colistin and Osteomyelitis

Topics: Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Biliary Tract Diseases; Carbenicillin; Cephalosporins; Chloramphenicol; Colistin; Endocarditis, Subacute Bacterial; Gentamicins; Humans; Meningitis; Osteomyelitis; Oxacillin; Sepsis; Tetracycline; Urinary Tract Infections

We retrospectively evaluated the safety and effectiveness of colistin alone or in combination with other antimicrobials in eight diabetic patients with severe diabetic foot infections due to multidrug resistant (MDR) Pseudomonas aeruginosa, complicated in 4 cases by osteomyelitis. All patients received colistin after other ineffective antimicrobial treatment, when MDR P. aeruginosa strains were isolated by cultural examination and together with a multidisciplinary care approach including revascularization, surgical debridement and adequate offloading. The mean duration of therapy was 72 +/- 52.9 days. Six out of 8 patients (75%) successfully benefited from colistin therapy, while 2 patients failed and/or experienced side effects that led to discontinuation of therapy. Serious adverse events (i.e. acute renal failure and pulmonary edema) were observed in 1 patient. Our data allow us to conclude that colistin, alone or in combination with other antimicrobials, is safe and effective when administered as part of a multidisciplinary approach, to promote healing of diabetic foot infection due to MDR P. aeruginosa.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Colistin; Combined Modality Therapy; Debridement; Diabetic Foot; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Female; Humans; Imipenem; Male; Middle Aged; Osteomyelitis; Pseudomonas Infections; Retrospective Studies; Rifampin; Treatment Outcome

Optimal treatment of carbapenemase-producing Enterobacterales (CPE) bone infections is poorly defined. This study evaluated the efficacy of the novel beta-lactam-beta-lactamase inhibitor-ceftazidime-avibactam (CAZ-AVI)-with different antibiotic combinations in an experimental model of CPE osteomyelitis.. KPC-99YC is a clinical strain of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae with intermediate susceptibility to meropenem (MIC 4 mg/L), gentamicin (MIC 0.25 mg/L), colistin (MIC 0.25 mg/L), fosfomycin (MIC 4 mg/L) and ceftazidime-avibactam (MIC 1 mg/L). Time-kill curves were performed at 4x MIC. Osteomyelitis was induced in rabbits by tibial injection of 2×10. In vitro, CAZ-AVI plus colistin or gentamicin were rapidly bactericidal in contrast with CAZ-AVI plus fosfomycin. In vivo, compared with controls, colistin alone (P = 0.045) and CAZ-AVI alone or in combination significantly lowered bone bacterial counts (P < 0.001). Bone sterilisation was achieved in 67% and 100% of animals with combinations of CAZ-AVI plus colistin or gentamicin (P = 0.001 and P < 0.001, respectively) whereas other treatments were no different from controls. CAZ-AVI plus gentamicin provided greater bone bacterial reduction than CAZ-AVI plus colistin (P = 0.033). No CAZ-AVI-resistant strains emerged in treated rabbits, regardless of combination.. CAZ-AVI plus gentamicin was the best effective combination therapy. Combinations with CAZ-AVI appear to be a promising treatment of KPC-producing Klebsiella pneumoniae osteomyelitis.

Topics: Animals; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamase Inhibitors; beta-Lactamases; Ceftazidime; Colistin; Drug Combinations; Fosfomycin; Gentamicins; Humans; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Osteomyelitis; Rabbits

