Lancet. 1979 Mar 10;1(8115):538-41.
Decline of the hospital Staphylococcus? Incidence of multiresistant Staph. aureus in three Birmingham hospitals.

Ayliffe GA, Lilly HA, Lowbury EJ.

The prevalance of antibiotic-resistant strains of Staphylococcus aureus was studied in three Birmingham hospitals. In a general hospital periodic surveys showed a progressive decline in the proportions of patients with Staph. aureus in their noses which were resistant to tetracycline, erythromycin, and kanamycin. This change was associated with a progressive reduction in the use of tetracycline without an overall reduction in the use of antibiotics. There was no similar decline in resistance of staphylococci isolated in a hospital for skin diseases. In a burns unit there was a sudden large reduction during September, 1978, in the proportions of Staph, aureus from burns which were resistant to tetracycline, methicillin, cephaloridine, erythromycin, lincomycin, novobiocin, gentamicin, and kanamycin, and in the proportions of multiresistant strains (resistant to penicillin, tetracycline, erythromycin, kanamycin, methicillin, novobiocin, cephaloridine, and lincomycin). This change was associated with a reduction in the number of patients and in the use of antibiotics; tetracycline was not in use except during one month of the study. Strains of Staph. aureus resistant to these antibiotics became common again in the burns unit when a larger number of patients were admitted and more antibiotics were used in the wards.

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Fundam Appl Toxicol. 1997 Dec;40(2):256-63.
Tetracycline-induced steatosis in primary canine hepatocyte cultures.

Amacher DE, Martin BA.

Department of Drug Safety Evaluation, Pfizer Central Research, Groton, Connecticut 06340, USA.

Primary hepatocyte cultures prepared from male beagle dog liver were used to determine susceptibility of the canine liver to tetracycline-induced steatosis. The effects of the drug on mitochondrial lipid metabolism and intracellular triglyceride accumulation were monitored at the same time that steatosis was detected by light microscopy and quantitated using lipid-specific stains. Exposure of primary canine hepatocyte cultures to tetracycline for 24-48 h resulted in concentration-dependent, significant increases in the Oil Red O-stained lipid inclusions. Microscopic examination of the total stained areas suggested that increases over control levels were due primarily to the increase in the size of the lipid inclusions rather than in the number. Biochemical analyses for triglyceride content and histological staining with Nile red, another neutral lipid-specific dye, confirmed a specific increase in intracellular triglyceride following a 24-h exposure to noncytotoxic levels of tetracycline beta-oxidation studies based on the oxidation of [14C]palmitic acid or [14C]palmitoyl carnitine demonstrated a concentration-dependent inhibition of mitochondrial but not peroxisomal beta-oxidation in hepatocytes after a 24-h exposure to tetracycline. In vitro incubation of tetracycline with mitochondria isolated from dog liver showed similar concentration-dependent inhibition. This study clearly indicates that the canine hepatocyte is susceptible to tetracycline-induced steatosis. Triglyceride accumulation was concomitant with the inhibition of mitochondrial lipid metabolism, indicating that this is a primary mechanism leading to steatosis in dog hepatocytes following tetracycline exposure.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9441722&dopt=Abstract antibiotics, tetracycline




Biochim Biophys Acta. 1982 Apr 29;720(2):172-80.
The effect of various stimuli and calcium antagonists on the fluorescence response of chlorotetracycline-loaded human neutrophils.

Smolen JE, Weissmann G.

Chlorotetracycline has been used in neutrophils and other cells as probe of the state of membrane-bound calcium. We report here that human neutrophils treated with chlorotetracycline response to soluble secretagogues by a prompt decrease in chlorotetracycline fluorescence. This response was observed within 2-5 s, making it one of the most immediate reactions in neutrophils to stimulation, and was obtained with three secretagogues studied: a chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine, a tumor promotor (phorbol myristate acetate) and a lectin (concanavalin A). The responses of neutrophils to the three stimuli differed both quantitatively and qualitatively. The calcium EGTA, did not effect the onset of the decrease in chlorotetracycline fluorescence, suggesting that the probe was measuring changes in intracellular calcium pools. The intracellular calcium antagonists, TMb-8, W-7 and trifluoperazine, did not block, but actually augmented, the fluorescence response. All four of these calcium antagonists blocked the recovery of chlorotetracycline fluorescence which was usually observed several minutes after stimulation with N-formyl-methionyl-leucyl-phenylalanine. This suggests that recovery was dependent upon both extracellular calcium and active calmodulin. The results are consistent with the hypothesis that changes in chlorotetracycline fluorescence reflect changes in a pool of membrane-bound 'trigger calcium', the release of which is an essential first step in stimulus-response coupling in human neutrophils.

