fosfomycin and Cross-Infection

The gap between the emergence of antibiotic resistance and new antibiotic development has drawn attention to old antibiotics whose spectrum of coverage frequently comprises highly resistant bacteria. However, these antibiotics have frequently not undergone the structured process of antibiotic development of modern antibiotics, from pharmacokinetic/pharmacodynamic (PK/PD) studies establishing safe and effective dosing, establishment of susceptibility breakpoints, to clinical trials establishing clinical safety and effectiveness. In this review, we highlight the gaps for which we need old antibiotics in community- and hospital-acquired infections. Reviewing recently published and ongoing randomised controlled trials (RCTs) shows advances in our understanding of the efficacy and effectiveness of oral fosfomycin, mecillinam and nitrofurantoin for cystitis, and of trimethoprim/sulfamethoxazole for complicated skin infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in the community. Summarising older evidence shows the inferiority of chloramphenicol versus modern antibiotics for severe infections. We lack studies on severe infections caused by carbapenem-resistant Gram-negative bacteria and other multidrug-resistant (MDR) bacteria in hospitalised and critically ill patients; ongoing studies assessing colistin and intravenous fosfomycin might fill in some gaps. In the re-development process of old antibiotics, we mandate modern PK/PD studies comprising special populations as well as RCTs addressing the target population of patients in need of these antibiotics powered to examine patient-relevant outcomes. Structured antibiotic re-development from the laboratory to evidence-based treatment recommendations requires public funding, multidisciplinary collaboration, international co-ordination, and methods to streamline the recruitment of critically ill patients infected by MDR bacteria.

Topics: Amdinocillin; Anti-Bacterial Agents; Carbapenem-Resistant Enterobacteriaceae; Cross Infection; Drug Combinations; Drug Resistance, Multiple, Bacterial; Evidence-Based Medicine; Fosfomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Nitrofurantoin; Staphylococcal Skin Infections; Sulfamethizole; Trimethoprim; Trimethoprim, Sulfamethoxazole Drug Combination

Klebsiella pneumoniae producing KPC-type carbapenemase causes severe nosocomial infection at a high mortality rate. Nosocomial pneumonia in particular is associated with high mortality, likely due to the unfavorable pulmonary pharmacokinetics of the antibiotics used against this agent. Therefore, early and accurate microbiological identification and susceptibility evaluation are crucial in order to optimize antibiotic therapy. We report a case of ventilator-associated pneumonia caused by colistin-resistant K. pneumoniae producing KPC-type carbapenemase treated using a carbapenem-sparing therapy and tailored according to the serum procalcitonin concentration in order to limit the duration of antibiotic therapy.

Topics: Adult; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Calcitonin; Calcitonin Gene-Related Peptide; Colistin; Cross Infection; Drug Resistance, Bacterial; Drug Therapy, Combination; Equipment Contamination; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Minocycline; Pneumonia, Bacterial; Protein Precursors; Tigecycline; Treatment Outcome; Ventilators, Mechanical

Our objective was to evaluate the antimicrobial susceptibility of Enterobacteriaceae causing urinary tract infections (UTIs) in adults in Africa. The PubMed database was systematically searched to identify relevant studies published after 2000. Google, World Health Organization, and African Field Epidemiology networks were also searched. Twenty-eight studies, accounting for 381,899 urine isolates from 14 African countries, met the inclusion criteria. Escherichia coli, Klebsiella spp., and Proteus spp. were the most commonly encountered uropathogens. Cefotaxime, imipenem, fosfomycin, and ciprofloxacin were the antibiotics with the highest activity against E. coli isolates from outpatients, with susceptibility being 92 to 99, 100, 100, and 68 to 91%, respectively. The susceptibility among Klebsiella spp. isolates from outpatients varied from 80 to 100% for amikacin and from 53 to 100% for ciprofloxacin, while susceptibility was 74 to 78, 97, and 77% for ciprofloxacin, amikacin, and fosfomycin, respectively, among Klebsiella species isolates from inpatients or patients with hospital-acquired UTIs. With regard to Proteus spp., the highest activity was observed among fluoroquinolones; 71 to 100% of the P. mirabilis isolates were susceptible to ciprofloxacin in four studies, and 74 to 100% of the P. vulgaris isolates were susceptible to ofloxacin in two studies. The currently available evidence suggests that the antimicrobial susceptibility patterns of Enterobacteriaceae uropathogens in African countries were similar to those in countries of southeast Europe. Further original studies are warranted from African countries for which there is limited published data.

