minocycline and Neoplasms

In recent years, research on tetracycline antibiotics has gradually shifted from their antibacterial effects to anticancer effects. Doxycycline, minocycline, and tigecycline as the US Food and Drug Administration (FDA) approved tetracycline antibiotics have been the main subjects of studies. Evidence indicated that they have anticancer properties and are able to control cancer progression through different mechanisms, such as anti-proliferation, anti-metastasis, and promotion of autophagy or apoptosis. In addition, studies have shown that these three tetracycline antibiotics can be utilized in conjunction with chemotherapeutic and targeted drugs to inhibit cancer progression and improve the quality of patient survival. Therefore, doxycycline, minocycline, and tigecycline are taken as examples in this work. Their mechanisms of action in different cancers and related combination therapies are introduced. Their current roles in alleviating the suffering of patients undergoing chemotherapy when used as adjuvant drugs in clinical treatment are also described. Finally, the research gaps and potential research directions at this stage are briefly summarized.

Topics: Anti-Bacterial Agents; Antineoplastic Agents; Doxycycline; Heterocyclic Compounds; Humans; Minocycline; Neoplasms; Tigecycline

Tigecycline is a novel glycylcycline antibacterial drug, which shows both antibiotic function and anti-tumor activity. This review summarizes the single and combined use of tigecycline for tumor treatment and the underpinning mechanisms. As an inhibitor for mitochondrial DNA translation, tigecycline affects the proliferation, migration, and invasion of tumor cells mainly through inhibiting mitochondrial protein synthesis and inducing mitochondrial dysfunction. Although the effect of tigecycline monotherapy is controversial, the efficacy of combined use of tigecycline is satisfactory. Therefore, it is important to explore the molecular mechanisms underpinning the anti-tumor activity of tigecycline, with the aim to use it as a cheap and effective new anti-tumor drug.

Topics: Anti-Bacterial Agents; Humans; Minocycline; Mitochondria; Neoplasms; Tigecycline

Bacterial infections, particularly those due to gram-positive bacteria, continue to predominate in patients with cancer. Coagulase-negative and coagulase-positive staphylococci and enterococci remain as common pathogenic microorganisms. Clostridium difficile has emerged as a significant pathogen. Major clinical syndromes include vascular catheter-related infection, febrile neutropenia, diarrhea and colitis. Rising antimicrobial resistance among gram-positive bacteria is of serious concern. The clinical utility of penicillin against streptococci and vancomycin against coagulase-negative and coagulase-positive staphylococci and enterococci may be rapidly diminishing. Liberal empiric use of vancomycin during neutropenic fever needs careful reconsideration. Newer promising anti-gram-positive bacterial drugs with activity against methicillin-resistant staphylococci include daptomycin, linezolid, tigecycline and telavancin. However, toxicity concerns, limited data in immunocompromised populations and high cost prevent the widespread use of these drugs among patients with cancer.

Topics: Acetamides; Aminoglycosides; Anti-Bacterial Agents; Daptomycin; Drug Resistance, Bacterial; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Humans; Linezolid; Lipoglycopeptides; Minocycline; Neoplasms; Oxazolidinones; Tigecycline

High-dose interleukin-2 (HDIL-2) has proven to be an effective treatment for metastatic renal cell carcinoma and melanoma. Previous studies have shown an increase in catheter-related bacteremia (CRB) in patients on HDIL-2. The primary objective of this study was to evaluate the effectiveness of minocycline and rifampin-coated catheters (M/R-C) in reducing CRB in cancer patients on HDIL-2. This was a retrospective study where non-coated catheters (NC-C) and M/R-C were used for the administration of HDIL-2 before and after December 2004, respectively. Data collected included demographics, cancer type, catheter type, antibiotic prophylaxis, and infection rates. A total of 107 episodes of catheter use for HDIL-2 were evaluated in 78 patients (30 episodes in patients with M/R-C vs. 77 with NC-C). A total of nine episodes of CRB were identified, all in patients with NC-C (M/R-C 0% vs. NC-C 12%; p=0.06). The median time to bacteremia was 11 days (range 1-315 days). A log-rank test showed a trend that the M/R-C group had lower probability of getting CRB than the NC-C group (p=0.06). The use of M/R-C in patients on HDIL-2 therapy for advanced melanoma and renal cell carcinoma may have reduced the risk of CRB to nil. CRB still occurred despite antibiotic prophylaxis in patients with NC-C.

