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PubMed1977

Antimicrobial activity of cefamandole against Salmonella typhi.

A patient with Salmonella typhi bacteremia was sucessfully treated with cefamandole, a new cephalosporin derivative. Infection has not recurred during 6 months of follow-up observation. Minimum inhibitory concentrations and minimum bactericidal concentrations of cefamandole, cephalothin, ampicillin, and chloramphenicol were compared against 26 strains of S. typhi. All the strains were susceptible to cefamandole in vitro. Seven of the strains were resistant to chloramphenicol, and another seven were resistant to both chloramphenicol and ampicillin. Cefamandole appears to warrant further clinical trial for the treatment of typhoid fever.

Adult↗

PubMed2026

Time-resolved proteomic adaptation of multidrug-resistant Acinetobacter baumannii to antimicrobial stress induced by partially purified fraction from Caesalpinia pulcherrima flower using DEqMS.

UNLABELLED: The global prevalence of multidrug-resistant (MDR) bacteria represents an urgent public health challenge, emphasizing the critical need for novel antimicrobial agents. MDR Acinetobacter baumannii, a nosocomial pathogen of critical global concern owing to its capacity to acquire and disseminate antimicrobial resistance, was employed as a bacterial model to investigate the antimicrobial potential of natural products derived from Caesalpinia pulcherrima (L.) Sw. (Fabaceae). This medicinal plant represents a promising reservoir of novel bioactive compounds; however, its molecular effects on the A. baumannii proteome had not previously been characterized. The partially purified ethyl acetate fraction of C. pulcherrima flowers (CPF4) exhibited potent bactericidal activity against susceptible A. baumannii (minimum inhibitory concentration and minimum bactericidal concentration = 31.25 µg/mL), and time-resolved label-free quantitative LC-MS/MS proteomics was subsequently performed on MDR A. baumannii cultures treated with CPF4 at 24 h, 48 h, and 72 h post-treatment alongside untreated controls in biological triplicate, with differential protein expression assessed using differential expression of quantified mass spectrometry data. No significantly differentially expressed proteins were detected at 24 h or 48 h relative to the control, indicating that the proteomic effects of CPF4 manifest predominantly at the late treatment stage. In contrast, a robust late-phase response was identified at 72 h, comprising the coordinated induction of proteins associated with DNA damage repair, transcriptional regulation, and cell surface glycosylation remodeling. The sensor histidine kinase PmrB was significantly upregulated at 72 h vs 48 h (adjusted P = 0.029), implicating the PmrA/PmrB two-component system in late-phase colistin tolerance acquisition under sustained CPF4 exposure. IMPORTANCE: These findings provide mechanistic insight into the adaptive survival strategies employed by multidrug-resistant Acinetobacter baumannii in response to plant-derived antimicrobial challenge and support the further development of Caesalpinia pulcherrima-derived natural products as candidate antimicrobial agents.

Acinetobacter baumannii↗

PubMed1977

Studies on antituberculotic action of some phenothiazine derivatives in vitro.

Five phenothiazine derivatives (chlorpromazine, levomepromazine, diethazine, promethazine and chlorpromazine) sulphoxyde were tested for antimycobacterial activity. The growth of Mycobacterium tuberculosis, M. bovis and M. butyricum was inhibited by chlorpromazine practically at identical concentrations. The minimum inhibitory concentrations for M. tuberculosis were: chlorpromazine and levomepromazine, 10 microgram/ml; diethazine and promethazine 20 microgram/ml, whilst chlorpromazine sulphoxyde was ineffective even at a concentration of 100 microgram/ml. Chlorpromazine and promethazine exerted a measurable bactericidal activity on M. tuberculosis at 50 microgram/ml; total destruction of the organism and loss of acid fastness in part of the cells were shown at 300 microgram/ml. Preliminary studies, in mouse experiments phenothiazine derivatives were ineffective.

Antipsychotic Agents↗

PubMed1978

Anaerobic resistance of clinical isolates of Staphylococcus aureus to aminoglycosides.

