colistin and Bacterial-Infections

Colistin is a member of cationic polypeptide antibiotics known as polymyxins. It is widely used in animal husbandry, plant cultivation, animal and human medicine and is increasingly used as one of the last available treatment options for patients with severe infections with carbapenem-resistant Gram-negative bacilli. Due to the increased use of colistin in treating infections caused by multidrug-resistant (MDR) bacteria, the resistance to this antibiotic ought to be monitored. Bacterial resistance to colistin may be encoded on transposable genetic elements (e.g. plasmids with the

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Colistin; Drug Resistance, Bacterial; Gammaproteobacteria; Humans

The key elements in the therapy of surgical site infections (SSI) are surgical debridement and local and systemic antibiotic therapy; however, due to increasing antibiotic resistance, the development of additional therapeutic measures is of great interest for future trauma and orthopedic surgery.. Against the background of our own experimental and clinical experiences and on the basis of the current literature, possible future anti-infective strategies were elaborated.. Bacteriophages were discovered and clinically implemented approximately one century ago and have been used in Western Europe for about one decade. They are currently used mainly in patients with burn injuries. It is likely that bacteriophages will become of great importance in view of the increasing antibiotic multi-drug resistance; however, they will probably not entirely replace antibiotic drugs. A combined use of bacteriophages and antibiotics is likely to be a more reasonable efficient therapy. In addition, the clinical importance of antimicrobial peptides (AMP) also increases. Up to now the possible use of AMPs is still experimental; however, individual AMPs are already established in the routine therapy (e. g. colistin). Further diagnostic and therapeutic measures may include photodynamic therapy, ultraviolet (UV) light application and differentiated genome analysis as well as the individual metabolism situation (metabolomics) of the pathogen cell and the patient tissue.

Topics: Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Colistin; Combined Modality Therapy; Debridement; Drug Resistance, Multiple, Bacterial; Genome, Bacterial; Humans; Metabolomics; Photochemotherapy; Surgical Wound Infection; Ultraviolet Therapy

Current evidence on the use of colistin in pediatric patients for infections caused by carbapenem-resistant bacteria is based on retrospective case series. The coadministration of colistin with other antimicrobial agents was associated with a relatively low rate of nephrotoxicity and a favorable outcome in >70% of these patients. Further study of colistin pharmacokinetics in children and neonates will likely lead to optimization of dosage recommendations.

Topics: Adult; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Carbapenems; Child; Child, Preschool; Clinical Trials as Topic; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Infant; Infant, Newborn

Nephrotoxicity is a common adverse effect of the clinically used polymyxins, colistin and polymyxin B. This adverse effect is dose limiting for both polymyxins, as the plasma polymyxin concentrations associated with renal damage overlap those required for antibacterial effect. Since development of acute kidney injury (AKI) during therapy is highly undesirable, it is extremely important to know whether there is any difference between the nephrotoxic potential of colistin (administered as its inefficient prodrug, colistimethate) and polymyxin B (administered as the active form). Both polymyxins are cytotoxic to renal tubular cells and are prone to cause nephrotoxicity

Topics: Acute Kidney Injury; Animals; Anti-Bacterial Agents; Bacterial Infections; Biological Transport; Clinical Trials as Topic; Colistin; Humans; Kidney; Mice; Polymyxin B; Prodrugs; Rats; Survival Analysis

This article reviews mechanisms, incidences, risk factors and preventive modalities of colistin toxicity as well as colistin use in special populations and through special routes. All clinical studies that examined the pharmacokinetic/pharmacodynamic, efficacy and side effects of colistin in the management of multidrug-resistant organisms in different patient population including pediatrics, adults, obese, critically ill, burn or cancer patients with any route of drug administration were considered. Compared with older recommended doses, current dosing approach improves cure rate without significant increase in the rate of colistin-induced nephrotoxicity. Efficacy and safety of high doses of colistin should be considered in the future studies. Also comparing efficacy and safety of different doses of aerosolized colistin and defining the appropriate dose in different populations is another open area of future researches.

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Dose-Response Relationship, Drug; Humans

The global spread of multi-drug resistant organisms (MDRO) is a major threat to public health. Fighting MDRO spread requires a multi-faceted approach as summarized in the German Antibiotic Resistance Strategy (DART). In the hospital, this includes antibiotic stewardship concepts and strict infection control measures. Treatment of MDRO is sophisticated. Within the last years, several antibiotics with activity against MRSA were launched and facilitate an individual therapy according to site of infection and co-morbidities. In contrast, novel antibiotics against carbapenemase producing Gram-negatives are still lacking. Current studies have shown, that a colistin-based combination treatment can improve the prognosis in these patients. The following article reviews MDRO definitions, burden of disease, treatment options and general strategies against MDRO.

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Cost of Illness; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Gram-Negative Bacterial Infections; Humans; Methicillin-Resistant Staphylococcus aureus; Staphylococcal Infections

Since its introduction in the 1950s, colistin has been used mainly as a topical treatment in human medicine owing to its toxicity when given systemically. Sixty years later, colistin is being used as a last-resort drug to treat infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa, Acinetobacter baumannii and Enterobacteriaceae (e.g., Escherichia coli, Klebsiella pneumoniae), for which mortality can be high. In veterinary medicine, colistin has been used for decades for the treatment and prevention of infectious diseases. Colistin has been administered frequently as a group treatment for animal gastrointestinal infections caused by Gram-negative bacteria within intensive husbandry systems. Given the ever-growing need to retain the efficacy of antimicrobials used to treat MDR infections in humans, the use of colistin in veterinary medicine is being re-evaluated. Despite extensive use in veterinary medicine, there is limited evidence for the development of resistance to colistin and no evidence has been found for the transmission of resistance in bacteria that have been spread from animals to humans. Since surveillance for colistin resistance in animals is limited and the potential for such transmission exists, there is a clear need to reinforce systematic monitoring of bacteria from food-producing animals for resistance to colistin (polymyxins). Furthermore, colistin should only be used for treatment of clinically affected animals and no longer for prophylaxis of diseases, in line with current principles of responsible use of antibiotics.

Topics: Acinetobacter baumannii; Animals; Anti-Bacterial Agents; Bacterial Infections; Chemoprevention; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; European Union; Humans; Pseudomonas aeruginosa

Teicoplanin and polymyxin E (colistin) are antibiotics consisting of multiple, closely related subcomponents, produced by fermentation. The principal components comprise a complex mixture of chemically related, active substances (teicoplanin A(2-1)-A(2-5) and polymyxin E(1-2), respectively), which might be required to be present in specific ratios to ensure optimal antibacterial and clinical efficacy. These subcomponents differ in their fatty acid and amino acid composition and, as such, the lipophilic and protein binding characteristics differ between components. This has therapeutic implications for critically ill patients, as the volume of distribution of the teicoplanin A2 and polymyxin E analogues at the onset of an intravenous infusion may impact on expected pharmacokinetics and influence outcome.

Topics: Amino Acids; Anti-Bacterial Agents; Bacterial Infections; Colistin; Complex Mixtures; Critical Illness; Drug Approval; Fatty Acids; Fermentation; Humans; Protein Binding; Solubility; Teicoplanin; Treatment Outcome

Colistin and polymyxin B have indistinguishable microbiological activity in vitro, but they differ in the form administered parenterally to patients. Polymyxin B is administered directly as the active antibiotic, whereas colistin is administered as the inactive prodrug, colistin methanesulfonate (CMS). CMS must be converted to colistin in vivo, but this occurs slowly and incompletely. Here we summarize the key differences between parenteral CMS/colistin and polymyxin B, and highlight the clinical implications. We put forth the view that overall polymyxin B has superior clinical pharmacological properties compared with CMS/colistin. We propose that in countries such as the United States where parenteral products of both colistin and polymyxin B are available, prospective studies should be conducted to formally examine their relative efficacy and safety in various types of infections and patients. In the meantime, where clinicians have access to both polymyxins, they should carefully consider the relative merits of each in a given circumstance.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Colistin; Humans; Polymyxin B

Topics: Anti-Bacterial Agents; Bacterial Infections; beta-Lactams; Biological Availability; Cephalosporins; Colistin; Cross Infection; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Fluoroquinolones; Half-Life; Humans; Infusions, Intravenous; Microbial Sensitivity Tests; Practice Patterns, Physicians'

Increased emergence of bacterial resistance and the decline in newly developed antibiotics have necessitated the reintroduction of previously abandoned antimicrobial agents active against multidrug-resistant bacteria. Having never been subjected to contemporary drug development procedures, these 'old' antibiotics require redevelopment in order to optimize therapy. This review focuses on colistin as an exemplar of a successful redevelopment process and briefly discusses two other old antibiotics, fusidic acid and fosfomycin.. Redevelopment of colistin led to an improved understanding of its chemistry, pharmacokinetics and pharmacodynamics, enabling important steps towards optimizing its clinical use in different patient populations. A scientifically based dosing algorithm was developed for critically ill patients, including those with renal impairment. As nephrotoxicity is a dose-limiting adverse event of colistin, rational combination therapy with other antibiotics needs to be investigated.. The example of colistin demonstrated that state-of-the-art analytical, microbiological and pharmacokinetic/pharmacodynamic methods can facilitate optimized use of 'old' antibiotics in the clinic. Similar methods are now being applied to fosfomycin and fusidic acid in order to optimize therapy. To improve and preserve the usefulness of these antibiotics rational approaches for redevelopment need to be followed.

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Humans

Although a worldwide increasing incidence of bacterial infections with panresistant pathogens may need innovative antiinfective agents, no breakthrough developments can be expected in the near future. As a consequence, well-tried antibiotics like aztreonam, fosfomycin and colistin, are experiencing a clinical revival, particularly if they are used in an improved manner. Even penicillin G with its narrow spectrum of antimicrobial activity remains an important considerable agent of first choice in special indications compared to broad spectrum antiinfectives.

Topics: Anti-Bacterial Agents; Aztreonam; Bacterial Infections; Colistin; Fosfomycin; Humans; Kidney Diseases; Penicillin G

The increasing incidence of multidrug-resistant (MDR) Gram-negative infections necessitates the use of neglected antibiotics such as colistin, even in the paediatric field. The objective of this review was to evaluate the available clinical evidence regarding the effectiveness and safety of systemic colistin in children without cystic fibrosis (CF). Relevant articles were identified from PubMed, Cochrane and Scopus databases. Ten case series and fifteen case reports, including a total of 370 children, were eligible for inclusion in this systematic review. Only 17 of the children were included in studies published after 1977. A total of 326 children received colistin for the treatment of infections and 44 for surgical prophylaxis or prophylaxis of infections in burns patients. Regarding the clinical outcome, 271 of 311 children included in the identified cases series were evaluable. From these 271 children, 235 (86.7%) were cured of the infection, 10/271 (3.7%) improved, 6/271 (2.2%) deteriorated and 20/271 (7.4%) died. Fourteen (70%) of the 20 deaths were attributed to the infection. No infection occurred in the 44 reported children with burns or surgical morbidity who received colistin for prophylaxis. Of these 44 children, 9 (20.5%) died; all deaths were attributed to co-morbidity. Nephrotoxicity occurred in 10/355 (2.8%) of the evaluable children in cases series included in this review. Most of the identified relevant case reports focused on treatment complications. The available evidence, mainly from old case series, suggests that systemic colistin is an effective and acceptably safe option for the treatment of children without CF who have MDR Gram-negative infections.

Topics: Adolescent; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Colistin; Female; Humans; Infant; Infant, Newborn; Infusions, Intravenous; Kidney; Male; Treatment Outcome

Despite the constantly increasing need for new antimicrobial agents, antibiotic drug discovery and development seem to have greatly decelerated in recent years. Presented with the significant problem of advancing antimicrobial resistance, the global scientific community has attempted to find alternative solutions; one of the most promising ones is the evaluation and use of old antibiotic compounds. Due to the low-level use of many of the old antibiotic compounds, these have remained active against a large number of currently prevalent bacterial isolates. Thus, clinicians are beginning to re-evaluate their use in various patient populations and infections, despite the fact that they were previously thought to be less effective and/or more toxic than newer agents. A number of old antibiotic compounds, such as polymyxins, fosfomycin, fusidic acid, cotrimoxazole, aminoglycosides and chloramphenicol, are re-emerging as valuable alternatives for the treatment of difficult-to-treat infections. The availability of novel genetic and molecular modification methods provides hope that the toxicity and efficacy drawbacks presented by some of these agents can be surpassed in the future.

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacterial Infections; Chloramphenicol; Colistin; Drug Resistance, Bacterial; Drug Utilization; Fosfomycin; Fusidic Acid; Humans; Trimethoprim, Sulfamethoxazole Drug Combination

Selective decontamination of the digestive tract (SDD) is a strategy designed to prevent or minimize the impact of infections by potentially pathogenic micro-organisms in critically ill patients requiring long-term mechanical ventilation. SDD is a four-component protocol to control the three types of infections occurring in intensive care patients: (a) a parenteral antibiotic, cefotaxime, for a few days to prevent primary endogenous infections that generally occur 'early'; (b) the topical antimicrobial drugs colistine (polymyxin E), tobramycin and amphotericin B (together: PTA) used throughout the stay in the intensive care unit (ICU) to prevent secondary endogenous infections developing in general 'late'; (c) a high standard of hygiene to prevent exogenous infections that may occur throughout the ICU stay; (d) surveillance samples of throat and rectum to distinguish between the three types of infection, to monitor compliance and efficacy of treatment and to detect emergence of resistance at an early stage. The most recent and rigorous meta-analysis examined 33 randomized SDD trials involving 5727 patients. It shows significant reductions, in overall mortality by 20% and in the incidence of lower airway infections by 65%. It failed to detect any report on the emergence of resistance and associated superinfections and/or out-breaks in the 33 studies covering a period of more than 10 years. Using the criterion of cost-per-survivor, four recent randomised trials showed that it is cheaper to produce a survivor using SDD than with the traditional approach.

Topics: Amphotericin B; Bacterial Infections; Cefotaxime; Clinical Protocols; Colistin; Critical Care; Critical Illness; Cross Infection; Decontamination; Digestive System; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Male; Survival Rate; Tobramycin

Several prospectively randomized trials have shown that the administration of prophylactic oral nonabsorbable antibiotics may be beneficial in decreasing the incidence of infection in granulocytopenic patients, whereas others have not. Intolerable nausea and vomiting have prevented the prolonged use of these agents in some studies. Discontinuation of therapy while patients are still granulocytopenic has carried the risk of life-threatening infections, often with aminoglycoside-resistant gram-negative organisms. The benefit of selective decontamination with trimethoprim/sulfamethoxazole used prophylactically remains controversial. The use of trimethoprim/sulfamethoxazole may also be associated with the development of resistant, potentially pathogenic, organisms or prolonged neutropenia. These regimens do not appear to be indicated when patients are anticipated to be neutropenic for less than three weeks. Even in patients with prolonged neutropenia, the risks of such treatment must be weighed against potential benefits.

Topics: Acute Disease; Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Colistin; Drug Combinations; Environment, Controlled; Gentamicins; Humans; Leukemia; Neoplasms; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

Topics: Bacteria; Bacterial Infections; Colistin; Humans; Kinetics; Polymyxin B; Polymyxins

Bacterial diseases of the central nervous system develop per continuitatem of haematogenically. Each of these two groups can further be subdivided. As an initial therapy when an unknown agent is present chloramphenicol in high doses (200 mg/kg KM) stood the test for adults and older children and ampicillin (200 to 400 mg/kg KM), respectively, for babies and infants. In case of need, this therapy is correlated according to the findings of the culture and the antibiogramme. In secondary meningitides the surgical cure of the focus should be performed only after improvement of the general condition. Recidivating meningitides undergo an operation when liquor fistulae are proved. In an unclarified cause a long-term therapy with oxacillin or lincomycin over 3-6 months is possible. In the meningitis of newborn the combination of ampicillin, carbenicillin or colistin with gentamycin is necessary, intravenously and intrathecally. Hydrocortisone and streptokinase shall prevent the transfer of the liquor spaces. Of great importance is the combat against the cerebral oedema. In mycetogenous meningitis amphotericin B, eventually in combination with 5-fluorocytosine, can be used. There are still no effective remedies against the amoebic meningo-encephalitis.