Topics: Africa; Amikacin; Anti-Bacterial Agents; Ciprofloxacin; Cross Infection; Databases, Factual; Drug Evaluation; Enterobacteriaceae; Enterobacteriaceae Infections; Fosfomycin; Humans; Microbial Sensitivity Tests; Prevalence; Urinary Tract Infections

Fosfomycin, originally named phosphonomycin, was discovered in Spain in 1969. There are three forms of fosfomycin: fosfomycin tromethamine (a soluble salt) and fosfomycin calcium for oral use, and fosfomycin disodium for intravenous use. Fosfomycin is a bactericidal antibiotic that interferes with cell wall synthesis in both Gram-positive and Gram-negative bacteria by inhibiting the initial step involving phosphoenolpyruvate synthetase. It has a broad spectrum of activity against a wide range of Gram-positive and Gram-negative bacteria. It is highly active against Gram-positive pathogens such as Staphylococcus aureus and Enterococcus, and against Gram-negative bacteria such as Pseudomonas aeruginosa and Klebsiella pneumoniae. Its unique mechanism of action may provide a synergistic effect to other classes of antibiotics including beta-lactams, aminoglycosides, and fluoroquinolones. Oral fosfomycin is mainly used in the treatment of urinary tract infections, particularly those caused by Escherichia coli and Enterococcus faecalis. Intravenous fosfomycin has been administered in combination with other antibiotics for the treatment of nosocomial infections due to multidrug-resistant (MDR) Gram-positive and Gram-negative bacteria. Fosfomycin has good distribution into tissues, achieving clinically relevant concentrations in serum, kidneys, bladder wall, prostate, lungs, inflamed tissues, bone, cerebrospinal fluid, abscess fluid, and heart valves. Fosfomycin is well tolerated, with a low incidence of adverse events. Further randomized controlled trials are needed in order to evaluate the efficacy of intravenous fosfomycin for the management of nosocomial infections due to MDR pathogens.

Topics: Anti-Bacterial Agents; Cross Infection; Enterococcus faecalis; Escherichia coli; Fosfomycin; Gram-Negative Bacterial Infections; Gram-Positive Bacterial Infections; Humans; Klebsiella pneumoniae; Pseudomonas aeruginosa; Urinary Tract Infections

The alarming epidemic of multidrug-resistant bacteria and the reluctance of the pharmaceutical industry to invest in the development of new antibiotics have forced clinicians to reintroduce forgotten antibiotics into their practice. This review highlights the effectiveness and safety of older antibiotics when used in the treatment of infections of critically ill patients.. Polymyxins emerged as useful antibiotics for the treatment of infections due to multidrug-resistant Gram-negative bacteria, in particular Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae. The nephrotoxicity and neurotoxicity associated with their use are less frequent and serious than previously reported. In addition, aerosolized polymyxins may be a useful weapon in the treatment of hospital-acquired pneumonia. Fosfomycin and chloramphenicol have a wide antimicrobial spectrum, are used extensively in Europe and Africa, respectively, and may have an expanded role in our antimicrobial arsenal. Fusidic acid remains active against various staphylococcal strains, while isepamicin (an aminoglycoside used in some European countries) is slightly more effective than amikacin against some Gram-negative bacteria.. The declining investment of the pharmaceutical industry in the development of new antibiotics and the increasing antimicrobial resistance create a fertile ground for the study and, probably, revival of older antibiotics for use, especially in critically ill patients.

Topics: Anti-Bacterial Agents; Chloramphenicol; Critical Illness; Cross Infection; Drug Resistance, Bacterial; Drug Utilization; Fosfomycin; Fusidic Acid; Gentamicins; Humans; Polymyxins

Multiresistant strains of Staphylococcus aureus (MRSA) are characterized by their virulence and clinical resistance to all known beta-lactam antibiotics. Furthermore, the representatives of most other classes of antibiotics are also proving to be no longer effective. While infections with the usual S. aureus strains can mostly be readily managed with penicillinase-resistant penicillins, the rescue antibiotic vancomycin, as also teicoplanin, in combination with, for example fosfomycin, are required in the treatment of MRSA and S. epidermidis infections. Since infections with S. aureus/MRSA are usually of endogenous origin, decolonization with mupirocin-containing nasal ointment applied as a prophylactic measure in patients with high colonization rates and/or immunosuppression, is of major importance. The best protection against further spread of highly resistant germs, such as MRSA is, in particular, profession hygiene management.

Topics: Aged; Anti-Bacterial Agents; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Fosfomycin; Humans; Immunosuppression Therapy; Microbial Sensitivity Tests; Risk Factors; Staphylococcal Infections; Staphylococcus aureus; Staphylococcus epidermidis; Teicoplanin; Time Factors; Vancomycin

Ninety-four patients infected with carbapenem-resistant Acinetobacter baumannii were randomized to receive colistin alone or colistin plus fosfomycin for 7 to 14 days. The patients who received combination therapy had a significantly more favorable microbiological response and a trend toward more favorable clinical outcomes and lower mortality than those who received colistin alone. (This study has been registered at ClinicalTrials.gov under registration no. NCT01297894.).

