Saroj Shah | Purvanchal University (original) (raw)

Papers by Saroj Shah

Research paper thumbnail of Vancomycin susceptibility as an aid to the identification of lactobacilli

Letters in Applied Microbiology, 1998

Forty strains of lactobacilli isolated from probiotic supplements or functional foods, and two cl... more Forty strains of lactobacilli isolated from probiotic supplements or functional foods, and two clinical isolates, have been identified by API 50 CHL and tested for susceptibility to vancomycin. All the Lactobacillus acidophilus (16) and Lact. delbreuckii (two) strains were sensitive to vancomycin, while all the other strains (mainly Lact. rhamnosus, 15) were resistant. Susceptibility to other antibiotics was not species-specific. Differential susceptibility to vancomycin may be helpful in speciation of lactobacilli.

Research paper thumbnail of Nondialyzable peptide-bound hydroxyproline in human amniotic fluid: An indicator of fetal growth

American Journal of Obstetrics and Gynecology, 1972

Research paper thumbnail of Role of Induced Abortion in Rhesus Immunisation

The Lancet, 1971

... published cases of Rhnegative patients whose pregnancies have been terminated 8 became immuni... more ... published cases of Rhnegative patients whose pregnancies have been terminated 8 became immunised to the Rh factor. This 5 middot;5 risk of immunisation warrants a policy of protection with Rhimmune globulin. Introduction THE risk of maternal rhesus immunisation due to a ...

Research paper thumbnail of Fetal blood typing after induced abortion

Obstetrics and gynecology, 1972

An attempt was made to determine the Rh type of saline induced aborted fetuses. Twenty-eight pati... more An attempt was made to determine the Rh type of saline induced aborted fetuses. Twenty-eight patients admitted to New York Hospital and Cornell Medical Center were studied. The blood was obtained (within 1 hour after abortion in most cases) from the piece of cord cut from the abortus. The blood cells were confirmed to be of fetal origin by the Kleihauer-Betke stain. In 27 of the 28 cases, the RH type could be determined. Two of the 28 fetuses (1 set of twins) were typed as Rh negative and the mother did not need Rh immunoglobulin. In no case did the blood group and Rh type conflict with the mother's blood group and Rh type. It is possible to determine the Rh type of fetal erythrocytes after saline-induced abortion. When practical, this simple procedure will prevent Rh immunoglobulin from being used when it is not indicated, and the approach towards the management of Rh-negative women undergoing saline induced abortions will be more methodical.

Research paper thumbnail of Transport Mechanisms in Iontophoresis. III. An Experimental Study of the Contributions of Electroosmotic Flow and Permeability Change in Transport of Low and High Molecular Weight Solutes

The objective of this research was to provide in vitro transport data designed to clarify the rel... more The objective of this research was to provide in vitro transport data designed to clarify the relative importance of permeability increase and electroosmotic flow in flux enhancement via iontophoresis. Iontophoretic fluxes were measured with both anode and cathode donor cells, and passive fluxes were measured both before iontophoresis (Passive 1) and after iontophoresis (Passive 2). Data were generated for three uncharged low molecular weight solutes (glycine, glucose, and tyrosine) and two high molecular weight anionic species (carboxy inulin and bovine serum albumin). Flux enhancement is greater for anodic delivery than for cathodic delivery, even for the negatively charged molecules, and anodic flux of glucose decreases as the concentration of NaCl increases. Both observations are consistent with a mass transfer mechanism strongly dependent on electroosmotic flow. Steady-state anodic flux at 0.32 mA/cm2, expressed as equivalent donor solution flux (in microliters/hr cm2), ranged from 6.1 for glycine to about 2 for the large anions. As expected, iontophoretic flux is higher at 3.2 mA/cm2 than at 0.32 mA/cm2, and passive flux measured after iontophoresis is about a factor of 10 greater than the corresponding flux measured before the skin was exposed to electric current. There are two mechanisms for flux enhancement relative to passive flux on "fresh" hairless mouse skin: (1) the effect of the voltage in increasing mass transfer over the passive diffusion level, the effect of electroosmotic flow dominating this contribution in the systems studied in this report; and (2) the effect of prior current flow in increasing the "intrinsic permeability" of the skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Errors arising from incorrect orientation of E test strips

Journal of clinical microbiology, 1995

Major errors arise if E test strips are placed upside down. Asymmetric zones, or no zone at all, ... more Major errors arise if E test strips are placed upside down. Asymmetric zones, or no zone at all, may result. MICs indicated by upside-down tests were almost always considerably higher than true values. This situation differs markedly from that for conventional testing, where orientation of disks is not important.