Topics: Adult; Aged; Anti-Bacterial Agents; Antineoplastic Agents; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Female; Humans; Interleukin-2; Male; Middle Aged; Minocycline; Neoplasms; Rifampin; Treatment Outcome

Cutaneous side effects of epidermal growth factor receptor inhibitors (EGFRIs) are very frequent and well known. The aim of our study was to investigate the efficacy and safety of pimecrolimus 1% cream in the treatment of papulopustular eruption caused by EGFRIs and to review the relevant literature on therapeutic approaches.. Twenty cancer patients being treated with EGFRIs were included in the study. Nine of the patients showed grade 1 and 11 showed grade 2 papulopustular eruption. All patients were treated with pimecrolimus 1% cream, which was applied twice daily. Patients with grade 2 eruption also received systemic minocycline 100 mg/day.. All patients with grade 1 eruption responded to treatment, with 4/9 experiencing complete resolution of the lesions 2 weeks after the initiation of treatment. Five out of 11 patients with grade 2 eruption had more than 50% improvement in erythema and pustules, and 1 had complete resolution of the skin lesions. Two patients did not respond to treatment but were significantly improved after substitution of pimecrolimus 1% cream with metronidazole 1% cream. No side effects were recorded.. Our case series shows that pimecrolimus cream may be an effective and safe approach in the management of papulopustular eruption related to EGFRIs.

Topics: Aged; Antineoplastic Agents; Dermatologic Agents; Drug Eruptions; ErbB Receptors; Female; Humans; Male; Metronidazole; Middle Aged; Minocycline; Neoplasms; Ointments; Prospective Studies; Protein Kinase Inhibitors; Rosacea; Tacrolimus; Treatment Outcome

Tetracyclines are broad-spectrum antibiotics that act as such at the ribosomal level where they interfere with protein synthesis. They were first widely prescribed by dermatologists in the early 1950s when it was discovered that they were effective as a treatment for acne. More recently, biologic actions affecting inflammation, proteolysis, angiogenesis, apoptosis, metal chelation, ionophoresis, and bone metabolism have been researched. The therapeutic effects of tetracycline and its analogues in various diseases have also been investigated. These include rosacea, bullous dermatoses, neutrophilic diseases, pyoderma gangrenosum, sarcoidosis, aortic aneurysms, cancer metastasis, periodontitis, and autoimmune disorders such as rheumatoid arthritis and scleroderma. We review the nonantibiotic properties of tetracycline and its analogues and their potential for clinical application.

Topics: Acne Vulgaris; Anti-Bacterial Agents; Anti-Inflammatory Agents; Aortic Aneurysm, Abdominal; Apoptosis; Arthritis, Rheumatoid; Doxycycline; Humans; Matrix Metalloproteinases; Minocycline; Neoplasms; Neovascularization, Physiologic; Periodontitis; Rosacea; Sarcoma, Kaposi; Skin Diseases; Skin Diseases, Vesiculobullous; Tetracyclines

Topics: Animals; Anti-Bacterial Agents; Antineoplastic Agents; Cell Hypoxia; Chick Embryo; Combined Modality Therapy; Cyclohexanes; Drug Therapy, Combination; Humans; Mice; Minocycline; Neoplasms; Neovascularization, Pathologic; O-(Chloroacetylcarbamoyl)fumagillol; Rabbits; Rats; Sesquiterpenes

In cancer patients with long-term central venous catheters (CVC), removal and reinsertion of a new CVC at a different site might be difficult because of the unavailability of accessible vascular sites. In vitro and animal studies showed that a minocycline-EDTA-ethanol (M-EDTA-EtOH) lock solution may eradicate microbial organisms in biofilms, hence enabling the treatment of central line-associated bloodstream infections (CLABSI) while retaining the catheter in situ Between April 2013 and July 2014, we enrolled 30 patients with CLABSI in a prospective study and compared them to a historical group of 60 patients with CLABSI who had their CVC removed and a new CVC inserted. Each catheter lumen was locked with an M-EDTA-EtOH solution for 2 h administered once daily, for a total of 7 doses. Patients who received locks had clinical characteristics that were comparable to those of the control group. The times to fever resolution and microbiological eradication were similar in the two groups. Patients with the lock intervention received a shorter duration of systemic antibiotic therapy than that of the control patients (median, 11 days versus 16 days, respectively; P < 0.0001), and they were able to retain their CVCs for a median of 74 days after the onset of bacteremia. The M-EDTA-EtOH lock was associated with a significantly decreased rate of mechanical and infectious complications compared to that of the CVC removal/reinsertion group, who received a longer duration of systemic antimicrobial therapy. (This study has been registered at ClinicalTrials.gov under registration no. NCT01539343.).