Topics: Ampicillin; Bacterial Infections; Carbenicillin; Chloramphenicol; Colistin; Drug Therapy; Encephalitis; Humans; Injections, Intravenous; Injections, Spinal; Lincomycin; Meningitis; Oxacillin

Topics: Anti-Bacterial Agents; Antifungal Agents; Bacteria; Bacterial Infections; Cephalosporins; Chemical Phenomena; Chemistry; Chloramphenicol; Colistin; DNA Replication; Gentamicins; Humans; Kanamycin; Mesylates; Natamycin; Neomycin; Penicillins; Polymyxins; Streptomycin; Tetracycline

Topics: Aerosols; Airway Obstruction; Anti-Bacterial Agents; Asthma; Bacteria; Bacterial Infections; Beclomethasone; Carbenicillin; Child; Clinical Trials as Topic; Colistin; Corticosterone; Dexamethasone; Gentamicins; Humans; Hydrocortisone; Kanamycin; Lung Diseases, Fungal; Placebos; Polymyxins; Respiratory Therapy; Triamcinolone Acetonide

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

The β-lactamase inhibitor relebactam can restore imipenem activity against imipenem-nonsusceptible gram-negative pathogens. We evaluated imipenem/relebactam for treating imipenem-nonsusceptible infections.. Randomized, controlled, double-blind, phase 3 trial. Hospitalized patients with hospital-acquired/ventilator-associated pneumonia, complicated intraabdominal infection, or complicated urinary tract infection caused by imipenem-nonsusceptible (but colistin- and imipenem/relebactam-susceptible) pathogens were randomized 2:1 to 5-21 days imipenem/relebactam or colistin+imipenem. Primary endpoint: favorable overall response (defined by relevant endpoints for each infection type) in the modified microbiologic intent-to-treat (mMITT) population (qualifying baseline pathogen and ≥1 dose study treatment). Secondary endpoints: clinical response, all-cause mortality, and treatment-emergent nephrotoxicity. Safety analyses included patients with ≥1 dose study treatment.. Thirty-one patients received imipenem/relebactam and 16 colistin+imipenem. Among mITT patients (n = 21 imipenem/relebactam, n = 10 colistin+imipenem), 29% had Acute Physiology and Chronic Health Evaluation II scores >15, 23% had creatinine clearance <60 mL/min, and 35% were aged ≥65 years. Qualifying baseline pathogens: Pseudomonas aeruginosa (77%), Klebsiella spp. (16%), other Enterobacteriaceae (6%). Favorable overall response was observed in 71% imipenem/relebactam and 70% colistin+imipenem patients (90% confidence interval [CI] for difference, -27.5, 21.4), day 28 favorable clinical response in 71% and 40% (90% CI, 1.3, 51.5), and 28-day mortality in 10% and 30% (90% CI, -46.4, 6.7), respectively. Serious adverse events (AEs) occurred in 10% of imipenem/relebactam and 31% of colistin+imipenem patients, drug-related AEs in 16% and 31% (no drug-related deaths), and treatment-emergent nephrotoxicity in 10% and 56% (P = .002), respectively.. Imipenem/relebactam is an efficacious and well-tolerated treatment option for carbapenem-nonsusceptible infections.. NCT02452047.

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Infections; Colistin; Humans; Imipenem; Microbial Sensitivity Tests

Following a 2-year study, the combination of oral ciprofloxacin and colistin has been used continuously for 10 years without the emergence of resistance. During a 2-year period (1987-1989), we compared ciprofloxacin + colistin (CIP + COL) with neomycin + colistin (NEO + COL) in a randomized trial--combinations chosen because of the potential for prophylaxis of Gram-negative infection by ciprofloxacin, with colistin given to reduce the risk of emergence of resistance. Sixty-four patients with similar demographics in each arm were evaluable for efficacy analysis. Patients on CIP + COL had a significantly lower proportion of neutropenic days with fever (P < 0.001) and neutropenic days on intravenous antibiotics (P < 0.001) than patients on NEO + COL. A total of 54 (15 bacteriologically documented) pyrexial episodes occurred in patients on CIP + COL and 77 (41 bacteriologically documented) in patients on NEO + COL. Only two Gram-negative bacterial infections occurred in the CIP + COL arm compared with 16 in the NEO + COL arm. No Staphylococcus aureus infections occurred in the CIP + COL group compared with 10 in the other patients. Two CIP-resistant Gram-negative bacilli were isolated from patients on CIP + COL compared with 13 NEO-resistant Gram-negative bacilli from patients on NEO + COL. Following a subsequent decade of unchanged use of this prophylactic strategy in neutropenic patients, a 2-year follow-up study between 1 January 1998 and 31 December 1999 showed 66 significant infections during 700 [corrected] neutropenic episodes. Thirty-five of the 111 (31%) isolates were ciprofloxacin-resistant, involving 5% of the neutropenic episodes [corrected].

Topics: Adolescent; Adult; Aged; Antibiotic Prophylaxis; Bacterial Infections; Bone Marrow Transplantation; Ciprofloxacin; Colistin; Drug Therapy, Combination; Humans; Middle Aged; Neomycin; Neutropenia; Statistics, Nonparametric; Transplantation Conditioning; Treatment Outcome

Nonabsorbable antibiotics for selective bowel decontamination (SBD) sometimes are administered to liver transplant patients to prevent postoperative infections, but the efficacy of SBD is not known. Accordingly, we prospectively studied 69 patients randomly assigned to receive conventional prophylaxis with systemic antibiotics (control patients) or conventional prophylaxis plus oral nonabsorbable antibiotics for SBD (SBD patients). Overall rates of bacterial and/or yeast infections were nearly equal among control patients (42%) and SBD patients (39%). However, the infection rate at SBD key sites (abdomen, bloodstream, surgical wound, and lungs) was lower among patients who received the SBD regimen > or = 3 days before transplantation (23%) than among control patients (36%). Administration of the SBD regimen was complicated by gastrointestinal intolerance and noncompliance but not by increased stool colonization with antibiotic-resistant gram-negative bacilli. Practical problems associated with administering an SBD regimen to patients awaiting cadaver liver transplants limit the regimen's usefulness, but we found a trend toward reduced key site infection when the regimen was given > or = 3 days before transplantation.

Topics: Ampicillin; Anti-Bacterial Agents; Antibiotic Prophylaxis; Bacterial Infections; Cefotaxime; Colistin; Drug Administration Schedule; Evaluation Studies as Topic; Feces; Female; Gentamicins; Humans; Intestines; Liver Transplantation; Male; Mycoses; Nystatin; Risk Factors; Treatment Outcome

To evaluate the efficacy of the technique of selective decontamination of the digestive tract in preventing the development of secondary infection and its influence on morbidity and mortality rates in multiple trauma patients with chest injuries requiring intermittent positive-pressure ventilation.. Prospective, double-blind, randomized study.. A multidisciplinary respiratory intensive care unit (ICU) in a 1,500-bed teaching hospital.. Seventy-two patients (mean Injury Severity Score of 29.5) who were intubated for > 48 hrs and remained in the ICU for > 5 days.. Patients were randomized on admission to receive selective decontamination therapy or placebo. All patients received intravenous cefotaxime for 72 hrs and the treatment group received oral and enteral selective decontamination with amphotericin B, polymyxin E, and tobramycin (n = 39), while the placebo group received a placebo containing oral paste and enteral solution (n = 33).. Secondary infection was determined clinically and microbiologically and surveillance cultures were monitored for gastrointestinal colonization.. The patient groups were fully comparable for age, severity of illness, and compromising factors. There was no difference in the number of patients infected (11 treatment group vs. 11 placebo), infections (17 vs. 16) and deaths (5 vs. 3); the duration of ICU (15.5 vs. 14.2 days) and hospital stays (26.3 vs. 25.5) were also similar. Microbiological surveillance cultures confirmed effective elimination of aerobic Gram-negative bacilli, and infections in the treatment group were largely due to Staphylococcus aureus and Staphylococcus epidermidis.. We have been unable to show any benefit from the use of selective decontamination of the digestive tract in the prevention of secondary infections in multiple trauma patients.

Topics: Adult; Amphotericin B; Bacterial Infections; Colistin; Double-Blind Method; Gastrointestinal Diseases; Humans; Injury Severity Score; Intensive Care Units; Intubation, Intratracheal; Length of Stay; Multiple Trauma; Prospective Studies; Tobramycin

To investigate whether selective intestinal decontamination from oral administration of poorly absorbable antibiotics is effective in preventing bacterial infection in patients with acute liver failure, the incidence of nosocomial infection in 34 patients consecutively admitted to hospital between 1985-1990 and treated with either neomycin + colistin + nystatin or norfloxacin + nystatin (group I) was compared to the incidence of infection in 57 patients who did not receive oral, poorly absorbable antibiotics and who were consecutively admitted between 1972-1984 (group II). Patients from groups I and II had similar clinical and laboratory data at hospital admission. Twelve patients from group I and 33 from group II developed bacterial infection during the study period. The probability of infection was significantly different (p = 0.0083) in the two groups: 19% vs. 39% at the 3rd day of admission, 33% vs. 74% at the 7th day, and 48% vs. 78% at the 14th day, respectively. This difference was due to a different rate of infection from enterobacteria. Enterobacteria caused one infectious episode in group I and 24 in group II (p less than 0.001). The incidence of infections caused by other organisms, however, was similar in both groups (15 and 19 episodes, respectively). These results suggest that selective intestinal decontamination is useful in reducing the risk of infection from enterobacteria in patients with acute liver failure.

Topics: Adult; Bacterial Infections; Colistin; Enterobacteriaceae; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Hepatic Encephalopathy; Humans; Liver Diseases; Male; Neomycin; Norfloxacin; Nystatin; Pregnancy

To test the value of pefloxacin for the prevention of infections in patients with chemotherapy-induced neutropenia, oral pefloxacin plus vancomycin (PV) (n = 76) or gentamicin, colistin sulphate and vancomycin (GCV) (n = 74) were administered in a randomised double-blind study. Infections were significantly less severe in the PV than in the GCV group. Patients receiving PV had significantly fewer episodes of bacteraemia and central venous line infections than patients treated with GCV. Gram-positive and gram-negative infections were significantly less frequent in patients receiving PV, because of fewer infections with Staphylococcus species and enterobacteriaceae. Stool culture detected significantly more gram-positive organisms in the PV group and more gram-negative organisms in the GCV group. Thus, PV was more efficacious than GCV for the prevention of gram-positive and gram-negative infections in the neutropenic patients, despite lower efficacy in eradicating gram-positive organisms from the lower intestinal tract.

Topics: Adult; Aged; Antineoplastic Agents; Bacterial Infections; Colistin; Double-Blind Method; Drug Therapy, Combination; Female; Gentamicins; Humans; Male; Middle Aged; Neutropenia; Pefloxacin; Vancomycin

In a prospective randomised study, the effects of two different colonisation prophylaxis techniques on colonisation and pulmonary infection were investigated in 40 critically ill patients with long-term ventilatory support (greater than or equal to 4 days). 20 patients were selectively decontaminated with 4 x 100 g polymyxin E, 4 x 80 mg tobramycin and 4 x 500 mg amphotericin B, administered through the gastric tube and with an antimicrobial sticky paste in the oropharynx (group I). 20 patients received 50 mg of polymyxin B and 80 mg of gentamicin dissolved in 10 ml of 0.9% saline at 6 h intervals into nose, oropharynx and stomach as well as 300 mg of amphotericin B in the oropharynx only (group II). All patients received cefotaxime systemically in the first 3 days. In group I gram-negative aerobic bacteria in the pharynx decreased from 35% to 0%, in group II from 40% to 10% and in the rectum from 80% to 61% (10% in the second week) in Group I and from 100% to 73% (33% in the second week) in group II. The decrease in gram-negative microorganisms was accompanied by an increase in the frequency of Staphylococcus epidermidis. In group I, two patients developed pneumonia and two patients urinary tract infections, in group II two patients suffered from pneumonia and 3 patients urinary tract infections. Both regimes are effective methods of prophylaxis for lowering colonisation with gram-negative aerobic bacteria and the frequency of pneumonia in patients requiring long-term mechanical ventilation. A possible selection of gram-positive bacteria must be appropriately monitored.

Topics: Adult; Aged; Aged, 80 and over; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Cefotaxime; Colistin; Critical Care; Female; Gentamicins; Humans; Male; Middle Aged; Pneumonia; Polymyxin B; Prospective Studies; Respiration, Artificial; Time Factors; Tobramycin

To study the effect of enterally administered polymyxin E, tobramycin, and amphotericin B (selective flora suppression) on bacterial colonization, infection, resistance, and mortality rate.. Prospective, consecutive crossover controlled study.. Two surgical ICUs in a university hospital; ICU I with ten beds, ICU II with eight beds.. Two hundred patients entered the 1-yr trial. Fifty of 111 patients received selective flora suppression during the first 6 months in ICU I (test group), while 61 of 111 patients served as the control group in the following 6 months. In ICU II, 49 of 89 patients received no selective flora suppression in the first 6 months (control group), followed by 40 of 89 patients receiving selective flora suppression during the second 6-month period (test group).. The test group got a mixture of nonabsorbable antibiotics (paste and suspension) in the digestive tract. The control group received paste and suspension without antimicrobial agents. All 200 patients received cefotaxime during the first 4 days.. With the use of selective flora suppression, colonization with aerobic Gram-negative bacilli was significantly (p less than .01) reduced. There was also a significant reduction in nosocomial bronchopulmonary (ICU I and II; p less than .001) and urinary tract (ICU II; p less than .001) infections. The difference in mortality was not significant. There was no development of resistance against the antibiotics used during the limited period evaluated.. Selective flora suppression is effective in reducing secondary colonization by aerobic Gram-negative bacilli. Reduction of bronchopulmonary and urinary tract infections most likely occurs with colonization prevention.

Topics: Administration, Oral; Adult; Aged; Amphotericin B; Bacterial Infections; Bronchopneumonia; Colistin; Critical Care; Cross Infection; Female; Gram-Negative Aerobic Bacteria; Humans; Intensive Care Units; Male; Middle Aged; Mortality; Mouth; Ointments; Prospective Studies; Sepsis; Suspensions; Tobramycin; Urinary Tract Infections

Preliminary results are presented of an ongoing, prospective, randomized, study comparing ofloxacin, ciprofloxacin and co-trimoxazole/colistin for the prevention of infection in patients with acute leukaemia. The results for 59 patients (median age 47 years, range 21-72) included 88 episodes of neutropenia, each associated with a course of cytotoxic therapy. The main factor measured was the time elapsed from the beginning of neutropenia (neutrophils less than 500/microliter) until the first infectious febrile episode. The median time for the period was 12 days (range 1-56) for the cotrimoxazole/colistin group, 15 days (range 1-38) for the ofloxacin group and 20 days (range 1-36) for the ciprofloxacin group (differences not significant). Microbiologically proven major infections occurred in 10/27 treatment courses with co-trimoxazole/colistin 7/31 courses with ofloxacin and 7/30 courses with ciprofloxacin (P not significant). These were mostly due to Gram-positive cocci. There were no Gram-negative infections in the quinolone groups compared with one major Pseudomonas aeruginosa infection in the co-trimoxazole/colistin group. No Pneumocystis carinii infections were encountered. Adverse reactions associated with co-trimoxazole/colistin required discontinuation of medication in 11/27 treatment courses because of compliance problems, skin reactions or gastrointestinal intolerance. There were significantly fewer discontinuations in the ofloxacin (n = 2) and in the ciprofloxacin groups (n = 3). Major side effects of the quinolones included persistent icterus in one patient receiving ofloxacin and psychiatric symptoms in one patient receiving ciprofloxacin. It is concluded from these data that there were no statistically significant differences between the three treatment groups in respect of the prevention of infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Bacterial Infections; Ciprofloxacin; Colistin; Humans; Neutropenia; Ofloxacin; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Trimethoprim, Sulfamethoxazole Drug Combination

Pipemidic acid (PPA) and colistin sodium methanesulfonate (CLM) may selectively suppress aerobic gram-negative bacilli. Twenty-nine patients with acute leukemia were randomized after each course of consolidation chemotherapy to receive a single agent of nystatin (NYS) (34 courses) versus a combination of NYS, PPA and CLM (36 courses). The duration of fever over 39 degrees C was longer with the three drug combination (4.6 +/- 5.1 days) than with NYS alone (1.8 +/- 1.8 days) (P less than 0.01). Four cases of pneumonia occurred and four patients including one having pneumonia died of infection with the three drug combination, while no pneumonia or death occurred with NYS alone (P = 0.06 and P = 0.06, respectively). The combination of NYS, PPA and CLM may be less effective than NYS alone for the prevention of infection in acute leukemia patients with chemotherapy-associated granulocytopenia.