Research paper thumbnail of Public health issues arising from microbiological and labelling quality of foods and supplements containing probiotic microorganisms

Public Health Nutrition, 1999

ObjectiveTo assess the accuracy and helpfulness of labelling on products containing probiotic bac... more ObjectiveTo assess the accuracy and helpfulness of labelling on products containing probiotic bacteria.Design and setting52 such products – 44 from the UK (21 supplements, 15 fermented functional foods, eight ‘health-care’ products) and eight from continental Europe – have been tested for microbiological content, and results compared to the information available on their labels. Products were stored in the dark at 4°C and analysed before their expiry or sell-by date. Careful note was taken of wording on labels, package inserts, packaging, promotional literature and catalogue descriptions, as applicable. Products were cultured on appropriate bacteriological media, and organisms grown were counted and identified.ResultsBioyoghurts gave no indication of numbers, and only five accurately described their bacterial content; results of culture were usually satisfactory. ‘Health-care’ products (mostly intended for the bowel) usually indicated the presence of bacteria, but the numerical cont...

Research paper thumbnail of Anomalous but helpful findings from the BBL Crystal ID kit with Haemophilus spp

Letters in Applied Microbiology, 1996

Fourteen strains of Haemophilus (12 H. influenzae, 1 H. parainfluenzae and 1 H. aphrophilus) were... more Fourteen strains of Haemophilus (12 H. influenzae, 1 H. parainfluenzae and 1 H. aphrophilus) were processed in BBL Crystal ID Enteric/Nonfermenter, API 20E and API 20NE kits, to determine whether the BBL kit misidentifies, as API kits may do, Haemophilus spp. as Pasteurella spp. The 13 H. influenzae and H. parainfluenzae strains produced uninterpretable colour reactions in the Crystal kit, thus signalling that an inappropriate species had been tested. On the other hand, the API kits (especially 20NE) often confidently ‘identified’Haemophilus spp. as Pasteurella spp., giving no warning that this was a misidentification.

Research paper thumbnail of Activity of ketolide ABT-773 (cethromycin) against erythromycin-resistant Streptococcus pneumoniae: correlation with extended MLSK phenotypes

Journal of Antimicrobial Chemotherapy, 2002

Objectives: (i) To determine the inhibitory and bactericidal activities of ABT-773, a novel ketol... more Objectives: (i) To determine the inhibitory and bactericidal activities of ABT-773, a novel ketolide, against sensitive and erythromycin-resistant pneumococci; (ii) to subdivide erythromycinresistant pneumococci into resistance phenotypes, more extensive than the conventional M and MLS B groups, by assessing susceptibilities to, and interactions between, erythromycin (14-membered macrolide), clindamycin (lincosamide), rokitamycin (16-membered macrolide), ABT-773 (ketolide), quinupristin (streptogramin B) and dalfopristin (streptogramin A). Methods: MICs and MBCs of ABT-773 were determined for 165 strains of pneumococci (113 resistant to erythromycin). Extended phenotypes for the erythromycin-resistant strains were described in terms of intrinsic susceptibility to, and induction of resistance by, the antibiotics listed above. Results: Erythromycin-resistant strains could be divided into 10 extended phenotypes (designated II-XI), two of which (II and IX) predominated. ABT-773 at 0.12 mg/L inhibited 109 strains (median 0.03 mg/L). MICs for the other four strains (of phenotypes X and XI) were 0.25-1 mg/L. MICs were only slighter higher when measured on agar in CO 2 than by the NCCLS method (in broth in air). MBCs were usually ≤2 × MIC, but for 10 strains (eight of phenotype X, one each of types IX and XI) MBCs were >1 mg/L, and three of the latter (all type X) were tolerant. Clones of reduced susceptibility (MICs 1-8 mg/L, increased by up to 32-fold) could be isolated from some strains of phenotypes VII, IX and X, but not from those of type II (efflux mechanism) or from erythromycin-sensitive strains. Conclusions: ABT-773 was active against all 113 erythromycin-resistant pneumococci tested, which belonged to 10 phenotypes. Extended phenotyping of pneumococci revealed interesting and potentially useful subdivisions of the classical phenotypes.