The anaerobic minimum inhibitory concentration of six aminoglycosides (amikacin, gentamicin, kanamycin, netilmicin, sisomicin, and tobramycin) averaged over 10-fold greater than the aerobic minimum inhibitory concentration for 50 clinical isolates of Staphylococcus aureus. Cultures from osteomyelitis and blood generally showed a somewhat greater increase in minimum inhibitory concentration due to anaerobiosis than did cultures from abscesses and wounds, and amikacin activity was most affected by anaerobiosis.

Aminoglycosides↗

PubMed1977

Cefoxitin activity against multiply antibiotic-resistance Klebsiella pneumoniae in vitro.

Due to the emergence of cephalothin- and gentamicin-resistant Klebsiella pneumoniae at this institution, we investigated the in vitro activity of two new cephalosporin compounds-cefoxitin and cefamandole. Whereas both drugs were active against cephalothin- and gentamicin-susceptible isolates of Klebsiella, only cefoxitin exhibited significant activity against cephalothin- and gentamicin-resistant isolates. Seventeen of 20 (85%) of the cephalothin- and gentamicin-resistant isolates were inhibited by </=12.5 mug of cefoxitin per ml. The minimum bactericidal concentration in broth of representative isolates equaled the agar dilution minimum inhibitory concentration. Kirby-Bauer disk susceptibility testing correlated well with the agar dilution minimum inhibitory concentration. Cephalothin and cefamandole resistance of isolates could be correlated with antibiotic degradation by beta-lactamase. Cephalothin and cefamandole evoked only a transient decrease in viable bacterial cell count with rapid inactivation of antibiotics, and full regrowth of the organisms. Cefoxitin, on the other hand, was quite effective in vitro against multiply resistant Klebsiella. No beta-lactamase degradation of cefoxitin was detected. Growth curves with antibiotics indicated rapid killing of cephalothin- and gentamicin-resistant isolates by cefoxitin.

Cefoxitin↗

PubMed1979

Resistance of Mycoplasma pneumoniae to macrolide and analogous antibiotics.

1. The susceptibility of M. pneumoniae to antibiotics can be determined by the microtiter method. The adequate technique requires that the final volume of broth medium in a well is 0.2 ml and that the dilution is made after the parent solution of antibiotic in the test tube is dropped into a well every fifth wells. 2. M. pneumoniae was cultured on agar media containing two-fold concentrations of macrolide and analogous antibiotics, and the following results were obtained. 1) The growth of eight strains of M. pneumoniae on agar media containing two-fold concentrations of the antibiotics revealed that, in six strains, one CFU (colony forming unit) per 10(5) to 10(6) CFU of an inoculum dose was resistant to the antibiotics. 2) The MIC (minimum inhibitory concentration) of erythromycin for the subculture of thet strains of M. pneumoniae on agar media containing two-fold concentrations of the antibiotics revealed that, in six strains, one CFU (colony forming unit) per 10(5) to 10(6) CFU of an inoculum dose was resistant to the antibiotics. 2) The MIC (minimum inhibitory concentration) of erythromycin for the subculture of thet strains of M. pneumoniae on agar media containing two-fold concentrations of the antibiotics revealed that, in six strains, one CFU (colony forming unit) per 10(5) to 10(6) CFU of an inoculum dose was resistant to the antibiotics. 2) The MIC (minimum inhibitory concentration) of erythromycin for the subculture of the colony grown as an average of 0.5 to eight on agar media containing erythromycin in four strains was 0.1 to 1.6 micrograms/ml in some colonies, and 400 to 800 micrograms/ml in most colonies. The results disclosed that the broth culture contains a small number of mycoplasma cells with a definite, high degree of resistance to the antibiotics, but no cells with intermediate degrees of resistance. 3) The FH strain was made resistant to erythromycin, oleandomycin, midecamycin, acetylspiramycin, leucomycin, josamycin, tylosin, lincomycin, or clindamycin by subculture in broth medium from the colony grown at the highest concentrations of each of the antibiotics in agar media. The degree of the resistance developed was 16 to 128,000 in the MIC radio and showed high values of MIC in most strains. The resistance developed was not lost by subculturing the resistant strain in broth medium without antibiotic. 4) The FH strain made resistant to the antibiotics had cross resistance to other macrolides. Strains resistant to some of the antibiotics had cross resistance to lincomycin and clindamycin, and strains resistant to others did not. Some strains made resistant to macrolides with cross resistance to lincomycin and clindaymycin and strains made resistant to lincomycin or clindamycin had no cross resistance to vernamycin B alpha, while all the resistant strains without cross resistance to lincomycin and clindamycin had cross resistance to vernamycin B alpha. No strain had cross resistance to vernamycin A...