Topics: Acute Disease; Adolescent; Adult; Agranulocytosis; Antineoplastic Combined Chemotherapy Protocols; Bacterial Infections; Colistin; Drug Therapy, Combination; Gram-Negative Bacteria; Humans; Leukemia; Middle Aged; Nicotinic Acids; Nystatin; Pipemidic Acid; Pneumonia; Random Allocation

The question to be answered in this study was: Is prophylactic selective florasuppression advantageous compared to conventional antibiotic policy as far as microbial colonisation, infection, mortality and development of resistance are concerned? A prospective, consecutive, placebo-controlled study in two ICU's was carried out during four 6-months periods. 200 patients who were intubated for at least 3 days, required intensive care for a minimum of 5 days, and belonged to either class III or IV according to the "Therapeutic Intervention Scoring System" were included in the study. They received either placebo or the prophylaxis regimen described by Stoutenbeek et al., consisting of polymyxin E, tobramycin and amphotericin B. Oropharyngeal, tracheobronchial and rectal colonisation with aerobic gram-negative bacilli markedly decreased in the test groups. The rates of nosocomial bronchopulmonary infections (ICU I and II) and urinary tract infections (ICU II) were significantly reduced. There was no significant reduction in wound infection, septicaemia and mortality rates. No development of resistance and no increase of multi-resistant strains occurred. Selective florasuppression is effective in reducing infection rates in critically ill patients without development of resistant strains.

Topics: Adult; Aged; Amphotericin B; Bacterial Infections; Bronchopneumonia; Clinical Trials as Topic; Colistin; Cross Infection; Drug Therapy, Combination; Female; Humans; Intensive Care Units; Male; Prospective Studies; Risk Factors; Sepsis; Surgical Wound Infection; Tobramycin; Urinary Tract Infections

Norfloxacin has been compared to placebo (136 patients), sulfamethoxazole plus trimethoprim (SXT, 72 patients) and oral vancomycin plus colistin (V/C, 61 patients) for the prevention of alimentary tract-associated infections during and after induction chemotherapy. These patients were evaluated for the safety and tolerability of each regimen by clinical and laboratory means. Most neutropenics involved, regardless of the regimen, experienced at least one adverse experience. The majority were felt to be unrelated to prophylactic study drug therapy. Of 139 patients who received norfloxacin, only two had drug-related adverse experiences, compared to two of 35 receiving SXT, five of 28 for VC, and none of 67 receiving placebo. In evaluating adverse experiences considered possibly drug related, 19 occurred on norfloxacin compared to 13 for placebo. Among neurologic adverse experiences, only one possibly related to norfloxacin occurred (confusion), while three occurred on placebo (confusion, decreased auditory acuity and hallucinations). Generally, no significant differences were seen between any of the regimens except for a higher frequency of diarrhea in those receiving V/C.

Topics: Agranulocytosis; Bacterial Infections; Clinical Trials as Topic; Colistin; Diarrhea; Gastrointestinal Diseases; Humans; Leukemia; Neutropenia; Norfloxacin; Skin Diseases; Sulfamethoxazole; Trimethoprim; Vancomycin

Ciprofloxacin, a new quinolone derivative, was given prophylactically (500 mg twice daily) to 15 patients with acute leukemia during remission induction treatment. The effect on the microbial flora of the alimentary tract was evaluated. A rapid elimination of Enterobacteriaceae was observed. Bacteriodes and Clostridium species were not affected. Few ciprofloxacin resistant strains were isolated but did not lead to colonization. In a randomized study 56 patients with acute leukemia received either ciprofloxacin or trimethoprim-sulfamethoxazole plus colistin for prevention of infections. Six major infections occurred in 28 patients receiving ciprofloxacin, and 11 major infections in 28 patients receiving trimethoprim-sulfamethoxazole plus colistin. No infections caused by Gram-negative bacilli were seen in the ciprofloxacin group compared to 17 in the other group (p less than 0.02). Ciprofloxacin prevented colonization with resistant Gram-negative bacilli while 12 resistant colonizing strains were isolated from 10 patients receiving trimethoprim-sulfamethoxazole (p less than 0.01). Ciprofloxacin was better tolerated than trimethoprim-sulfamethoxazole + colistin; fewer side effects occurred.

Topics: Adult; Bacterial Infections; Ciprofloxacin; Clinical Trials as Topic; Colistin; Drug Combinations; Drug Therapy, Combination; Humans; Leukemia; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Fifty-six patients receiving remission induction treatment for acute leukemia were studied in a randomized trial comparing ciprofloxacin with trimethoprim-sulfamethoxazole plus colistin for prevention of infections. Both groups received amphotericin B for antifungal prophylaxis. Six major infections occurred in 28 patients receiving ciprofloxacin, and 11 major infections occurred in 28 patients receiving trimethoprim-sulfamethoxazole plus colistin. No infections caused by gram-negative bacilli were seen in the ciprofloxacin group (p less than 0.02). Ciprofloxacin prevented colonization with resistant gram-negative bacilli, but 12 resistant colonizing strains were isolated from 10 patients receiving trimethoprim-sulfamethoxazole plus colistin (p less than 0.01). Ciprofloxacin was better tolerated: 23 of 28 patients were highly compliant to the drug, compared with 15 of 28 patients in the trimethoprim-sulfamethoxazole group (p less than 0.05). These results suggest that ciprofloxacin is a promising drug for the prevention of infection in patients with granulocytopenia.

Topics: Acute Disease; Agranulocytosis; Bacterial Infections; Ciprofloxacin; Colistin; Drug Combinations; Drug Resistance, Microbial; Humans; Leukemia; Leukemia, Lymphoid; Patient Compliance; Random Allocation; Sulfamethizole; Sulfathiazoles; Trimethoprim

Several prospectively randomized trials have shown that the administration of prophylactic oral nonabsorbable antibiotics may be beneficial in decreasing the incidence of infection in granulocytopenic patients, whereas others have not. Intolerable nausea and vomiting have prevented the prolonged use of these agents in some studies. Discontinuation of therapy while patients are still granulocytopenic has carried the risk of life-threatening infections, often with aminoglycoside-resistant gram-negative organisms. The benefit of selective decontamination with trimethoprim/sulfamethoxazole used prophylactically remains controversial. The use of trimethoprim/sulfamethoxazole may also be associated with the development of resistant, potentially pathogenic, organisms or prolonged neutropenia. These regimens do not appear to be indicated when patients are anticipated to be neutropenic for less than three weeks. Even in patients with prolonged neutropenia, the risks of such treatment must be weighed against potential benefits.

Topics: Acute Disease; Agranulocytosis; Anti-Bacterial Agents; Bacterial Infections; Clinical Trials as Topic; Colistin; Drug Combinations; Environment, Controlled; Gentamicins; Humans; Leukemia; Neoplasms; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination; Vancomycin

43 patients undergoing treatment for acute leukaemia were randomised to receive either co-trimoxazole alone or co-trimoxazole with framycetin and colistin as antibacterial prophylaxis during periods of neutropenia. There were no significant differences between the two treatment groups in the time before the onset of the first fever, the number of episodes of fever or of septicaemia per patient, the number of neutropenic days during which patients remained afebrile or did not require systemic antibiotics, or the number of resistant organisms acquired. Co-trimoxazole alone is cheaper and easier to take than co-trimoxazole with framycetin and colistin, and it is therefore preferable to the three-drug combination for the prophylaxis of bacterial infection.

Topics: Acute Disease; Adult; Aged; Bacterial Infections; Clinical Trials as Topic; Colistin; Drug Combinations; Drug Therapy, Combination; Female; Framycetin; Humans; Leukemia; Male; Middle Aged; Neutropenia; Random Allocation; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

This study was designed to compare the efficacy and safety of gentamicin otic solution versus colistin-neomycin-hydrocortisone otic suspension in the treatment of otorrhoea due to infection. Fifty-five patients (mean age 36.6 +/- 22.1 years) with sixty infected ears with otorrhoea complicating otitis externa, recurrent otitis media with tympanic membrane perforation, or infected mastoid cavities and post-operative tympanoplasties, were treated for 14 days with either an aqueous solution of gentamicin 0.3% or an aqueous suspension of colistin 0.3%, neomycin 0.33% and hydrocortisone 1.0%. The two possible treatments were assigned randomly and the results were assessed double-blind using usual ordinal scales for monitoring the severity of symptoms. Both otic preparations were found to be equally safe in the treatment of otorrhoea due to infection. No side-effects were observed and hearing status was either unchanged or improved. The antibiotic-steroid combination appeared to be more effective in relieving inflammation in a shorter period of time while gentamicin was observed to be more effective in eradicating the infecting organisms.

Topics: Adult; Bacterial Infections; Chronic Disease; Clinical Trials as Topic; Colistin; Double-Blind Method; Gentamicins; Hearing; Humans; Hydrocortisone; Neomycin; Otitis; Otitis Externa; Otitis Media; Tympanoplasty

A randomized study of intestinal decontamination was undertaken in 68 children with leukemia and solid tumours. Framycetin, colymycin, nystatin, and metronidazole were given in 35 neutropenic episodes in 33 children, while co-trimoxazole and lactobacilli preparation were administered in 35 episodes in 35 children. The diseases, severity of neutropenia, and incidence of infection at entry into study were comparable in the two groups. There was no significant difference in the incidence of infections developing during the phase of neutropenia. The median and range of time required to recover from neutropenia were also not different. Co-trimoxazole and lactobacilli were significantly better tolerated, there being no nausea and vomiting, no refusal to take medication, no dose reduction or change to an alternative regimen. We conclude that co-trimoxazole and lactobacilli preparation improve quality of life during a neutropenic episode and have the additional advantage of being relatively inexpensive.

Topics: Agranulocytosis; Anti-Bacterial Agents; Antifungal Agents; Bacterial Infections; Biological Products; Child; Child, Preschool; Colistin; Drug Combinations; Framycetin; Humans; Lactobacillus; Neoplasms; Neutropenia; Nystatin; Sulfamethoxazole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

113 patients being treated for acute non-lymphoblastic leukaemia were investigated to determine the effect of suppression of body microbial flora on prevention of infection. They were randomly allocated to a control group or a group which received non-absorbed antibiotics by mouth and topical applications of cutaneous and mucosal antiseptic preparations. The group receiving oral non-absorbed antibiotics had significantly few infections, fewer deaths from infection, fewer pyrexial episodes, and consequently received less systemic antibiotic therapy than the controls.

Topics: Acute Disease; Administration, Oral; Administration, Topical; Adolescent; Adult; Antineoplastic Agents; Bacterial Infections; Bacteroides Infections; Chlorhexidine; Colistin; Drug Combinations; Enterobacteriaceae Infections; Framycetin; Humans; Leukemia; Nystatin; Remission, Spontaneous; Sepsis; Staphylococcal Infections; Staphylococcus aureus; Streptococcal Infections

Topics: Aerosols; Airway Obstruction; Anti-Bacterial Agents; Asthma; Bacteria; Bacterial Infections; Beclomethasone; Carbenicillin; Child; Clinical Trials as Topic; Colistin; Corticosterone; Dexamethasone; Gentamicins; Humans; Hydrocortisone; Kanamycin; Lung Diseases, Fungal; Placebos; Polymyxins; Respiratory Therapy; Triamcinolone Acetonide

Topics: Anti-Bacterial Agents; Bacterial Infections; Blast Injuries; Chloramphenicol; Colistin; Conjunctiva; Corneal Injuries; Drug Combinations; Ethnicity; Eye Diseases; Eye Foreign Bodies; Eye Injuries; Humans; Injections; Military Medicine; Sclera; Soil Microbiology; United States; Vietnam; Wound Infection

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Humans; Organ Transplantation; Transplant Recipients

Compared to parenteral administration of colistin, its direct pulmonary administration can maximize lung drug deposition while reducing systemic adverse side effects and derived nephrotoxicity. Current pulmonary administration of colistin is carried out by the aerosolization of a prodrug, colistin methanesulfonate (CMS), which must be hydrolized to colistin in the lung to produce its bactericidal effect. However, this conversion is slow relative to the rate of absorption of CMS, and thus only 1.4 % (w/w) of the CMS dose is converted to colistin in the lungs of patients receiving inhaled CMS. We synthesized several aerosolizable nanoparticle carriers loaded with colistin using different techniques and selected particles with sufficient drug loading and adequate aerodynamic behavior to efficiently deliver colistin to the entire lung. Specifically, we carried out (i) the encapsulation of colistin by single emulsion-solvent evaporation with immiscible solvents using polylactic-co-glycolic (PLGA) nanoparticles; (ii) its encapsulation using nanoprecipitation with miscible solvents using poly(lactide-co-glycolide)-block-poly(ethylene glycol) as encapsulating matrix; (iii) colistin nanoprecipitation using the antisolvent precipitation method and its subsequent encapsulation within PLGA nanoparticles; and (iv) colistin encapsulation within PLGA-based microparticles using electrospraying. Nanoprecipitation of pure colistin using antisolvent precipitation showed the highest drug loading (55.0 ± 4.8 wt%) and spontaneously formed aggregates with adequate aerodynamic diameter (between 3 and 5 μm) to potentially reach the entire lung. These nanoparticles were able to completely eradicate Pseudomonas aeruginosa in an in vitro lung biofilm model at 10 µg/mL (MBC). This formulation could be a promising alternative for the treatment of pulmonary infections improving lung deposition and, therefore, the efficacy of aerosolized antibiotics.

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Drug Carriers; Humans; Nanoparticles; Particle Size; Respiratory Tract Infections; Solvents

Antimicrobial peptides (AMPs) offer a promising solution to the antibiotic resistance crisis. However, an unresolved serious concern is that the evolution of resistance to therapeutic AMPs may generate cross-resistance to host AMPs, compromising a cornerstone of the innate immune response. We systematically tested this hypothesis using globally disseminated mobile colistin resistance (MCR) that has been selected by the use of colistin in agriculture and medicine. Here, we show that MCR provides a selective advantage to

Topics: Animals; Anti-Bacterial Agents; Antimicrobial Peptides; Bacterial Infections; Colistin; Drug Resistance, Bacterial; Escherichia coli; Escherichia coli Proteins; Humans; Microbial Sensitivity Tests; Plasmids; Virulence

Antimicrobial resistance endangers the successful combat of bacterial infections in humans and animals. The common use of antibiotic classes including those of high clinical value in human as well as veterinary medicine is a critical factor contributing to or suspected to promote the emergence of antibiotic resistance. New legal provisions laid down in veterinary drug legislations and related guidelines and advice are in force in the European Union to safeguard the effectiveness, accessibility and availability of antibiotics. Categorisation of antibiotics in classes of importance for treatment of infections of humans by the WHO was one of the first steps. This task is also undertaken for antibiotics for treatment of animals by the EMA's Antimicrobial Advice Ad Hoc Expert Group. The new veterinary Regulation (EU) 2019/6 has extended restrictions for use of some antibiotics in animals to a full ban of certain antibiotics. While some (but not all) antibiotic compounds not being authorized in veterinary medicine may still be used in companion animals more strict provisions were already applicable for treatment of food producing animal species. Distinct regulations are in place for the treatment of animals kept in large numbers in flocks. Initial regulations focussed on the protection of consumers from residues of veterinary drugs in food commodities, new regulations address prudent (not routinely) and responsible selection, prescription and use of antibiotics, and have improved the practicality for cascade use outside the terms of marketing authorisation. Mandatory recording of use of veterinary medicinal products for food safety reasons is extended to rules for veterinarians and owners or holders of animals to regularly report the use of antibiotics for the purpose of official surveillance of consumption. National sales data of antibiotic veterinary medicinal products have been collected on a voluntary basis until 2022 by ESVAC, which has created awareness of major differences between EU member states. A significant decline in sales was reported for third and fourth generation cephalosporines, polymyxins (colistin), and (fluoro)quinolones since the initiation in 2011.

Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Colistin; European Union; Humans

Colistin is a potent antibiotic but its severe side effects including nephrotoxicity and neurotoxicity are the roadblock for their wide use in clinics. To solve this problem, we synthesized a new prodrug, mannose-maltose-colistin conjugate, termed MMCC that can reversibly mask the five amines of colistin that are primarily responsible for the toxicity. The deliberated design of disulfide-based self-immolative linker warranted the reversibly release of the pristine amines of colistin on demand without sacrificing antimicrobial efficacy. Once MMCC was delivered in cells, reducing agents cleaves the disulfide bond and release the pristine amines. The targeting ligands of maltose and mannose were grafted on colistin conjugate for targeting delivery of colistin to bacteria and macrophages, respectively. Taken together, MMCC as a new class of antimicrobial biomaterials, demonstrates its great potential for the treatment of intracellular bacterial infections.

