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1.  Synergistic Activity of Gentamicin with Trimethoprim or Sulfamethoxazole-Trimethoprim Against Escherichia coli and Klebsiella pneumoniae 
The effect of combinations of gentamicin with trimethoprim or sulfamethoxazole-trimethoprim against clinical isolates of Escherichia coli (11 strains) and Klebsiella pneumoniae (12 strains) was examined by using a microdilution checkerboard technique. All isolates were susceptible to each antimicrobial agent. Synergism, defined as at least a 2-log2-dilution lowering of the minimal inhibitory concentration of either antibiotic in the combination compared with the minimal inhibitory concentration of the antibiotic alone, was observed with 15 of 23 (65%) isolates tested against trimethoprim and gentamicin and 14 of 23 (61%) isolates tested against sulfamethoxazole-trimethoprim and gentamicin. A 3-log2-dilution lowering of the minimal inhibitory concentration of either antibiotic was observed in 7 of 23 (30%) trimethoprim and gentamicin trials and 3 of 23 (13%) sulfamethoxazole-trimethoprim and gentamicin trials. Antagonism was observed in 3 of 46 combination trials and only with strains of K. pneumoniae.
PMCID: PMC352530  PMID: 365085
2.  In Vitro Sensitivity of Salmonella to Ten Antimicrobial Agents Including Sulfamethoxazole and Trimethoprim, Alone and in Combination 
The activities of trimethoprim (TMP) and sulfamethoxazole (SMZ), alone and in combination (SMZ-TMP), and of the following antibiotics were tested against 115 clinical isolates of nontyphoid Salmonella species: tobramycin, gentamicin, ampicillin, amoxicillin, neomycin, kanamycin, chloramphenicol, and tetracycline. The methods of disk diffusion, microtiter broth dilution, and agar dilution were employed for all single antimicrobial agents as well as for SMZ-TMP studies. Growth curves were performed in broth. SMZ-TMP, TMP, gentamicin, tobramycin, and neomycin were the most active drugs in vitro. All strains were inhibited by ≤1 μg of TMP per ml, but >100 μg of SMZ per ml was required for at least 10% of strains. SMZ and TMP in a ratio of 10:0.5, respectively, inhibited all isolates and were synergistic for 105 strains. All strains inhibited by the combination of 10:0.5 SMZ-TMP had a zone diameter of ≥22 mm by using a combination disk containing 1.25 μg of TMP and 23.75 μg of SMZ. Seven isolates were resistant to >100 μg/ml of ampicillin or amoxicillin; all isolates were sensitive to chloramphenicol at ≤6.3 μg/ml. SMZ-TMP appears to be active against nontyphoid salmonellae in vitro; this is usually due to a synergistic effect.
PMCID: PMC444594  PMID: 4791490
3.  Asynchronous magnetic bead rotation (AMBR) micro-viscometer for rapid, sensitive and label-free studies of bacterial growth and drug sensitivity 
Analytical Chemistry  2012;84(12):5250-5256.
The long turnaround time in antimicrobial susceptibility testing (AST) endangers patients and encourages the administration of wide spectrum antibiotics, thus resulting in alarming increases of multi-drug resistant pathogens. A method for faster detection of bacterial proliferation presents one avenue towards addressing this global concern. We report on a label-free asynchronous magnetic bead rotation (AMBR) based viscometry method that rapidly detects bacterial growth and determines drug sensitivity by measuring changes in the suspension’s viscosity. With this platform, we observed the growth of a uropathogenic Escherichia coli isolate, with an initial concentration of 50 cells per drop, within 20 minutes; in addition, we determined the gentamicin minimum inhibitory concentration (MIC) of the E. coli isolate within 100 minutes. We thus demonstrated a label-free, micro-viscometer platform that can measure bacterial growth and drug susceptibility more rapidly, with lower initial bacterial counts than existing commercial systems, and potentially with any microbial strains.