Topics: Acinetobacter baumannii; Acinetobacter Infections; Aged; Anti-Bacterial Agents; Carbapenems; Colistin; Cross Infection; Drug Resistance, Multiple, Bacterial; Drug Therapy, Combination; Female; Fosfomycin; Humans; Male; Microbial Sensitivity Tests; Pilot Projects; Treatment Outcome

Intensive care unit (ICU)-acquired infections as a result of multidrug-resistant Gram-negative pathogens remain a serious problem in critically ill patients. Adult ICU patients who received intravenous fosfomycin were prospectively examined to assess its safety and effectiveness as an adjunct to the antimicrobial therapy of life-threatening infections caused by carbapenem-resistant Klebsiella pneumoniae. Fosfomycin was administered intravenously in 11 patients for treatment of hospital-acquired infections caused by carbapenem-resistant K. pneumoniae. Fosfomycin (2-4 g every 6 h) was administered in combination with other antibiotics. The mean +/- SD duration of treatment was 14 +/- 5.6 days. All patients had good bacteriological and clinical outcome of infection. All-cause hospital mortality was two out of 11 (18.2%) patients. No patient experienced adverse events related to the administration of fosfomycin. Intravenous fosfomycin may be a beneficial and safe adjunctive treatment in the management of life-threatening ICU-acquired infections caused by carbapenem-resistant K. pneumoniae.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactam Resistance; Carbapenems; Critical Illness; Cross Infection; Female; Fosfomycin; Humans; Infusions, Intravenous; Intensive Care Units; Klebsiella Infections; Klebsiella pneumoniae; Male; Middle Aged; Prospective Studies; Treatment Outcome

The aim of this study was to determine the in-vitro activity of fosfomycin against

Topics: Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cross Infection; Escherichia coli; Escherichia coli Infections; Fosfomycin; Humans; Klebsiella pneumoniae; Microbial Sensitivity Tests

Fosfomycin exhibits excellent in vitro activity against multidrug-resistant pathogens, including methicillin-resistant Staphylococcus aureus (MRSA). Increasing fosfomycin resistance among clinical MRSA isolates was reported previously, but little is known about the relative abundance of Fosfomycin resistance genes in MRSA isolates circulating in Taiwan.. All MRSA isolates, collected in 2002 and 2012 by the Taiwan Surveillance of Antimicrobial Resistance (TSAR) program, were used in this study. Susceptibility to various antimicrobial agents, including fosfomycin, was determined by broth microdilution. Genetic determinants of fosfomycin resistance, including fosB carriage and murA, glpT and uhpT mutations, were investigated using PCR and sequencing of amplicons. Staphylococcal protein A (spa) typing was also performed to determine the genetic relatedness of MRSA isolates.. A total of 969 MRSA strains, 495 in the year 2002 and 474 in the year 2012, were analyzed. The overall in vitro susceptibility was 8.2% to erythromycin, 18.0% to clindamycin, 29.0% to tetracycline, 44.6% to ciprofloxacin, 57.5% to trimethoprim/sulfamethoxazole, 86.9% to rifampicin, 92.9% to fosfomycin and 100% to linezolid and vancomycin. A significant increase in the fosfomycin resistance rate was observed from 3.4% in 2002 to 11.0% in 2012. Of 68 fosfomycin-resistant MRSA isolates, several genetic backgrounds probably contributing to fosfomycin resistance were identified. Twelve isolates harbored the fosB gene, and various mutations in murA, uhpT, and glpT genes were noted in 11, 59, and 66 isolates, respectively. The most prevalent gene mutations were found in the combination of uhpT and glpT genes (58 isolates). The vast majority of the fosfomycin-resistant MRSA isolates belonged to spa type t002.. An increased fosfomycin resistance rate of MRSA isolates was observed in our present study, mostly due to mutations in the glpT and uhpT genes. Clonal spread probably contributed to the increased fosfomycin resistance.

Topics: Anti-Bacterial Agents; Bacterial Proteins; Cross Infection; Drug Resistance, Bacterial; Fosfomycin; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Mutation; Prevalence; Staphylococcal Infections; Taiwan

Antimicrobial resistance (AMR) is of increasing global concern, threatening to undermine recent progress in reducing child and neonatal mortality. Repurposing older antimicrobials is a prominent strategy to combat multidrug-resistant sepsis. A potential agent is fosfomycin, however, there is scarce data regarding its in vitro activity and pharmacokinetics in the paediatric population.. We analysed a contemporary, systematically collected archive of community-acquired (CA) and hospital-acquired (HA) paediatric Gram-negative bacteraemia isolates for their susceptibility to fosfomcyin. MICs were determined using agar serial dilution methods and validated by disk diffusion testing where breakpoints are available. Disk diffusion antimicrobial susceptibility testing was also conducted for current empirical therapies (ampicillin, gentamicin, ceftriaxone) and amikacin (proposed in the literature as a new combination empirical therapeutic option).. Fosfomycin was highly active against invasive Gram-negative isolates, including 90  % (202/224) of Enterobacteriaceae and 96  % (22/23) of Pseudomonas spp. Fosfomycin showed high sensitivity against both CA isolates (94 %, 142/151) and HA isolates (81 %, 78/96; P =0.0015). CA isolates were significantly more likely to be susceptible to fosfomycin than the current first-line empirical therapy (96  % vs 59  %, P <0.0001). Extended spectrum β-lactamases (ESBL) production was detected in 34  % (85/247) of isolates with no significant difference in fosfomycin susceptibility between ESBL-positive or -negative isolates [73/85 (86  %) vs 147/162 (91  %) respectively, P =0.245]. All isolates were susceptible to a fosfomycin-amikacin combination.. Gram-negative paediatric bacteraemia isolates are highly susceptible to fosfomycin, which could be combined with aminoglycosides as a new, carbapenem-sparing regimen to achieve excellent coverage to treat antimicrobial-resistant neonatal and paediatric sepsis.