Topics: Amines; Anti-Bacterial Agents; Bacterial Infections; Colistin; Disulfides; Humans; Maltose; Mannose; Prodrugs

Colistin, considered a drug of last resort as it is effective towards multidrug-resistant Gram-negative bacterial infections. Oral administration of colistin in the poultry industry is a common practice, not only to prevent and reduce bacterial infections, but also as a rapid-growth promoter. Long-term exposure to any antibiotic will eventually lead to the development of bacterial resistance towards all antibiotics through various mechanisms in the physiological system and environment. Chicken is the most consumed source of animal protein for humans throughout the world. In addition, the manure of poultry, containing traces of the used antibiotics, is being used in farming. Exposure to excess amounts of colistin causes a great concern not only to the humans but to the environment as a whole. In the present contribution, colistin has been detected in chicken hepatocyte cells through in vivo confocal microscopy. In addition, the amount of colistin in the chicken excrements has been estimated. A simple chemosensor NAF, a dye-based on napthaldehyde furfural, was developed for the detection of colistin, supplemented with experimental evidence and theoretical calculations.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Colistin; Drug Resistance, Bacterial; Fluorescence; Gram-Negative Bacterial Infections; Microbial Sensitivity Tests

Topics: Azabicyclo Compounds; Bacterial Infections; Colistin; Double-Blind Method; Humans; Imipenem

Topics: Anti-Bacterial Agents; Azabicyclo Compounds; Bacterial Infections; Carbapenems; Colistin; Double-Blind Method; Gram-Negative Bacteria; Humans; Imipenem

In order to render potent, but toxic antibiotics more selective, we have explored a novel conjugation strategy that includes drug accumulation followed by infection-triggered release of the drug. Bacterial targeting was achieved using a modified fragment of the human antimicrobial peptide ubiquicidin, as demonstrated by fluorophore-tagged variants. To limit the release of the effector colistin only to infection-related situations, we introduced a linker that was cleaved by neutrophil elastase (NE), an enzyme secreted by neutrophil granulocytes at infection sites. The linker carried an optimized sequence of amino acids that was required to assure sufficient cleavage efficiency. The antibacterial activity of five regioisomeric conjugates prepared by total synthesis was masked, but was released upon exposure to recombinant NE when the linker was attached to amino acids at the 1- or the 3-position of colistin. A proof-of-concept was achieved in co-cultures of primary human neutrophils and Escherichia coli that induced the secretion of NE, the release of free colistin, and an antibacterial efficacy that was equal to that of free colistin.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacterial Infections; Cells, Cultured; Coculture Techniques; Colistin; Dose-Response Relationship, Drug; Escherichia coli; Humans; Microbial Sensitivity Tests; Molecular Conformation; Pseudomonas aeruginosa

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Colistin; Drug Resistance, Bacterial; Humans; Lipid A; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

The increasing prevalence of antimicrobial resistance is a serious threat to global public health. One of the most concerning trends is the rapid spread of Carbapenemase-Producing Organisms (CPO), where colistin has become the last-resort antibiotic treatment. The emergence of colistin resistance, including the spread of mobilized colistin resistance (mcr) genes, raises the possibility of untreatable bacterial infections and motivates the development of improved diagnostics for the detection of colistin-resistant organisms. This work demonstrates a rapid response for detecting the most recently reported mcr gene, mcr-9, using a portable and affordable lab-on-a-chip (LoC) platform, offering a promising alternative to conventional laboratory-based instruments such as real-time PCR (qPCR). The platform combines semiconductor technology, for non-optical real-time DNA sensing, with a smartphone application for data acquisition, visualization and cloud connectivity. This technology is enabled by using loop-mediated isothermal amplification (LAMP) as the chemistry for targeted DNA detection, by virtue of its high sensitivity, specificity, yield, and manageable temperature requirements. Here, we have developed the first LAMP assay for mcr-9 - showing high sensitivity (down to 100 genomic copies/reaction) and high specificity (no cross-reactivity with other mcr variants). This assay is demonstrated through supporting a hospital investigation where we analyzed nucleic acids extracted from 128 carbapenemase-producing bacteria isolated from clinical and screening samples and found that 41 carried mcr-9 (validated using whole genome sequencing). Average positive detection times were 6.58 ± 0.42 min when performing the experiments on a conventional qPCR instrument (n = 41). For validating the translation of the LAMP assay onto a LoC platform, a subset of the samples were tested (n = 20), showing average detection times of 6.83 ± 0.92 min for positive isolates (n = 14). All experiments detected mcr-9 in under 10 min, and both platforms showed no statistically significant difference (p-value > 0.05). When sample preparation and throughput capabilities are integrated within this LoC platform, the adoption of this technology for the rapid detection and surveillance of antimicrobial resistance genes will decrease the turnaround time for DNA detection and resistotyping, improving diagnostic capabilities, patient outcomes, and the management of infectious diseases.

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacterial Proteins; Colistin; Drug Resistance, Bacterial; Humans; Lab-On-A-Chip Devices; Nucleic Acids

Sodium colistimethate (SCM) and amikacin (AMK) are among the few antibiotics effective against resistant P. aeruginosa, K. pneumoniae and A. baumannii; however, their toxicity severely limits their use. Enclosing antibiotics into nanostructured lipid carriers (NLC) might decrease drug toxicity and improve antibiotic disposition. In this work, SCM or AMK was loaded into different NLC formulations, through high pressure homogenization, and their in vitro and in vivo effectiveness was analyzed. The encapsulation process did not reduce drug effectiveness since in vitro SCM-NLC and AMK-NLC drug activity was equal to that of the free drugs. As cryoprotectant, trehalose showed better properties than dextran. Instead, positive chitosan coating was discarded due to its limited cost-efficiency. Finally, the in vivo study in acute pneumonia model revealed that intraperitoneal administration was superior to the intramuscular route and confirmed that (-) SCM-NLC with trehalose, was the most suitable formulation against an extensively drug-resistant A. baumannii strain.

Topics: Amikacin; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Colistin; Drug Carriers; Drug Resistance, Bacterial; Humans; Lipids; Nanostructures; Pseudomonas aeruginosa

Multidrug-resistant pathogens often lead to treatment failure of antimicrobial regimens. After a period of imbalance between the occurrence/spread of resistance mechanisms and the development of new substances, some new substances have meanwhile been approved and many more are currently undergoing clinical testing. They are particularly effective against specific resistance mechanisms/pathogens and should be preserved for definitive treatment of an isolated pathogen. In the absence of alternatives reserve antibiotics, such as aztreonam and colistin have experienced a renaissance. They are again used in special infection scenarios and clinically tested in combination with new substances. Despite the introduction and development of new substances the building of resistance will at some time also render these (at least partially) ineffective. Therefore, their implementation must be carried out according to the antibiotic or infectious diseases stewardship.

Topics: Anti-Bacterial Agents; Aztreonam; Bacterial Infections; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Microbial Sensitivity Tests

Multidrug-resistant organisms (MDROs) have been a major concern in King Saud Medical City (KSMC) recently. The number of cases with colistin resistance was growing rapidly in the first half of 2016, challenging the infection control practices and mandating a thorough outbreak investigation. The objective of this study was to determine the extent of the outbreak, identify potential risk factors and prevent further increase in the rates of MDROs.. Reviewing the medical records of the 22 admitted cases with colistin resistance using an abstraction form composed of demographical data, comorbidities, details of current admissions, and procedures. Also, tracking patients' movements in the hospital, reviewing all cultures isolates, and reviewing the surveillance and infection control strategies.. Mean age was 49.71±17.824 (20-79 years), 90.9% were males, 63.6% cases admitted under medical unit. The average duration of stay in the ED was 1.23 day. Over 2/3 had hypertension and diabetes mellitus. Majority of patients staying between 20-40 days in the hospital & the average number of days until developing colistin resistance was 44.18. Resistance was solely related to two organisms that were Acinetobacter baumanni (59.1%) and Klebsiella pneumoniae (40. 9%). Ventilators and folly's catheters were equally (95.5%) used by 21 patients. The most common site of infection was respiratory (41.3%), of which most were sputum samples. Resistance of over 75% is recorded by antibiotics like tazocin, ciprofloxacin, imepenen and oxacillin.. The uncontrolled use of antibiotics, prolonged stay in the Intensive Care Unit (ICU), frequent uses of different devices, are the potential risk factors of developing colistin resistance.

Topics: Adult; Aged; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Colistin; Disease Outbreaks; Drug Resistance, Multiple, Bacterial; Emergency Service, Hospital; Female; Humans; Intensive Care Units; Length of Stay; Male; Middle Aged; Risk Factors; Saudi Arabia; Tertiary Care Centers; Young Adult

Owing to the emerging problem of MDR bacteria, interest in 'old' antibiotics such as colistin has re-emerged. However, research on the dosing of colistin in patients undergoing renal replacement therapy (RRT), such as prolonged intermittent renal replacement therapy (PIRRT), is scarce.. The aim of this study was to evaluate single- and multiple-dose pharmacokinetics of colistin and its prodrug colistin methanesulfonate in ICU patients with acute kidney injury (AKI) undergoing PIRRT.. We performed a prospective clinical pharmacokinetic single- and multiple-dose study. Eight ICU patients with AKI undergoing treatment with PIRRT and receiving intravenous colistin were studied on day 1 and days 5-9 of treatment, depending on the timing of dialysis. Six million IU (MIU) of colistin methanesulfonate was administered 8 h prior to the PIRRT session followed by 3 MIU every 8 h. The study was registered under clinicaltrails.gov (NCT02556190).. PIRRT removed a considerable amount of colistin and colistin methanesulfonate with a median dialyser plasma CL of 70.1 mL/min (IQR 36.6-96.2) for colistin and 69.3 mL/min (IQR 56.3-318.7) for colistin methanesulfonate. The median amount of colistin in the total collected dialysate was 154 mg (IQR 105-175), corresponding to about 50% of the daily dose. Median colistin peak concentrations accumulated from 5.79 mg/L (IQR 4.14-8.79) on day 1 to 9.49 mg/L (IQR 8.39-10.41) on days 5-9. Cmax was significantly and inversely correlated with body weight.. PIRRT eliminates about half of the daily administered colistin dose. Even a 6 MIU loading dose of colistin methanesulfonate may not ensure immediate sufficient colistin plasma levels in all critically ill patients. However, we measured significant colistin accumulation, suggesting that the dose of colistin methanesulfonate should be adjusted according to body weight and RRT intensity.

Topics: Acute Kidney Injury; Adult; Anti-Bacterial Agents; Bacterial Infections; Colistin; Critical Illness; Drug Administration Schedule; Drug Monitoring; Female; Humans; Intermittent Renal Replacement Therapy; Male; Middle Aged

Increasing rate of resistant infections is a challenge to healthcare negatively impacting therapeutic and financial outcomes. Targeted antimicrobial stewardship interventions are needed to counteract this global crisis. On large scale, we sought to identify the prevalence of resistant pathogens and their susceptibility pattern in Northern Oman.. Retrospective analysis of all isolates processed by Suhar Hospital microbiology laboratory between Jan1st, 2016 and Dec31st, 2017. Organism identification, susceptibility and phenotyping were performed following CLSI standards and duplicate isolates were excluded. Pertinent microbiological data were collected and analyzed.. Of 15,733 samples included, Gram-negative bacteria predominate by 67.76%, Gram-positive (29%) and Candida species (2.63%). Frequently isolated Gram-negative bacteria were Escherichia coli (32.39%), Pseudomonas aeruginosa (22.16%), Klebsiellapneumoniae (19.97%) and Acinetobacter baumannii (5.22%), there was virtually no resistance to colistin and tigecycline, while a growing resistance toward ciprofloxacin and meropenem was observed. Resistant E. coli and K. pneumoniae were isolated from bloodstream infection (12%). While Gram-positives were MSSA (27.23%), Streptococcus agalactiae (25.36%), MRSA (16.10%) and CoNS (12.1 %), they were almost universally susceptible to daptomycin and linezolid with low resistance (8˜20%) to clindamycin. Approximately, 50% of Staphylococci (MRSA and CoNS) required vancomycin treatment.. Study findings should guide targeted stewardship interventions to optimize antibiotic prescriptions. Empirical treatment options should be revised, drug-bug match therapy instituted promptly and newer agents considered. Prescribing restriction of formulary antimicrobials that still retain their activity towards bugs - like colistin, linezolid and tigecycline- is a mandatory action. Review empiric use of ciprofloxacin and meropenem to counteract growing resistance.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Antimicrobial Stewardship; Bacterial Infections; Colistin; Drug Resistance, Bacterial; Escherichia coli; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Oman; Pseudomonas aeruginosa; Retrospective Studies; Tigecycline

Nonreplicating bacteria are known to be (or at least commonly thought to be) refractory to antibiotics to which they are genetically susceptible. Here, we explore the sensitivity to killing by bactericidal antibiotics of three classes of nonreplicating populations of planktonic bacteria: (i) stationary phase, when the concentration of resources and/or nutrients are too low to allow for population growth; (ii) persisters, minority subpopulations of susceptible bacteria surviving exposure to bactericidal antibiotics; and (iii) antibiotic-static cells, bacteria exposed to antibiotics that prevent their replication but kill them slowly if at all, the so-called bacteriostatic drugs. Using experimental populations of

Topics: Aminoglycosides; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Colistin; Daptomycin; Microbial Sensitivity Tests

The growing incidence and the wide diversity of carbapenemase-producing bacterial strains is a major concern as only a few antimicrobial agents are active on carbapenem-resistant bacteria. This study was designed to study molecular epidemiology of carbapenem-resistant Gram-negative bacterial (GNB) isolates from the community and hospital settings.. In this study, non-duplicate GNB were isolated from clinical specimens, and phenotypic test such as modified Hodge test, metallo β-lactamase E-strip test, etc. were performed on carbapenem-resistant bacteria. Multiplex PCR was performed to identify the presence of bla. Of the 3414 GNB studied, carbapenem resistance was 9.20 per cent and maximum resistance (11.2%) was present at tertiary care centre, followed by secondary care (4%) and primary centre (2.1%). Among the carbapenem-resistant bacteria, overall, the most common isolate was Pseudomonas aeruginosa (24%). On multiplex PCR 90.3 per cent carbapenem-resistant isolates were positive for carbapenemase gene. The bla. Carbapenem resistance in GNB isolates from the community and hospital settings was found to be on the rise and should be closely monitored. In the absence of new antibiotics in pipeline and limited therapeutic options, prudent use of antibiotics and strict infection control practices should be followed in hospital to limit the emergence and spread of multidrug-resistant bacteria.

Topics: Acinetobacter; Bacterial Infections; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Multiple, Bacterial; Escherichia coli; Gram-Negative Bacteria; Humans; India; Microbial Sensitivity Tests; Molecular Epidemiology; Pseudomonas aeruginosa

The incidence of carbapenem-resistant Enterobacteriaceae has been steadily rising. The morbidity, mortality and financial implications of such patients are significant. We did a retrospective analysis of the case records of 11 patients who had culture report positive for pan drug-resistant (PDR) organisms. There were total 15 isolates of PDR organisms in 11 patients. These were associated with catheter-associated urinary tract infections (7), tracheitis (4), bacteraemia (2), meningitis (1) and soft-tissue infection (1). Average APACHE II score was 23.72 (range 7-36) indicating patients with multiple co-morbidities and organ dysfunction. The average length of hospital stay was 60.72 (25-123) days. The overall mortality rate was 81.81 per cent, while PDR infection-related mortality was 18.18 per cent. Strict implementation of antibiotic stewardship programme is essential to limit use and prevent abuse of colistin.

Topics: Adult; Aged; Aged, 80 and over; Bacterial Infections; beta-Lactamases; Carbapenems; Colistin; Drug Resistance, Bacterial; Enterobacteriaceae; Female; Humans; Male; Microbial Sensitivity Tests; Middle Aged; Tertiary Care Centers; Urinary Tract Infections

We examined whether long-term use of selective digestive tract decontamination (SDD) was effective in reducing intensive care unit (ICU)-acquired infection and antibiotic consumption while decreasing colistin-, tobramycin-, and most of the antibiotic-resistant colonization rates in a mixed ICU with a high endemic level of multidrug-resistant bacteria (MDRB).. In this cohort study, which was conducted in a 30-bed medical-surgical ICU, clinical outcomes before (1 year, non-SDD group) and after (4 years) implementation of SDD were compared. ICU patients who were expected to require tracheal intubation for > 48 hours were given a standard prophylactic SDD regimen. Oropharyngeal and rectal swabs were obtained on admission and once weekly thereafter.. ICU-acquired infections occurred in 110 patients in the non-SDD group and in 258 in the SDD group. A significant (P <  0.001) reduction of infections caused by MDRB (risk ratio [RR], 0.31; 95% CI, 0.23-0.41) was found after SDD and was associated with low rates of colistin- and tobramycin-resistant colonization. Colistin- and tobramycin-acquired increasing rate of ICU colonization resistance by 1000 days, adjusted by the rate of resistances at admission, was nonsignificant (0.82; 95% CI, 0.56 to 1.95; 1.13; 95% CI, 0.75 to 1.70, respectively). SDD was also a protective factor for ICU-acquired infections caused by MDR gram-negative pathogens and Acinetobacter baumannii in the multivariate analysis. In addition, a significant (P <  0.001) reduction of ventilator-associated pneumonia (VAP) (RR, 0.43; 95% CI, 0.32-0.59) and secondary bloodstream infection (BSI) (RR, 0.35; 95% CI, 0.24-0.52) was found. A decrease in antibiotic consumption was also observed.. Treatment with SDD during 4 years was effective in an ICU setting with a high level of resistance, with clinically relevant reductions of infections caused by MDRB, and with low rates of colistin- and tobramycin-resistant colonization with nonsignificant increasing rate of ICU colonization resistance by 1000 days, adjusted by the rate of resistances at ICU admission. In addition, VAP and secondary BSI rates were significantly lower after SDD. Notably, a decrease in antimicrobial consumption was also observed.