Research paper thumbnail of The effect of a component of tea (Camellia sinensis) on methicillin resistance, PBP2' synthesis, and beta-lactamase production in Staphylococcus aureus

Journal of Antimicrobial Chemotherapy, 1998

Bacterial strains Methicillin-resistant S. aureus (MRSA) were from our collection of distinct str... more Bacterial strains Methicillin-resistant S. aureus (MRSA) were from our collection of distinct strains from different countries 3 and methicillin-sensitive S. aureus (MSSA) were separate recent clinical isolates, as were two strains of bla methicillin-resistant Staphylococcus epidermidis (MRSE). Indicator strains used in bioassays (see below) were: S. aureus Oxford (bla), S. aureus US12 (an MRSA 3) and S. aureus 16084 (MSSA, bla). Strains of other species resistant to penicillin as a result of altered penicillin-binding proteins (PBPs), pneumococci, bla gonococci and Haemophilus influenzae, were recent clinical isolates. Tea Activities I, II and III were found in various Indian and China black teas, Oolong tea and green tea. We used 211

Research paper thumbnail of Activity of the tea component epicatechin gallate and analogues against methicillin-resistant Staphylococcus aureus

Journal of Antimicrobial Chemotherapy, 2000

Research paper thumbnail of In-vitro microbiological assessment of a new penem, Men 10700

Journal of Antimicrobial Chemotherapy, 1997

Stock solutions were made with reference to the stated potencies. Amoxycillin was dissolved in 2%... more Stock solutions were made with reference to the stated potencies. Amoxycillin was dissolved in 2% sodium bicarbonate solution, the other compounds in distilled water. Amoxycillin and clavulanate were combined in a ratio of 2:1 to give co-amoxiclav. Concentrations of co-amoxiclav stated below refer to the amoxycillin content. Bacterial strains The following strains were tested: 40 Staphylococcus aureus (20 methicillin-sensitive), 38 coagulase-negative staphylococci (18 methicillin-resistant), 57-haemolytic streptococci (20 group A, 20 group B, six group C, 11 575 Original articles In-vitro microbiological assessment of a new penem, Men 10700

Research paper thumbnail of Comparative in-vitro activity of ketolide HMR 3647 and four macrolides against gram-positive cocci of known erythromycin susceptibility status

Journal of Antimicrobial Chemotherapy, 1998

Brain-heart infusion broth (BHI) and IsoSensitest agar (ISA) were supplied by Unipath (Basingstok... more Brain-heart infusion broth (BHI) and IsoSensitest agar (ISA) were supplied by Unipath (Basingstoke, UK). Columbia agar (CA) and Mueller-Hinton agar (MHA) and broth (MHB) were supplied by Mast (Bootle, UK). Horse blood was lysed when required by freezing and thawing. Antibiotics Roxithromycin and HMR 3647 were from Roussel UCLAF (Romainville, France), clarithromycin from Abbott Laboratories (Queenborough, UK), miocamycin from Meiji Seika Pharma (Tokyo, Japan), and erythromycin BP (free base) from Lilly Industries (Basingstoke, UK). Stock solutions were made in methanol, except for clarithromycin, which was dissolved in acetone. Further dilutions were made in water, and final concentrations of solvent in growth media did not exceed 1%. Bacterial strains These were either from stock collection or were selected from strains isolated in the Diagnostic Microbiology Laboratory at the Royal Free Hospital. Susceptibility to erythromycin was determined before MIC testing, and resistant staphylococci were subdivided 649

Research paper thumbnail of Activity of glycylcyclines CL 329998 and CL 331002 against minocycline-resistant and other strains of methicillin-resistant Staphylococcus aureus

Journal of Antimicrobial Chemotherapy, 1996

Two glycylcyclines have been tested against 191 strains of methicillin-resistant Staphylococcus a... more Two glycylcyclines have been tested against 191 strains of methicillin-resistant Staphylococcus aureus, 72 of which were resistant to minocycline, isolated from many parts of the world. MICs of CL 329998 ranged from 0.06 to 4 mg/L, with MIC, and MIG» 0.5 and 2 mg/L, respectively. CL 331002 was slightly less potent, having an MIC range 0.12-16 mg/L and MIC50 and MIG» values of 1 and 4 mg/L, respectively.

Research paper thumbnail of In-vitro activity of a novel penem, Men 10700, against meningococci and gonococci, and the effect of a cysteine-containing supplement

Journal of Antimicrobial Chemotherapy, 1998

Research paper thumbnail of Activity of the semi-synthetic kanamycin B derivative, arbekacin against methicillin-resistant Staphylococcus aureus

Journal of Antimicrobial Chemotherapy, 1995

Arbekacin (1-N-((S)-4-amino-2-hydroxybutyryl)-3',4'-dideoxykanamycin B) was activ... more Arbekacin (1-N-((S)-4-amino-2-hydroxybutyryl)-3',4'-dideoxykanamycin B) was active against 54 strains of methicillin-resistant Staphylococcus aureus from 16 different countries, all of which were resistant to > or = 32 mg/L amikacin. MICs of arbekacin ranged from 1 to 16 mg/L, the MIC50 was 3.2 mg/L and the mode geometric mean MICs were 4 and 4.5 mg/L respectively.