Topics: Anti-Bacterial Agents; Bacteremia; Child, Preschool; Community-Acquired Infections; Cross Infection; Enterobacteriaceae; Enterobacteriaceae Infections; Escherichia coli Infections; Female; Fosfomycin; Gram-Negative Bacteria; Humans; Infant; Infant, Newborn; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Pseudomonas; Sepsis

The emergence of extended-spectrum β-lactamase-producing Enterobacteriaceae (ESBL-E) infections requires re-assessment of therapeutic choices. Here we report the efficacy of cefoxitin-based antibiotic therapy for ESBL-E prostatitis. A prospective study including patients with ESBL-E prostatitis resistant to trimethoprim/sulfamethoxazole and fluoroquinolones from January 2014 to March 2016 was conducted. Cefoxitin was administered by continuous infusion for 3 weeks in the case of acute bacterial prostatitis or 6 weeks in the case of chronic bacterial prostatitis (CBP), with intravenous fosfomycin for the first 5 days. Urological investigations were performed to diagnose underlying urinary tract pathology. Clinical and microbiological efficacy were evaluated 3 months (M3) and 6 months (M6) after the end of therapy. A total of 23 patients were included in the study. The median patient age was 74 years (range 48-88 years). Of the 23 infections, 14 (61%) were CBP and 12 (52%) were healthcare-associated infections. The bacteria involved were Escherichia coli in 11 cases, Klebsiella pneumoniae in 10 cases and Klebsiella oxytoca in 2 cases. Clinical cure was observed in 19/23 patients (83%) at M3 and in 17/22 patients (77%) at M6. Urocultures were sterile in 13/23 patients (57%) at M3 and in 9/19 patients (47%) and M6. Urinary colonisation was observed in 6/19 patients (32%) with clinical cure at M3 and 5/14 patients (36%) with clinical cure at M6. No resistance to cefoxitin was detected. Surgical treatment was required for 7/23 patients (30%). In conclusion, cefoxitin-based antibiotic therapy is suitable for difficult-to-treat ESBL-E infections such as prostatitis.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cefoxitin; Cross Infection; Escherichia coli; Escherichia coli Infections; Fluoroquinolones; Fosfomycin; Humans; Klebsiella Infections; Klebsiella oxytoca; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Pilot Projects; Prospective Studies; Prostatitis; Treatment Outcome; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

In this study, we investigated the fosfomycin susceptibility rates among different methicillin-resistant Staphylococcus aureus (MRSA) clones. A total of 293 MRSA isolates obtained from Sir Run Run Shaw hospital during 2013-2015 were tested for fosfomycin susceptibility. The overall fosfomycin resistance rate among these MRSA isolates was 53.2%. Although 91.9% of the ST5 MRSA isolates (MIC50>1,024 mg/L) were resistant to fosfomycin, no fosfomycin-resistant isolate was found among the 69 ST59 MRSA isolates (MIC50/90, 0.5/4 mg/L). The fosfomycin resistance rate among the MRSA isolates recovered from skin and soft tissue infections was 19.1%, which was lower than the rates detected among MRSA isolates from other types of invasive infections. The fosfomycin resistance rate in community-onset MRSA was 30.2%, which was lower than that detected in healthcare-associated MRSA of 70.7%. One MRSA isolate had the fosB7 gene, whereas most (127/156) of the fosfomycin-resistant MRSA isolates had deletions in glpT genes. These findings highlight the importance of monitoring the fosfomycin susceptibility in MRSA isolates for epidemiological purposes.

Topics: Anti-Bacterial Agents; China; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Fosfomycin; Genotype; Hospitals, University; Humans; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Prevalence; Staphylococcal Infections

To determine in vitro susceptibility of multiresistant bacterial isolates to fosfomycin.. In this prospective in vitro study (local non-random sample, level of evidence 3), 288 consecutively collected multiresistant bacterial isolates from seven medical centers in Croatia were tested from February 2014 until October 2016 for susceptibility to fosfomycin and other antibiotics according to Clinical and Laboratory Standards Institute methodology. Susceptibility to fosfomycin was determined by agar dilution method, while disc diffusion was performed for in vitro testing of other antibiotics. Polymerase chain reaction and sequencing were performed for the majority of extended spectrum β-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) and carbapenem-resistant isolates.. The majority of 288 multiresistant bacterial isolates (82.6%) were susceptible to fosfomycin. The 236 multiresistant Gram-negative isolates showed excellent susceptibility to fosfomycin. Susceptibility rates were as follows: Escherichia coli ESBL 97%, K. pneumoniae ESBL 80%, Enterobacter species 85.7%, Citrobacter freundii 100%, Proteus mirabilis 93%, and Pseudomonas aeruginosa 60%. Of the 52 multiresistant Gram-positive isolates, methicillin-resistant Staphylococcus aureus showed excellent susceptibility to fosfomycin (94.4%) and vancomycin-resistant enterococcus showed low susceptibility to fosfomycin (31%). Polymerase chain reaction analysis of 36/50 ESBL-producing K. pneumoniae isolates showed that majority of isolates had CTX-M-15 beta lactamase (27/36) preceded by ISEcp insertion sequence. All carbapenem-resistant Enterobacter and Citrobacter isolates had blaVIM-1 metallo-beta-lactamase gene.. With the best in vitro activity among the tested antibiotics, fosfomycin could be an effective treatment option for infections caused by multiresistant Gram-negative and Gram-positive bacterial strains in the hospital setting.