doi:10.1021/ac300128p
PMCID: PMC3381929  PMID: 22507307
4.  Synergy of fosmidomycin (FR-31564) and other antimicrobial agents. 
Fosmidomycin (FR-31564), a phosphonic acid derivative, was combined with cefazolin, cephalexin, ampicillin, carbenicillin, ticarcillin, gentamicin, and trimethoprim. Synergy between fosmidomycin and penicillins or cephalosporins was found for 37 to 52% of the Enterobacteriaceae tested. Synergy with trimethoprim was found against 55% of bacteria isolated, but only 17% of the strains showed synergy between formidomycin and gentamicin. Synergy between fosmidomycin and ticarcillin was shown for 35% of the Pseudomonas isolates. Cefazolin-, ampicillin-, and gentamicin-resistant isolates of various species were synergistically inhibited by fosmidomycin, as were ticarcillin- and gentamicin-resistant isolates. Antagonism was not encountered. This study illustrates another example of synergistic activity of compounds which attack different mechanisms in bacterial cells.
PMCID: PMC183793  PMID: 7181471
5.  Susceptibility of Pseudomonas aeruginosa to Tobramycin or Gentamicin Alone and Combined with Carbenicillin 
To explore more effective therapy for Pseudomonas aeruginosa, 264 recent clinical isolates were tested by agar dilution using gentamicin and tobramycin alone and combined with carbenicillin to seek synergistic effects. Synergism was defined as a fourfold or greater decrease in the minimal inhibitory concentration of each drug in a pair. At a concentration of 3.12 μg/ml, gentamicin inhibited 73% of the strains and tobramycin inhibited 98%. The gentamicin-carbenicillin combination was synergistically active against 57% of the strains, and tobramycin-carbenicillin was active against 46%. The effect did not correlate with either susceptibility or resistance to gentamicin or tobramycin alone. The data suggest that tobramycin or tobramycin plus carbenicillin may provide alternate therapy where susceptibility to gentamicin or synergism between gentamicin and carbenicillin cannot be demonstrated; however, the degree of susceptibility to either aminoglycoside antibiotic alone cannot be used to predict a synergistic effect.
PMCID: PMC429310  PMID: 810083
6.  Differences in Antimicrobial Susceptibilities of Clinical Isolates in Saudi Arabia and the United States 
In vitro antimicrobial susceptibilities of 3,530 clinical isolates at King Faisal Specialist Hospital and Research Center (KFSH), in Riyadh, Saudi Arabia, were compared with those of 11,041 bacterial isolates at two hospitals of comparable size in the United States. The gram-negative bacteria, especially Escherichia coli, Proteus-Morganella group, Enterobacter sp, Serratia marcescens, and Pseudomonas aeruginosa were generally more resistant to ampicillin, carbenicillin, cephalosporin, gentamicin, piperacillin, and trimethoprim-sulfamethoxazole at KFSH than in the United States. A larger number of isolates of Klebsiella pneumoniae were more resistant to cephalosporin, chloramphenical, gentamicin, piperacillin, and trimethoprim-sulfamethoxazole at one of the tertiary care hospitals in the United States. Hemophilus influenzae and gram-positive cocci exhibited similar susceptibilities toward commonly used antibiotics at all three institutions.
PMCID: PMC2625486  PMID: 3586042
7.  In Vitro Effects of Carbenicillin Combined with Gentamicin or Polymyxin B Against Pseudomonas aeruginosa1 
Applied Microbiology  1969;18(3):469-473.
Disodium carbenicillin and gentamicin sulfate have both shown promise in the treatment of infections caused by Pseudomonas aeruginosa. This study was designed to explore possible synergistic relationships among the new as well as the established antimicrobial agents used to treat such infections. With an agar dilution technique, minimum inhibitory concentrations of 27 strains of P. aeruginosa were determined in two-dimensional tests. Graphs of equal biological activity (isobolograms) demonstrated moderate synergistic effects of the carbenicillin-gentamicin combination over therapeutically feasible concentration ranges. In contrast, the combination of carbenicillin and polymyxin B showed only additive or slightly antagonistic effects. Tests of bacterial killing confirmed the presence of carbenicillin-gentamicin synergy in 3 of 6 strains of P. aeruginosa, but did not show true antagonism between carbenicillin and polymyxin B. Clinical trials of both drug combinations are advisable to determine whether therapeutic results can be improved, and whether the dosages of gentamicin or polymyxin B can thereby be reduced to lessen their toxic hazards.