Research paper thumbnail of Activity of quinupristin/dalfopristin against Staphylococcus epidermidis in biofilms: a comparison with ciprofloxacin

Journal of Antimicrobial Chemotherapy, 1997

Bactericidal effects of quinupristin/dalfopristin and ciprofloxacin have been studied against six... more Bactericidal effects of quinupristin/dalfopristin and ciprofloxacin have been studied against six strains of Staphylococcus epidermidis, with varying erythromycin resistance phenotypes and varying abilities to form slime and adhere, growing as biofilms. Ciprofloxacin and quinupristin/dalfopristin killed (2-3 log 10 cfu/mL) planktonic and sessile cells slowly, but progressively, over the course of 48 h. Rates of killing by quinupristin/dalfopristin were independent of concentration over the range 5-30 mg/L, and were somewhat slower than those seen with ciprofloxacin. These findings suggest that quinupristin/dalfopristin may be useful in the treatment of line-associated infections.

Research paper thumbnail of Modulation of β-lactam resistance in Staphylococcus aureus by catechins and gallates

International Journal of Antimicrobial Agents, 2004

Aqueous extracts of Japanese green tea (Camellia sinensis) are able to reverse beta-lactam resist... more Aqueous extracts of Japanese green tea (Camellia sinensis) are able to reverse beta-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA). We have attributed the capacity to reverse oxacillin resistance in the homogeneous PBP2a producer BB568 and in EMRSA-16 to (-)-epicatechin gallate (ECG) and (-)-catechin gallate (CG). Minimum inhibitory concentration (MIC) values for oxacillin were reduced from 256 and 512 to 1-4 mg/l, respectively, in the presence of these polyphenols. In addition, (-)-epigallocatechin gallate (EGCG) had a moderate capacity to modulate oxacillin activity against S. aureus BB568, but none against EMRSA-16. ECG, CG and EGCG increased the sensitivity of EMRSA-15 to oxacillin. The gallate moiety was essential for the oxacillin-modulating activity of ECG, as both (-)-epicatechin and (-)-epicatechin-3-cyclohexylcarboxylate were unable to reverse resistance to oxacillin. Gallic acid and three alkyl gallates (methyl gallate, propyl gallate, and octyl gallate) did not modulate beta-lactam resistance in MRSA. Octyl gallate exhibited direct antibacterial activity against S. aureus BB568 (16 mg/l). Modulation of beta-lactam resistance by ECG significantly enhanced the activities of flucloxacillin and the carbapenem antibiotics imipenem and meropenem against 40 MRSA isolates, with MIC(90) values for the antibiotics reduced to the susceptibility breakpoint or below. Consequently, EGCG, CG and, particularly, ECG warrant further investigation as agents to combat beta-lactam resistance in S. aureus.

Research paper thumbnail of Anti-Staphylococcus aureus activity and oxacillin resistance modulating capacity of 3-O-acyl-catechins

International Journal of Antimicrobial Agents, 2004

Epicatechin gallate (ECg), a component of green tea with weak activity against Staphylococcus aur... more Epicatechin gallate (ECg), a component of green tea with weak activity against Staphylococcus aureus, reduces oxacillin resistance in methicillin-resistant S. aureus at concentrations below the MIC. Because catechins bind to artificial lipid bilayers, we investigated whether the anti-staphylococcal activity of catechins could be improved by increasing their capacity to interact with the cytoplasmic membrane. Substitution of the gallate group of ECg with 3-O-acyl chains of varying lengths (C(4)-C(18)) led to enhanced anti-staphylococcal activity with chain lengths of C(8) (octanoyl) and C(10) (decanoyl). 3-O-octanoyl catechin was bactericidal against MRSA as the result of membrane damage. 3-O-acyl catechins tested at a 1/4 MIC did not reduce the oxacillin MIC greater than two-fold. 3-O-acyl catechins warrant further investigation as anti-staphylococcal agents.

Research paper thumbnail of Comparative anti-anaerobic activity of Men 10700, a penem antibiotic

International Journal of Antimicrobial Agents, 1998

The in vitro activity of Men 10700, a new penem, has been compared with that of metronidazole, cl... more The in vitro activity of Men 10700, a new penem, has been compared with that of metronidazole, clindamycin, ciprofloxacin, co-amoxiclav, imipenem and three third generation cephalosporins against 120 strains of anaerobes. The organisms tested comprised Clostridium perfringens, Clostridium difficile, Bacteroides fragilis and speciated members of the genera Fusobacterium, Veillonella and Peptostreptococcus. Men 10700 showed activity similar to that of imipenem, and was more potent than metronidazole against all species except C. difficile and P. anaerobius. The spectrum of activity of Men 10700 suggests this agent may be useful for treating infections caused by anaerobes.