Agar↗

PubMed1976

National gonorrhea therapy monitoring study: in vitro antibiotic susceptibility and its correlation with treatment results.

To monitor temporal trends and regional differences in antibiotic susceptibility, we measured the minimum inhibitory concentrations for penicillin G, ampicillin, tetracycline, and spectinomycin of 4405 pre-treatment gonococcal isolates from patients with uncomplicated gonorrhea. As compared to isolates studied in 1970-1971, recent United States isolates appeared equally sensitive to penicillin G and more sensitive to tetracycline. Relatively resistant strains were found throughout the country. We also studied 1974 patients, treated for uncomplicated gonorrhea according to the 1972 regimens recommended by the United States Public Health Service, to determine the relation between pretreatment minimum inhibitory concentrations and treatment results. For patients receiving the procaine penicillin-probenecid and ampicillin-probenecid regimens, minimum inhibitory concentrations to the treatment drugs were significantly higher in patients not cured than in those cured (P less than 0.01 fr penicillin and P less than 0.05 for ampicillin). In contrast, spectinomycin-treatment results appeared to be independent of the isolate's susceptibility to spectinomycin and other antibiotics.

Ampicillin↗

PubMed1978

Bactericidal activity of cephalosporins in an in vitro model simulating serum levels.

The bactericidal activity of cefazolin, cephaloridine, and cephalothin in a simulated intramuscular study (500 mg) and a simulated intravenous drip infusion study (2 g/2 h) is reported. In both model systems, the bactericidal activity of cefazolin surpassed that of cephalothin, and there were certain differences between cefazolin and cephaloridine in the simulated intramuscular study when human serum was used as a medium. In a routine reference static system, the drug levels were constant at the simulated peak level of each cephalosporin by both routes. In this system the three cephalosporins were equal in activity. In a third experiment, the effect of drug concentrations and exposure time on bactericidal activity of the cephalosporins was studied. The bactericidal activity of cephaloridine was the strongest of the three drugs when exposure time was 2 h and drug concentration was less than four times the minimal inhibitory concentration. At concentrations above four times the minimum inhibitory concentration, all three cephalosporins were equal in activity when the exposure time was 2 h.

Bacteria↗

PubMed1979

In vitro activity of LY127935, a new 1-oxa cephalosporin, against aerobic gram-negative bacilli.

A total of 434 clinical aerobic gram-negative bacillary isolates were tested against LY127935, a new 1-oxa cephalosporin, and compared with other cephalosporins, penicillins, and aminoglycosides by a broth microdilution technique. Cefotaxime (HR756), a new semisynthetic cephalosporin, and LY127935 were more active, and showed lower minimum inhibitory concentrations (ranges, less than or equal to 0.12 to 2.0 micrograms/ml), than cefamandole, cefoxitin, and cefazolin against Escherichia coli, Klebsiella spp., Enterobacter spp., Proteus mirabilis, indole-positive Proteus spp., Serratia marcescens, Providencia spp., and Citrobacter spp. Against P. aeruginosa, pepercillin, azlocillin, and mezlocillin were the most active beta-lactam agents; 64 micrograms/ml inhibited 99, 93, and 87% of the isolates, respectively. LY127935 and cefotaxime at 16 micrograms/ml inhibited 71% of Pseudomonas isolates, whereas the aminoglycosides gentamicin, tobramycin, and amikacin at a concentration of 4 micrograms/ml inhibited 84, 88, and 93%, respectively. Minimum bactericidal concentrations were determined for all isolates and were generally the same as the minimum inhibitory concentrations.

Aminoglycosides↗

PubMed1977

Quantitative antibiotic sensitivity determinations of Staphylococcus aureus isolated from eye cultures.