PMCID: PMC378006  PMID: 4313764
8.  Susceptibilities of Gram-Negative Bacteria to Combinations of Antimicrobial Agents In Vitro 
Combinations of either clindamycin or erythromycin with gentamicin, colimycin, or carbenicillin were studied for their antimicrobial effects on clinical isolates of Escherichia coli, Klebsiella sp., Proteus mirabilis, Serratia marcescens, Enterobacter aerogenes, and Pseudomonas aeruginosa. No antagonistic effects of the antibiotic combinations were observed. Synergistic effects of the antibiotic combinations were noted against most strains of E. coli tested, especially when either clindamycin or erythromycin was combined with gentamicin or colimycin. Of 16 other combinations of antibiotics examined with strains of E. coli as the test organisms, only the combination of penicillin G with either gentamicin or colimycin showed consistent synergy. The marked synergy of clindamycin combined with either gentamicin or colimycin was further demonstrated by following the kinetics of the bactericidal action of the antibiotic combinations and the effects on bacterial protein synthesis.
PMCID: PMC429284  PMID: 810077
9.  Klebsiella species: antimicrobial susceptibilities, bactericidal kinetics, and in vitro inactivation of beta-lactam agents. 
In vitro properties of 19 antimicrobial agents were tested with 56 isolates of Klebsiella spp. The aminoglycosides and the new beta-lactam compounds cefotaxime and moxalactam were the most inhibitory drugs tested. Chloramphenicol, tetracycline, trimethoprim, and trimethoprim-sulfamethoxazole were moderately active, whereas piperacillin, mezlocillin, and furazlocillin were ineffective against 25% of the isolates. Gentamicin was the only agent tested that was uniformly bactericidal in time-kill experiments with drug concentrations of four times the minimal inhibitory concentration. In combination studies with gentamicin, moxalactam and furazlocillin each increased the rate of bacterial killing for three of five isolates as compared with gentamicin alone, whereas chloramphenicol significantly retarded the rate of bacterial killing for the same number of strains. Furazlocillin was completely inactivated after 24 h of incubation with each of five selected strains. The inactivation of moxalactam, cefoxitin, and cephalothin was 36, 56, and 72%, respectively. In all instances in which these four agents were inactivated to levels below the minimal bactericidal concentration, there was accelerated growth after initial inhibition. However, regrowth also occurred in three instances in which drug levels were higher than the minimal bactericidal concentration. Retesting after drug exposure revealed a 4- to 32-fold rise in the minimal inhibitory concentration and minimal bactericidal concentration in two of these isolates.
PMCID: PMC352982  PMID: 7235676
10.  Antimicrobial Susceptibility of Udder Pathogens Isolated from Dairy Herds in the West Littoral Region of Uruguay 
Acta Veterinaria Scandinavica  2002;43(1):31-41.
A total of 522 strains belonging to streptococci, enterococci and staphylococci isolated from sub-clinical and clinical cases of bovine mastitis from the west littoral region of Uruguay were analysed for their susceptibility to several antimicrobial agents. The susceptibility patterns were studied by agar disk diffusion methods (ADDM) and broth micro-dilution to determine the minimum inhibitory concentration (MIC). The concentration that inhibits 90% (MIC90) of the analysed strains reported in micrograms per millilitre, for Staphylococcus aureus were > 8, 8, ≤ 0.5, ≤ 4, ≤ 1, ≤ 0.5, > 64, ≤ 0.25, 0.5, ≤ 1 and ≤ 1 to penicillin, ampicillin, oxacillin, cephalotin, gentamicin, erythromycin, oxitetracycline, enrofloxacin, trimethoprim/sulfamethoxazole, neomycin, and clindamycin, respectively. Coagulase-negative staphylococci (CNS) had different values for penicillin (4) and ampicillin (2), while the other antimicrobial agents had the same MIC90 values as reported for S. aureus. The MIC90 values for streptococci were 0.12, 0.25, ≤ 4, 16, ≤ 0.25, 0.5, 0.25 for penicillin, ampicillin, cephalotin, gentamicin, erythromycin, oxytetracycline and trimethoprim-sulfamethoxazole, whereas MIC90 for enterococci were 4, 4, 4, ≤ 0.5, 2, > 8 for penicillin, ampicillin, gentamicin, erythromycin, oxytetracycline and trimethoprim-sulfamethoxazole, respectively. Of 336 strains of S. aureus, 160 (47.6%) were resistant to penicillin. For 41 CNS strains, 10 (27%) presented penicillin-resistance. All the streptococcal strains were susceptible to penicillin, while 3 (7%) of the 43 enteroccocal strains were resistant. Non significant statistical differences were found between the results obtained by ADDM and broth micro-dilution for classifying bacterial isolates as susceptible or resistant according to the National Committee of Clinical Laboratory Standards.