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Cohort Studies; Colistin; Decontamination; Drug Resistance, Bacterial; Female; Gastrointestinal Tract; Humans; Intensive Care Units; Male; Middle Aged; Prospective Studies; Protective Factors; Spain; Tobramycin

Topics: Animals; Anti-Infective Agents; Bacterial Infections; Cats; Colistin; Dogs; Drug Resistance, Microbial; Humans; Infections; Mycoses; Parasitic Diseases; Virus Diseases; Zoonoses

Since 2013, wounded and ill children from Syria have received treatment in Israel. Screening cultures indicated that multidrug-resistant (MDR) pathogens colonized 89 (83%) of 107 children. For 58% of MDR infections, the pathogen was similar to that identified during screening. MDR screening of these children is valuable for purposes of isolation and treatment.

Topics: Adolescent; Amikacin; Anti-Bacterial Agents; Armed Conflicts; Bacterial Infections; Child; Child, Preschool; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Gram-Negative Bacteria; Gram-Positive Bacteria; Hospitalization; Humans; Infant; Infant, Newborn; Israel; Male; Meropenem; Multiple Trauma; Syria; Thienamycins

Colistin is a polypeptide antibiotic of the polymyxin family (polymyxin E) which has been reported to be active against many multidrug-resistant (MDR) Gram-negative aerobic bacteria collected across the globe. While this agent was not currently licensed in Japan, the emergence of MDR organisms has necessitated its off-label used in the country. However, colistin was approved in March, 2015. This retrospective observational report includes nine patients with MDR Gram-negative infections due to Pseudomonas aeruginosa (n=6) and Klebsiella spp. (n=3) who received intravenous colistin therapy as part of their antimicrobial regimen. The median age and duration of administration were 40 years (range 7-90) and 8 days (range 1-19). Clinical success was observed in all eight patients for whom efficacy could be evaluated. Two patients encountered colistin related adverse effects 22.2% (2/9). In both cases the nephrotoxicity and dysgeusia resolved after discontinuation of colistin therapy. In vitro studies conducted with these clinical isolates of P aeruginosa displayed synergy with the combination of colistin plus ceftazidime, rifampicin, meropenem or aztreonam. This report provides early evidence that colistin is generally safe, effective and demonstrates in vitro synergy when used in combination for the management of MDR Gram-negative pathogens derived from Japanese patients.

Topics: Adult; Aged, 80 and over; Anti-Bacterial Agents; Bacterial Infections; Child; Colistin; Drug Combinations; Drug Resistance, Multiple, Bacterial; Humans; Male; Middle Aged; Retrospective Studies

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Critical Care; Critical Illness; Drug Resistance, Multiple, Bacterial; Humans

In this work different nebulisers were investigated in order to assess their efficiency in combination with colistimethate sodium (CMS) inhalation products. Four nebulisers, namely I-neb(®), Aeroneb(®) Go, eFlow(®)rapid and PARI LC(®) Sprint were studied in terms of delivered dose (DD), drug delivery rate (DDR) and respirable dose (RD) of CMS. The goal was to provide scientific data to physicians for prescribing the most appropriate nebuliser for the CMS specific user. All the apparatuses nebulised ColiFin 1MIU/3 ml solution (80 mg of CMS) with delivered doses between 31% and 41% of the loaded amount. Aeroneb Go showed the longest nebulisation time (more than 20 min). When ColiFin 2 MIU/4 ml was nebulised with eFlow rapid or PARI LC Sprint, the CMS respirable dose was 45.3mg and 39.2mg, in times of 5.6 and 10.8 min, respectively. I-neb, having a medication cup capacity limited to 0.4 ml, loaded with Promixin 0.4 MIU/0.4 ml (32 mg of CMS), provided in a time of 9 min a RD of 21.5mg, a value slightly higher than those obtained by nebulising ColiFin 1 MIU/3 ml with the other nebulisers (range 15.9-17.6 mg). The results illustrate that the clinical outcome depends on the comparative analysis of nebulisation efficiency (respirable dose) and convenience (time), not disregarding the ratios between the amount loaded, delivered and deposited at lung level.

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Cystic Fibrosis; Humans; Lung Diseases; Nebulizers and Vaporizers; Solutions

Topics: Anti-Bacterial Agents; Bacterial Infections; Canada; Colistin; Drug Resistance, Bacterial; Epidemiological Monitoring; Escherichia coli; Escherichia coli Infections; Humans; Morbidity

Antibiogram profile of 1590 clinical bacterial isolates based on thirteen different antimicrobial compounds showed that 1.6% of the bacterial isolates are multidrug resistant. Distribution pattern based on 16S rRNA sequence analysis showed that Pseudomonas aeruginosa constituted the largest group (83.6%) followed by Burkholderia pseudomallei sp. A191 (5.17%), Staphylococcus sp. A261 (3.45%). Among the various antibiotics used, colistin appeared to be the most effective against the Gram negative bacteria. Burkholderia pseudomallei sp. A191 and Pseudomonas aeruginosa sp. A111 showed resistance to 1500 μg/ml and 750 μg/ml of colistin respectively which constitutes 7.7% of the bacterial population. A functional genomics strategy was employed to discover the molecular support for colistin resistance in Burkholderia pseudomallei sp. A191. A pUC plasmid-based genomic expression library was constructed with an estimated library size of 2.1 × 10(7)bp. Five colistin resistant clones were obtained after functional screening of the library. Analysis of DNA sequence of five colistin resistant clones showed homology to two component regularity systems (TCRS) encoding for a histidine kinase (mrgS) and its regulatory component (mrgR). Cross complementation assay showed that mutations in mrgS were sufficient enough to confer colistin resistant phenotype in a sensitive strain.

Topics: Adolescent; Adult; Aged; Bacteria; Bacterial Infections; Bacterial Proteins; Child; Cloning, Molecular; Colistin; Drug Resistance, Multiple, Bacterial; Female; Genome, Bacterial; Histidine Kinase; Humans; Male; Middle Aged; Phylogeny; RNA, Bacterial; RNA, Ribosomal, 16S; Young Adult

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Drug Resistance, Bacterial; Gene Transfer, Horizontal; Humans; Interspersed Repetitive Sequences; Plasmids

Colistin is an ultimate line of refuge against multidrug-resistant Gram-negative pathogens. Very recently, the emergence of plasmid-mediatedmcr-1colistin resistance has become a great challenge to global public health, raising the possibility that dissemination of themcr-1gene is underestimated and diversified. Here, we report three cases of plasmid-carried MCR-1 colistin resistance in isolates from gut microbiota of diarrhea patients. Structural and functional analyses determined that the colistin resistance is conferred purely by the singlemcr-1gene. Genetic and sequence mapping revealed thatmcr-1-harbouring plasmid reservoirs are present in diversity. Together, the data represent the first evidence of diversity inmcr-1-harbouring plasmid reservoirs of human gut microbiota.. The plasmid-mediated mobile colistin resistance gene (mcr-1) challenged greatly the conventional idea mentioned above that colistin is an ultimate line of refuge against lethal infections by multidrug-resistant Gram-negative pathogens. It is a possibility that diversified dissemination of themcr-1gene might be greatly underestimated. We report three cases of plasmid-carried MCR-1 colistin resistance in isolates from gut microbiota of diarrhea patients and functionally define the colistin resistance conferred purely by the singlemcr-1gene. Genetic and sequence mapping revealed unexpected diversity among themcr-1-harbouring plasmid reservoirs of human gut microbiota.

Topics: Anti-Bacterial Agents; Bacterial Infections; China; Colistin; Diarrhea; Drug Resistance, Bacterial; Ethanolaminephosphotransferase; Feces; Gastrointestinal Microbiome; Genes, Bacterial; Genetic Variation; Gram-Negative Bacteria; Humans; Plasmids; Sequence Analysis, DNA

To monitor the effectiveness and safety of colistin for therapy in resistant Gram-negative bacterial infections at Siriraj Hospital 10 years after colistin was first introduced in Thailand at Siriraj Hospital in 2005.. Study subjects were hospitalized adult patients with documented Gram-negative bacterial infections that received parenteral colistin (Colistate) for longer than 48 hours between October 2014 and June 2015. Patient information regarding demographics, characteristics of infections, antibiotic therapy, clinical outcomes, microbiological responses, and nephrotoxicity were identified and retrieved from patient medical records. The data were analyzed using descriptive statistics.. One hundred thirty eight patients were included in the study. Many of the patients were elderly males. The most common type of infection was pneumonia and A. baumannii was the most common cause of infection. Nearly all isolates of A. baumannii and P. aeruginosa were resistant to carbapenems. A loading dose of colistin (300 mg) was given in 94.9% of patients. Only 19.6% of patients received colistin alone. Most patients received concomitant antibiotics, especially carbapenems, and piperacillin-tazobactam. Favorable clinical outcome was observed in 71.7% of patients at the end of colistin therapy. Patient mortality at the end of colistin therapy and at 30 days after colistin therapy was completed was 23.2% and 39.9%, respectively. Microbiological eradication of target bacteria at the end of colistin therapy was found in 50.0% of patients. Overall incidence of acute kidney injury was 39.9%, with most cases classified as either risk (20.3%) or injury (13%). Colistin-related renal dysfunction was reversible in most cases.. Colistin remains the principal antibiotic in carbapenem-resistant Gram-negative bacterial infections. Colistin's effectiveness and safety is still rated as moderate for therapy in difficult-to-treat resistant Gram-negative bacterial infections.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacterial Infections; Colistin; Demography; Female; Humans; Male; Middle Aged; Thailand; Young Adult

Patients undergoing intensive chemotherapy for acute myeloid leukemia are at high risk for bacterial infections during therapy-related neutropenia. However, the use of specific antibiotic regimens for prophylaxis in afebrile neutropenic acute myeloid leukemia patients is controversial. We report a retrospective evaluation of 172 acute myeloid leukemia patients who received 322 courses of myelosuppressive chemotherapy and had an expected duration of neutropenia of more than seven days. The patients were allocated to antibiotic prophylaxis groups and treated with colistin or ciprofloxacin through 2 different hematologic services at our hospital, as available. The infection rate was reduced from 88.6% to 74.2% through antibiotic prophylaxis (vs without prophylaxis; P=0.04). A comparison of both antibiotic drugs revealed a trend towards fewer infections associated with ciprofloxacin prophylaxis (69.2% vs 79.5% in the colistin group; P=0.07), as determined by univariate analysis. This result was confirmed through multivariate analysis (OR: 0.475, 95%CI: 0.236-0.958; P=0.041). The prophylactic agents did not differ with regard to the microbiological findings (P=0.6, not significant). Of note, the use of ciprofloxacin was significantly associated with an increased rate of infections with pathogens that are resistant to the antibiotic used for prophylaxis (79.5% vs 9.5% in the colistin group; P<0.0001). The risk factors for higher infection rates were the presence of a central venous catheter (P<0.0001), mucositis grade III/IV (P=0.0039), and induction/relapse courses (vs consolidation; P<0.0001). In conclusion, ciprofloxacin prophylaxis appears to be of particular benefit during induction and relapse chemotherapy for acute myeloid leukemia. To prevent and control drug resistance, it may be safely replaced by colistin during consolidation cycles of acute myeloid leukemia therapy.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antineoplastic Agents; Bacterial Infections; Central Venous Catheters; Ciprofloxacin; Cohort Studies; Colistin; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mucositis; Neutropenia; Retrospective Studies; Young Adult

Current antimicrobial susceptibility testing has limited screening capability for identifying empirical antibiotic combinations to treat severe bacterial infections with multidrug-resistant (MDR) organisms. We developed a new antimicrobial susceptibility assay using automated ultra-high-throughput screen technology in combination with a simple bacterial growth assay. A rapid screening of 5170 approved drugs and other compounds identified 25 compounds with activities against MDR Klebsiella pneumoniae. To further improve the efficacy and reduce the effective drug concentrations, we applied a targeted drug combination approach that integrates drugs' clinical antimicrobial susceptibility breakpoints, achievable plasma concentrations, clinical toxicities and mechanisms of action to identify optimal drug combinations. Three sets of three-drug combinations were identified with broad-spectrum activities against 10 MDR clinical isolates including K. pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, Citrobacter freundii, Enterobacter cloacae and Escherichia coli. Colistin-auranofin-ceftazidime and colistin-auranofin-rifabutin suppressed >80% growth of all 10 MDR strains; while rifabutin-colistin-imipenem inhibited >75% of these strains except two Acinetobacter baumannii isolates. The results demonstrate this new assay has potential as a real-time method to identify new drugs and effective drug combinations to combat severe clinical infections with MDR organisms.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Anti-Bacterial Agents; Antirheumatic Agents; Auranofin; Bacterial Infections; Colistin; Drug Combinations; Drug Discovery; Drug Resistance, Multiple, Bacterial; Drug Synergism; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests; Pseudomonas aeruginosa

The concern over antibiotic resistance has been voiced since the discovery of modern antibiotics > 75 years ago. The concerns have only increased with time, with efforts to control resistance caused by widespread overuse of antibiotics in human medicine and far more than appreciated use in the feeding of animals for human consumption to promote growth. The problem is worldwide, but certain regions and selected health care institutions report far more resistance, including strains of Gram-negative bacteria that are susceptible only to the once discarded drugs polymyxin B or colistin, and pan-resistant strains are on the rise. One of the central efforts to control resistance, apart from antimicrobial stewardship, is the development of new antimicrobial agents. This has lagged significantly over the past 10 - 15 years, for a variety of reasons; but promising new agents are being developed, unfortunately none thus far addressing all potentially resistant strains. There is the unlikely, but not unreal, possibility that we could return to a pre-antibiotic era, where morbidity and mortality rates have risen dramatically and routine surgical procedures are not performed for fear of post-operative infections. The onus of control of resistance is a moral imperative that falls on the shoulders of all.

Topics: Animals; Anti-Bacterial Agents; Bacterial Infections; Colistin; Costs and Cost Analysis; Drug Resistance, Microbial; Humans

Recent meta-analyses showed that antibiotic prophylaxis in patients with neutropenia after chemotherapy reduced the incidence of fever and mortality rate. Fluoroquinolones appear to be most effective and well tolerated. Thus, in April 2008, we changed our antibiotic prophylaxis regimen from cotrimoxazole/colistin (COT/COL) to the fluoroquinolone ciprofloxacin (CIP) in patients with acute myeloid leukemia (AML). The aim of this retrospective study was to compare efficacy and development of bacterial resistance with two different prophylaxis regimens over a time period of more than 4 years.. Induction chemotherapy courses given for AML during the antibiotic prophylaxis period with COT/COL (01/2006-04/2008) and CIP (04/2008-06/2010) were retrospectively analyzed with a standard questionnaire.. Eighty-five courses in the COT/COL group and 105 in the CIP group were analyzed. The incidence of fever was not significantly different (COT/COL 80 % vs CIP 77 %; p = 0.724). Also, the rate of microbiologically documented infections was nearly the same (29 vs 26 %; p = 0.625). In addition, there was no significant difference in the incidence of clinically documented infections (11 vs 19 %; p = 0.155) or in the rates of detected gram-positive and gram-negative bacteria. Of note, there was no increase in resistance rates or cases with Clostridium difficile-associated diarrhea in the CIP group.. The antibiotic prophylaxis with CIP compared to COT/COL in AML was similarly effective with no increase in bacterial resistance. COT/COL may have the advantages of providing additional prophylaxis against Pneumocystis jirovecii pneumonia and leaving fluoroquinolones as an additional option for treatment of febrile neutropenia.