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteremia; Biofilms; Catheter-Related Infections; Catheterization, Central Venous; Central Venous Catheters; Edetic Acid; Ethanol; Female; Humans; Male; Middle Aged; Minocycline; Neoplasms; Pilot Projects; Prospective Studies; Treatment Outcome; Young Adult

Contamination of central catheters is frequent, and biofilm perpetuates infections. Heparin does not protect against infections because it has no antibiotic action. Minocycline and edetic acid (M-EDTA), a potent calcium chelating agent that destroys bacterial and fungal cell membrane and disrupts biofilm, may be an alternative to allow the associated antibiotic to act locally at a high and safe concentration.. Fifty children with cancer and a port-a-cath were followed up: 26 received heparin (group 1) and 24 M-EDTA (group 2). A total of 762 serial prospective blood cultures were obtained, 387 from group 1 and 375 from group 2.. In group 1 (heparin), 19 blood cultures were positive, and infection incidence was 73.1% (19/26 ports). In group 2 (M-EDTA), 5 blood cultures were positive, and the incidence rate was 20.8% (5/24 ports).. M-EDTA, compared with heparin, prevents and treats catheter infections, and is a promising alternative to decrease sepsis during chemotherapy.

Topics: Anti-Bacterial Agents; Biofilms; Blood; Catheter-Related Infections; Catheterization, Peripheral; Catheters, Indwelling; Child; Edetic Acid; Female; Heparin; Humans; Male; Minocycline; Neoplasms

Cutaneous side effects of epidermal growth factor receptor inhibitors (EGFRIs) are very frequent and well known. The aim of our study was to investigate the efficacy and safety of pimecrolimus 1% cream in the treatment of papulopustular eruption caused by EGFRIs and to review the relevant literature on therapeutic approaches.. Twenty cancer patients being treated with EGFRIs were included in the study. Nine of the patients showed grade 1 and 11 showed grade 2 papulopustular eruption. All patients were treated with pimecrolimus 1% cream, which was applied twice daily. Patients with grade 2 eruption also received systemic minocycline 100 mg/day.. All patients with grade 1 eruption responded to treatment, with 4/9 experiencing complete resolution of the lesions 2 weeks after the initiation of treatment. Five out of 11 patients with grade 2 eruption had more than 50% improvement in erythema and pustules, and 1 had complete resolution of the skin lesions. Two patients did not respond to treatment but were significantly improved after substitution of pimecrolimus 1% cream with metronidazole 1% cream. No side effects were recorded.. Our case series shows that pimecrolimus cream may be an effective and safe approach in the management of papulopustular eruption related to EGFRIs.

Topics: Aged; Antineoplastic Agents; Dermatologic Agents; Drug Eruptions; ErbB Receptors; Female; Humans; Male; Metronidazole; Middle Aged; Minocycline; Neoplasms; Ointments; Prospective Studies; Protein Kinase Inhibitors; Rosacea; Tacrolimus; Treatment Outcome

To evaluate the efficacy of long-term nontunneled silicone catheters impregnated with minocycline and rifampin (M-R) in reducing catheter-related bloodstream infections.. This prospective, randomized, double-blind clinical trial was conducted at M.D. Anderson Cancer Center, a tertiary care hospital in Houston, TX. All patients in the trial had a malignancy.. Between September 1999 and May 2002, 356 assessable catheters were used: 182 M-R and 174 nonimpregnated. The patients' characteristics were comparable between the two study groups. The mean (+/- standard deviation) duration of catheterization with M-R catheters was comparable to that of nonimpregnated catheters (66.21 +/- 30.88 v 63.01 +/- 30.80 days). A total of 17 catheter-related bloodstream infections occurred during the course of the study. Three were associated with the use of M-R catheters and 14 were associated with the nonimpregnated catheters, with a rate of catheter-related bloodstream infection of 0.25 and 1.28/1,000 catheter-days, respectively (P = .003). Gram-positive cocci accounted for the majority of the organisms causing the infections. There were no allergic reactions associated with M-R catheters.. Long-term nontunneled central venous catheters impregnated with minocycline and rifampin are efficacious and safe in reducing catheter-related bloodstream infections in cancer patients.

