Carriage of Antibiotic-Resistant Pneumococci among Asian Children: A Multinational Surveillance by the Asian Network for Surveillance of Resistant Pathogens (ANSORP)

Abstract: To investigate the nasal carriage of antibiotic-resistant pneumococci by children, anterior nasal swabs were done for 4963 children <5 years old in 11 countries in Asia and the Middle East. In total, 1105 pneumococci isolates (carriage rate, 22.3%) were collected, 35.8% of which were found to be nonsusceptible to penicillin. Prevalence of penicillin nonsusceptibility was highest in Taiwan (91.3%), followed by Korea (85.8%), Sri Lanka (76.5%), and Vietnam (70.4%). Penicillin resistance was related to residence in urban areas, enrollment in day care, and a history of otitis media. The most common serogroups were 6 (21.5%), 23 (16.5%), and 19 (15.7%). The most common clone, as assessed by pulsed-field gel electrophoresis, was identical to the Spanish 23F clone and to strains of invasive isolates from adult patients. Data in this study documented the high rate of penicillin or multidrug resistance among isolates of pneumococci carried nasally in children in Asia and the Middle East and showed that this is due to the spread of a few predominant clones in the region.

Unexplained reduced microbiological efficacy of intramuscular benzathine penicillin G and of oral penicillin V in eradication of group a streptococci from children with acute pharyngitis.

Abstract: Objective To evaluate the efficacy of oral penicillin V and intramuscular benzathine penicillin G (BPG) in eradicating group A streptococci from the upper respiratory tract Methodology Two randomized, single-blind, multicenter antibiotic efficacy trials in children using recommended doses of either oral penicillin V or intramuscular BPG for treatment of acute-onset pharyngitis associated with isolation of group A streptococci were conducted Throat examinations and cultures were obtained at enrollment and on days 5 to 8, 10 to 14, and 29 to 31 Results Thirty-five percent of 284 evaluable patients treated with oral penicillin V and 37% of BPG-treated patients were microbiologic treatment failures at either 10 to 14 or 29 to 31 days Conclusions Although these findings do not provide sufficient evidence to change current treatment recommendations or public health policy, important questions are raised about currently recommended penicillin doses, about the role of the carrier state, and possibly about adequate bioavailability of intramuscular BPG These findings require confirmation

Plasmid-Borne smr Gene Causes Resistance to Quaternary Ammonium Compounds in Bovine Staphylococcus aureus

Abstract: Resistance to quaternary ammonium compounds (QAC) in staphylococci is common in hospital environments and has been described in the food industry. Little is known about staphylococcal QAC resistance associated with animal disease, although such disinfectants are widely used in veterinary medicine. In order to investigate the occurrence of QAC resistance in staphylococci isolated from QAC-exposed animals, 32 penicillin- and tetracycline-resistant and 23 penicillin- and tetracycline-susceptible Staphylococcus aureus isolates collected from milk from cows with mastitis during a 4-year period were selected for QAC susceptibility studies and genetic characterization. The isolates originated from four different herds that used a common pasture with a joint milking parlor in the summer. During the pasture season, a teat cream containing the QAC cetyltrimethylammonium bromide had been used daily for more than 10 years for mastitis control. Three of the penicillin- and tetracycline-resistant isolates, which were recovered from three different cows during a 20-month period, were resistant to QAC. Plasmid analysis, PCR, and DNA sequencing revealed a novel plasmid of 2,239 bp containing the smr gene. The plasmid, designated pNVH99, has similarities to small, smr-containing staphylococcal plasmids previously found in human and food isolates. pNVH99 is a new member of the pC194 family of rolling-circle replication plasmids. The three QAC-resistant isolates, as well as 28 of the 29 remaining penicillin- and tetracycline-resistant isolates, were indistinguishable by pulsed-field gel electrophoresis. The study indicates that the occurrence and spread of QAC-resistant S. aureus among dairy cows may be a problem that needs further investigation.