Topics: Adult; Aged; Anti-Bacterial Agents; Antibiotic Prophylaxis; Antineoplastic Agents; Bacterial Infections; Ciprofloxacin; Clostridioides difficile; Colistin; Diarrhea; Drug Resistance, Bacterial; Enterocolitis, Pseudomembranous; Female; Fever; Fluoroquinolones; Humans; Incidence; Leukemia, Myeloid, Acute; Male; Middle Aged; Neutropenia; Pneumocystis carinii; Pneumonia, Pneumocystis; Retrospective Studies; Surveys and Questionnaires; Trimethoprim, Sulfamethoxazole Drug Combination

Cation-dependent inhibition of antimicrobial activity was reported for polymyxin antibiotics. Ca(2+) and Mg(2+) concentrations recommended by the Clinical and Laboratory Standards Institute (CLSI) for the supplementation of Müller-Hinton broth (MHB) are markedly lower than interstitial space fluid (ISF) concentrations in vivo. Hence, it was speculated that the antimicrobial activity of colistin might be overestimated if tested using conventional cation-adjusted MHB. The antimicrobial activity of colistin against n = 100 clinical isolates of Pseudomonas aeruginosa, Acinetobacter baumannii, Klebsiella pneumoniae and Escherichia coli (n = 25 each) was evaluated by broth microdilution and, for selected isolates, by time-kill curves, in MHB without cations (MHB(ONLY)), MHB supplemented with 25 mg/L Ca(2+) and 12.5 mg/L Mg(2+) according to CLSI recommendations (MHB(CLSI)), and in MHB adjusted to 50 mg/L Ca(2+) and 20 mg/L Mg(2+) simulating ISF concentrations (MHB(ISF)). The minimum inhibitory concentration (MIC) values of colistin against the vast majority of isolates of both P. aeruginosa and A. baumannii increased significantly with higher cation concentrations. The susceptibility of K. pneumoniae isolates to colistin did not show significant changes between cation-supplemented media, while the MICs of E. coli decreased with ascending cation concentrations. These findings were confirmed in time-kill studies, where colistin killing against P. aeruginosa 1514 and A. baumannii 1485 declined with increasing cation concentrations. Contrarily, the killing of selected concentrations of colistin against K. pneumoniae 15 and E. coli 16 was enhanced in the presence of increasing cation concentrations. The present data suggest that the clinical antimicrobial activity of colistin might be misestimated in vitro if tested in conventional growth media.

Topics: Acinetobacter baumannii; Anti-Bacterial Agents; Bacterial Infections; Cell Proliferation; Colistin; Escherichia coli; Humans; Klebsiella pneumoniae; Pseudomonas aeruginosa

Colistin is the first revived antibiotic to undergo substantial 'redevelopment' in academic settings. This study investigated the variation and accuracy of information in the summary of product characteristics (SPC) of intravenous colistin products approved in the European Union.. The dosing, indication and pharmacokinetic information in the SPCs of approved intravenous colistin products in 21 European countries were compared.. In general, some SPCs have been updated over recent years though vital aspects of dosing recommendations, indications and pharmacokinetic information show a rather broad variation. The importance of a loading dose and of a daily dose >6 million international units in critically ill patients with good renal function is not considered in all SPCs. The pharmacokinetic section and dosing recommendations for special patient populations require careful review and updating, in order to take account of newly published data.. This study highlights the challenges of integrating new rapidly evolving scientific knowledge into approved SPCs in Europe.

Topics: Administration, Intravenous; Anti-Bacterial Agents; Bacterial Infections; Colistin; European Union; Humans; Product Labeling

Bacterial infections are major causes of early morbidity and mortality after liver transplantation. Selective digestive decontamination (SDD) can be used pre-operatively for living-donor liver transplant (LD-LT), but its role in this setting remains controversial.. To evaluate this strategy, we retrospectively analyzed a cohort of consecutive LD-LTs performed in our center from March 2007 to February 2011 and compared the incidence and nature of early infectious complications, length of intensive care unit stay and hospitalization, antibiotic use, and emergence of resistant bacteria in patients with or without SDD prophylaxis.. Of 148 LD-LTs in the study period, 111 received SDD prophylaxis while 37 did not. In a multivariate model, the independent factors associated with an increased risk of early post-transplant infections were length of postoperative mechanical ventilation (for every additional day odds ratio [OR] = 2.37, 95% confidence interval [CI] 1.4-4.0; P = 0.002), and choledochojejunostomy (OR = 4.5, 95% CI 1.95-10.5; P < 0.001). Use of SDD did not affect the rate or distribution of infectious complications, duration of hospitalization, antibiotic use, or acquisition of resistant bacteria (OR = 3.52, 95% CI 0.43-15.17; P = 0.376).. In conclusion, the use of SDD prophylaxis in LD-LT was not beneficial and should be avoided, as it offers no advantage and could potentiate the emergence of multidrug-resistant organisms.

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Colistin; Decontamination; Digestive System; Drug Therapy, Combination; Female; Gentamicins; Humans; Liver Transplantation; Living Donors; Male; Middle Aged; Odds Ratio; Postoperative Complications; Retrospective Studies; Young Adult

The purpose of this study was to take advantage of the nematode Caenorhabditis elegans to perform a whole-animal chemical screen to identify potential immune activators that may confer protection against bacterial infections. We identified 45 marketed drugs, out of 1,120 studied compounds, that are capable of activating a conserved p38/PMK-1 mitogen-activated protein kinase pathway required for innate immunity. One of these drugs, the last-resort antibiotic colistin, protected against infections by the Gram-negative pathogens Yersinia pestis and Pseudomonas aeruginosa but not by the Gram-positive pathogens Enterococcus faecalis and Staphylococcus aureus. Protection was independent of the antibacterial activity of colistin, since the drug was administered prophylactically prior to the infections and it was also effective against antibiotic-resistant bacteria. Immune activation by colistin is mediated not only by the p38/PMK-1 pathway but also by the conserved FOXO transcription factor DAF-16 and the transcription factor SKN-1. Furthermore, p38/PMK-1 was found to be required in the intestine for immune activation by colistin. Enhanced p38/PMK-1-mediated immune responses by colistin did not reduce the bacterial burden, indicating that the pathway plays a role in the development of host tolerance to infections by Gram-negative bacteria.. The innate immune system represents the front line of our defenses against invading microorganisms. Given the ever-increasing resistance to antibiotics developed by bacterial pathogens, the possibility of boosting immune defenses represents an interesting, complementary approach to conventional antibiotic treatments. Here we report that the antibiotic colistin can protect against infections by a mechanism that is independent of its microbicidal activity. Prophylactic treatment with colistin activates a conserved p38/PMK-1 pathway in the intestine that helps the host better tolerate a bacterial infection. Since p38/PMK-1-mediated immune responses appear to be conserved from plants to mammals, colistin may also activate immunity in higher organisms, including humans. Antibiotics with immunomodulatory properties have the potential of improving the long-term outcome of patients with chronic infectious diseases.

Topics: Animals; Bacterial Infections; Caenorhabditis elegans; Colistin; Drug Evaluation, Preclinical; Enterococcus faecalis; Immunity, Innate; Immunomodulation; Microarray Analysis; Mitogen-Activated Protein Kinases; Models, Animal; p38 Mitogen-Activated Protein Kinases; Pseudomonas aeruginosa; Staphylococcus aureus; Yersinia pestis

Topics: Administration, Oral; Administration, Topical; Adrenal Cortex Hormones; Amoxicillin-Potassium Clavulanate Combination; Bacitracin; Bacterial Infections; Child, Preschool; Colistin; Germany; Humans; Hydrocortisone; Middle Ear Ventilation; Otitis Media, Suppurative; Postoperative Complications; Randomized Controlled Trials as Topic

Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Colistin; Humans; Infant; Infant, Newborn; Penicillanic Acid; Piperacillin; Piperacillin, Tazobactam Drug Combination; Public Health Administration; Virus Diseases

This study evaluated the in vitro and in vivo performance of antibiotic-releasing porous polymethylmethacrylate (PMMA)-based space maintainers comprising a gelatin hydrogel porogen and a poly(dl-lactic-co-glycolic acid) (PLGA) particulate carrier for antibiotic delivery. Colistin was released in vitro from either gelatin or PLGA microparticle loaded PMMA constructs, with gelatin-loaded constructs releasing colistin over approximately 7 days and PLGA microparticle-loaded constructs releasing colistin for up to 8 weeks. Three formulations with either burst release or extended release at different doses were tested in a rabbit mandibular defect inoculated with Acinetobacter baumannii (2×10(7) colony forming units ml(-1)). In addition, one material control that released antibiotic but was not inoculated with A. baumannii was tested. A. baumannii was not detectable in any animal after 12 weeks on culture of the defect, saliva, or blood. Defects with high dose extended release implants had greater soft tissue healing compared with defects with burst release implants, with 8 of 10 animals showing healed mucosae compared with 2 of 10 respectively. Extended release of locally delivered colistin via a PLGA microparticle carrier improved soft tissue healing compared with implants with burst release of colistin from a gelatin carrier.

Topics: Acinetobacter; Animals; Anti-Bacterial Agents; Bacterial Infections; Blood Urea Nitrogen; Colistin; Creatinine; Disease Models, Animal; Humans; Kidney Function Tests; Male; Mandible; Microbial Sensitivity Tests; Mouth Mucosa; Polymethyl Methacrylate; Porosity; Prostheses and Implants; Rabbits

Colistin is a decades-old drug that fell out of favour due to its nephrotoxicity. Today, colistin is experiencing a renaissance as a treatment against multiresistant Gram-negative bacteria such as Pseudomonas and Acinetobacter in critically ill patients. The optimal dosing of colistin for most infections is unknown. Here we present the intravenous dosing, optimised by therapeutic drug monitoring (TDM), of a borderline patient with severe burns and a consecutive transfemoral amputation. A 32-year-old woman with severe burns (35% total body surface area) and sepsis exhibited normal serum creatinine (SCr) concentrations at the beginning of her intensive care unit (ICU) stay, but over the course of her ICU stay her SCr increased to 100 μmol/L. With the colistin standard dose of 3 × 3 million units (MU) colistin/day after a loading dose of 9 MU, she failed to achieve effective plasma concentrations. The estimated glomerular filtration rate (eGFR) via CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) revealed GFRs between 180 mL/min and 63 mL/min after correcting for body surface. The patient required a high daily dosage of colistin (3 × 6 MU) that exceeded the approved maximum dose. Most clinicians rely heavily on SCr concentrations as the primary biochemical marker of GFR. At most, the CKD-EPI formula is helpful in determining creatinine clearance. The pharmacokinetics of colistin are currently poorly understood. TDM of colistin methanesulfonate and colistin may represent an invaluable approach to optimise colistin drug exposure in ICU patients with fluctuating renal clearance.

Topics: Administration, Intravenous; Adult; Amputation, Surgical; Anti-Bacterial Agents; Bacterial Infections; Burns; Colistin; Creatinine; Drug Monitoring; Female; Glomerular Filtration Rate; Humans; Sepsis

The aim of this study was to investigate the efficacy and safety of colistin therapy in pediatric patients with severe nosocomial infections in pediatric intensive care unit.. The medical records of patients treated with colistin at a 200-bed university children hospital were reviewed.. Thirty-one patients (male/female = 22/9; median age, 3 years; range, 3 months-17 years) received forty-one courses of colistin. The average dose of colistin was 4.9 ± 0.5 mg/kg/day and average treatment duration was 19.8 ± 10.3 days. Three patients who received concomitant nephrotoxic agent with colistin developed nephrotoxicity. Colistin treatment was well tolerated in other patients, and neurotoxicity was not seen in any patient. Favourable outcome was achieved in 28 (68.3%) episodes. Twelve patients died during the colistin therapy. Six of these patients died because of primary underlying disease. The infection-related mortality rate was found 14.6% in this study.. In our study, colistin therapy was found to be acceptable treatment option for the severe pediatric nosocomial infections caused by multi-drug resistant bacteria. However, the use of concomitant nephrotoxic drugs with colistin must be avoided and renal function test should be closely monitored.

Topics: Acute Kidney Injury; Adolescent; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Colistin; Cross Infection; Female; Hospitals, University; Humans; Infant; Intensive Care Units, Pediatric; Male; Treatment Outcome

Colistin is a venerable drug that has found renewed interest because of multidrug resistance (MDR) and the shortfall of effective antibiotics. We present a synthesis of publication trends on MDR infection, colistin, and its adverse events, as a measure of the medical-academic community's interest, to inform current redevelopment strategies.. This was a multidatabase electronic search over 50 years with back- and forward-referencing through Web of Knowledge. Studies were grouped into MDR, colistin, and adverse events and were plotted in 5-year clusters.. Three periods could be mapped with distinct literature trends: A, 1940 to 1975; B, 1975 to 2000; and C, post-2000. Period A was characterized by increasing publications, soon followed by adverse-effect-themed publications. Period B reported a sharp publication decline; and period C reported a sharp increase in interest, mirroring the exponential increase in MDR literature. Period B predated standardized modern pharmacologic requirements. Period C coincided with novel drug development techniques.. Two current trends (period C) were identified. Optimization of the current formulation may have been influenced by period B. Current research efforts within this trend include pharmacokinetic/pharmacodynamic analysis, purification, formulation, and resistance surveillance. The second trend involved colistin's redevelopment by tailored chemical reengineering to produce novel and patentable chemical entities, with an interdisciplinary approach emphasis. It is hoped that an analysis of the interplay between historical trends and current redevelopment strategies of this colistin case study may highlight strategies to stoke the drying antibiotic pipeline.

Topics: Anti-Bacterial Agents; Bacterial Infections; Bibliometrics; Colistin; Drug Resistance, Multiple, Bacterial; Humans

A rapid increase in multidrug-resistant Gram-negative infections has led to a reemergence of colistin use globally. Although it is well described among adults, colistin use and its associated toxicities in children are poorly understood. We report findings from the largest case series of pediatric colistin use to date.. We queried pediatric infectious diseases specialists from the Emerging Infections Network to identify members who had prescribed intravenous colistin within the past 7 years. We collected relevant demographic and clinical data. Bivariate analyses and multivariable logistic regression were performed.. Two hundred twenty-nine pediatric infectious diseases specialists completed the survey (84% response); 22% had prescribed colistin to children. Among respondents, 92 cases of colistin use from 25 institutions were submitted. The most commonly targeted organisms were multidrug-resistant Pseudomonas (67.4%), multidrug-resistant Acinetobacter -baumanii (11.9%), carbapenemase-producing Enterobacteriaceae (13.0%) and extended-spectrum β-lactamase producing Enterobacteriaceae (5.4%). Development of resistance to colistin was observed in 20.5% of patients. Additional antimicrobial therapy was administered to 84% of patients, and 22% of children experienced nephrotoxicity (not associated with dosage or interval of colistin prescribed). Renal function returned to baseline in all patients. Children aged ≥13 years had approximately 7 times the odds of developing nephrotoxicity than younger children, even after controlling for receipt of additional nephrotoxic agents (odds ratio 7.16; 95% confidence interval: 1.51-14.06; P = 0.013). Four children exhibited reversible neurotoxicity.. Most pediatric infectious diseases specialists have no experience prescribing colistin. Colistin use in children has been associated primarily with nephrotoxicity and, to a lesser extent, neurotoxicity, both of which are reversible. Emergence of resistance to colistin is concerning.

Topics: Administration, Intravenous; Adolescent; Analysis of Variance; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Colistin; Drug Resistance, Bacterial; Humans; Infant; Kidney Diseases; Logistic Models; Practice Patterns, Physicians'; Retrospective Studies; Treatment Outcome; United States

Recently, colistin has become a salvage therapy in the treatment of serious Intensive Care Unit infections owing to the emergence of extensively drug-resistant (XDR) bacterial isolates. This study aimed to show the effectiveness of colistin in critically ill patients with renal failure. A prospective case-control study of 94 patients admitted to medical intensive care units of a university hospital from December 2008 to June 2010 was conducted. All patients had infections with XDR Acinetobacter baumannii or Pseudomonas aeruginosa and received colistin. Cases comprised 39 patients with chronic renal failure (CRF) and controls were other patients without CRF. Apart from the male dominancy in the CRF group, there was no statistical difference between the two groups regarding demographic characteristics, Acute Physiology and Chronic Health Evaluation (APACHE) II score, and site and type of infection. In patients who completed colistin therapy, bacteriological cure was seen in 87% of patients with CRF and 95% of patients without CRF (P=0.890). Mortality in patients with CRF was similar to that in patients without CRF (44% and 42%, respectively) (P=0.999). Nephrotoxicity developed in 23.6% of patients in the control group. Concomitant nephrotoxic agents and total defined daily dose of colistin did not affect the development of nephrotoxicity. The mortality rate was 38% in patients with nephrotoxicity, similar to the mortality rate in patients without nephrotoxicity (36%) (P=0.999). In conclusion, in critically ill patients with CRF, colistin therapy, although used at a reduced dosage, was as effective as in patients without CRF.

