Antibiotic perturbation of the murine gut microbiome introduces inter-individual susceptibility to arsenic.

Arsenic is a Group 1 human carcinogen and at least 200 million people around the world are exposed to unsafe levels of arsenic, predominantly through contaminated drinking water. Arsenic has also been used for hundreds, if not thousands, of years as an intentional poison due to its odorless/tasteless properties and the general lack of technology required to identify it. Both acute and chronic arsenic-related health outcomes are highly variable among similarly exposed individuals even after controlling for important factors, like host genetics, making the mechanisms underlying this often-made epidemiologic observation difficult to experimentally address and not fully understood. Here, we describe an experimental model of arsenic exposure in C57BL/6 mice that recapitulates key aspects of inter-individuality in disease observed in humans. We show that co-administration of the antibiotic, cefoperazone, and high-level arsenic (100 ppm, inorganic sodium arsenate) results in incomplete mortality with a ratio of 60 % lethality to 40 % survival, and that survival, at least in part, depends not only on an intact microbiome but also a regulated response involved with water transport. This work provides an experimental framework for identifying critical pathways involved in generating inter-individual variability in disease outcome following arsenic exposure.

Steroid-resistant nephrotic syndrome in infants caused by a novel compound heterozygous mutation of the NUP93: A CARE case report.

RATIONALE: Steroid-resistant nephrotic syndrome (SRNS) is a special kidney disease. SRNS is characterized by steroid-resistant, clinical variability, and genetic heterogeneity. Patients with SRNS often may eventually need renal transplantation. PATIENT CONCERNS: A 10-month-old Chinese male infant presented with oliguria, renal dysfunction, hypertension, and anemia. DIAGNOSES: Combined with clinical manifestations, laboratory testing and sequencing results, the patient was diagnosed as SRNS. INTERVENTIONS: Combined intravenous methylprednisolone and cefoperazone sulbactam did not improve the patient's condition. Thus, SRNS associated with hereditary nephrotic syndrome was strongly suspected. Genetic testing for hereditary renal disease of the patient revealed 2 novel heterozygous mutations in the Nucleoporin 93 (NUP93) gene, which were predicted pathogenic and harmful by bioinformatic softwares of SIFT, PolyPhen_2 and REVEL. OUTCOMES: As general physical health deterioration and renal dysfunction, the patient died of a severe infection. LESSONS: The novel NUP93 heterozygous mutations identified in the current study broadened the genetic spectrum of SRNS and further deepened our insight into pathogenic mutations of NUP93 to improve disease diagnosis.

Campylobacter upsaliensis isolated from a giant hepatic cyst.

Campylobacter upsaliensis is an enteropathogenic bacterium in animals, and is also rarely isolated from humans, where it can cause enteritis and bacteremia. This report describes the first case of isolation of C. upsaliensis from an infected giant hepatic cyst. This bacterium could not be cultured from abscess punctuate in a usual Campylobacter-selection medium (charcoal cefoperazone deoxycholate agar medium), because of high concentration of cefoperazone as a selection agent. It could not identified by matrix-assisted laser desorption ionization-time of flight mass spectrum. Rather, it was identified as C. upsaliensis by whole genome sequencing, including by multilocus sequence typing.

Multidrug-resistance Acinetobacter baumannii pneumonia in a rheumatoid arthritis patient receiving tumor necrosis factor inhibitor: A case report.

INTRODUCTION: Multidrug-resistant Acinetobacter baumannii (MDRAB) pneumonia with severe sepsis in a patient with rheumatoid arthritis (RA), who is predisposed after treatment with tumor necrosis factor inhibitor (TNFI), is a rare severe infection and can be successfully treated with prompt antibiotics. CASE PRESENTATION: A 75-year-old woman was diagnosed with RA >30 years previously. After inadequate treatment responses to conventional disease-modifying antirheumatic drugs (DMARDs), she developed progressive RA, including swollen joints in both hands, and had a high disease activity score of 4.96 when presenting at our rheumatology clinic. She had started taking the TNFI, golimumab (50 mg/month), 3 years before and developed a productive cough 4 weeks before this admission. One week after admission, she developed fever, dyspnea, hypoxemia, tachycardia, and increased serum C-reactive protein level. DIAGNOSIS: Chest plain film (CxR) and computed tomography of the chest showed hospital-acquired pneumonia; microbial examination of the sputum showed the presence of MDRAB. THERAPEUTICS: She was prescribed a full course of antibiotics with cefoperazone sulbactam. OUTCOMES: CxR showed complete remission of pneumonia. CONCLUSION: Biological DMARDs, such as TNFI, act as a double-edged sword: these drugs are used to treat autoimmune diseases, but they increase the risk of infection. The trend toward antibiotic resistance and persistent environmental survival of MDRAB is an emerging problem in countries with high rates of antibiotic abuse. TNFI may affect intestinal immunity by inducing dysbiosis, which affects T helper 17-mediated mucosal immunity and can contribute to A baumannii colonization and the development of MDRAB in frequently hospitalized patients.