Topics: Anti-Bacterial Agents; beta-Lactamases; Croatia; Cross Infection; Drug Resistance, Multiple, Bacterial; Escherichia coli; Fosfomycin; Gram-Negative Bacteria; Gram-Positive Bacteria; Humans; Klebsiella pneumoniae; Methicillin-Resistant Staphylococcus aureus; Prospective Studies

Topics: Anti-Bacterial Agents; Cross Infection; Drug Monitoring; Drug Resistance, Multiple, Bacterial; Early Diagnosis; Fosfomycin; Heart Failure; Humans; Natriuretic Peptide, Brain; Peptide Fragments

The appearance of extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacteria in urinary tract infection (UTI) constitutes an important therapeutic challenge. The aim of this study was to describe drug susceptibility profiles of ESBL-producing bacteria isolated from urine samples. We also determined the antimicrobial co-resistance to several agents, including fosfomycin.. The computerized database was used to identify ESBL-positive urine samples. We analyzed E. coli and Klebsiella isolates obtained from urine cultures, and duplicate isolates and isolates not tested against fosfomycin were excluded. The cases were further categorized according to UTI definition [community-acquired (CoA) UTI, community-onset health care-associated (HCA) UTI, and hospital-acquired (HA) UTI]. ESBL isolates were stratified according to their origin into two groups: urology and non-urology isolates.. Antimicrobial susceptibilities of the strains to fosfomycin were tested in 277 ESBL-positive strains, 217 ESBL-EC strains, and 60 ESBL-KP strains. The most effective agents were carbapenems, such as imipenem and meropenem. The least active substances were ciprofloxacin (20.7 %), levofloxacin (22.7 %), trimethoprim-sulfamethoxazole (34.3 %), and ampicillin-clavulanate (42.9 %). Overall, 243 out of the 277 (87.7 %) isolates tested were susceptible to fosfomycin. Higher fosfomycin sensitivity was observed in E. coli (94.9 %) compared to Klebsiella (61.7 %) (p = 0.001). ESBL-positive isolates from urological (68 isolates) and non-urological patients (209 isolates) showed similar susceptibility profiles. Other than carbapenems, isolates from CoA-UTI showed higher sensitivity to fosfomycin (100 %) and nitrofurantoin (93.1 %), isolates from HCA-UTI showed higher sensitivity to amikacin (94.1 %), and isolates from HA-UTI showed overall poor sensitivity to antibiotics.. Fosfomycin could be an alternative treatment option for UTIs related to ESBL-producing E. coli spp. and CoA-UTI, but not for UTIs related to ESBL-producing Klebsiella spp. Antimicrobial susceptibilities of ESBL-producing strains were different according to the UTI classification. Fosfomycin showed decreased activity against isolates from HCA-UTI and HA-UTI. However, further clinical verification is required to assess the clinical efficacy of fosfomycin for the treatment of UTIs caused by ESBL-producing E. coli isolates.

Topics: Adolescent; Adult; Aged, 80 and over; Anti-Bacterial Agents; beta-Lactamases; Cross Infection; Escherichia coli; Escherichia coli Infections; Female; Fosfomycin; Humans; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Outcome Assessment, Health Care; Republic of Korea; Retrospective Studies; Urinary Tract Infections

The molecular epidemiology of 66 NDM-producing isolates from 2 Pakistani hospitals was investigated, with their genetic relatedness determined using repetitive sequence-based PCR (Rep-PCR). PCR-based replicon typing and screening for antibiotic resistance genes encoding carbapenemases, other β-lactamases, and 16S methylases were also performed. Rep-PCR suggested a clonal spread of Enterobacter cloacae and Escherichia coli. A number of plasmid replicon types were identified, with the incompatibility A/C group (IncA/C) being the most common (78%). 16S methylase-encoding genes were coharbored in 81% of NDM-producing Enterobacteriaceae.