Natural Antibiotic Susceptibilities of Edwardsiella tarda, E. ictaluri, and E. hoshinae

Abstract: The natural antibiotic susceptibilities to 71 antibiotics of 102 Edwardsiella strains belonging to E. tarda (n = 42), E. ictaluri (n = 41), and E. hoshinae (n = 19) were investigated. MICs were determined using a microdilution procedure according to NCCLS criteria and German standards. All edwardsiellae were naturally sensitive to tetracyclines, aminoglycosides, most beta-lactams, quinolones, antifolates, chloramphenicol, nitrofurantoin, and fosfomycin. Edwardsiella species were naturally resistant to macrolides, lincosamides, streptogramins, glycopeptides, rifampin, fusidic acid, and oxacillin. Although slight species-dependent differences in natural susceptibilities to some antibiotics (e.g., macrolides and cefaclor) were seen, differences in natural susceptibility affecting clinical assessment criteria were only seen with benzylpenicillin. Whereas E. tarda was naturally resistant to benzylpenicillin, E. hoshinae was naturally sensitive. Natural sensitivity and resistance to this penicillin were found among the strains of E. ictaluri. The observed oxacillin sensitivity of E. ictaluri was attributed to the failure of the species to grow at higher salt concentrations found in oxacillin-containing microtiter plates. The present study describes a database concerning the natural susceptibility of Edwardsiella species to a wide range of antibiotics, which can be applied to validate forthcoming antibiotic susceptibility tests of these microorganisms.

Clinical isolates of Streptococcus pneumoniae that exhibit tolerance of vancomycin.

Abstract: The ability of Streptococcus pneumoniae to escape lysis and killing by vancomycin, a property termed "tolerance," has recently been noted in a laboratory strain of the species. Vancomycin tolerance in clinical isolates represents a potential new health risk. We determined the prevalence of vancomycin and penicillin tolerance among 116 clinical isolates of pneumococci by monitoring lysis and viability after exposure to the respective antibiotic for 4 hours. Eight percent of the strains were tolerant to penicillin and 3% were tolerant to vancomycin. The 3 vancomycin-tolerant isolates also had a high ratio of minimum bactericidal concentration to minimum inhibitory concentration, in contrast to nontolerant strains. They were of serotype 9V and had reduced susceptibility to penicillin. Only 1 was also tolerant to penicillin. Growth rate and ability to divide were not affected in the 3 vancomycin-tolerant strains, and they all lysed with deoxycholate, which indicates autolysin production. Vancomycin tolerance among clinical isolates of pneumococci will necessitate tracking to determine the magnitude of the evolving health risk, since tolerance may contribute to treatment failure (in particular, cases of meningitis, in which bactericidal activity is critical for eradication) and since it may also be a favored background for acquisition of resistance of vancomycin.

The Development of β-Lactam Antibiotics in Response to the Evolution of β-Lactamases

Abstract: β-Lactam antibiotics, viz., penicillin, penicillin derivatives, cephalosporins, cephamycins, carbapenems, monobactams, and monocarbams, are the most widely used of all antimicrobial classes by virtue of their high efficacy and specificity and the availability of several derivatives. The expression of one or several β-lactamases (β-lactam antibiotic-inactivating enzymes) represents the most widespread and the most clinically relevant resistance mechanism to these antibiotics. The development of β-lactam antibiotics has thus been a continuous battle of the design of new compounds to withstand inactivation by the ever-increasing diversity of β-lactamases. This article traces antibiotic development in response to the evolution of β-lactamases.