Topics: Acinetobacter baumannii; Acute Kidney Injury; Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; APACHE; Bacterial Infections; Case-Control Studies; Colistin; Critical Illness; Drug Resistance, Multiple, Bacterial; Female; Hospitals, University; Humans; Kidney Failure, Chronic; Male; Middle Aged; Prospective Studies; Pseudomonas aeruginosa; Survival Analysis; Treatment Outcome

Recent exposure to azoles is an important risk factor for infection with fluconazole-resistant Candida spp., but little is known about the role of antibacterial drug exposure in the emergence of drug-resistant Candida. We did a prospective nationwide surveillance study of candidemia in Israel and analyzed the propensity score-adjusted association between antifungal and antibacterial drug exposure and bloodstream infection with C. glabrata and fluconazole-resistant Candida isolates. Four hundred forty-four episodes of candidemia (450 Candida isolates, 69 [15%] C. glabrata isolates, and 38 [8.5%] fluconazole-resistant isolates) from 18 medical centers in Israel were included. C. glabrata bloodstream infection was strongly associated with recent metronidazole exposure (odds ratio [OR], 3.2; P < 0.001). Infection with a fluconazole-resistant isolate was associated with exposure to carbapenems, trimethoprim-sulfamethoxazole, clindamycin, and colistin (odds ratio, 2.8; P = 0.01). The inclusion of antibacterial drug exposure in a multivariable model significantly enhanced the model's predictive accuracy for fluconazole-resistant Candida bloodstream infection. Our findings may be relevant to the selection of empirical antifungal treatment and broaden the scope of antibiotic-associated collateral damage.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Antifungal Agents; Bacteria; Bacterial Infections; Candida glabrata; Candidemia; Candidiasis; Carbapenems; Clindamycin; Coinfection; Colistin; Drug Resistance, Fungal; Female; Fluconazole; Humans; Israel; Microbial Sensitivity Tests; Middle Aged; Odds Ratio; Prospective Studies; Risk Factors; Trimethoprim, Sulfamethoxazole Drug Combination

Topics: Adjuvants, Pharmaceutic; Anti-Bacterial Agents; Bacterial Infections; Biofilms; Colistin; Drug Discovery; Drug Resistance, Bacterial; Drug Therapy, Combination; Humans; Iron Chelating Agents

Colistimethate sodium (CMS) was recently re-introduced into clinical practice as a last resort for the treatment of nosocomial infections caused by multiresistant bacteria. This retrospective cohort study was designed to identify predictors of acute kidney injury (AKI) associated with intravenous (i.v.) CMS treatment. From March 2007 to July 2008, 71 adult patients receiving CMS for > or = 72h were enrolled. AKI was defined using Risk, Injury, Failure, Loss and End-stage kidney disease (RIFLE) criteria according to serum creatinine. The median total dose of CMS was 54.3mg/kg (range 27.5-94.5mg/kg). AKI developed in 38 patients (53.5%). Cox regression analysis based of cumulative CMS dose (mg/kg) identified four independent predictors of AKI: male sex [hazard ratio (HR)=3.55, 95% confidence interval (CI), 1.47-8.55]; concomitant use of a calcineurin inhibitor (HR=6.74, 95% CI 2.49-18.24); hypoalbuminaemia (serum albumin level <2.0g/dL) (HR=6.29, 95% CI 2.04-19.39); and hyperbilirubinaemia (total bilirubin level >5mg/dL) (HR=3.53, 95% CI 1.17-10.71). In conclusion, AKI was a common complication of i.v. CMS treatment. Male sex, concomitant use of calcineurin inhibitors, hypoalbuminaemia and hyperbilirubinaemia were independent predictors of AKI. The effect of AKI on patient outcomes was not determined.

Topics: Aged; Anti-Bacterial Agents; Bacterial Infections; Cohort Studies; Colistin; Creatinine; Cross Infection; Female; Humans; Infusions, Intravenous; Kidney; Kidney Diseases; Male; Middle Aged; Retrospective Studies; Risk Factors

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Critical Illness; Cross Infection; Humans; Infusions, Intravenous; Male; Plasma; Renal Insufficiency

The emergence of Pseudomonas aeruginosa, Acinetobacter baumanii, and Enterobacteriaceae strains resistant to all beta-lactams (including carbapemenases producing strains), quinolones, aminoglycosides and no new antibiotics have led to reconsider the colimycin use. This antibiotic known since the 50s, had been completely abandoned, in one hand due to poor clinical activity and in other hand because of its toxicity (renal and neurological). The colimycin is an antibiotic complex like no other (until now, we have more questions than answers) and extremely difficult to use. It should be prescribed only when absolutely necessary and only after isolation of the strain responsible of the infection and determination of the in vitro susceptibility tests confirming both resistance to other antibiotics and sensitivity to colimycin. Even if the strain is resistant to other antibiotics, a synergy can be observed with many antibiotics. Monotherapy is not recommended because it promotes rapid development of resistance. Because of low serum concentrations, very close to MICs of targeted bacteria, the dosages are necessarily high.

Topics: Acinetobacter; Anti-Bacterial Agents; Bacterial Infections; Colistin; Drug Resistance, Bacterial; Drug Therapy, Combination; Enterobacteriaceae; Humans; Pseudomonas

Several guidelines on infection control and treatment of infection exist for cystic fibrosis (CF) caregivers, although the extent of implementation is variable.. Adherence to European Consensus Guidelines for CF was studied by sending surveys to named healthcare professionals in 487 European CF centres/units. Qualitative data analysis was performed.. A total of 177/547 (32%) surveys were returned. Infection control policies were implemented by most (77%) respondents. Separation of patients with Burkholderia cepacia was more common in adults (95%) than children (9%), and was implemented by 53% of respondents for Pseudomonas aeruginosa. Nebulised colistin plus oral ciprofloxacin was the most common (43%) therapy for P. aeruginosa infection. First infections of P. aeruginosa were usually treated with inhaled tobramycin; 41% of repondents did not intervene until lung function deteriorated. Most exacerbations were treated for less than the recommended period.. European Consensus Guidelines are widely adhered to. Areas for improvement include: initiating therapy for exacerbations early, separating infected patients and optimising duration of antibiotic therapy.

Topics: Administration, Inhalation; Adult; Anti-Bacterial Agents; Bacterial Infections; Burkholderia cepacia; Burkholderia Infections; Child; Child, Preschool; Ciprofloxacin; Colistin; Cystic Fibrosis; Europe; Guideline Adherence; Humans; Infection Control; Practice Guidelines as Topic; Pseudomonas aeruginosa; Pseudomonas Infections; Respiratory Tract Infections; Surveys and Questionnaires; Tobramycin; Young Adult

The incidence of acute renal failure, defined by the risk, injury, or failure criteria of the RIFLE criteria (risk, injury, failure, loss, and end-stage kidney disease), in 66 patients who received colistimethate sodium was 45%, and 21% of patients stopped therapy because of nephrotoxicity. The RIFLE criteria should be used in the future to allow for comparison of nephrotoxicity among studies.

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Colistin; Female; Humans; Incidence; Injections, Intravenous; Male; Renal Insufficiency; United States; Withholding Treatment; Young Adult

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Humans; Kidney Diseases

Topics: Adult; Anti-Bacterial Agents; Bacterial Infections; Colistin; Female; Humans; Incidence; Injections, Intravenous; Male; Renal Insufficiency; United States; Withholding Treatment; Young Adult

We sought to approach a practical question: Should polymyxins be used in the initial empirical antibiotic regimen in the intensive care unit (ICU) patient with fever that is thought to be due to infection? By retrieving data from the literature and the WHONET Greece, we formulated a mathematical model to estimate the probability (Ptotal) that a gram-negative bacterium susceptible only to polymyxins is isolated from an ICU patient. Ptotal = P1 * P2 * P3 * P4, where Ptotal = total probability; P1 = probability that fever is due to infection; P2 = probability that infection is due to gram-negative bacteria; P3 = probability that the gram-negative bacterium is Acinetobacter baumannii, Pseudomonas aeruginosa, or Klebsiella pneumoniae; and P4 = probability that A. baumannii, P. aeruginosa, or K. pneumoniae is susceptible only to polymyxins. Using the information from our data sources, we estimated that P1 (before physician input in differential diagnosis) = 0.5, P2 = 0.523, P3 = 0.79, and P4 = 0.567, thus Ptotal = P1 * P2 * P3 * P4 = 0.5 * 0.523 * 0.79 * 0.567 = 0.117 = 11.7%. Based on this information and combining it with data regarding the attributable mortality of inappropriate empirical antimicrobial treatment, 4 to 5 patients in every 100 ICU patients will die if physicians do not include polymyxins in the initial empirical regimen in the ICU setting for an episode of fever due to infection. Polymyxins should probably be included in the empirical antibiotic regimen in the ICU setting in hospitals, where the observed probability that a gram-negative bacterium (A. baumannii, P. aeruginosa, or K. pneumoniae) is polymyxin-only-susceptible is close to that (50%) used in our model (based on the individual hospital data).

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Critical Care; Critical Illness; Decision Support Techniques; Fever; Gram-Negative Bacteria; Humans; Polymyxin B; Polymyxins; Probability; Sensitivity and Specificity; Shock

Increasing antibiotic resistance in gram-negative bacteria has recently renewed interest in colistin as a therapeutic option. The increasing use of colistin necessitates the availability of rapid and reliable methods for colistin susceptibility testing. We compared seven methods of colistin susceptibility testing (disk diffusion, agar dilution on Mueller-Hinton [MH] and Isosensitest agar, Etest on MH and Isosensitest agar, broth microdilution, and VITEK 2) on 102 clinical isolates collected from patient materials during a selective digestive decontamination or selective oral decontamination trial in an intensive-care unit. Disk diffusion is an unreliable method to measure susceptibility to colistin. High error rates and low levels of reproducibility were observed in the disk diffusion test. The colistin Etest, agar dilution, and the VITEK 2 showed a high level of agreement with the broth microdilution reference method. Heteroresistance for colistin was observed in six Enterobacter cloacae isolates and in one Acinetobacter baumannii isolate. This is the first report of heteroresistance to colistin in E. cloacae isolates. Resistance to colistin in these isolates seemed to be induced upon exposure to colistin rather than being caused by stable mutations. Heteroresistant isolates could be detected in the broth microdilution, agar dilution, Etest, or disk diffusion test. The VITEK 2 displayed low sensitivity in the detection of heteroresistant subpopulations of E. cloacae. The VITEK 2 colistin susceptibility test can therefore be considered to be a reliable tool to determine susceptibility to colistin in isolates of genera that are known not to exhibit resistant subpopulations. In isolates of genera known to (occasionally) exhibit heteroresistance, an alternative susceptibility testing method capable of detecting heteroresistance should be used.

Topics: Acinetobacter baumannii; Acinetobacter Infections; Agar; Anti-Bacterial Agents; Bacterial Infections; Colistin; Cross Infection; Culture Media; Drug Resistance, Multiple, Bacterial; Enterobacter cloacae; Enterobacteriaceae Infections; Humans; Intensive Care Units; Microbial Sensitivity Tests; Polymyxin B

Topics: Bacterial Infections; Colistin; Drug Resistance, Bacterial; Humans; Time Factors

Topics: Anti-Bacterial Agents; Bacteria; Bacterial Infections; Colistin; Drug Resistance, Multiple, Bacterial; Humans; Safety

The intravenous use of polymyxins has been considered to be associated with considerable nephrotoxicity and neurotoxicity. For this reason, the systemic administration of polymyxins had been abandoned for about 20 years in most areas of the world. However, the problem of infections due to multidrug-resistant (MDR) Gram-negative bacteria such us Pseudomonas aeruginosa and Acinetobacter baumanniii has led to the re-use of polymyxins. Our objective was to study the toxicity of prolonged intravenous administration of colistin (polymyxin E).. An observational study of a retrospective cohort at "Henry Dunant" Hospital, a 450-bed tertiary care center in Athens, Greece, was undertaken.Patients who received intravenous colistin for more than 4 weeks for the treatment of multidrug resistant Gram-negative infections were included in the study. Serum creatinine, blood urea, liver function tests, symptoms and signs of neurotoxicity were the main outcomes studied.. We analyzed data for 19 courses of prolonged intravenous colistin [mean duration of administration (+/- SD) 43.4 (+/- 14.6) days, mean daily dosage (+/- SD) 4.4 (+/- 2.1) million IU, mean cumulative dosage (+/- SD) 190.4 (+/- 91.0) million IU] in 17 patients. The median creatinine value increased by 0.25 mg/dl during the treatment compared to the baseline (p < 0.001) but returned close to the baseline at the end of treatment (higher by 0.1 mg/dl, p = 0.67). No apnea or other evidence of neuromuscular blockade was noted in any of these patients who received prolonged treatment with colistin.. No serious toxicity was observed in this group of patients who received prolonged intravenous colistin. Colistin should be considered as a therapeutic option in patients with infections due to multidrug resistant Gram-negative bacteria.

Topics: Adolescent; Adult; Aged; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Biliary Tract; Cohort Studies; Colistin; Creatinine; Female; Humans; Infusion Pumps; Kidney; Liver; Liver Function Tests; Male; Middle Aged; Nervous System; Neuromuscular Junction; Pneumonia; Retrospective Studies; Time Factors; Urea

We compared the performance of selected ultrasonic and jet nebulizers when aerosolizing several antibiotic formulations to determine optimum combinations for delivery of a respirable antibiotic aerosol. Three ultrasonic devices were tested: the UltraNeb 99/100, the UltraAIR and the Aerosonic. The reusable jet nebulizers were the Dura ProNeb, Pari-LL and the Sidestream. The six disposable jet nebulizers were Marquest Acorn II, Hudson T Updraft II, Baxter MistyNeb, Pari-LC, Pari IS-2, and a disposable Sidestream. Each jet was tested with four compressors: a DeVilbiss AP-50, a Pulmo-Aide, a DuraNeb and a PariMaster. All nebulizing systems were initially tested with normal saline. From the initial data, six jet nebulizers and one ultrasonic device were tested with varying concentrations of tobramycin, gentamicin, ceftazidime, ciprofloxacin and colistin. Output was assessed by measuring volume (milliliters per minute), and amount of drug (milligrams per minute) nebulized. We then measured mean particle size of the antibiotic aerosol with seven jet nebulizers and two different compressors, Pulmo-Aide and PariMaster, and two ultrasonic devices. The rate of nebulization of saline and antibiotic solutions (milliliters per minute) was greater with the ultrasonic device(s) than all jet nebulizer systems tested. Increasing the reservoir antibiotic concentration increased the drug output (milligrams per minute) with the jet nebulizers to a maximum, followed by decreasing output. When antibiotic concentrations were increased the output decreased more precipitously with the ultrasonic devices than with the jet nebulizers. At the highest antibiotic concentrations tested, the ultrasonic devices had the lowest output. Particle size distribution was most dependent on the specific jet device, with particle size distribution less affected by a specific antibiotic or its concentration. Higher reservoir concentrations can be utilized for increasing output of respirable antibiotic aerosols by jet nebulizers. We conclude that antibiotic output is dependent upon both the nebulizing system and the reservoir concentration of antibiotic.