Research paper thumbnail of Vancomycin susceptibility as an aid to the identification of lactobacilli

Letters in Applied Microbiology, 1998

Forty strains of lactobacilli isolated from probiotic supplements or functional foods, and two cl... more Forty strains of lactobacilli isolated from probiotic supplements or functional foods, and two clinical isolates, have been identified by API 50 CHL and tested for susceptibility to vancomycin. All the Lactobacillus acidophilus (16) and Lact. delbreuckii (two) strains were sensitive to vancomycin, while all the other strains (mainly Lact. rhamnosus, 15) were resistant. Susceptibility to other antibiotics was not species-specific. Differential susceptibility to vancomycin may be helpful in speciation of lactobacilli.

Research paper thumbnail of Nondialyzable peptide-bound hydroxyproline in human amniotic fluid: An indicator of fetal growth

American Journal of Obstetrics and Gynecology, 1972

Research paper thumbnail of Role of Induced Abortion in Rhesus Immunisation

The Lancet, 1971

... published cases of Rhnegative patients whose pregnancies have been terminated 8 became immuni... more ... published cases of Rhnegative patients whose pregnancies have been terminated 8 became immunised to the Rh factor. This 5 middot;5 risk of immunisation warrants a policy of protection with Rhimmune globulin. Introduction THE risk of maternal rhesus immunisation due to a ...

Research paper thumbnail of Fetal blood typing after induced abortion

Obstetrics and gynecology, 1972

An attempt was made to determine the Rh type of saline induced aborted fetuses. Twenty-eight pati... more An attempt was made to determine the Rh type of saline induced aborted fetuses. Twenty-eight patients admitted to New York Hospital and Cornell Medical Center were studied. The blood was obtained (within 1 hour after abortion in most cases) from the piece of cord cut from the abortus. The blood cells were confirmed to be of fetal origin by the Kleihauer-Betke stain. In 27 of the 28 cases, the RH type could be determined. Two of the 28 fetuses (1 set of twins) were typed as Rh negative and the mother did not need Rh immunoglobulin. In no case did the blood group and Rh type conflict with the mother's blood group and Rh type. It is possible to determine the Rh type of fetal erythrocytes after saline-induced abortion. When practical, this simple procedure will prevent Rh immunoglobulin from being used when it is not indicated, and the approach towards the management of Rh-negative women undergoing saline induced abortions will be more methodical.

Research paper thumbnail of Transport Mechanisms in Iontophoresis. III. An Experimental Study of the Contributions of Electroosmotic Flow and Permeability Change in Transport of Low and High Molecular Weight Solutes

The objective of this research was to provide in vitro transport data designed to clarify the rel... more The objective of this research was to provide in vitro transport data designed to clarify the relative importance of permeability increase and electroosmotic flow in flux enhancement via iontophoresis. Iontophoretic fluxes were measured with both anode and cathode donor cells, and passive fluxes were measured both before iontophoresis (Passive 1) and after iontophoresis (Passive 2). Data were generated for three uncharged low molecular weight solutes (glycine, glucose, and tyrosine) and two high molecular weight anionic species (carboxy inulin and bovine serum albumin). Flux enhancement is greater for anodic delivery than for cathodic delivery, even for the negatively charged molecules, and anodic flux of glucose decreases as the concentration of NaCl increases. Both observations are consistent with a mass transfer mechanism strongly dependent on electroosmotic flow. Steady-state anodic flux at 0.32 mA/cm2, expressed as equivalent donor solution flux (in microliters/hr cm2), ranged from 6.1 for glycine to about 2 for the large anions. As expected, iontophoretic flux is higher at 3.2 mA/cm2 than at 0.32 mA/cm2, and passive flux measured after iontophoresis is about a factor of 10 greater than the corresponding flux measured before the skin was exposed to electric current. There are two mechanisms for flux enhancement relative to passive flux on "fresh" hairless mouse skin: (1) the effect of the voltage in increasing mass transfer over the passive diffusion level, the effect of electroosmotic flow dominating this contribution in the systems studied in this report; and (2) the effect of prior current flow in increasing the "intrinsic permeability" of the skin.(ABSTRACT TRUNCATED AT 250 WORDS)

Research paper thumbnail of Errors arising from incorrect orientation of E test strips

Journal of clinical microbiology, 1995

Major errors arise if E test strips are placed upside down. Asymmetric zones, or no zone at all, ... more Major errors arise if E test strips are placed upside down. Asymmetric zones, or no zone at all, may result. MICs indicated by upside-down tests were almost always considerably higher than true values. This situation differs markedly from that for conventional testing, where orientation of disks is not important.