While the treatment of ESBL-producing Enterobacterales osteomyelitis relies on carbapenems, the optimal regimen for OXA48 types remains unclear. We evaluated the efficacy of ceftazidime/avibactam in different combinations in an experimental model of OXA-48-/ESBL-producing Escherichia coli osteomyelitis.. E. coli pACYC184 is a clinical strain harbouring blaOXA-48 and blaCTX-M-15 inserts, with 'increased exposure susceptibility' to imipenem (MIC, 2 mg/L), gentamicin (MIC, 0.5 mg/L), colistin (MIC, 0.25 mg/L), ceftazidime/avibactam (MIC, 0.094 mg/L) and fosfomycin (MIC, 1 mg/L), and resistance to ceftazidime (MIC, 16 mg/L). Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 cfu of OXA-48/ESBL E. coli. Treatment started 14 days later for 7 days in six groups: (1) control, (2) colistin 150.000 IU/kg subcutaneously (SC) q8h, (3) ceftazidime/avibactam 100/25 mg/kg SC q8h, (4) ceftazidime/avibactam + colistin, (5) ceftazidime/avibactam + fosfomycin 150 mg/kg SC q12h, (6) ceftazidime/avibactam + gentamicin 15 mg/kg intramuscularly (IM) q24h. Treatment was evaluated at Day 24 according to bone cultures.. In vitro, time-kill curves of ceftazidime/avibactam in combination showed a synergistic effect. In vivo, compared with controls, rabbits treated with colistin alone had similar bone bacterial density (P = 0.50), whereas ceftazidime/avibactam alone or in combinations significantly decreased bone bacterial densities (P = 0.004 and P < 0.0002, respectively). Bone sterilization was achieved using ceftazidime/avibactam in combination with colistin (91%) or fosfomycin (100%) or gentamicin (100%) (P < 0.0001), whereas single therapies were not different from controls. No ceftazidime/avibactam-resistant strains emerged in rabbits treated, regardless of the combination.. In our model of E. coli OXA-48/ESBL osteomyelitis, ceftazidime/avibactam in combination was more effective than any single therapy, whatever the companion drug used (gentamicin or colistin or fosfomycin).

Topics: Animals; Anti-Bacterial Agents; Azabicyclo Compounds; beta-Lactamases; Colistin; Drug Combinations; Escherichia coli; Fosfomycin; Gentamicins; Microbial Sensitivity Tests; Osteomyelitis; Rabbits

Osteomyelitis is an inflammatory process of bone and bone marrow that may even lead to patient death. Even though this disease is mainly caused by Gram-positive organisms, the proportion of bone infections caused by Gram-negative bacteria, such as Escherichia coli, has significantly increased in recent years. In this work, mesoporous silica nanoparticles have been employed as platform to engineer a nanomedicine able to eradicate E. coli- related bone infections. For that purpose, the nanoparticles have been loaded with moxifloxacin and further functionalized with Arabic gum and colistin (AG+CO-coated MX-loaded MSNs). The nanosystem demonstrated high affinity toward E. coli biofilm matrix, thanks to AG coating, and marked antibacterial effect because of the bactericidal effect of moxifloxacin and the disaggregating effect of colistin. AG+CO-coated MX-loaded MSNs were able to eradicate the infection developed on a trabecular bone in vitro and showed pronounced antibacterial efficacy in vivo against an osteomyelitis provoked by E. coli. Furthermore, AG+CO-coated MX-loaded MSNs were shown to be essentially non-cytotoxic with only slight effect on cell proliferation and mild hepatotoxicity, which might be attributed to the nature of both antibiotics. In view of these results, these nanoparticles may be considered as a promising treatment for bone infections caused by enterobacteria, such as E. coli, and introduce a general strategy against bone infections based on the implementation of antibiotics with different but complementary activity into a single nanocarrier. STATEMENT OF SIGNIFICANCE: In this work, we propose a methodology to address E.coli bone infections by using moxifloxacin-loaded mesoporous silica nanoparticles coated with Arabic gum containing colistin (AG+CO-coated MX-loaded MSNs). The in vitro evaluation of this nanosystem demonstrated high affinity toward E. coli biofilm matrix thanks to the Arabic gum coating, a disaggregating and antibacterial effect of colistin, and a remarkable antibiofilm action because of the bactericidal ability of moxifloxacin and colistin. This anti-E. coli capacity of AG+CO-coated MX-loaded MSNs was brought out in an in vivo rabbit model of osteomyelitis where the nanosystem was able to eradicate more than 90% of the bacterial load within the infected bone.