Topics: Anti-Bacterial Agents; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Double-Blind Method; Female; Humans; Male; Middle Aged; Minocycline; Neoplasms; Prospective Studies; Rifampin; Silicones

In this prospective cohort study, minocycline-ethylenediaminetetraacetate (M-EDTA) was used as a lock solution in indwelling ports inserted in 14 children with cancer. No port infections, thrombotic events, or other adverse events were observed, compared with 10 port infections that occurred in 48 control patients whose ports were flushed with heparin. M-EDTA is a promising lock solution in long-term catheters.

Topics: Anti-Bacterial Agents; Catheters, Indwelling; Chelating Agents; Child; Child, Preschool; Cohort Studies; Drug Therapy, Combination; Edetic Acid; Female; Humans; Male; Minocycline; Neoplasms; Prospective Studies; Prosthesis-Related Infections; Thrombosis

Between February 1994 and November 1998, 56 oncology patients infected with vancomycin-resistant enterococci (VRE) were treated with quinopristin-dalfopristin (Q-D) plus minocycline (MIN). Infections included bacteremia, urinary tract infection, pneumonia, and wound infection. The response rate was 68%, and the most frequent adverse event was arthralgia or myalgia (36%). Q-D-MIN is effective for VRE infection in cancer patients but is associated with a substantial frequency of arthralgia or myalgia.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antineoplastic Agents; Child; Drug Therapy, Combination; Enterococcus; Enterococcus faecalis; Enterococcus faecium; Female; Gram-Positive Bacterial Infections; Humans; Immunity; Male; Middle Aged; Minocycline; Neoplasms; Pain; Vancomycin Resistance; Virginiamycin

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Child; Child, Preschool; Disease-Free Survival; Female; Gram-Negative Bacterial Infections; Humans; Male; Middle Aged; Minocycline; Neoplasms; Retrospective Studies; Risk Factors; Stenotrophomonas maltophilia; Survival Rate; Tertiary Care Centers; Trimethoprim, Sulfamethoxazole Drug Combination

Clostridium difficile infection (CDI) is the most frequent cause of nosocomial diarrhoea in adults. Cancer patients, in particular, are at a higher risk for CDI. Limited clinical data exist regarding the use of tigecycline for the treatment of CDI, especially in patients with oncologic and haematologic malignancies.. To characterize the use of tigecycline for treatment of CDI in oncology patients at an academic cancer centre.. This was a retrospective, single-centre, single-arm, chart review evaluating the use of tigecycline for the management of CDI in oncology patients at an academic cancer centre.. The median age of CDI diagnosis in this patient group (N=66) was 65 years (range: 16-84) and the majority of patients had solid tumour malignancies. Fifty-six percent of patients had severe CDI, 70.3% of which were classified as having severe complicated disease. The median time to initiation of tigecycline therapy was 2 days (mean: 3.83) and the median number of tigecycline doses was 13 (range: 1-50). Twelve non-CDI breakthrough infections were observed, and four patients developed CDI while receiving tigecycline for non-CDI indications. The rate of death was 18% and the recurrence rate was 15.2%.. Tigecycline did not lead to overt benefits in outcomes of oncology patients with CDI when compared to historical data. In addition, several breakthrough CDIs were observed in patients who received the drug for a non-CDI indication. Further prospective research is needed to validate the use of tigecycline for management of CDI.