Topics: Aminoglycosides; Anti-Bacterial Agents; Anti-Infective Agents; Bacterial Infections; Ceftazidime; Ciprofloxacin; Colistin; Cystic Fibrosis; Equipment Design; Humans; Hydrogen-Ion Concentration; Nebulizers and Vaporizers; Osmolar Concentration; Particle Size; Viscosity

Topics: Animals; Antibiotic Prophylaxis; Bacteria, Aerobic; Bacteria, Anaerobic; Bacterial Infections; Cefazolin; Colistin; Cyclosporine; Drug Therapy, Combination; Enterobacteriaceae; Female; Intestine, Small; Liver; Liver Transplantation; Lung; Lymph Nodes; Nystatin; Spleen; Swine; Tobramycin; Transplantation, Homologous; Vancomycin

To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non-lymphoblastic leukaemia (ANLL) patients, 16 acute lymphoblastic leukaemia (ALL) patients] received TD and 31 patients (8 ANLL patients, 23 ALL patients) received SD from 1987 until 1991. TD consisted of colistin sulphate, neomycin, cephaloridine and amphotericin B orally as well as Orabase and sterilized food, while the patients were nursed in a single room. SD consisted of oral colistin sulphate, neomycin and amphotericin B. Those patients with ANLL were nursed in a single room; patients with ALL were nursed in a single room during remission induction therapy only. All patients except those with ANLL receiving TD received Pneumocystis carinii pneumonia prophylaxis with cotrimoxazole. Because the two groups were heterogeneous for diagnosis and chemotherapy the occurrence of fever (central body temperature at least 38.5 degrees C) and major infections (septicaemia of infections of the deep tissues or organs) were registered during periods of neutropenia (neutrophilic granulocytes < or = 500/mm3 for at least 8 days). Patients on TD had 55 periods of neutropenia, patients on SD 80. Patients on TD had 89.1 periods of fever/100 periods of neutropenia whereas patients on SD had 56.3. Also patients on TD had 27.3 major infections/100 periods of neutropenia whereas patients on SD had 11.3. Major infections predominantly consisted of septicaemia caused by gram-positive bacteria. We conclude that, in this study, TD in a non-protective environment does not offer better protection against major infections that SD in patients with ALL or ANLL.

Topics: Adolescent; Amphotericin B; Anti-Bacterial Agents; Bacteremia; Bacterial Infections; Carboxymethylcellulose Sodium; Cephaloridine; Cephalosporins; Child; Child, Preschool; Colistin; Drug Therapy, Combination; Food Handling; Gram-Negative Bacterial Infections; Humans; Infant; Intestines; Leukemia, Myeloid, Acute; Neomycin; Neutropenia; Pneumonia, Pneumocystis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Retrospective Studies; Sterilization; Trimethoprim, Sulfamethoxazole Drug Combination

The authors test antibiotic strategies aimed at either mitigating bacterial translocation from the gut or delivering antibiotics specifically concentrated by the pancreas for prevention of early secondary infection after acute necrotizing pancreatitis.. Infection currently is the principal cause of death after severe pancreatitis. The authors have shown that the risk of bacterial infection correlates directly with the degree of tissue injury in a rodent model of pancreatitis. Bacteria most likely arrive by translocation from the colon.. Severe acute necrotizing pancreatitis was induced in rats by a combination of low-dose controlled intraductal infusion of glycodeoxycholic acid superimposed on intravenous cerulein hyperstimulation. At 6 hours, animals were randomly allocated to five treatment groups: controls, selective gut decontamination (oral antibiotics and cefotaxime), oral antibiotics alone, cefotaxime alone, or imipenem. At 96 hours, surviving animals were killed for quantitative bacterial study of the cecum, pancreas, and kidney.. The 96-hour mortality (35%) was unaffected by any treatment regimen. Cecal gram-negative bacteria were significantly reduced only by the oral antibiotics. Pancreatic infection was significantly reduced by full-gut decontamination and by imipenem, but not by oral antibiotics or by cefotaxime alone. Renal infection was reduced by both intravenous antibiotics.. Early pancreatic infection after acute necrotizing pancreatitis can be reduced with a full-gut decontamination regimen or with an antibiotic concentrated by the pancreas (imipenem) but not by unconcentrated antibiotics of similar spectrum (cefotaxime) or by oral antibiotics alone. These findings suggest that 1) both direct bacterial translocation from the gut and hematogenous seeding interplay in pancreatic infection while hematogenous seeding is dominant at extrapancreatic sites and 2) imipenem may be useful in clinical pancreatitis.

Topics: Acute Disease; Administration, Oral; Amphotericin B; Animals; Bacteria; Bacterial Infections; Bacterial Physiological Phenomena; Cecal Diseases; Cefotaxime; Colistin; Disease Models, Animal; Drug Therapy, Combination; Imipenem; Injections, Intravenous; Kidney Diseases; Male; Necrosis; Pancreas; Pancreatic Diseases; Pancreatitis; Rats; Rats, Sprague-Dawley; Survival Rate; Tobramycin

Topics: Animals; Bacteria, Aerobic; Bacterial Infections; Colistin; Drug Therapy, Combination; Enterobacteriaceae; Female; Intestine, Small; Liver; Liver Transplantation; Lung; Lymph Nodes; Mycoses; Nystatin; Postoperative Complications; Spleen; Swine; Tobramycin; Transplantation, Autologous; Vancomycin

The purpose of selective decontamination of the digestive tract (SDD) is to eradicate potentially disease-producing micro-organisms from the oropharynx and gastro-intestinal tract of intensive care unit (ICU) patients, thereby reducing the incidence of nosocomial sepsis, particularly pneumonia. Microbial biofilms form on endotracheal (ET) tubes even when SDD is being administered and may represent a persistent focus for infection. The aim of this investigation was to determine the susceptibilities of organisms adherent to ET tubes to SDD antibiotics (amphotericin B, tobramycin and polymyxin) and to measure the concentrations of these agents in the tracheal aspirates of 11 patients who were being mechanically ventilated. Following extubation, a section was cut from the tip of each ET tube and any adherent microorganisms subsequently isolated were identified and their MICs determined. Samples of tracheal aspirate were obtained three hours after administration of the SDD regimen and the concentrations of the constituent antimicrobials were measured. Enterobacteriaceae were not recovered from any of the tubes but six strains of Staphylococcus aureus, three Pseudomonas spp., three enterococci and four yeasts were isolated. Wide variations in the concentrations of all antibiotics were observed and in many cases they were below the MICs for the organisms isolated. In particular, tobramycin concentrations were uniformly less than the median MIC for the S. aureus isolates and this may account for the predominance of Gram-positive bacteria adherent to the ET tubes. Microbial biofilms attached to these tubes may have a role in the pathogenesis of nosocomial pneumonia in ICU patients.

Topics: Amphotericin B; Bacteria; Bacterial Adhesion; Bacterial Infections; Colistin; Critical Care; Digestive System; Humans; Intubation, Intratracheal; Microbial Sensitivity Tests; Pseudomonas; Staphylococcus aureus; Tobramycin; Trachea

Topics: Administration, Oral; Bacterial Infections; Chloramphenicol; Colistin; Fosfomycin; Humans; Injections; Polymyxin B; Vancomycin

Two cases of gastrointestinal bleeding due to bacterial overgrowth syndrome are presented. The microbial contamination was confirmed by quantitative studies of the intestinal microflora and by therapeutic test; the association colistin-metronidazole could stop the digestive hemorrhage.

Topics: Bacterial Infections; Child; Colistin; Female; Gastrointestinal Hemorrhage; Humans; Metronidazole

Emergence of bacterial resistance to antimicrobial agents was studied during a period of 30 months of continuous use of parenteral cefotaxime combined with oral non-absorbable polymyxin E and tobramycin (selective decontamination) in a surgical intensive care unit (ICU). No increase in drug-resistance micro-organisms was found. Colonisation of the oropharyngeal cavity or intestine or both by strains resistant to polymyxin E occurred in 8% of patients (invariably Proteus and Morganella species). Tobramycin-resistant strains (Escherichia coli, Acinetobacter and Pseudomonas species) were found in 4% of patients. Intestinal colonisation with cefotaxime-resistant bacilli (e.g. Enterobacter, Pseudomonas and Acinetobacter species) occurred in 10% of patients, but in most patients these strains were eliminated by therapy with the topical antibiotics within one week. The control of emergence of resistance has major implications for the antibiotic policy in the ICU: firstly, the number of different antimicrobials used is sharply reduced since the switching of antibiotics to treat suprainfections is seldom necessary; secondly, it is possible to use a third generation cephalosporin such as cefotaxime for systemic prophylaxis, without risk of induction of resistance.

Topics: Administration, Oral; Bacterial Infections; Cefotaxime; Colistin; Critical Care; Drug Resistance, Microbial; Drug Therapy, Combination; Female; Gram-Negative Bacteria; Humans; Infusions, Intravenous; Male; Time Factors; Tobramycin

Topics: Adolescent; Adult; Aerobiosis; Bacterial Infections; Candida; Candidiasis; Child; Colistin; Gentamicins; Gram-Negative Bacteria; Humans; Intestines; Liver Transplantation; Nystatin; Pharynx; Postoperative Complications; Rectum

Topics: Administration, Topical; Adult; Anti-Bacterial Agents; Bacterial Infections; Burn Units; Burns; Child; Colistin; Environment, Controlled; Female; Gentamicins; Humans; Male; Methicillin; Penicillin Resistance; Pseudomonas aeruginosa; Pseudomonas Infections; Silver Sulfadiazine; Staphylococcus aureus; United Kingdom; Wound Infection

Topics: Animals; Animals, Domestic; Bacterial Infections; Colistin; Dogs; Endotoxins; Humans; Mesylates; Polymyxin B; Polymyxins; Rabbits; Urinary Tract Infections

Topics: Acute Disease; Bacterial Infections; Colistin; Drug Evaluation; Drug Therapy, Combination; Framycetin; Humans; Leukemia; Neomycin; Nystatin; Patient Isolation

The effect of antibiotic therapy on the intestinal flora was studied qualitatively and quantitatively in 41 infants. The results have been compared with 27 normal children of the same age and background. Antibiotics were responsible for the suppression of sensitive strains and for their replacement by resistant organisms but above all to a rapid multiplication of the intestinal flora. Colistin and pristinamycin caused these changes when given orally. Ampicillin when given both orally and parenterally but Colistin and the aminoglycosides when given parenterally did not have any effect. Fourteen cases of secondary septicaemia due to resistant organisms were observed but other factors were also important, namely the young age of the patients and intestinal problems (stasis and diarrhoea).

Topics: Age Factors; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Child; Child, Preschool; Colistin; Feces; Follow-Up Studies; Humans; Infant; Infant, Newborn; Infant, Newborn, Diseases; Intestinal Diseases; Intestines; Klebsiella Infections; Penicillin Resistance; Proteus Infections; Sepsis; Staphylococcal Infections

Topics: Adolescent; Adrenal Cortex Hormones; Asparaginase; Bacterial Infections; Child; Child, Preschool; Colistin; Cyclophosphamide; Cytarabine; Daunorubicin; Drug Therapy, Combination; Female; Humans; Infant; Injections, Spinal; Leukemia, Lymphoid; Male; Mercaptopurine; Methotrexate; Remission, Spontaneous; Skull; Vincristine

The therapeutic potencies of colistin methanesulfonate (CLM) was assessed quantitatively in acute infection of mice with clinically isolated strains of Escherichia coli and Pseudomonas aeruginosa, and effect of different routes of administration was compared. There was no detectable difference in the therapeutic effect of CLM when intramuscular (im) or intravenous (iv) administration was initiated one hour after the infection. On the other hand, a significant difference in ED50 given by im and iv administrations was observed, indicating the superiority of iv administration, when the treatment started 4 to approximately hours after the infection. No difference in the therapeutic effect of polymyxin B (PMB) and tetracycline (TC) administered via either im or iv route was found even in the delayed administration. In contrast to PMB and TC, lower toxicity of CLM was determined when it was administered iv rather than im.

Topics: Acute Disease; Animals; Bacterial Infections; Colistin; Escherichia coli; Escherichia coli Infections; Female; Injections, Intramuscular; Injections, Intravenous; Male; Mesylates; Mice; Polymyxins; Pseudomonas aeruginosa; Pseudomonas Infections; Tetracycline

35 patients were secondarily infected in our hospital with a strain of A. calcoaceticus resistant to the usual antibiotics and sulfonamides, but sensitive to colimycin. The epidemic lasted 118 days and is not yet finished. Each of the infected patients had a severe surgical or medical illness, underwent operations, trachetomy, etc. and was treated with antibiotics. A. calcoaceticus persisted alone or was associated with other bacteria from 1 to 46 days, in specimens (sputum, etc. or in blood) sometimes until death. It is not pathogenic for rabbits and mice; its pathogenicity in man is discussed in the text. The epidemic strain was not harboured by 15 doctors, students or nurses, nor present on 147 objects in the vicinity of the patients, but was found in a bottle of aqueous 1% eosin solution in the room of an infected child. Experiments show that A. calcoaceticus is not killed by a 1% eosin solution, and freely multiplies in broth containing 0,5% eosin. It is easy to identify the first case and chronology of the epidemic, but it is less easy to identify each time the means of propagation. Usually, infected patients seem to be the source of further infection. Does eosin paly more than an occasional role? Were the germs transported by dust? This not very disturbing epidemic suggests that less pathogenic germs may still cause unsuspected hospital epidemics.

Topics: Acinetobacter; Adolescent; Adult; Aged; Alcaligenes; Anti-Bacterial Agents; Bacterial Infections; Bronchopneumonia; Child; Child, Preschool; Colistin; Cross Infection; Disease Outbreaks; Drug Resistance, Microbial; Female; Humans; Infant; Male; Meningitis; Microbial Sensitivity Tests; Middle Aged; Pseudomonas aeruginosa

Topics: Adult; Age Factors; Aged; Ampicillin; Anti-Bacterial Agents; Bacterial Infections; Bile; Cephalosporins; Chloramphenicol; Cholecystectomy; Cholecystitis; Cholelithiasis; Clostridium perfringens; Colistin; Enterobacteriaceae; Escherichia coli; Female; Gentamicins; Humans; Kanamycin; Klebsiella; Male; Middle Aged; Penicillin Resistance; Prospective Studies; Proteus; Streptococcus; Streptomycin; Surgical Wound Infection; Tetracycline

Topics: Ampicillin; Bacitracin; Bacterial Infections; Carbenicillin; Cephalexin; Cephaloridine; Chloramphenicol; Colistin; Dexamethasone; Dicloxacillin; Enterobacteriaceae; Enterobacteriaceae Infections; Gentamicins; Humans; Microbial Sensitivity Tests; Neomycin; Penicillin G; Penicillin Resistance; Root Canal Therapy; Streptococcal Infections; Streptococcus; Tetracycline; Tooth Diseases

Topics: Ampicillin; Anti-Bacterial Agents; Bacteria; Bacterial Infections; Bacteriuria; Chloramphenicol; Colistin; Drug Resistance, Microbial; Enterococcus faecalis; Escherichia coli; Escherichia coli Infections; Humans; Hungary; Kanamycin; Klebsiella; Microbial Sensitivity Tests; Nalidixic Acid; Neomycin; Nitrofurantoin; Penicillin Resistance; Polymyxins; Proteus; Proteus Infections; Proteus mirabilis; Pseudomonas aeruginosa; Streptomycin; Tetracycline; Time Factors; Urinary Tract Infections; Urine

Topics: Ampicillin; Bacterial Infections; Carbenicillin; Cephalothin; Child, Preschool; Chloramphenicol; Colistin; Erythromycin; Gentamicins; Humans; Lincomycin; Male; Microbial Sensitivity Tests; Moraxella; Neomycin; Oleandomycin; Oxacillin; Penicillins; Sepsis; Stomatitis; Streptomycin; Sulfamethoxazole; Sulfonamides; Tetracycline; Trimethoprim

Topics: Anti-Bacterial Agents; Bacterial Infections; Cephalosporins; Chloramphenicol; Colistin; Drug Therapy, Combination; Erythromycin; Gentamicins; Humans; Kidney Failure, Chronic; Lincomycin; Nalidixic Acid; Nitrofurantoin; Penicillin Resistance; Penicillins; Sulfamethoxazole; Sulfonamides; Tetracycline; Trimethoprim

Topics: Acute Kidney Injury; Adolescent; Adult; Amphotericin B; Anti-Bacterial Agents; Bacterial Infections; Colistin; Deafness; Endocarditis, Bacterial; Female; Humans; Kanamycin; Kidney; Kidney Function Tests; Male; Middle Aged; Pseudomonas Infections; Sepsis; Staphylococcal Infections; Streptococcal Infections; Urea; Vancomycin

Topics: Bacterial Infections; Child; Child, Preschool; Colistin; Drug Combinations; Humans; Infant; Infant, Newborn; Otorhinolaryngologic Diseases; Penicillins

Topics: Anti-Bacterial Agents; Bacitracin; Bacterial Infections; Cataract; Cataract Extraction; Cephalothin; Chloramphenicol; Colistin; Drug Therapy; Erythromycin; Eye Diseases; Humans; Kanamycin; Neomycin; Novobiocin; Penicillins; Polymyxins; Postoperative Complications; Sulfadiazine; Tetracycline; Toxicology; Vancomycin

Topics: Anti-Bacterial Agents; Bacterial Infections; Child; Colistin; Diarrhea; Dysentery; Humans; Infant

Topics: Anti-Bacterial Agents; Bacterial Infections; Colistin; Humans; Infections; Pseudomonas Infections