The sensitivities of 108 strains of Staphylococcus aureus, isolated from patients with a variety of ocular conditions, were tested quantitatively against nine antibiotics by means of a microtiter broth-dilution method. Of the nine antibiotics, cephalothin sodium had the lowest (and therefore the best) minimum bactericidal concentration (MBC) and minimum inhibitory concentration (MIC). The MBC and MIC of gentamicin sulfate were very close to those of cephalothin. The MBCs and MICs of erythromycin, ampicillin sodium, penicillin, tetracycline, methicillin sodium, and carbenicillin disodium were moderately good. Chloramphenicol had the poorest response.

Anti-Bacterial Agents↗

PubMed2026

Antibacterial activity and mechanistic insights of Lucilia illustris antimicrobial peptide Cecropin A2 against Pseudomonas aeruginosa.

Pseudomonas aeruginosa (P. aeruginosa) poses a serious public health threat due to multidrug resistance and biofilm formation. This study investigated the antibacterial mechanisms of the antimicrobial peptide, Cecropin A2 (CA2), against P. aeruginosa. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of CA2 against P. aeruginosa ATCC 9027 (PA ATCC 9027) were determined by broth microdilution. Antibacterial activity was evaluated using growth curves and time-kill assays. The mechanism was explored by assessing membrane integrity (outer/inner membrane permeability, SEM, and fluorescence microscopy), and intracellular responses (ATP, SDH activity, and ROS). Biofilm effects were assessed by crystal violet staining (biomass) and viable cell counting (biofilm-embedded bacteria). The MIC and MBC of CA2 against PA ATCC 9027 were 37.34 μM and 74.68 μM, respectively. CA2 exhibited moderate antibacterial activity against PA ATCC 9027. Scanning electron microscopy (SEM) revealed marked morphological damage after treatment. CA2 affected intracellular metabolism, potentially interacted with genomic DNA, and reduced biofilm biomass. Cecropin A2 exhibits concentration-dependent in vitro antibacterial activity against P. aeruginosa ATCC 9027, providing mechanistic insights and a theoretical basis for the development of alternative antimicrobial strategies.

Antimicrobial activity↗

PubMed1977

Susceptibility of anaerobic bacteria to metronidazole, ornidazole, and tinidazole and routine susceptibility testing by standardized methods.

A total of 114 strains of anaerobic bacteria were examined for their susceptibility to metronidazole, ornidazole, and tinidazole by measuring the minimum inhibitory concentration (MIC) and minimum bactericidal concentration in different media. All strains, with the exception of the isolates of Propionibacterium acnes, were inhibited by 3.1 mug each and killed by 6.3 mug each of all three nitroimidazole compounds per ml. No significant differences in MIC values were found among metronidazole, ornidazole, and tinidazole. Only minor differences were detected by comparing MIC values obtained in brain heart infusion agar with and without sheep blood, brucella agar, and Mueller-Hinton agar (both containing blood). When the strains were tested by the modified broth-disk method proposed by the Anaerobe Laboratory of the Virginia Polytechnic Institute (VPI), there was good correlation with the MIC values (97.4% agreement for metronidazole and 94.7% for ornidazole and tinidazole). For routine testing, use of a 30-mug-class disk of either nitroimidazole derivative is proposed for the broth-disk method, resulting in a final concentration of 6 mug/ml in the test tubes, a concentration easily attainable in body fluids. In contrast to the broth-disk method, there was very poor correlation between inhibition zone diameters by the standardized VPI agar diffusion test and MIC values.

Anaerobiosis↗

PubMed1979

Effect of ampicillin and chloramphenicol alone and in combination on ampicillin-susceptible and -resistant Haemophilus influenzae type B.