Topics: Academic Medical Centers; Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Clostridioides difficile; Clostridium Infections; Colitis; Female; Humans; Male; Middle Aged; Minocycline; Neoplasms; Retrospective Studies; Tigecycline; Treatment Outcome; Young Adult

The aim of this study was to evaluate the in vitro effects and clinical efficacies of trimethoprim-sulfamethoxazole (SXT) combined with other antimicrobial agents against Stenotrophomonas maltophilia.. In vitro analysis was conducted on 89 S. maltophilia strains isolated from blood and the respiratory tract between June 2012 and October 2014. Levofloxacin (LVX), ticarcillin-clavulanic acid (TIM), and minocycline (MIN) were selected for an examination of their effects when individually combined with SXT by the checkerboard method. In addition, 29 S. maltophilia bacteremia cases were reviewed and the clinical efficacies of SXT-based combination therapies were analyzed.. SXT+LVX showed synergy in 21, no interactions in 61, and antagonism in 7. SXT+TIM showed synergy in 71, and no interactions in 18. SXT+MIN showed synergy in 10, and no interactions in 79. The review of clinical data indicated that a combination of SXT+fluoroquinolone was not associated with improved prognosis compared with monotherapy.. The in vitro data indicated that SXT+TIM had beneficial microbiological effects and was not antagonistic. Our in vitro and clinical data analyses do not support the routine use of SXT+fluoroquinolone combination therapy for S. maltophilia infection.

Topics: Aged; Anti-Bacterial Agents; Bacteremia; Clavulanic Acids; Drug Therapy, Combination; Female; Fluoroquinolones; Gram-Negative Bacterial Infections; Humans; Levofloxacin; Male; Middle Aged; Minocycline; Neoplasms; Stenotrophomonas maltophilia; Ticarcillin; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination

Cardiovascular dysfunction as a result of tumor burden is becoming a recognized complication; however, the mechanisms remain unknown. A murine model of cancer cachexia has shown marked increases of matrix metalloproteinases (MMPs), known mediators of cardiac remodeling, in the left ventricle. The extent to which MMPs are involved in remodeling remains obscured. To this end a common antibiotic, minocycline, with MMP inhibitory properties was used to elucidate MMP involvement in tumor induced cardiovascular dysfunction. Tumor-bearing mice showed decreased cardiac function with reduced posterior wall thickness (PWTs) during systole, increased MMP and collagen expression consistent with fibrotic remodeling. Administration of minocycline preserved cardiac function in tumor bearing mice and decreased collagen RNA expression in the left ventricle. MMP protein levels were unaffected by minocycline administration, with the exception of MMP-9, indicating minocycline inhibition mechanisms are directly affecting MMP activity. Cancer induced cardiovascular dysfunction is an increasing concern; novel therapeutics are needed to prevent cardiac complications. Minocycline is a well-known antibiotic and recently has been shown to possess MMP inhibitory properties. Our findings presented here show that minocycline could represent a novel use for a long established drug in the prevention and treatment of cancer induced cardiovascular dysfunction.

Topics: Animals; Cachexia; Calcium; Calcium Signaling; Collagen; Disease Models, Animal; Electrocardiography; Extracellular Matrix; Female; Gene Expression; Heart Diseases; Matrix Metalloproteinases; Mice; Minocycline; Muscle Contraction; Myocytes, Cardiac; Neoplasms; Tissue Inhibitor of Metalloproteinase-1

MicroRNAs (miRNAs) are non-coding RNAs that regulate gene expression at the post-transcriptional level. It is now well established that the overexpression of some miRNAs (oncogenic miRNAs) is responsible for initiation and progression of human cancers and the discovery of new molecules able to interfere with their production and/or function represents one of the most important challenges of current medicinal chemistry of RNA ligands. In this work, we studied the ability of 18 different antibiotics, known as prokaryotic ribosomal RNA, to bind to oncogenic miRNA precursors (stem-loop structured pre-miRNAs) in order to inhibit miRNAs production. In vitro inhibition, binding constants, thermodynamic parameters and binding sites were investigated and highlighted that aminoglycosides and tetracyclines represent interesting pre-miRNA ligands with the ability to inhibit Dicer processing.