Research paper thumbnail of Public health issues arising from microbiological and labelling quality of foods and supplements containing probiotic microorganisms

Public Health Nutrition, 1999

ObjectiveTo assess the accuracy and helpfulness of labelling on products containing probiotic bac... more ObjectiveTo assess the accuracy and helpfulness of labelling on products containing probiotic bacteria.Design and setting52 such products – 44 from the UK (21 supplements, 15 fermented functional foods, eight ‘health-care’ products) and eight from continental Europe – have been tested for microbiological content, and results compared to the information available on their labels. Products were stored in the dark at 4°C and analysed before their expiry or sell-by date. Careful note was taken of wording on labels, package inserts, packaging, promotional literature and catalogue descriptions, as applicable. Products were cultured on appropriate bacteriological media, and organisms grown were counted and identified.ResultsBioyoghurts gave no indication of numbers, and only five accurately described their bacterial content; results of culture were usually satisfactory. ‘Health-care’ products (mostly intended for the bowel) usually indicated the presence of bacteria, but the numerical cont...

Research paper thumbnail of Anomalous but helpful findings from the BBL Crystal ID kit with Haemophilus spp

Letters in Applied Microbiology, 1996

Fourteen strains of Haemophilus (12 H. influenzae, 1 H. parainfluenzae and 1 H. aphrophilus) were... more Fourteen strains of Haemophilus (12 H. influenzae, 1 H. parainfluenzae and 1 H. aphrophilus) were processed in BBL Crystal ID Enteric/Nonfermenter, API 20E and API 20NE kits, to determine whether the BBL kit misidentifies, as API kits may do, Haemophilus spp. as Pasteurella spp. The 13 H. influenzae and H. parainfluenzae strains produced uninterpretable colour reactions in the Crystal kit, thus signalling that an inappropriate species had been tested. On the other hand, the API kits (especially 20NE) often confidently ‘identified’Haemophilus spp. as Pasteurella spp., giving no warning that this was a misidentification.

Research paper thumbnail of Activity of ketolide ABT-773 (cethromycin) against erythromycin-resistant Streptococcus pneumoniae: correlation with extended MLSK phenotypes

Journal of Antimicrobial Chemotherapy, 2002

Objectives: (i) To determine the inhibitory and bactericidal activities of ABT-773, a novel ketol... more Objectives: (i) To determine the inhibitory and bactericidal activities of ABT-773, a novel ketolide, against sensitive and erythromycin-resistant pneumococci; (ii) to subdivide erythromycinresistant pneumococci into resistance phenotypes, more extensive than the conventional M and MLS B groups, by assessing susceptibilities to, and interactions between, erythromycin (14-membered macrolide), clindamycin (lincosamide), rokitamycin (16-membered macrolide), ABT-773 (ketolide), quinupristin (streptogramin B) and dalfopristin (streptogramin A). Methods: MICs and MBCs of ABT-773 were determined for 165 strains of pneumococci (113 resistant to erythromycin). Extended phenotypes for the erythromycin-resistant strains were described in terms of intrinsic susceptibility to, and induction of resistance by, the antibiotics listed above. Results: Erythromycin-resistant strains could be divided into 10 extended phenotypes (designated II-XI), two of which (II and IX) predominated. ABT-773 at 0.12 mg/L inhibited 109 strains (median 0.03 mg/L). MICs for the other four strains (of phenotypes X and XI) were 0.25-1 mg/L. MICs were only slighter higher when measured on agar in CO 2 than by the NCCLS method (in broth in air). MBCs were usually ≤2 × MIC, but for 10 strains (eight of phenotype X, one each of types IX and XI) MBCs were >1 mg/L, and three of the latter (all type X) were tolerant. Clones of reduced susceptibility (MICs 1-8 mg/L, increased by up to 32-fold) could be isolated from some strains of phenotypes VII, IX and X, but not from those of type II (efflux mechanism) or from erythromycin-sensitive strains. Conclusions: ABT-773 was active against all 113 erythromycin-resistant pneumococci tested, which belonged to 10 phenotypes. Extended phenotyping of pneumococci revealed interesting and potentially useful subdivisions of the classical phenotypes.