To evaluate ampicillin (Amp) and chloramphenicol (Cm) alone and in combination against Haemophilus influenzae type b, we examined the viability of 5 log(10) colony-forming units (CFU) of early-log-phase organisms per ml after 4 and 8 h of incubation with the drug(s). Nine Amp-susceptible (Amp(s)) and five Amp-resistant (Amp(r)) systemic isolates were examined. Antibiotic concentrations included: the minimum inhibitory concentration (MIC) of Amp, 50% of the MIC of Amp, 25% of the MIC of Amp, the MIC of Cm, 50% of the MIC of Cm, 25% of the MIC of Cm, and nine combinations of these concentrations. Both Amp and Cm at their MIC significantly reduced bacterial titers of Amp(s)H. influenzae type b after 8 h of incubation (1.36 and 1.47 log(10) CFU/ml, respectively; both p < 0.01); only Cm at its MIC significantly reduced the number of viable organisms after 4 h (0.91 log(10) CFU/ml; P < 0.001). With Amp(r) organisms, significant reductions in mean bacterial titers occurred after 4 and 8 h of incubation in the presence of Amp at its MIC (1.66 and 2.06 log(10) CFU/ml, respectively; both P < 0.02); smaller but significant reductions were noted after 4 and 8 with Cm at its MIC (0.56 and 0.87 log(20) CFU/ml, respectively; both P < 0.025). Antagonism with Amp(s) or Amp(r) strains was not seen. We conclude that combinations of Amp and Cm have indifferent effects on Amp(s) and Amp(r)H. influenzae type b.

Ampicillin↗

PubMed1979

In vitro antibacterial activity of cefoperazone (T-1551), a new semisynthetic cephalosporin.

Cefoperazone, a new semisynthetic cephalosporin, has a broad spectrum of antibacterial activity. It is as active as cefazolin and cefamandole against gram-positive bacteria and is more active than cefazolin and cefamandole against such gram-negative bacilli as Escherichia coli, Klebsiella pneumoniae, Proteus species, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae, and Serratia marcescens. The superiority of cefoperazone over cefazolin and cefamandole with respect to activity against P. aeruginosa by more than 200-fold was especially remarkable. As with other beta-lactam antibiotics, there was only a small spread between the minimum inhibitory concentrations and the minimum bactericidal concentrations of cefoperazone and a significant decrease in activity with an increase in inoculum size. Activity was not altered significantly by the addition of human serum to the test medium. Cefoperazone is relatively stable to hydrolysis to beta-lactamases produced by gram-negative bacteria. Relative rates of hydrolysis of cefoperazone by cephalosporinases are 7.0 to 0.01, with reference to cephaloridine hydrolysis (base, 100). Cefoperazone is also more stable than penicillin G and cephaloridine to various types of penicillinases.

Bacteria↗

PubMed1978

Therapy of gonorrhea. Comparison of trimethoprim-sulfamethoxazole and ampicillin.

Eighty-nine men with gonococcal urethritis were randomly treated with trimethoprim-sulfamethoxazole, four tablets (trimethoprin, 320 mg, and sulfamethoxazole, 1,600 mg) twice daily for two days, or ampicillin, 3.5 g, plus probenecid, 1 g, in a single dose. Forty-one (95.3%) of 43 patients who received trimethoprin-sulfamethosazole and 41 (97.6%) of 42 given ampicillin were cured. Neither drug caused major side effects. All isolates of Neisseria gonorrhoeae were susceptible in vitro to trimethoprim-sulfame-thoxazole, and all but one were inhibited by ampicillin. The ampicillin-resistant strain (minimum inhibitory concentration, 4 micrograms/ml) produced penicillinase and was reovered from a patient who responded to treatment with trimethoprim-sulfamethoxazole. There was no significant correlation between the minimum inhibitory concentrations of trimethoprim-sulfamethoxazole and ampicillin. It is concluded that trimethoprim-sulfamethoxazole is as efficacious and safe as ampicillin in the therapy of gonococcal urethritis.

Ampicillin↗

PubMed2026

No phenotypic resistance observed for most group-3 and -4 variants in Mycobacterium tuberculosis genes related to bedaquiline, clofazimine, delamanid, and pretomanid in a Central and West African context.