Topics: Acinetobacter baumannii; Amdinocillin; Anti-Bacterial Agents; Bacterial Proteins; beta-Lactamases; Carbapenems; Cross Infection; DNA, Bacterial; Doripenem; Enterobacteriaceae; Fosfomycin; Humans; Meropenem; Methyltransferases; Microbial Sensitivity Tests; Molecular Epidemiology; Multilocus Sequence Typing; Pakistan; Thienamycins

The aim of this study was to evaluate the in vitro activities of antimicrobial agents including fosfomycin tromethamine against Gram-negative isolates recovered from urine samples.. A total of 2334 strains (1562 Escherichia coli, 509 Klebsiella spp, 85 Proteus spp, 75 Pseudomonas spp, 45 Enterobacter spp, 37 Acinetobacter baumannii, 8 Citrobacter spp, 7 Morganella morganii, and 6 Serratia spp) were identified by VITEK 2 during the study period, November 2008 to June 2012. Antimicrobial susceptibilities of the strains were also evaluated using the Kirby-Bauer disk diffusion method, in accordance with the Clinical and Laboratory Standards Institute guidelines.. Overall, 2160 (92.5%) of the isolates tested were susceptible to fosfomycin tromethamine. Higher resistance rates were observed among inpatients compared to outpatients. Resistance rates by strain were: 2.0% for E. coli, 4.4% for Enterobacter spp, 6.9% for Klebsiella spp, 9.4% for Proteus spp, 48.6% for A. baumannii, 56.0% for Pseudomonas spp, and 100% for Morganella morganii. All Serratia spp and Citrobacter spp strains were susceptible. Extended-spectrum beta-lactamase (ESBL)-producing isolates displayed higher fosfomycin resistance rates than negative strains (19.2% vs. 2.9%). The highest in vitro activity was detected for amikacin, piperacillin-tazobactam, and imipenem for all strains including ESBL-producers.. Regardless of ESBL production, the excellent activity of fosfomycin against E. coli, Enterobacter spp, Serratia spp, and Citrobacter spp, indicates that the drug is a valuable therapeutic option for urinary tract infections, even those with co-trimoxazole- and ciprofloxacin-resistant isolates, but not in ESBL-producing Klebsiella spp, Pseudomonas spp, A. baumannii, and Proteus spp. Further studies should be carried out to determine the in vivo drug activity among Enterobacteriaceae other than E. coli.

Topics: Anti-Bacterial Agents; Community-Acquired Infections; Cross Infection; Drug Resistance, Bacterial; Fosfomycin; Gram-Negative Bacteria; Gram-Negative Bacterial Infections; Humans; Microbial Sensitivity Tests; Urinary Tract Infections

Topics: Carbapenems; Colistin; Cross Infection; Doripenem; Drug Resistance, Bacterial; Drug Therapy, Combination; Female; Fosfomycin; Humans; Infusions, Intravenous; Male; Microbial Sensitivity Tests; Middle Aged; Pneumonia, Ventilator-Associated; Pseudomonas aeruginosa; Retrospective Studies; Time Factors

Seven carbapenem-resistant NDM-1-positive Klebsiella pneumoniae isolates were recovered from patients hospitalized between 2007 and 2009 in different wards at a referral and tertiary care center in Nairobi. Most of the isolates were obtained from urine. All isolates carried the bla(NDM-1) carbapenemase gene previously reported from India, Pakistan, and the United Kingdom. These isolates were clonally related and expressed many other resistance determinants, including β-lactamases CTX-M-15, OXA-1, OXA-9, CMY-6, and aminoglycoside resistance methylase RmtC. This work corresponds to the first report of NDM-1 producers in Africa.

Topics: Adult; Aged; Anti-Bacterial Agents; beta-Lactamases; Carbapenems; Cross Infection; DNA, Bacterial; Drug Resistance, Multiple, Bacterial; Electrophoresis, Gel, Pulsed-Field; Female; Humans; Kenya; Klebsiella Infections; Klebsiella pneumoniae; Male; Microbial Sensitivity Tests; Middle Aged; Polymerase Chain Reaction

Nosocomial infections are a matter of concern in surgical wards. Their incidence is constantly increasing, especially among immunocompromised patients who are vulnerable to colonization by opportunistic pathogens such as Staphylococcus aureus. The bacterium accumulates resistance mechanisms against antibiotics such as vancomycin. The objective of our study was to explore this resistance, to screen for Staphylococcus aureus strains resistant to vancomycin, and to try various antibiotic combinations against these strains.. The antibiotic susceptibility of 220 S. aureus strains was determined by agar diffusion and evaluation of minimal inhibitory concentrations (MICs), by dilution technique on solid medium according to clinical and laboratory standard institute (CLSI) standards. The screening of strains resistant to vancomycin was performed on brain heart infusion agar medium, supplemented with 6μg/mL of vancomycin according to CLSI standards, and confirmed by determining MICs. The effectiveness of various antibiotic combinations was assessed by the checkerboard microplate method.. The results show multidrug resistance to agents known for their antistaphylococcal activity with fluctuations in the level of resistance.. Three strains proved resistant to vancomycin. The vancomycin/gentamycin combination was the most effective.