doi:10.1186/1751-0147-43-31
PMCID: PMC1764182  PMID: 12071114
cow; mammary qland; bacteria; resistant; sensitive
11.  Outbreak of Multiply Drug-Resistant Proteus mirabilis Originating in a Surgical Intensive Care Unit: In Vitro Susceptibility Pattern 
A multiply drug-resistant strain of Proteus mirabilis was isolated from 14 patients on a surgical service. Antimicrobial susceptibility studies demonstrated that the organism was highly resistant to numerous antibiotics, including gentamicin, tobramycin, and sisomicin. The organism was susceptible in vitro to amikacin but had low-level resistance to netilmicin. In vitro susceptibility studies with combinations of cephalothin with netilmicin and trimethoprim with sulfamethoxazole showed these drugs to be synergistic. Other drug combinations failed to act synergistically.
PMCID: PMC352209  PMID: 348093
12.  Therapy of Antimicrobial-Resistant Typhoid Fever 
Antimicrobial-resistant typhoid fever in Saigon was studied by examining in vitro antimicrobial susceptibilities of Salmonella typhi strains and conducting a randomized clinical trial of ampicillin and trimethoprim-sulfamethoxazole (TMP-SMZ). Isolates of S. typhi were obtained from blood or stool cultures of 90 patients. Of 87 isolates tested for antimicrobial susceptibility, 65 (75%) were resistant (R) to chloramphenicol, streptomycin, sulfonamide, and tetracycline, and 22 (25%) were susceptible (S). The drug resistance was transferable to Escherichia coli and was found in 11 different Vi-phage types. All isolates were susceptible to ampicillin and to TMP-SMZ. Agar dilution studies of TMP and SMZ showed synergistic inhibition of growth in all 18 S isolates and in 12 of 48 R isolates tested. The clinical trial of ampicillin and TMP-SMZ showed that both drugs were equally effective. Treatment failure with both drugs was more frequent in patients with S isolates than in patients with R isolates. Therefore, in an area where antimicrobial-resistant typhoid fever exists, patients with R isolates should receive either ampicillin or TMP-SMZ, but patients with S isolates should be treated with chloramphenicol.
PMCID: PMC352043  PMID: 324398
13.  Combination of Alpha-Melanocyte Stimulating Hormone with Conventional Antibiotics against Methicillin Resistant Staphylococcus aureus 
PLoS ONE  2013;8(9):e73815.
Our previous studies revealed that alpha-melanocyte stimulating hormone (α-MSH) is strongly active against Staphylococcus aureus (S. aureus) including methicillin resistant S. aureus (MRSA). Killing due to α-MSH occurred by perturbation of the bacterial membrane. In the present study, we investigated the in vitro synergistic potential of α-MSH with five selected conventional antibiotics viz., oxacillin (OX), ciprofloxacin (CF), tetracycline (TC), gentamicin (GM) and rifampicin (RF) against a clinical MRSA strain which carried a type III staphylococcal cassette chromosome mec (SCCmec) element and belonged to the sequence type (ST) 239. The strain was found to be highly resistant to OX (minimum inhibitory concentration (MIC) = 1024 µg/ml) as well as to other selected antimicrobial agents including α-MSH. The possibility of the existence of intracellular target sites of α-MSH was evaluated by examining the DNA, RNA and protein synthesis pathways. We observed a synergistic potential of α-MSH with GM, CF and TC. Remarkably, the supplementation of α-MSH with GM, CF and TC resulted in ≥64-, 8- and 4-fold reductions in their minimum bactericidal concentrations (MBCs), respectively. Apart from membrane perturbation, in this study we found that α-MSH inhibited ∼53% and ∼47% DNA and protein synthesis, respectively, but not RNA synthesis. Thus, the mechanistic analogy between α-MSH and CF or GM or TC appears to be the reason for the observed synergy between them. In contrast, α-MSH did not act synergistically with RF which may be due to its inability to inhibit RNA synthesis (<10%). Nevertheless, the combination of α-MSH with RF and OX showed an enhanced killing by ∼45% and ∼70%, respectively, perhaps due to the membrane disrupting properties of α-MSH. The synergistic activity of α-MSH with antibiotics is encouraging, and promises to restore the lost potency of discarded antibiotics.