The interpretation of genetic variants' association (or not) with phenotypic resistance to newly introduced and repurposed antituberculosis drugs remains challenging, as many mutations detected by whole-genome sequencing (WGS) are classified as of uncertain significance (group 3) or not associated with resistance-interim (group 4) by the World Health Organization (WHO) mutation catalog v2. We evaluated the phenotypic impact of such variants on minimum inhibitory concentrations (MICs) for bedaquiline (BDQ), clofazimine (CFZ), delamanid (DLM), and pretomanid (PA) in Mycobacterium tuberculosis complex isolates from the multi-country DIAMA cohort in sub-Saharan Africa (SSA), which recruited RR/RS-TB patients naïve to these drugs. Among 1,475 isolates with available WGS data, 163 variants met eligibility criteria; due to viable strain unavailability, 89 isolates carrying 29 unique BDQ/CFZ-related and 60 unique DLM/PA-related variants were tested for MIC determination using broth microdilution. Additional structural modeling was performed to explore potential effects of amino-acid substitutions on protein stability. Among BDQ/CFZ-related variants, MICs above the critical concentrations (CCs) were consistently associated with mmpR5 variants, whereas variants in atpE, pepQ, and Rv1979c were not. DLM/PA variants (ddn, fbiA-D, and fgd1) were frequently detected as non-fixed populations, yet rarely yielding MIC values above the CC. Predicted structural destabilization showed no consistent association with MIC values or variant fixation status. Under the conditions tested, phenotypic resistance was not detected for most group 3 and 4 variants detected by WGS. Our data provide evidence from SSA to support improved interpretation of resistance-associated mutations for new and repurposed antituberculosis drugs.IMPORTANCEWhole-genome sequencing increasingly detects Mycobacterium tuberculosis complex mutations classified by the World Health Organization (WHO) mutation catalog v2 as group 3 variants of uncertain significance or group 4 variants not associated with resistance-interim, limiting reliable prediction of resistance to new and repurposed antituberculosis drugs. By generating minimum inhibitory concentration (MIC) data for such variants identified in a multi-country sub-Saharan African cohort, this study provides phenotypic evidence to support future refinement and expansion of the WHO mutation catalog v2. Notably, mmpR5 variants associated with elevated bedaquiline/clofazimine MICs were identified in eight isolates, suggesting that some patients in this cohort may have harbored pre-existing resistance-associated variants yet remained potentially eligible for bedaquiline-containing regimens. These findings contribute to improving the interpretation of genomic resistance data and strengthening surveillance of resistance to bedaquiline, clofazimine, delamanid, and pretomanid.

Mycobacterium tuberculosis↗

PubMed1979

The feasibility of replacing antibiotics by quaternary ammonium compounds in topical antimicrobial acne therapy.

Determinations of the minimum inhibitory concentrations for various antimicrobial surfactants with reference to the bacteria P. acnes, P. granulosum, and St. epidermidis are reported. The results show that quaternary ammonium compounds can display minimum inhibitory concentrations corresponding to those of relevant antibiotics. With the especially effective substance fractionated dimethylcocobenzalkoniumchloride )ARQUAD DMMCD-B), it could be further shown that with in vivo application in 70% isopropanol or in an ethanol-containing film mask ointment suppression can be obtained of P. acnes, all propionibacteria added, and all pilosebaceous duct bacteria which can be cultured under anaerobic conditions. The studies may point out a way of replacing antibiotics in the antimicrobial therapy of acne by quaternary ammonium compounds.

Acne Vulgaris↗

PubMed1976

Persistence of transferable drug resistance in the lactose-fermenting enteric flora of swine following antimicrobial feeding.

Six groups of swine (85 animals) were fed a combination of antimicrobial drugs (sulfamethazine 100 g/ton, chlortetracycline 100 g/ton and penicillin 50 g/ton). After two weeks the antimicronial drugs were removed from the diet of two groups (28 animals). These swine were compared to four groups fed the medicated diet to determine the effect of duration of treatment and degree of animal isolation on the persistence of resistance in lactose-fermenting enteric organisms. The degree of resistance to penicillin, oxytetracycline, dihydrostreptomycin and neomycin as determined by minimum inhibitory concentrations and the incidence of resistant organisms were examined during and after antibiotic feedings. Ninety-two percent or greater of all isolates tested during and after treatment had minimum inhibitory concentrations for oxytetracycline of greater than 100 mug/ml. Thirty-two weeks after cessation of dietary antibiotic, resistance to oxytetracycline and dihydrostreptomycin remained at 100% and 89% respectively. Variation in degree of contact between swine receiving medicated feed and those receiving nonmedicated feed was not sufficient to reduce the incidence of resistance to oxytetracycline or dihydrostreptomycin in all animals. Factors influencing persistence of resistant enteric organisms are discussed. Addition of the antimicrobials to the ration resulted in significantly greater weight gains for treated animals than for the controls but did not alter feed conversion.

Animal Feed↗