Topics: Animals; Anti-Bacterial Agents; Colistin; Escherichia coli; Moxifloxacin; Nanoparticles; Osteomyelitis; Rabbits; Silicon Dioxide

Topics: Animals; Bacterial Proteins; beta-Lactamases; Carbapenem-Resistant Enterobacteriaceae; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Drugs, Generic; Klebsiella Infections; Klebsiella pneumoniae; Meropenem; Microbial Sensitivity Tests; Osteomyelitis; Rabbits; Therapeutic Equivalency

In a new experimental model of carbapenemase-producing Klebsiella pneumoniae osteomyelitis we evaluated the efficacy of colistin alone and in various combinations and examined the emergence of colistin-resistant strains and cross-resistance to host defence peptides (HDPs).. KPC-99YC is a clinical strain with intermediate susceptibility to meropenem (MIC = 4 mg/L) and full susceptibility to gentamicin, colistin and tigecycline (MICs = 1 mg/L) and fosfomycin (MIC = 32 mg/L). Time-kill curves were performed at 4× MIC. Osteomyelitis was induced in rabbits by tibial injection of 2 × 108 cfu. Treatment started 14 days later for 7 days in seven groups: (i) control; (ii) colistin; (iii) colistin + gentamicin; (iv) colistin + tigecycline; (v) colistin + meropenem; (vi) colistin + meropenem + gentamicin; and (vii) colistin + fosfomycin.. In vitro, colistin was rapidly bactericidal, but regrowth occurred after 9 h. Combinations of colistin with meropenem or fosfomycin were synergistic, whereas combination with tigecycline was antagonistic. In vivo, colistin alone was not effective. Combinations of colistin with meropenem or fosfomycin were bactericidal (P < 0.001) and the addition of gentamicin enhanced the efficacy of colistin + meropenem (P = 0.025). Tigecycline reduced the efficacy of colistin (P = 0.007). Colistin-resistant strains emerged in all groups except colistin + fosfomycin and two strains showed cross-resistance to HDP LL-37.. In this model, combinations of colistin plus meropenem, with or without gentamicin, or colistin plus fosfomycin were the only effective therapies. The combination of colistin and tigecycline should be administered with caution, as it may be antagonistic in vitro and in vivo.

Topics: Animals; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Colistin; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Resistance, Bacterial; Drug Resistance, Multiple, Bacterial; Drug Synergism; Drug Therapy, Combination; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Osteomyelitis; Rabbits

Topics: Acute Disease; Anti-Bacterial Agents; Child; Colistin; Drug Administration Schedule; Humans; Male; Metabolic Clearance Rate; Osteomyelitis; Practice Guidelines as Topic; Pseudomonas aeruginosa; Pseudomonas Infections

Topics: Adult; Anti-Bacterial Agents; Coinfection; Colistin; Combined Modality Therapy; Disease Susceptibility; Drug Substitution; Drug Therapy, Combination; Humans; Kidney Failure, Chronic; Male; Muscle Hypotonia; Osteomyelitis; Renal Dialysis; Reoperation; Respiration, Artificial; Respiratory Insufficiency; Shock, Septic; Spinal Dysraphism; Surgical Wound Infection

Discovered in 1949, the antibiotic colistin was initially used for therapeutic purposes. Parenteral use of colistin was gradually abandoned because of its side-effect profile, especially its nephrotoxicity and neurotoxicity. Despite the risk of these potentially serious adverse effects, increasing resistance of Gram-negative bacteria has led to a renaissance of intravenous use of colistin in the last few years. Local administration of colistin is an alternative method to minimise the risk of systemic toxicity. We present a case of extensively drug-resistant Pseudomonas aeruginosa osteomyelitis treated successfully with high-dose colistin- and tobramycin-impregnated bone cement as a drug delivery vehicle. For the first time, local colistin concentrations in drainage and synovial fluid were quantified in order to determine the optimal dose and to minimise serious side effects. Insertion of a bone cement spacer loaded with a high dose of tobramycin and colistin resulted in local colistin levels at the infection site that exceeded the minimum inhibitory concentration (MIC) of colistin against the isolated P. aeruginosa five-fold on Day 4. Thus, the treatment may be expected to exert a prolonged effect. Whereas systemic administration of colistin alone was not sufficient to treat the infection, combined local and parenteral therapy led to eradication of P. aeruginosa in this patient. Plasma colistin levels remained in the therapeutic range, which confirms the systemic safety of the method.