Cefepime vs. cefoperazone/sulbactam in combination with amikacin as empirical antibiotic therapy in febrile neutropenia.

PURPOSE: Beta lactams are standard empirical therapy for febrile neutropenia (FN). The aim of this study was to evaluate the efficacy and safety of cefepime monotherapy compared with cefoperazone/sulbactam plus amikacin (CS + A) for empirical treatment of high risk FN. METHODS: One hundred seventy-five patients with 336 FN episodes were randomized to receive either cefepime (2 g q8h for adults and 50 mg/kg q8h for children) or CS (2 g q8h for adults and 50 mg/kg q8h for children) plus amikacin (15 mg/kg once a day). Positive response was defined as afebrile within 72 h of starting antibiotics, persistent afebrile status more than 48 h and no requirement of second-line antibiotics and antifungal agents. RESULTS: Three hundred thirty-six episodes were assessable for efficacy (168 cefepime, 168 CS + A). The positive response to antibiotics was identical for cefepime (53%) and CS + A (53%). Positive response was similar in MDI (microbiologically documented infection), 50 vs. 35% (p = 0.248), CDI (clinically documented infection), 50 vs. 35% (p = 0.259), combination CDI + MDI, 25 vs. 15% (p = 0.400), FUO (fever of unknown origin), 68 vs. 72% (p = 0.577) respectively in the two groups. The successful discontinuation of antibiotics at 72 h in FUO was similar in both groups (60 vs. 59%, p = 0.544). Total drug-related adverse events were similar in both groups (8 vs. 6%) except renal dysfunction was high in CS + A (1 vs. 7 events). Mortality was the same between two groups (8 vs 7%). CONCLUSIONS: Cefepime monotherapy and CS + A had similar efficacy as first-line therapy for FN. Discontinuation of empirical antibiotics is safe and feasible approach in selected group of FUO patients.

Effects of specific egg yolk immunoglobulin on pan-drug-resistant Acinetobacter baumannii.

With the growing emergence of pan-drug-resistant Acinetobacter baumannii (PDR-Ab) strains in clinical, new strategies for the treatment of PDR-Ab infections are urgently needed. Egg yolk immunoglobulin (IgY) as a convenient and inexpensive antibody has been widely applied to the therapy of infectious diseases. The aim of this study was to produce IgY specific to PDR-Ab and investigate its antibacterial effects in vitro and in vivo. IgYs specific to two PDR-Ab strains were produced by immunizing hens with formaldehyde inactivated PDR-Ab cells and isolated from yolks with a purity of 90% by water dilution, salt precipitations and ultrafiltration. IgYs showed high titers when subjected to an ELISA and inhibited the growth of PDR-Ab in a dose-dependent manner in liquid medium. Scanning electron microscopy assay showed structural modification and aggregation of PDR-Ab treated with specific IgYs. Freshly cultured PDR-Ab cells were nasally inhaled in BALB/c mice to induce acute pneumonia. The infected mice were intraperitoneally injected with specific IgYs using cefoperazone/sulbactam and dexamethasone as positive controls. The IgYs specific to PDR-Ab lowered the mortality of mice with PDR-Ab-induced acute pneumonia, decreased the level of TNF-α and IL-1ß in serum and reduced inflammation in lung tissue. Specific IgY has the potential to be used as a new therapeutic approach for the treatment of A. baumannii-induced infections.

The First Case Report of Acute Cholangitis and Bacteremia Due to Neisseria subflava.

We herein report a case of acute cholangitis and bacteremia caused by a commensal Neisseria species, Neisseria subflava, in an 82-year-old man with cholangiocarcinoma. Emergency endoscopic nasobiliary drainage and cefoperazone/sulbactam therapy were effective. Gram negative coccobacilli were isolated from both blood and bile cultures on 5% sheep blood agar. The isolate was identified as N.subflava biovar perflava by mass spectrometry, a sequence analysis of the 16S rRNA, and biochemical testing. Although biliary infections due to commensal Neisseria are extremely rare, this case demonstrates the possibility of its occurrence in patients undergoing bile duct treatment.

Effects of cefazolin and cefoperazone on glutamate transporter 1 isoforms and cystine/glutamate exchanger as well as alcohol drinking behavior in male alcohol-preferring rats.