doi:10.1371/journal.pone.0073815
PMCID: PMC3767696  PMID: 24040081
14.  Antimicrobial-resistant Klebsiella species isolated from free-range chicken samples in an informal settlement 
Introduction
Sub-therapeutic doses of antimicrobial agents are administered routinely to poultry to aid growth and to prevent disease, with prolonged exposure often resulting in bacterial resistance. Crossover of antibiotic resistant bacteria from poultry to humans poses a risk to human health.
Material and methods
In this study, 17 chicken samples collected from a vendor operating in an informal settlement in the Cape Town Metropolitan area, South Africa were screened for antimicrobial-resistant Gram-negative bacilli using the Kirby Bauer disk diffusion assay.
Results
In total, six antibiotics were screened: ampicillin, ciprofloxacin, gentamicin, nalidixic acid, tetracycline and trimethoprim. Surprisingly, Klebsiella ozaenae was identified in 96 and K. rhinoscleromatis in 6 (n=102) of the samples tested. Interestingly, ∼40% of the isolated Klebsiella spp. showed multiple resistance to at least three of the six antibiotics tested.
Conclusions
Klebsiella ozaenae and K. rhinoscleromatis cause clinical chronic rhinitis and are almost exclusively associated with people living in areas of poor hygiene.
doi:10.5114/aoms.2012.27278
PMCID: PMC3309434  PMID: 22457672
antibiotic-resistant; poultry; resistance; Klebsiella species
15.  Effect of Clavulanic Acid on the In Vitro Synergism Between Carbenicillin and Gentamicin Against Serratia marcescens 
Clavulanic acid, a potent β-lactamase inhibitor, reduced the minimum inhibitory concentrations of carbenicillin for 13 of 15 clinical isolates of Serratia marcescens by at least eightfold. The combination of clavulanic acid and carbenicillin also exhibited synergistic activity with gentamicin against 11 of 15 isolates tested, including 9 of 10 strains which were highly resistant to carbenicillin (minimum inhibitory concentration ≥ 8,000 μg/ml) and had previously been found resistant to the synergistic activity between carbenicillin and gentamicin.
PMCID: PMC352723  PMID: 380465
16.  In Vitro Activity, Synergism, and Testing Parameters of Amikacin, with Comparisons to Other Aminoglycoside Antibiotics 
The activity of the new aminoglycoside antibiotic, amikacin, was evaluated in vitro against 219 clinical bacterial isolates. One hundred eighty-nine of the 219 strains had agar dilution minimal inhibitory concentration values of 8.0 μg/ml or less for amikacin. Comparative agar dilution studies were performed for gentamicin, kanamycin, and tobramycin. Gentamicin was the most active overall, but tobramycin and amikacin also had significant activity against most bacterial groups. The effects of divalent cations on the susceptibility of Pseudomonas aeruginosa to amikacin were evaluated, and the minimal inhibitory concentration values varied sixfold over a range of divalent cation concentrations from 0.2 to 8.75 mg%. The effects of media and inoculum size on disk susceptibility testing with amikacin were also evaluated. In addition, a synergistic interaction between carbenicillin and amikacin against P. aeruginosa was demonstrated. Amikacin appears to be a promising new broad spectrum antimicrobial agent.