Topics: Anti-Bacterial Agents; Colistin; Drug Carriers; Drug Resistance, Multiple, Bacterial; Humans; Male; Middle Aged; Osteomyelitis; Plasma; Polymethyl Methacrylate; Pseudomonas aeruginosa; Pseudomonas Infections; Synovial Fluid; Tobramycin; Treatment Outcome

Osteomyelitis (OM) from multidrug-resistant (MDR) Acinetobacter has emerged in >30% of combat-related injuries in Iraq and Afghanistan. While most of these strains are sensitive to colistin, the drug is not available in bone void fillers for local high-dose delivery. To address this, we developed a mouse model with MDR strains isolated from wounded military personnel. In contrast to S. aureus OM, which is osteolytic and characterized by biofilm in necrotic bone, A. baumannii OM results in blastic lesions that do not contain apparent biofilm. We also found that mice mount a specific IgG response against three proteins (40, 47, and 56 kDa) regardless of the strain used, suggesting that these may be immuno-dominant antigens. PCR for the A. baumannii-specific parC gene confirmed a 100% infection rate with 75% of the MDR strains, and in vitro testing confirmed that all strains were sensitive to colistin. We also developed a real-time quantitative PCR (RTQ-PCR) assay that could detect as few as 10 copies of parC in a sample. To demonstrate the efficacy of colistin prophylaxis in this model, mice were treated with either parenteral colistin (0.2 mg colistinmethate i.m. for 7 days), local colistin (PMMA bead impregnated with 1.0 mg colistin sulfate), or an unloaded PMMA bead control. While the parenteral colistin failed to demonstrate any significant effects versus the placebo, the colistin PMMA bead significantly reduced the infection rate such that only 29.2% of the mice had detectable levels of parC at 19 days (p < 0.05 vs. i.m. colistin and placebo).

Topics: Acinetobacter baumannii; Acinetobacter Infections; Animals; Anti-Bacterial Agents; Colistin; Disease Models, Animal; Drug Resistance, Multiple, Bacterial; Female; Fractures, Bone; Mice; Mice, Inbred C57BL; Osteomyelitis

Multidrug resistant Gram-negative rods are emerging as major pathogens and are the cause of difficulty to treat infections. In certain situations colistin is the only active drug.. A retrospective review of the patient's charts admitted at Hôtel-Dieu de France hospital, Beirut, between October 2002 and February 2004 and treated with intravenous colistin.. Fifteen patients were identified; they were suffering from urinary tract infections, cellulitis, osteomyelitis, mediastinitis and intra-abdominal abscess. The microorganisms were resistant to all available antibiotics except colistin. Three strains were also susceptible to aminoglycosides. Pseudomonas aeruginosa was the most frequently isolated pathogen. Colistin was used in monotherapy in 12 patients and combined with amikacin in three patients. At the end of therapy, a 93% rate of favorable clinical outcome was observed. Renal toxicity was encountered among 12 patients. It was severe in only two cases in which creatinine clearance decline surpassed 50% of the baseline value. No neurological toxicity was observed.. Colistin has an important role to play when used for the treatment of infections with multiresistant Gram-negative bacteria. Nephrotoxicity seems much lower than expected and neurotoxicity is minimal.

Topics: Abdominal Abscess; Anti-Bacterial Agents; Colistin; Gram-Negative Bacteria; Humans; Infusions, Intravenous; Kidney; Osteomyelitis; Pseudomonas aeruginosa; Pseudomonas Infections; Pyelonephritis; Retrospective Studies; Urinary Tract Infections

Topics: Acinetobacter baumannii; Acinetobacter calcoaceticus; Aged; Anti-Bacterial Agents; Bacteremia; Calcaneus; Colistin; Humans; Male; Microbial Sensitivity Tests; Osteomyelitis

A case of osteomyelitis caused by multidrug-resistant Pseudomonas aeruginosa is reported in a patient who underwent allogeneic bone marrow transplantation for acute lymphoblastic leukaemia. The patient was successfully treated by prolonged administration of a full dose of colistin and tigecycline, and surgical curettage with the positioning of resorbable calcium sulfate pellets loaded with colistin.