Topics: Adult; Aged; Algeria; Aminoglycosides; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactams; Cross Infection; Dose-Response Relationship, Drug; Drug Resistance, Multiple, Bacterial; Female; Fosfomycin; Gentamicins; Hospitals, University; Humans; Male; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Middle Aged; Rifampin; Staphylococcal Infections; Surgical Wound Infection; Vancomycin; Vancomycin Resistance

Effective therapeutic options are needed for community-onset urinary tract infections due to Escherichia coli strains that produce CTX-M extended-spectrum beta-lactamases. We examined 46 urinary isolates producing CTX-M against several oral or long-acting parenteral antimicrobial agents. Approximately 90% were susceptible to fosfomycin and to a combination of cefdinir plus amoxicillin-clavulanate. All were susceptible to ertapenem.

Topics: Administration, Oral; Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactamases; beta-Lactams; Cefdinir; Cephalosporins; Cross Infection; Enterobacteriaceae; Ertapenem; Escherichia coli; Fosfomycin; Humans; Infusions, Parenteral; Microbial Sensitivity Tests; Outpatients; Urinary Tract Infections

Rational antibiotic prophylaxis and antibacterial therapy of nosocomial infections is an actual problem in surgery. Improvement of antimicrobial chemotherapy and prophylaxis of nosocomial infections is of special importance in urgent cases in oncologic units. Data on the design of rational schemes for antibacterial prophylaxis of nosocomial infections developing during the postoperative period in patients with cancer of the urinary bladder as one of the unfavourable complications of the main disease treatment are presented. The use of fosfomycin in the schemes of the antibiotic prophylaxis was shown to be more efficient vs. the use of the traditional beta-lactam antibiotics.

Topics: Aged; Amoxicillin; Anti-Bacterial Agents; Cefuroxime; Clavulanic Acid; Cross Infection; Female; Fosfomycin; Humans; Male; Middle Aged; Retrospective Studies; Urinary Bladder Neoplasms

Topics: Acetamides; Cross Infection; Enterococcus faecium; Fosfomycin; Gram-Positive Bacterial Infections; Humans; Linezolid; Microbial Sensitivity Tests; Oxazolidinones; Vancomycin Resistance

Infection due to extended-spectrum beta-lactamase (ESBL)-producing microorganisms is an emerging problem in the community; a high proportion of these microorganisms have been isolated from urine samples of women with uncomplicated urinary tract infections (UTI). The options for oral treatment of uncomplicated UTI are limited because of the multiple drug resistance typical of ESBL-producing strains.. The in vitro activity of fosfomycin (FOS) was determined against 428 ESBL-producing strains, including 290 (68%) E. coli and 138 (32%) K. pneumoniae. Activity of fosfomycin was compared with that of amoxicillin-clavulanate (AMC), ciprofloxacin (CIP) and cotrimoxazole (SxT). MICs of AMC, CIP, and SxT, and detection of ESBL production were tested by the broth microdilution method, whereas FOS MICs were determined by the agar dilution method. ESBLs were characterized by isoelectric focusing, polymerase chain reaction (PCR) and direct sequencing of encoding genes. The genetic relationship among the isolates was determined by REP-PCR.. Among the 428 ESBL-producing isolates studied, 417 (97.4%) were susceptible to FOS (MIC < or = 64 microg/mL). The resistance rate of E. coli to FOS was 0.3%, and was lower than resistance to AMC (11.7%), whereas the resistance rate of K. pneumoniae was 7.2% and was equal to resistance to AMC. SxT and CIP were the least active antibiotic agents against ESBL-producing isolates (sensitivity < 50%). There were no differences in fosfomycin activity against strains expressing different types of ESBLs.. Fosfomycin showed maintained activity against ESBL-producing strains and did not present co-resistance with other antimicrobial groups.

Topics: Amoxicillin-Potassium Clavulanate Combination; Anti-Bacterial Agents; beta-Lactam Resistance; beta-Lactamases; Ciprofloxacin; Cross Infection; Escherichia coli; Escherichia coli Infections; Fosfomycin; Klebsiella Infections; Klebsiella pneumoniae; Microbial Sensitivity Tests; Multicenter Studies as Topic; Substrate Specificity; Trimethoprim, Sulfamethoxazole Drug Combination; Urinary Tract Infections

The combination of cefotaxime and fosfomycin (CTX-FOS) has been proposed in France for the empirical treatment of postoperative nosocomial meningitis since the late 1980s. The purpose of this work was to evaluate this strategy today, as well as other possible treatments.. Each patient undergoing a neurosurgical procedure was prospectively included in a database designed for the surveillance of surgical site infection (SSI). For each meningitis detected, we analysed the in vitro susceptibility of the causative micro-organisms to cefotaxime alone (CTX), cefotaxime-fosfomycin (CTX-FOS), vancomycin (VAN) and cefotaxime-vancomycin (CTX-VAN) combinations. The patient population was divided into two groups according to the presence or absence of CSF shunting material.. 116 patients had had a postoperative meningitis/ventriculitis during the last 36 months, among 6447 patients undergoing neurosurgery in our department (1.8%). Ten patients had aseptic meningitis (8.6%). Overall sensitivity to CTX was 69.8%, as compared to 77.3% with CTX-FOS combination (NS). This result was due to a large proportion of fosfomycin resistant cocci in our population. The CTX-VAN combination increased the overall in vitro susceptibility up to 91.5%, but the benefit of this combination was only significant in CSF shunting material patients. In these latter patients, VAN was as effective as CTX-FOS combination.. CTX-FOS combination is no longer the best choice for empirical treatment of post neurosurgical meningitis. CTX alone can be safely used in patients without a CSF shunt; in those with either a ventriculostomy or a CSF shunt associated ventriculitis, a CTX-VAN combination could improve treatment efficacy, provided that high doses of vancomycin are used to ensure correct CSF diffusion.