Research paper thumbnail of The effect of a component of tea (Camellia sinensis) on methicillin resistance, PBP2' synthesis, and beta-lactamase production in Staphylococcus aureus

Journal of Antimicrobial Chemotherapy, 1998

Bacterial strains Methicillin-resistant S. aureus (MRSA) were from our collection of distinct str... more Bacterial strains Methicillin-resistant S. aureus (MRSA) were from our collection of distinct strains from different countries 3 and methicillin-sensitive S. aureus (MSSA) were separate recent clinical isolates, as were two strains of bla methicillin-resistant Staphylococcus epidermidis (MRSE). Indicator strains used in bioassays (see below) were: S. aureus Oxford (bla), S. aureus US12 (an MRSA 3) and S. aureus 16084 (MSSA, bla). Strains of other species resistant to penicillin as a result of altered penicillin-binding proteins (PBPs), pneumococci, bla gonococci and Haemophilus influenzae, were recent clinical isolates. Tea Activities I, II and III were found in various Indian and China black teas, Oolong tea and green tea. We used 211

Research paper thumbnail of Activity of the tea component epicatechin gallate and analogues against methicillin-resistant Staphylococcus aureus

Journal of Antimicrobial Chemotherapy, 2000

Research paper thumbnail of In-vitro microbiological assessment of a new penem, Men 10700

Journal of Antimicrobial Chemotherapy, 1997

Stock solutions were made with reference to the stated potencies. Amoxycillin was dissolved in 2%... more Stock solutions were made with reference to the stated potencies. Amoxycillin was dissolved in 2% sodium bicarbonate solution, the other compounds in distilled water. Amoxycillin and clavulanate were combined in a ratio of 2:1 to give co-amoxiclav. Concentrations of co-amoxiclav stated below refer to the amoxycillin content. Bacterial strains The following strains were tested: 40 Staphylococcus aureus (20 methicillin-sensitive), 38 coagulase-negative staphylococci (18 methicillin-resistant), 57-haemolytic streptococci (20 group A, 20 group B, six group C, 11 575 Original articles In-vitro microbiological assessment of a new penem, Men 10700

Research paper thumbnail of Comparative in-vitro activity of ketolide HMR 3647 and four macrolides against gram-positive cocci of known erythromycin susceptibility status

Journal of Antimicrobial Chemotherapy, 1998

Brain-heart infusion broth (BHI) and IsoSensitest agar (ISA) were supplied by Unipath (Basingstok... more Brain-heart infusion broth (BHI) and IsoSensitest agar (ISA) were supplied by Unipath (Basingstoke, UK). Columbia agar (CA) and Mueller-Hinton agar (MHA) and broth (MHB) were supplied by Mast (Bootle, UK). Horse blood was lysed when required by freezing and thawing. Antibiotics Roxithromycin and HMR 3647 were from Roussel UCLAF (Romainville, France), clarithromycin from Abbott Laboratories (Queenborough, UK), miocamycin from Meiji Seika Pharma (Tokyo, Japan), and erythromycin BP (free base) from Lilly Industries (Basingstoke, UK). Stock solutions were made in methanol, except for clarithromycin, which was dissolved in acetone. Further dilutions were made in water, and final concentrations of solvent in growth media did not exceed 1%. Bacterial strains These were either from stock collection or were selected from strains isolated in the Diagnostic Microbiology Laboratory at the Royal Free Hospital. Susceptibility to erythromycin was determined before MIC testing, and resistant staphylococci were subdivided 649

Research paper thumbnail of Activity of glycylcyclines CL 329998 and CL 331002 against minocycline-resistant and other strains of methicillin-resistant Staphylococcus aureus

Journal of Antimicrobial Chemotherapy, 1996

Two glycylcyclines have been tested against 191 strains of methicillin-resistant Staphylococcus a... more Two glycylcyclines have been tested against 191 strains of methicillin-resistant Staphylococcus aureus, 72 of which were resistant to minocycline, isolated from many parts of the world. MICs of CL 329998 ranged from 0.06 to 4 mg/L, with MIC, and MIG» 0.5 and 2 mg/L, respectively. CL 331002 was slightly less potent, having an MIC range 0.12-16 mg/L and MIC50 and MIG» values of 1 and 4 mg/L, respectively.

Research paper thumbnail of In-vitro activity of a novel penem, Men 10700, against meningococci and gonococci, and the effect of a cysteine-containing supplement

Journal of Antimicrobial Chemotherapy, 1998

Research paper thumbnail of Activity of the semi-synthetic kanamycin B derivative, arbekacin against methicillin-resistant Staphylococcus aureus

Journal of Antimicrobial Chemotherapy, 1995

Arbekacin (1-N-((S)-4-amino-2-hydroxybutyryl)-3',4'-dideoxykanamycin B) was activ... more Arbekacin (1-N-((S)-4-amino-2-hydroxybutyryl)-3',4'-dideoxykanamycin B) was active against 54 strains of methicillin-resistant Staphylococcus aureus from 16 different countries, all of which were resistant to > or = 32 mg/L amikacin. MICs of arbekacin ranged from 1 to 16 mg/L, the MIC50 was 3.2 mg/L and the mode geometric mean MICs were 4 and 4.5 mg/L respectively.