Previously, we have reported that cefazolin and cefoperazone treatments attenuated ethanol consumption, at least in part, through upregulation of GLT-1 expression in male alcohol-preferring (P) rats. In this study, we determined the effects of these compounds on the expression of GLT-1 isoforms (GLT-1a and GLT-1b), cysteine/glutamate exchanger (xCT), which is another glial glutamate transporter co-localized with GLT-1, and glutamate/aspartate transporter (GLAST). We found that cefazolin and cefoperazone treatments decreased ethanol intake and upregulated both GLT-1 isoforms, GLT-1a and GLT-1b, in nucleus accumbens (NAc) and prefrontal cortex (PFC) compared to saline treated group. In addition, cefazolin increased the expression of xCT in NAc and PFC, while cefoperazone upregulated xCT expression only in NAc. However, we did not find any significant differences in GLAST expression between the treated and control groups. Overall, our findings suggest that cefazolin and cefoperazone may be considered as potential compounds for the treatment of ethanol dependence.

Profile of urinary tract infections in paediatric patients.

BACKGROUND & OBJECTIVES: This cross-sectional study was conducted at a tertiary care centre in Puducherry, south India, with the aim of finding the profile of the paediatric urinary tract infection (UTI), bacterial pathogens involved, and also to observe vesicoureteric reflux (VUR) and renal scarring in these patients. METHODS: A total of 524 paediatric patients ≤13 yr, suspected to have UTI, were included in the study. Urine samples were collected, processed for uropathogen isolation and antibiotic susceptibility test was performed as per the Clinical and Laboratory Standards Institute (CLSI) guidelines. Thirty two culture proven children with UTI underwent micturating cysto-urethrography (MCU) and dimercaptosuccinic acid (DMSA) scanning was done for 69 children. RESULTS: o0 f the 524 children, 186 (35.4%) had culture proven UTI with 105 (56.4%) being infants, 50 (27.4%) between 1-5 yr, 30 (16.12%) between 5-13 yr and 129 (69.35%) males. Posterior urethral valve (PUV) was noted in three, hydronephrosis in one, VUR in 18 and renal scarring in 33. VUR as well as renal scarring were more in males >1 yr of age. A significant association (P=0.0054) was noted with a combined sensitivity and specificity of these investigations being 83 and 90 per cent, respectively of the MCU and DMSA scans for detecting VUR. Escherichia coli was the most common pathogen isolated, sensitive to nitrofurantoin, followed by cefoperazone-sulbactam, aminoglycosides and meropenem. INTERPRETATION & CONCLUSIONS: Our results indicate that UTI varies with age and gender and extensive evaluation is required in boys over one year of age with UTI. This study also highlights the better efficacy of aminoglycosides, cefoperazone-sulbactam and nitrofurantoin in vitro compared with meropenem in Gram-negative uropathogens.

Role of GM-CSF in the inflammatory cytokine network that regulates neutrophil influx into the colonic mucosa during Clostridium difficile infection in mice.

Clostridium difficile infection in antibiotic-treated mice results in acute colitis characterized by severe intestinal histopathology, robust neutrophil influx, and increased expression of numerous inflammatory cytokines, including GM-CSF. We utilized a neutralizing monoclonal antibody (mAb) against GM-CSF in a murine model to study the role of GM-CSF during acute C. difficile colitis. Cefoperazone-treated mice were challenged with C. difficile (strain 630) spores. Expression of GM-CSF was significantly increased in animals challenged with C. difficile. Treatment with an anti-GM-CSF mAb did not alter C. difficile colonization levels, weight loss, or expression of IL-22 and RegIIIγ. However, expression of the inflammatory cytokines TNFα and IL-1ß, as well as iNOS, was significantly reduced following anti-GM-CSF treatment. Expression of the neutrophil chemokines CXCL1 and CXCL2, but not the chemokines CCL2, CCL4, CXCL9, and CXCL10, was significantly reduced by anti-GM-CSF treatment. Consistent with a decrease in neutrophil-attractant chemokine expression, there were fewer neutrophils in histology sections and a reduction in the expression of secretory leukocyte protease inhibitor (SLPI), a tissue anti-protease that protects against damage by secreted neutrophil elastase. These data indicate that GM-CSF plays a role in the inflammatory signaling network that drives neutrophil recruitment in response to C. difficile infection but does not appear to play a role in clearance of the infection.

The efficiency of continuous regional intra-arterial infusion in the treatment of infected pancreatic necrosis.