PMCID: PMC429549  PMID: 1259402
17.  Molecular Analysis of and Identification of Antibiotic Resistance Genes in Clinical Isolates of Salmonella typhi from India 
Journal of Clinical Microbiology  1998;36(6):1595-1600.
A representative sample of 21 Salmonella typhi strains isolated from cultures of blood from patients at the Christian Medical College and Hospital, Vellore, India, were tested for their susceptibilities to various antimicrobial agents. Eleven of the S. typhi strains possessed resistance to chloramphenicol (256 mg/liter), trimethoprim (64 mg/liter), and amoxicillin (>128 mg/liter), while four of the isolates were resistant to each of these agents except for amoxicillin. Six of the isolates were completely sensitive to all of the antimicrobial agents tested. All the S. typhi isolates were susceptible to cephalosporin agents, gentamicin, amoxicillin plus clavulanic acid, and imipenem. The antibiotic resistance determinants in each S. typhi isolate were encoded by one of four plasmid types. Plasmid-mediated antibiotic resistance genes were identified with specific probes in hybridization experiments; the genes responsible for chloramphenicol, trimethoprim, and ampicillin resistance were chloramphenicol acetyltransferase type I, dihydrofolate reductase type VII, and TEM-1 β-lactamase, respectively. Pulsed-field gel electrophoresis analysis of XbaI-generated genomic restriction fragments identified a single distinct profile (18 DNA fragments) for all of the resistant isolates. In comparison, six profiles, different from each other and from the resistance profile, were recognized among the sensitive isolates. It appears that a single strain containing a plasmid conferring multidrug-resistance has emerged within the S. typhi bacterial population in Vellore and has been able to adapt to and survive the challenge of antibiotics as they are introduced into clinical medicine.
PMCID: PMC104883  PMID: 9620383
18.  Synergism of Oxacillin and Gentamicin Against Enterococci 
Strains of enterococci isolated from 34 patients were studied for susceptibility to oxacillin and gentamicin alone and in combination. The minimal bactericidal concentrations of oxacillin and gentamicin for these strains ranged from 16 to 250 μg/ml (median 32 μg/ml) for oxacillin and 12 to 48 μg/ml (median 24 μg/ml) for gentamicin. The minimal bactericidal concentration of oxacillin for 50% of strains in the presence of 12, 6, 3, and 1.5 μg of gentamicin per ml, respectively, was 2, 8, 16, and 32 μg/ml. The combination of oxacillin and gentamicin at clinically attainable serum levels was synergistically bactericidal against 27/34 (80%) of these strains using strict criteria. This report reconfirms the original observation that antibiotics which affect the synthesis of bacterial cell walls combine synergistically with aminoglycosides against enterococci. This is so even though enterococci are far more resistant to oxacillin than to penicillin or ampicillin. In addition, this report suggests that the combination of oxacillin and gentamicin administered in the usual dosages includes enterococci in its bactericidal spectrum.
PMCID: PMC429423  PMID: 1211912
19.  Sulfamethoxazole-trimethoprim synergism for Neisseria gonorrhoeae. 
Sulfamethoxazole and trimethoprim are synergistic against many bacteria in sulfamethoxazole/trimethoprim concentrations of 20:1, but single-dose therapy of gonorrhea with the combination is disappointing. We used agar dilution techniques to determine minimal inhibitory concentrations of sulfamethoxazole and trimethoprim for 168 gonococci isolated from men with acute urethritis in Atlanta, Ga. The geometric mean minimal inhibitory concentrations were 5.6 microgram of sulfamethoxazole per ml and 24.3 microgram of trimethoprim per ml, a ratio of 1:4. The concentration of sulfamethoxazole inhibiting 50% of gonococcal strains dropped only from 4.7 microgram/ml to 2.9 microgram/ml with the addition of a 1/20 dilution of trimethoprim. We studied synergism with various ratios of sulfamethoxazole to trimethoprim against 20 random strains. A ratio of 1:1 was always synergistic and was the most synergistic ratio for 15 strains, whereas the 19:1 ratio was never the most syngergistic. The 19:1 ratio failed to show synergism against seven strains, but showed antagonism at this ratio with five of these seven. The sulfamethoxazole/trimethoprim ratio of 19:1 usually achieved in serum after oral administration is minimally syngergistic and is sometimes antagonistic for gonococci.