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Circ Res. 1984 Nov;55(5):595-608.
Intracellular calcium storage and release in the human platelet. Chlorotetracycline as a continuous monitor.

Jy W, Haynes DH.

The calcium-sensitive fluorescent probe chlorotetracycline was used to monitor calcium movement in human platelets. The chlorotetracycline fluorescence signal is a linear measure of the level of free calcium in the dense tubules and in the mitochondria, with probe sensitivity in the millimolar range. Experiments perturbing the system with the calcium ionophore A23187 shows that the level of free internal calcium in the organelle depends upon the cytoplasmic level, which, in turn, depends upon the passive permeability of the plasma membrane. Chlorotetracycline in the cytoplasmic compartment does not respond to changes in the cytoplasmic calcium concentration, which is held in the micromolar to submicromolar range by an extrusion system. The calcium concentration in the cytoplasmic compartment can be directly manipulated by the calcium ionophore A23187 and is measured in parallel experiments with Quin 2, a high-affinity indicator. The calcium transport systems of the organelles are shown to be less susceptible to short circuit by A23187. Analysis shows that mitochondrial uptake is slow (t 1/2 = 20 minutes), produces a large increase in chlorotetracycline fluorescence, and is inhibited by sodium azide plus oligomycin. Uptake by the dense tubules is more rapid (t 1/2 = 2 minutes), produces a smaller increase in chlorotetracycline fluorescence, is inhibited by trifluoperazine, and is less sensitive to A23187. The Km is estimated as 1 microM or lower. Studies show that the chlorotetracycline technique is useful for the monitoring of calcium uptake and release by the platelet organelles, and suggests that the Quin 2/chlorotetracycline technique will be useful as a diagnostic of both physiological and pathological activation mechanisms.

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Eur J Clin Microbiol Infect Dis. 1995 Jan;14(1):34-40.
Nasopharyngeal carriage of Staphylococcus aureus and carriage of tetracycline-resistant strains associated with HIV-seropositivity.

Amir M, Paul J, Batchelor B, Kariuki S, Ojoo J, Waiyaki P, Gilks C.

Wellcome Trust Research Laboratories, Kilifi, Kenya.

The aim of this prospective study was to investigate the relationship between carriage of antibiotic-resistant Staphylococcus aureus and infection with the human immunodeficiency virus (HIV). A total of 554 pernasal swabs was taken during a six-month period from 554 adult patients attending three outpatient clinics and from inpatients from a hospital in Nairobi, Kenya. Overall, 121 swabs (22%) yielded Staphylococcus aureus, there being significantly higher carriage in HIV-positive patients (71/264, 27%) than in HIV-negative patients (50/290, 17%); p = 0.008. Antimicrobial resistance rates were determined for 110 isolates and were high for penicillin (91%) and tetracycline (72%) and low for erythromycin (8%), methicillin (3%), gentamicin (5%) and chloramphenicol (0%). Genetic analysis showed plasmids in the range of 24-42 MDa to be associated with beta-lactamase production and plasmids in the range of 3-5 MDa to be associated with resistance to tetracycline, erythromycin and trimethoprim. All nine erythromycin-resistant strains were from HIV-positive patients (p = 0.02). There was a significant association of tetracycline resistance with HIV seropositivity (p = 0.002). The association of HIV seropositivity with Staphylococcus aureus carriage and carriage of antibiotic-resistant strains against the background of the HIV epidemic are of relevance in individual patient care and raise concern for public health.