Topics: Aminoglycosides; Anti-Bacterial Agents; Base Sequence; DEAD-box RNA Helicases; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Models, Molecular; Molecular Sequence Data; Neoplasms; Ribonuclease III; Ribosomes; Tetracyclines

Intra-abdominal infection (IAI) is a frequent complication found in surgical intensive care unit (SICU) and continues to be associated with considerable mortality. Tigecycline, the first-in-class glycylcycline has demonstrated a broad spectrum of activity against a wide range of bacteria commonly found in IAI. This observational retrospective study aimed to describe the experience with tigecycline for serious nosocomial IAI in the SICU. Data were collected from 23 consecutive patients admitted to SICU with serious nococomial IAI who had received empirical treatment with tigecycline. In all cases, IAI was diagnosed via emergency surgery. Severe sepsis was found in 56.5% and 43.5% developed septic shock. Oncological disease was the most common comorbidity (60%). The mean Simplified Acute Physiology Score (SAPS) III within 24 hours from IAI diagnosis was 57.5±14.7, and 87% showed a McCabe score >1 (2 or 3). Escherichia coli was the most common pathogen (43.5%), followed by Bacteroides spp. and Streptococcus spp. (30.4%, respectively). All but one patient received tigecycline in combination (95.7%), particularly with fluconazole (52.2%), followed by piperacillin-tazobactam (43.5%). Empirical antibiotic therapy was considered adequate in 95%. The mean duration of treatment was 8.5±4.5 days. A favorable response was achieved in 78%. Failure of the antibiotic therapy was not observed in any patient. None of the patients discontinued tigecycline due to adverse reactions. SICU mortality was 13%, with no deaths attributable to tigecycline. These findings suggest that tigecycline combination therapy is an effective and well tolerated empirical treatment of serious nosocomial IAI in the SICU.

Topics: Adult; Aged; Anti-Bacterial Agents; Combined Modality Therapy; Comorbidity; Critical Care; Critical Illness; Cross Infection; Drug Evaluation; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Gram-Positive Bacteria; Gram-Positive Bacterial Infections; Hospital Mortality; Humans; Male; Middle Aged; Minocycline; Neoplasms; Postoperative Complications; Retrospective Studies; Sepsis; Shock, Septic; Tigecycline; Treatment Outcome

Criteria of tigecycline (Tygacil) use for the treatment of surgical site infections in oncologic inpatients were developed. High efficacy of tigecycline in vitro and in vivo against multiresistant hospital strains persistent in the surgical department of the gastrointestinal oncologic division was shown.

Topics: Aged; Anti-Bacterial Agents; Cross Infection; Female; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Minocycline; Neoplasms; Surgical Wound Infection; Tigecycline

Cancer patients with complicated infections following abdominal surgery represent one of the worst clinical scenarios that is useful for testing the efficacy of empirical antimicrobial therapy. No study so far has evaluated the performance of tigecycline (TIG) when administered as empirical first-line treatment in a homogeneous population of surgical cancer patients with a febrile episode. An observational review of the data records of 24 sequential patients receiving TIG for a febrile episode following a major abdominal procedure in a single cancer institute was performed. Large bowel surgery represented 68% of all procedures, followed by gastric surgery (16%) and urinary-gynaecologic-biliary surgery (16%). Complications following surgery were observed in 68% of febrile episodes, with peritonitis and sepsis accounting for 59% and 24% of complications, respectively. Eight patients needed repeat surgery for source control. The mean duration of TIG treatment was 8 days. Causative pathogens were detected in 16 episodes (64%), and a total of 44 microorganisms were recovered (29% Escherichia coli, 9% Enterococcus faecalis and 9% coagulase-negative staphylococci). TIG was effective in 12 episodes (48%). The success rate was 67% when infectious episodes sustained by intrinsically resistant bacteria and fungi were excluded. Treatment failure was associated with the presence of complications and with microbiologically documented infection. TIG may be useful as a first-line treatment option in cancer patients requiring antibiotic treatment following surgery when complications are not present or suspected on clinical grounds and when local microbial epidemiology shows a low incidence of primary resistant bacteria.

Topics: Abdominal Neoplasms; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Enterococcus faecalis; Escherichia coli; Female; Fever of Unknown Origin; Humans; Male; Middle Aged; Minocycline; Neoplasms; Peritonitis; Sepsis; Staphylococcus; Surgical Wound Infection; Tigecycline; Treatment Outcome