Topics: Adult; Anti-Bacterial Agents; Bone Marrow Transplantation; Colistin; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Humans; Minocycline; Osteomyelitis; Pseudomonas aeruginosa; Pseudomonas Infections; Tigecycline; Transplantation, Homologous

The evaluation of the safety and effectiveness of colistin in association with rifampin and imipenem in 1 diabetic patient with severe diabetic foot infection (DFI) due to multidrug-resistant (MDR) Pseudomonas aeruginosa, complicated by osteomyelitis, is presented in this "Case Report". The patient received colistin after other ineffective antimicrobial treatment when an MDR P aeruginosa strain was isolated by cultural examination, together with a multidisciplinary care approach including surgical debridement and adequate offloading. The efficacy of combination colistin plus rifampin plus imipenem was observed with a checkerboard method and bactericidal activity of the serum. The patient received colistin combination therapy for 6 weeks with cure of the infection and without renal toxicity. These data suggest that colistin, in combination with rifampin and imipenem, is safe and effective, in promoting healing in DFI due to MDR P aeruginosa and suggest the need for controlled clinical studies.

Topics: Aged; Anti-Bacterial Agents; Colistin; Diabetic Foot; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Follow-Up Studies; Humans; Imipenem; Male; Metatarsal Bones; Osteomyelitis; Pseudomonas aeruginosa; Pseudomonas Infections; Rifampin

Serious complications occurred in 29 of 887 children with puncture wounds of the feet treated over a four-year period at the Dr. Charles A. Janeway Child Health Centre. Osteomyelitis in one of the small bones of the foot was the commonest complication and occurred when a cartilaginous surface (physeal plate or articular cartilage) had been violated. Although systemic signs of osteomyelitis frequently are absent, this infectious process is refractory to medical management. The combined surgical and medical management of this complication is outlined. Management of puncture wounds in the emergency room should include a thorough history concisely recorded, tetanus prophylaxis, and cleansing, debridement, and probing of the wound. Antimicrobial agents are not routinely required but should be reserved for patients presenting late with cellulitis or an established infection. A semisynthetic penicillinase-penicillin appears to be the agent of choice until the results of microbiologic studies are available.

Topics: Adolescent; Cellulitis; Child; Child, Preschool; Colistin; Erythromycin; Female; Foot Injuries; Humans; Klebsiella Infections; Lincomycin; Male; Osteomyelitis; Penicillins; Pseudomonas Infections; Staphylococcal Infections; Streptococcal Infections; Tetracyclines; Wounds, Penetrating

A myopathy caused by the activity of polymyxin E on the cell membrane was accompained by immunological manifestations. There were also disturbances of the central nervous system, contrasting with the absence of serious renal lesion.

Topics: Aged; Antigen-Antibody Reactions; Autoantibodies; Brain Diseases; Colistin; Electromyography; Fluorescent Antibody Technique; Frontal Lobe; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Muscles; Muscular Diseases; Neural Conduction; Osteomyelitis; Paralysis

Topics: Colistin; Femur; gamma-Globulins; Humans; Infant, Newborn; Infant, Newborn, Diseases; Male; Osteomyelitis; Pseudomonas Infections; Streptomycin

Topics: Child; Colistin; Foot Injuries; Humans; Male; Osteomyelitis; Penicillins; Pseudomonas; Pseudomonas Infections; Radiography; Wound Infection

Topics: Child; Colistin; Foot Diseases; Foot Injuries; Gentamicins; Humans; Male; Osteomyelitis; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Radiography; Wounds and Injuries

Topics: Brain Diseases; Child; Colistin; Gentamicins; Humans; Injections, Intravenous; Male; Osteomyelitis; Patella; Pseudomonas aeruginosa; Seizures

Topics: Administration, Oral; Adolescent; Adult; Aged; Blood Sedimentation; C-Reactive Protein; Child; Chloramphenicol; Chronic Disease; Cloxacillin; Colistin; Female; Fistula; Humans; Injections; Male; Middle Aged; Osteomyelitis; Probenecid; Prognosis; Recurrence; Staphylococcal Infections; Staphylococcus

Topics: Bacteriophages; Chloramphenicol; Chlortetracycline; Colistin; Drug Resistance, Microbial; Genetics, Microbial; Osteomyelitis; Proteus; Suppuration

Topics: Apnea; Colistin; Dexamethasone; Escherichia coli Infections; Femoral Fractures; Fractures, Spontaneous; Hydrocortisone; Injections; Injections, Intramuscular; Osteomyelitis; Spinal Injuries; Tetracycline; Toxicology