PIP: The authors report findings from a prospective study conducted to investigate the relationship between the carriage of antibiotic-resistant Staphylococcus aureus and infection with HIV. 554 pernasal swabs were taken during a six-month period from 554 adult patients attending three outpatient clinics and from inpatients in a hospital in Nairobi, Kenya. 22% of swabs yielded Staphylococcus aureus, with significantly higher carriage in HIV-positive patients than in HIV-negative patients: 27% and 17%, respectively. Antimicrobial resistance rates determined for 110 isolates were 91% for penicillin, 72% for tetracycline, 8% for erythromycin, 3% for methicillin, 5% for gentamicin, and 0% for chloramphenicol. Genetic analysis identified plasmids in the range of 24-42 MDa associated with B-lactamase production and plasmids in the range of 3-5 MDa associated with resistance to tetracycline, erythromycin, and trimethoprim. All nine erythromycin-resistant strains were from HIV-positive patients. There was a significant association of tetracycline resistance with HIV seropositivity.

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Zentralbl Bakteriol Mikrobiol Hyg [A]. 1986 Jul;261(4):425-31.
The susceptibility of a strain of Leptospira interrogans serogroup icterohaemorrhagiae to amoxycillin, erythromycin, lincomycin, tetracycline, oxytetracycline and minocycline.

Broughton ES, Flack LE.

The failure of prophylactic penicillin to prevent a laboratory acquired case of Icterohaemorrhagiae leptospirosis prompted determination of the MIC and MBC of amoxycillin, erythromycin, lincomycin, tetracycline, oxytetracycline and minocycline for the infecting strain. Amoxycillin followed by erythromycin were the most effective, with MBCs of 0.5 mg/l after 7 days exposure and 0.1 mg/l after 21 days exposure respectively. Leptospires grew in the presence of high concentrations of tetracycline hydrochloride and oxytetracycline after prolonged incubation. This effect was less pronounced with minocycline, with MIC's of 0.025, 0.05 and 0.1 mg/l after 7, 14 and 21 days exposure respectively. The MIC of lincomycin was 0.25 mg/l at each time interval. These results support the high dose, long duration antibiotic regimens recommended in the literature.

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Appl Environ Microbiol. 1993 Jul;59(7):2220-8.
Genetic instability and strain degeneration in Streptomyces rimosus.

Gravius B, Bezmalinovic T, Hranueli D, Cullum J.

Universitat Kaiserslautern, Germany.

During a strain selection program to improve oxytetracycline production in Streptomyces rimosus R6, isolates that showed extreme morphological instability appeared. Propagation via spores gave much higher instability than did propagation via mycelial fragments. Five phenotypic traits were affected: sporulation, pigmentation, colony morphology, oxytetracycline production, and oxytetracycline resistance. The variants were classified on the basis of oxytetracycline resistance into three classes. Class I variants (99% of variants) showed parental levels of resistance but were very heterogeneous regarding the other phenotypes. No DNA rearrangements were detected in primary class I variants. Class II variants (1% of variants, oxytetracycline sensitive) were phenotypically uniform, and most variants carried the same large deletion of ca. 455 kb, including the oxytetracycline resistance gene otrB. Class III variants (0.1% of variants, increased oxytetracycline resistance) were phenotypically uniform and overproduced a brown pigment and oxytetracycline. Most of these variants also showed a reproducible large-scale DNA rearrangement, which probably included deletion and a low-level reiteration (three or four copies) of a DNA fragment. "Revertants" of some class I variants show a similar DNA rearrangement to the class III variants, but there is extensive reiteration of sequences of about 200 kb, including the otrB gene. The significance of these results for the problem of strain degeneration and overproduction of antibiotics is discussed.

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Am J Med Technol. 1979 Oct;45(10):835-9.
Susceptibility of streptococci to newer tetracyclines and cephalosporins and to other antimicrobial agents.

Freundlich LF, Zanfordino E, Rosenthal SL.

Two hundred and thirty-nine strains of Streptococcus including 71 strains of Group A, 81 strains of Group B, 69 strains of enterococci, and 18 strains of S. pneumoniae were tested against 12 antimicrobial agents using an agar dilution method. Cefamandole was the most active cephalosporin tested. Doxycycline and minocycline were more active than tetracycline, although the tetracyclines were considerably less inhibitory than the cephalosporins. Regression line analysis of zones of inhibition versus minimal inhibitory concentration values for tetracycline and minocycline showed the tetracycline disc to be unacceptable for predicting the susceptibility of the Group A Streptococcus to minocycline. Minimal inhibitory concentrations for clindamycin, erythromycin, chloramphenicol, nitrofurantoin, and spectinomycin are also given.

Source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=40435&dopt=Abstract antibiotics, tetracycline