Research paper thumbnail of Activity of quinupristin/dalfopristin against Staphylococcus epidermidis in biofilms: a comparison with ciprofloxacin

Journal of Antimicrobial Chemotherapy, 1997

Bactericidal effects of quinupristin/dalfopristin and ciprofloxacin have been studied against six... more Bactericidal effects of quinupristin/dalfopristin and ciprofloxacin have been studied against six strains of Staphylococcus epidermidis, with varying erythromycin resistance phenotypes and varying abilities to form slime and adhere, growing as biofilms. Ciprofloxacin and quinupristin/dalfopristin killed (2-3 log 10 cfu/mL) planktonic and sessile cells slowly, but progressively, over the course of 48 h. Rates of killing by quinupristin/dalfopristin were independent of concentration over the range 5-30 mg/L, and were somewhat slower than those seen with ciprofloxacin. These findings suggest that quinupristin/dalfopristin may be useful in the treatment of line-associated infections.

Research paper thumbnail of Modulation of β-lactam resistance in Staphylococcus aureus by catechins and gallates

International Journal of Antimicrobial Agents, 2004

Aqueous extracts of Japanese green tea (Camellia sinensis) are able to reverse beta-lactam resist... more Aqueous extracts of Japanese green tea (Camellia sinensis) are able to reverse beta-lactam resistance in methicillin-resistant Staphylococcus aureus (MRSA). We have attributed the capacity to reverse oxacillin resistance in the homogeneous PBP2a producer BB568 and in EMRSA-16 to (-)-epicatechin gallate (ECG) and (-)-catechin gallate (CG). Minimum inhibitory concentration (MIC) values for oxacillin were reduced from 256 and 512 to 1-4 mg/l, respectively, in the presence of these polyphenols. In addition, (-)-epigallocatechin gallate (EGCG) had a moderate capacity to modulate oxacillin activity against S. aureus BB568, but none against EMRSA-16. ECG, CG and EGCG increased the sensitivity of EMRSA-15 to oxacillin. The gallate moiety was essential for the oxacillin-modulating activity of ECG, as both (-)-epicatechin and (-)-epicatechin-3-cyclohexylcarboxylate were unable to reverse resistance to oxacillin. Gallic acid and three alkyl gallates (methyl gallate, propyl gallate, and octyl gallate) did not modulate beta-lactam resistance in MRSA. Octyl gallate exhibited direct antibacterial activity against S. aureus BB568 (16 mg/l). Modulation of beta-lactam resistance by ECG significantly enhanced the activities of flucloxacillin and the carbapenem antibiotics imipenem and meropenem against 40 MRSA isolates, with MIC(90) values for the antibiotics reduced to the susceptibility breakpoint or below. Consequently, EGCG, CG and, particularly, ECG warrant further investigation as agents to combat beta-lactam resistance in S. aureus.

Research paper thumbnail of Anti-Staphylococcus aureus activity and oxacillin resistance modulating capacity of 3-O-acyl-catechins

International Journal of Antimicrobial Agents, 2004

Epicatechin gallate (ECg), a component of green tea with weak activity against Staphylococcus aur... more Epicatechin gallate (ECg), a component of green tea with weak activity against Staphylococcus aureus, reduces oxacillin resistance in methicillin-resistant S. aureus at concentrations below the MIC. Because catechins bind to artificial lipid bilayers, we investigated whether the anti-staphylococcal activity of catechins could be improved by increasing their capacity to interact with the cytoplasmic membrane. Substitution of the gallate group of ECg with 3-O-acyl chains of varying lengths (C(4)-C(18)) led to enhanced anti-staphylococcal activity with chain lengths of C(8) (octanoyl) and C(10) (decanoyl). 3-O-octanoyl catechin was bactericidal against MRSA as the result of membrane damage. 3-O-acyl catechins tested at a 1/4 MIC did not reduce the oxacillin MIC greater than two-fold. 3-O-acyl catechins warrant further investigation as anti-staphylococcal agents.

Research paper thumbnail of Comparative anti-anaerobic activity of Men 10700, a penem antibiotic

International Journal of Antimicrobial Agents, 1998

The in vitro activity of Men 10700, a new penem, has been compared with that of metronidazole, cl... more The in vitro activity of Men 10700, a new penem, has been compared with that of metronidazole, clindamycin, ciprofloxacin, co-amoxiclav, imipenem and three third generation cephalosporins against 120 strains of anaerobes. The organisms tested comprised Clostridium perfringens, Clostridium difficile, Bacteroides fragilis and speciated members of the genera Fusobacterium, Veillonella and Peptostreptococcus. Men 10700 showed activity similar to that of imipenem, and was more potent than metronidazole against all species except C. difficile and P. anaerobius. The spectrum of activity of Men 10700 suggests this agent may be useful for treating infections caused by anaerobes.