Topics: Adult; Aged; Cefotaxime; Central Nervous System Diseases; Cerebrospinal Fluid Shunts; Craniotomy; Cross Infection; Dose-Response Relationship, Drug; Drug Therapy, Combination; Female; Fosfomycin; Humans; Male; Meningitis, Aseptic; Meningitis, Bacterial; Methicillin Resistance; Microbial Sensitivity Tests; Middle Aged; Prospective Studies; Staphylococcal Infections; Surgical Wound Infection; Treatment Outcome; Vancomycin

To investigate at what time the peak level should be determined under conventional thrice daily (t.i.d.) administration of the aminoglycoside netilmicin and to study its serum concentrations under once daily (od) treatment to define the required daily dose and to gain information about convenient drug monitoring.. The design of the study was a consecutive sample trial.. The study took place in a university hospital.. 41 intubated patients of a surgical ICU who received netilmicin as a short-term infusion over 30 min for life-threatening infections were included in the study.. In 21 patients netilmicin was administered t.i.d. The virtual peak levels which had been determined by pharmacokinetic dosage calculation were compared with the serum concentrations obtained directly after the administration as well as after 15, 30, 60 and 180 min. In 20 patients the netilmicin serum concentrations during od treatment were determined directly before and immediately after the application as well as 0.5, 1, 3, 7 and 12 h later. To achieve a virtual peak level of 25 mg/l and a trough level of 0.5 mg/l individual adjustment of the dosage based on pharmacokinetic calculations was performed.. In t.i.d. treatment the serum concentration measured after 30 min was closest to the virtual peak level; therefore, this is the best time to determine the peak level. In od treatment the required daily dose was 7.86 mg/kg body weight (median) in patients with normal renal function. During od dosing the trough level was extremely important in drug monitoring, whereas determination of the high peak level was of doubtful value.. The peak level should be determined during t.i.d. administration at 30 min. In od treatment the initial daily dose should be 7 mg/kg body weight; in drug monitoring the trough level is very important.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cefotaxime; Cross Infection; Dose-Response Relationship, Drug; Drug Administration Schedule; Female; Fosfomycin; Gram-Negative Bacterial Infections; Humans; Infusions, Intravenous; Intensive Care Units; Male; Metabolic Clearance Rate; Metronidazole; Middle Aged; Netilmicin; Piperacillin; Respiration, Artificial; Staphylococcal Infections; Teicoplanin

In newborn, fosfomycin-cefotaxime in combination is more and more commonly used for the treatment of nosocomial infections. A pharmacokinetic study was conducted in ten newborns in the aim of suggesting a therapeutic schedule of the fosfomycin. Each newborn received 200 mg/kg, intravenously twice a day. Two groups have been formed according to the time of perfusion: 2 h or 30 min. The study of pharmacokinetic parameters do not demonstrated significant difference between the two populations. In addition, residual serum concentrations, twelve hours after the administration, are greater than the minimal inhibitory concentrations of most common pathogens causing nosocomial infections in neonates.

Topics: Age Factors; Bacterial Infections; Cross Infection; Fosfomycin; Humans; Infant, Newborn; Infusions, Intravenous; Injections, Intravenous

Topics: Cefotaxime; Child; Child, Preschool; Cross Infection; Female; Fosfomycin; Humans; Infant; Infant, Newborn; Intensive Care Units; Male; Sepsis; Staphylococcal Infections

We tested 148 strains of clinical isolates of methicillin-resistant Staphylococcus aureus against fosfomycin alone and in combination with methicillin, cefamandole, gentamicin, trimethoprim, and vancomycin. Fosfomycin inhibited 90% of the 148 methicillin-resistant S. aureus strains at a concentration of 4 micrograms/ml. Synergism was observed in 97 strains (66%) with fosfomycin-cefamandole and in 69 strains (46%) with fosfomycin-methicillin. The combinations of fosfomycin with vancomycin, gentamicin, and trimethoprim were indifferent in most strains.

Topics: Cross Infection; Drug Synergism; Fosfomycin; Humans; Methicillin; Microbial Sensitivity Tests; Penicillin Resistance; Staphylococcal Infections; Staphylococcus aureus

Topics: Anti-Bacterial Agents; Cross Infection; Drug Evaluation; Drug Resistance, Microbial; Female; Fosfomycin; Humans; Male; Microbial Sensitivity Tests; Staphylococcal Infections; Staphylococcus