PMCID: PMC283765  PMID: 6770754
20.  The two peptide lantibiotic lacticin 3147 acts synergistically with polymyxin to inhibit Gram negative bacteria 
BMC Microbiology  2013;13:212.
Background
The emergence of bacterial drug resistance encourages the re-evaluation of the potential of existing antimicrobials. Lantibiotics are post-translationally modified, ribosomally synthesised antimicrobial peptides with a broad spectrum antimicrobial activity. Here, we focussed on expanding the potential of lacticin 3147, one of the most studied lantibiotics and one which possesses potent activity against a wide range of Gram positive species including many nosocomial pathogens. More specifically, our aim was to investigate if lacticin 3147 activity could be enhanced when combined with a range of different clinical antibiotics.
Results
Initial screening revealed that polymyxin B and polymyxin E (colistin) exhibited synergistic activity with lacticin 3147. Checkerboard assays were performed against a number of strains, including both Gram positive and Gram negative species. The resultant fractional inhibitory concentration (FIC) index values established that, while partial synergy was detected against Gram positive targets, synergy was obvious against Gram negative species, including Cronobacter and E. coli.
Conclusions
Combining lacticin 3147 with low levels of a polymyxin could provide a means of broadening target specificity of the lantibiotic, while also reducing polymyxin use due to the lower concentrations required as a result of synergy.
doi:10.1186/1471-2180-13-212
PMCID: PMC3849175  PMID: 24069959
Antimicrobial; Synergy; Lantibiotic; Bacteriocin; Lacticin 3147; Polymyxin
21.  Comparative Activity of Netilmicin, Gentamicin, Amikacin, and Tobramycin Against Pseudomonas aeruginosa and Enterobacteriaceae 
Netilmicin (Sch 20569), a semisynthetic aminoglycoside antibiotic, was compared with gentamicin, tobramycin, and amikacin against 242 clinical isolates of Pseudomonas and Enterobacteriaceae. The minimum inhibitory concentration (MIC) was determined in both solid and liquid media. Netilmicin exhibited typical aminoglycoside properties, such as little effect of inoculum size on MIC, relatively small gap between MIC and minimum bactericidal concentration, and potentiation of anti-Pseudomonas activity in the presence of carbenicillin. Netilmicin provided no advantage in antimicrobial activity over gentamicin for either Pseudomonas or Enterobacteriaceae. Nearly complete cross-resistance to netilmicin was encountered with isolates resistant to gentamicin in either solid or liquid media. Netilmicin was less active than gentamicin against isolates of Pseudomonas and Providencia. Major discrepancies between MIC values determined in agar as opposed to those determined in broth were encountered for most isolates of Pseudomonas but also, depending upon antibiotic tested, for between 15 and 40% of isolates of Enterobacteriaceae. This new aminoglycoside agent will be useful clinically only if it is shown to be significantly less toxic than presently available analogues.
PMCID: PMC429798  PMID: 825032
22.  Inhibitory activity of cranberry juice on adherence of type 1 and type P fimbriated Escherichia coli to eucaryotic cells. 
Inhibition of bacterial adherence to bladder cells has been assumed to account for the beneficial action ascribed to cranberry juice and cranberry juice cocktail in the prevention of urinary tract infections (A. E. Sobota, J. Urol. 131:1013-1016, 1984). We have examined the effect of the cocktail and juice on the adherence of Escherichia coli expressing surface lectins of defined sugar specificity to yeasts, tissue culture cells, erythrocytes, and mouse peritoneal macrophages. Cranberry juice cocktail inhibited the adherence of urinary isolates expressing type 1 fimbriae (mannose specific) and P fimbriae [specific for alpha-D-Gal(1----4)-beta-D-Gal] but had no effect on a diarrheal isolate expressing a CFA/I adhesin. The cocktail also inhibited yeast agglutination by purified type 1 fimbriae. The inhibitory activity for type 1 fimbriated E. coli was dialyzable and could be ascribed to the fructose present in the cocktail; this sugar was about 1/10 as active as methyl alpha-D-mannoside in inhibiting the adherence of type 1 fimbriated bacteria. The inhibitory activity for the P fimbriated bacteria was nondialyzable and was detected only after preincubation of the bacteria with the cocktail. Cranberry juice, orange juice, and pineapple juice also inhibited adherence of type 1 fimbriated E. coli, most likely because of their fructose content. However, the two latter juices did not inhibit the P fimbriated bacteria. We conclude that cranberry juice contains at least two inhibitors of lectin-mediated adherence of uropathogens to eucaryotic cells. Further studies are required to establish whether these inhibitors play a role in vivo.