Antibiotic Susceptibilities of Genetically Characterized Streptococcus milleri Group Strains

Abstract: Previous studies of the antibiotic susceptibility of Streptococcus milleri group organisms have distinguished among species by using phenotypic techniques. Using 44 isolates that were speciated by 16S rRNA gene sequencing, we studied the MICs and minimum bactericidal concentrations of penicillin, ampicillin, ceftriaxone, and clindamycin for Streptococcus intermedius, Streptococcus constellatus, and Streptococcus anginosus. None of the organisms was resistant to beta-lactam antibiotics, although a few isolates were intermediately resistant; one strain of S. anginosus was tolerant to ampicillin, and another was tolerant to ceftriaxone. Six isolates were resistant to clindamycin, with representation from each of the three species. Relatively small differences in antibiotic susceptibilities among species of the S. milleri group show that speciation is unlikely to be important in selecting an antibiotic to treat infection caused by one of these isolates.

Levofloxacin Failure in a Patient with Pneumococcal Pneumonia

Abstract: OBJECTIVE:To report a case of levofloxacin failure in a patient with a penicillin-sensitive Streptococcus pneumoniae pneumonia.CASE SUMMARY:A previously healthy, immunocompetent, 53-year-old white man presented with penicillin-sensitive S. pneumoniae pneumonia. The patient was empirically placed on levofloxacin monotherapy, which was continued due to a local penicillin shortage. When the patient failed to improve, further susceptibility testing was ordered. The organism was found to have a penicillin minimum inhibitory concentration (MIC) of 0.023 μg/mL and a levofloxacin MIC of 6 μg/mL. Effective antimicrobial therapy was delayed, as clinicians did not anticipate fluoroquinolone resistance.DISCUSSION:Newer fluoroquinolones such as levofloxacin have good activity against most S. pneumoniae isolates and are used for the treatment of pneumonia. Although resistance to these agents is rare, it has been reported. Current guidelines from the National Committee for Clinical Laboratory Standards do not recommend ...

Linezolid - a review of the first oxazolidinone

Abstract: Linezolid is the first of a truly new class of antibiotics, the oxazolidinones. It acts as an inhibitor of bacterial protein synthesis by blocking the formation of the 70S ribosomal initiation complex. Its activity is bacteriostatic against some species (e.g., enterococci) and bactericidal against others (e.g., pneumococci). The antibacterial spectrum of linezolid includes Gram-positive pathogens and some Gram-negative anaerobic species but not Gram-negative aerobes. Importantly, multi-drug resistant organisms such as methicillin-resistant staphylococci, staphylococci with reduced susceptibility to vancomycin, penicillin- and macrolide-resistant pneumococci and vancomycin-resistant enterococci are fully susceptible to linezolid. Linezolid has almost 100% bioavailability and the area under the plasma concentration curve is identical after oral and iv. administration. This enables initial oral administration of linezolid in those patients who can absorb the drug normally and also an early step-down therapy from iv. to oral. Controlled, randomised clinical studies have documented efficacy and safety of linezolid in hospital- and community-acquired pneumonia, uncomplicated and complicated skin and soft tissue infections and infections caused by vancomycin-resistant enterococci. The safety and tolerability of linezolid are advantageous. Linezolid is a weak and reversible monoamine oxidase (MAO) inhibitor and although no increased frequency of adrenergic or serotonergic adverse events has been reported, it is recommended that linezolid is used with caution in patients treated with other MAO inhibitors.

Short communication Penicillin and clindamycin differentially inhibit the production of pyrogenic exotoxins A and B by group A streptococci

Abstract: Streptococcal pyrogenic exotoxins A (SPE-A) and B (SPE-B) have been implicated in the pathogenesis of serious group A streptococcal infections including streptococcal toxic shock-syndrome. Current antibiotics used for the treatment of these infections are penicillin and clindamycin. The effects of sub- and suprainhibitory concentrations of penicillin and clindamycin were evaluated in 14 isolates of Streptococcus pyogenes that were fully susceptible to both antibiotics. Clindamycin was superior to penicillin in reducing the production of SPE-A and SPE-B by invasive and non-invasive Dutch group A streptococcal isolates in vitro. © 2001 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.