Minocycline exerts anti-inflammatory and anti-apoptotic effects distinct from its antimicrobial function. In this study we investigated the effect of this drug on chemotherapy-induced gut damage. Body weight loss results, diarrhea scores, and villi measurements showed that minocycline attenuated the severity of intestinal mucositis induced by 5-fluorouracil (5-FU). Minocycline repressed the expression of TNF-alpha, IL-1beta, and iNOS, decreased the apoptotic index, and inhibited poly(ADP-ribose) polymerase-1 (PARP-1) activity in the mouse small intestine. In vitro experiments showed that minocycline suppressed the upregulation of PARP-1 activity in enterocyte IEC-6 cells treated with 5-FU. In addition, minocycline treatment appeared to enhance the antitumor effects of 5-FU in tumor CT-26 xenograft mice. Our results indicate that minocycline protects mice from gut injury induced by 5-FU and enhances the antitumor effects of 5-FU in xenograft mice. These observations suggest that minocycline treatment may benefit patients undergoing standard cancer chemotherapy by alleviating chemical-associated intestinal mucositis.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Antimetabolites, Antineoplastic; Apoptosis; Cell Proliferation; Cytokines; Disease Models, Animal; Fluorouracil; Intestine, Small; Male; Mice; Mice, Inbred BALB C; Minocycline; Mucositis; Neoplasms; Nitric Oxide Synthase Type II; Poly (ADP-Ribose) Polymerase-1; Poly(ADP-ribose) Polymerase Inhibitors; Xenograft Model Antitumor Assays

To evaluate the impact of using central venous catheters (CVCs) impregnated with the combination of minocycline and rifampin on nosocomial bloodstream infections (BSIs), morbidity, and mortality in cancer patients in the ICU.. Prospective surveillance study consisting of the following two time periods: September 1997 through August 1998 (ie, fiscal year [FY] 1998); and from September 1998 through August 1999 (ie, FY 1999).. ICUs of a tertiary care hospital in Houston, TX.. Cancer patients in the medical ICU (MICU) and surgical ICU (SICU).. ICUs started using CVCs impregnated with the minocycline-rifampin combination at the beginning of FY 1999.. The rates of nosocomial BSIs and other patients' characteristics were compared for the two study periods to determine the impact of using the impregnated catheters in the ICU. Patients' characteristics, including antibiotic use, were comparable for the two study periods in both the MICU and the SICU. The rate of nosocomial BSIs in the MICU unit decreased from 8.3 to 3.5 per 1,000 patient-days (p < 0.01), and decreased in the SICU from 4.8 to 1.3 per 1,000 patient-days (p < 0.01) in FY 1999. Nosocomial vancomycin-resistant enterococcus (VRE) bacteremia also decreased significantly (p = 0.004). Length of stay in the MICU and SICU significantly decreased in FY 1999 (p < 0.01 and p = 0.03, respectively). The duration of hospitalization decreased for MICU and SICU patients (p = 0.06 and p < 0.01, respectively). The rate of catheter-related infections decreased from 3.1 to 0.7 per 1,000 patient-days in FY 1999 (p = 0.02). The decrease in infections resulted in net savings of at least $1,450,000 for FY 1999.. The use of antibiotic-impregnated CVCs in the MICU and SICU was associated with a significant decrease in nosocomial BSIs, including VRE bacteremia, catheter-related infections, and lengths of hospital and ICU stays.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Catheterization, Central Venous; Catheters, Indwelling; Cause of Death; Child; Child, Preschool; Coated Materials, Biocompatible; Critical Care; Cross Infection; Drug Resistance, Multiple; Drug Therapy, Combination; Enterococcus; Female; Hospital Mortality; Humans; Male; Middle Aged; Minocycline; Neoplasms; Opportunistic Infections; Prospective Studies; Rifampin; Survival Rate; Texas; Vancomycin Resistance

Mycobacterium vaccae is a rapidly growing mycobacterial species that was previously not considered a human pathogen. We report four cases of M. vaccae infection that occurred in the southern United States; one patient had cutaneous disease, and three patients had cavitary lung disease. Two of the three patients with pulmonary disease had a history of exposure to cattle. The conditions of all patients improved with therapy: the cutaneous infection responded to therapy with minocycline and trimethoprim-sulfamethoxazole, and the pulmonary infections responded to therapy with ciprofloxacin.

Topics: Aged; Animals; Anti-Bacterial Agents; Cattle; Ciprofloxacin; Humans; Male; Middle Aged; Minocycline; Mycobacterium; Mycobacterium Infections; Neoplasms; Pneumonia, Bacterial; Skin Diseases, Bacterial; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Bacteria; Bacterial Infections; Doxycycline; Humans; Leukemia; Minocycline; Neoplasms; Tetracycline