PMCID: PMC171427  PMID: 2653218
23.  Interaction of Clindamycin and Gentamicin In Vitro 
The minimal inhibitory concentrations of clindamycin and gentamicin alone and in combinations were determined by a microdilution method for 163 aerobic, facultative, and anaerobic clinical isolates. All 77 strains of Staphylococcus aureus, Diplococcus pneumoniae, Streptococcus pyogenes, and anaerobic bacteria (except for three strains of Clostridium) were inhibited by 1.6 μg or less of clindamycin per ml. Gentamicin did not interfere with the activity of clindamycin within the range of concentrations tested (0.1 to 100 μg/ml); for some strains combinations were synergistic. Sixty-two (94%) of 66 strains of Enterobacteriaceae and Pseudomonas aeruginosa were inhibited by 6.2 μg or less of gentamicin per ml. Combinations of clindamycin and gentamicin were indifferent for 29 strains and synergistic for 33 strains. All 20 strains of enterococcus, three strains of Clostridium, three strains of Escherichia coli, and one strain of Proteus rettgeri were resistant to both clindamycin (minimal inhibitory concentration greater than 3.1 μg/ml) and gentamicin (minimal inhibitory concentration greater than 6.2 μg/ml). Combinations of clindamycin and gentamicin were indifferent for 16 and synergistic for 11 of the resistant strains. Except for clindamycin-sensitive isolates, synergy was usually observed only at concentrations of one or both drugs which are not readily obtainable in vivo. Antagonism was never observed.
PMCID: PMC444696  PMID: 15825309
24.  Comparative In Vitro Activity of Three Aminoglycosidic Antibiotics: BB-K8, Kanamycin, and Gentamicin 
Kanamycin, BB-K8, and gentamicin were tested in parallel against 1,037 bacterial strains isolated from clinical material. The activity of BB-K8 at 20 μg/ml was comparable to that of gentamicin at 8 μg/ml against Pseudomonas aeruginosa and against Enterobacteriaceae, with the exception of gentamicin-resistant strains of Proteus rettgeri and Providencia stuartii, in which case the activities of BB-K8 and kanamycin were the same. BB-K8 exhibited little or no activity against streptococci. The activity of BB-K8 was affected by pH and inoculum size. A regression graph for inhibition data with a 10-μg disk of BB-K8 was developed, and synergistic activity of penicillin and BB-K8 against Streptococcus faecalis was tested.
PMCID: PMC444518  PMID: 4208506
25.  Effects of changes in pH, medium, and inoculum size on the in vitro activity of amifloxacin against urinary isolates of Staphylococcus saprophyticus and Escherichia coli. 
The in vitro activity of amifloxacin (WIN 49375), a new fluoroquinolone, was compared with the activities of antimicrobial agents that are commonly used for the treatment of urinary tract infection (cinoxacin, cephalexin, gentamicin, amoxicillin, trimethoprim, and trimethoprim-sulfamethoxazole) against 25 strains of Staphylococcus saprophyticus and 28 strains of Escherichia coli. Bacterial strains were isolated from urine specimens of college women with acute urinary tract infections. Bacterial isolates were more susceptible to trimethoprim-sulfamethoxazole, trimethoprim, and amifloxacin than to the other drugs tested. The in vitro activity of amifloxacin against S. saprophyticus had an inverse relation to increases in the pH of the test medium. Changes in the type of culture medium had no effect on the in vitro activity of amifloxacin. There was a direct relationship between increases in inoculum size and the MICs of amifloxacin.
PMCID: PMC180072  PMID: 3890724

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