Outbreak of Cefozopran (Penicillin, Oral Cephems, and Aztreonam)-Resistant Neisseria gonorrhoeae in Japan

Abstract: We have previously reported that the Neisseria gonorrhoeae isolates from clinical failure cases treated with cefdinir and aztreonam, beta-lactams exhibited high MICs. These resistant isolates were clearly separated from the isolates exhibiting a low level of resistance to beta-lactams as shown by the MIC distribution of cefozopran. Restriction fragment length polymorphism DNA typing revealed that the outbreak of cefozopran-resistant isolates in Kitakyushu, Japan, occurred as a result of clonal spread.

Alterations in MurM, a cell wall muropeptide branching enzyme, increase high-level penicillin and cephalosporin resistance in Streptococcus pneumoniae.

Abstract: We report that alteration in MurM, an enzyme involved in the biosynthesis of branched-stem cell wall muropeptides, is required for maximal expression of penicillin and cefotaxime resistance in the pneumococcus. Hungarian isolate 3191 (penicillin MIC, 16 microg/ml; cefotaxime MIC, 4 microg/ml) was a source of donor DNA in transformation experiments. Penicillin-binding protein DNA was insufficient to transform recipient strain R6 to full resistance. Further transformation with altered murM DNA was required for full expression of donor penicillin and cefotaxime resistance.

Energetics of growth and penicillin production in a high‐producing strain of Penicillium chrysogenum

Abstract: The results of a large number of carbon-limited chemostat cultures of Penicillium chrysogenum carried out on glucose, ethanol, and acetate as the growth limiting substrate have been used to obtain an estimation of the adenosine triphosphate (ATP) costs for mycelium growth, penicillin production, and maintenance and the overall stoichiometry of oxidative phosphorylation of the fungus. It was found that penicillin production was accompanied by a significant additional energy drain (73 mol of ATP per mole of penicillin-G) from primary metabolism. This finding has been confirmed in independent experiments and has been shown to result in a significantly lower estimate for the maximum theoretical yield of penicillin-G on the carbon source.

Nasopharyngeal Carriage of Antimicrobial-Resistant Streptococcus pneumoniae among Young Children Attending 79 Kindergartens and Day Care Centers in Hong Kong

Abstract: Resistance to penicillin and multiple antimicrobial agents among Streptococcus pneumoniae strains is becoming an increasing problem worldwide and in Asia. To determine the prevalence of carriage of S. pneumoniae isolates not susceptible to penicillin in young children, we obtained nasopharyngeal swab specimens from 1,978 children (ages, 2 to 6 years) attending 79 day care centers or kindergartens. Three hundred eighty-three strains of S. pneumoniae were isolated from these children. Fifty-eight percent of these isolates had reduced susceptibility to penicillin, 123 (32.1%) were intermediate, and 100 (26.1%) were resistant. A very high penicillin MIC (4 μg/ml) was found in 3.3% of the isolates. The isolates also demonstrated high rates of resistance to other antimicrobial agents (51.2% to cefaclor, 50.2% to cefuroxime, 42.8% to cefotaxime, 80.7% to trimethoprim-sulfamethoxazole, 77% to erythromycin, 60% to clindamycin, and 33.7% to chloramphenicol). No isolate was resistant to fluoroquinolone. Multidrug resistance (not susceptible to the β-lactams and three or more other classes) was found in 39.4% of the isolates. Risk factors for the carriage of S. pneumoniae not susceptible to penicillin were multiple physician visits in the preceding 3 months and use of antimicrobial agents by the individual or by household members in the preceding 3 months. In the logistic regression analysis, only the use of antimicrobial agents in the preceding 3 months was an independent risk factor (P = 0.004; odds ratio, 2; 95% confidence interval, 1.2 to 3.2). This study demonstrated the high prevalence of antibiotic-resistant S. pneumoniae in healthy young children in the community in Hong Kong.