OBJECTIVE: Our aim was to investigate the efficiency of continuous regional intra-arterial infusion (CRAI) with antisecretory agents and antibiotics in the treatment of infected pancreatic necrosis. MATERIALS AND METHODS: CRAI was used as a new clinical technique to treat acute pancreatitis patients during a 4-year period at the First Affiliated Hospital, Wenzhou Medical College, China. In this retrospective study, thirty-four patients with proven infected pancreatic necrosis were included. Twelve patients were treated with CRAI, and were matched according to age, sex, APACHE II scores, Ranson scores and remote organ dysfunction, with 22 patients with IPN treated surgically. The clinical outcome following surgery and CRAI were compared. RESULTS: No difference was found between the two groups when comparing age, gender, APACHE II scores, Ranson scores and remote organ dysfunction (p > 0.05). The patients treated with CRAI had a lower incidence of complications (33.3% vs 72.7%), duration of hospitalization (27.1 ± 4.7 days vs 43.0 ± 12.0 days) and cost of hospitalization (4.09 ± 1.64 thousand RMB vs 8.77 ± 3.74 thousand RMB) as compared to patients treated with surgery (p < 0.05). The survival rate was significantly higher in the CRAI group as compared to the surgical group (91.7% vs 63.6%; p < 0.01). However, the two groups had similar rates of concomitant operative treatment and incidence of remote organ dysfunction (p > 0.05). CONCLUSIONS: CRAI or CRAI in combination with abscess drainage seemingly improve the clinical outcome in patients with infected pancreatic necrosis. Further confirmative prospective randomized multicenter studies are warranted prior to broad introduction of the CRAI concept.

Randomized comparison of piperacillin-tazobactam plus amikacin versus cefoperazone-sulbactam plus amikacin for management of febrile neutropenia in children with lymphoma and solid tumors.

The objective of this study was to compare the effectiveness of piperacillin-tazobactam (PIP/TAZO) plus amikacin (AMK) (PIP/TAZO+AMK) versus cefoperazone-sulbactam (CS) plus AMK (CS+AMK) for the treatment of febrile neutropenia (FN) in children with cancer. The study was designed prospectively and randomized in 0- to 18-year-old children with lymphoma or solid tumor who were hospitalized with FN diagnosis. Consecutively randomized patients received either PIP/TAZO 360 mg/kg/day in 4 doses plus AMK 15 mg/kg/day in 3 doses or CS 100 mg/kg/day in 3 doses plus AMK 15 mg/kg/day in 3 doses intravenously. Treatment modification was defined as any change in the initial empirical antibiotic therapy. A total of 116 FN episodes were managed in 46 patients (26 boys and 20 girls) with a median age of 6.5 years (range .8-17.0) during the study period. Success rates without modification of therapy were 47.5% and 52.6% in PIP/TAZO+AMK group and CS+AMK group, respectively (P >.05). No statistical difference was found between treatment groups in terms of durations of neutropenia, fever, and hospitalization. The overall success rate in all groups was 97.4%. No major side effect was observed in either group during the course of the study. Our study is the first to compare the effectiveness of PIP/TAZO+AMK and CS+AMK therapies. Both combinations were effective and safe as empirical therapy for febrile neutropenic patients.

Comparison of piperacillin tazobactam and cefoperazone sulbactam monotherapy in treatment of febrile neutropenia.

BACKGROUND: Monotherapy has tended to replace the combination therapy in emprical treatment of febrile neutropenia. There is no reported trial which compares the efficacy of cefoperazone-sulbactam (CS) and piperacillin-tazobactam (PIP/TAZO) monotherapies in the treatment of febrile neutropenia. In this prospective randomized study, we aimed to compare the safety and efficacy of CS versus PIP/TAZO as empirical monotherapies in febrile neutropenic children with cancer. PROCEDURE: The study included febrile, neutropenic children hospitalized at our center for cancer. They were randomly selected to receive CS 100 mg/kg/day or PIP/TAZO 360 mg/kg/day. Duration of fever and neutropenia, absolute neutrophil count, modification, and success rate were compared between the two groups. Resolution of fever without antibiotic change was defined as success and resolution of fever with antibiotic change or death of a patient was defined as failure. Modification was defined as changing the empirical antimicrobial agent during a febrile episode. RESULTS: One hundred and two febrile neutropenic episodes were documented in 55 patients with a median age of 4 years. In 50 episodes CS and in 52 episodes PIP/TAZO was used. Duration of fever and neutropenia, neutrophil count, age, sex, and primary disease were not different between two groups. Success rates in the CS and PIP/TAZO groups were respectively 56 and 62% (P > 0.05). Modification rate between two groups showed no significant difference (P > 0.05). No serious adverse effect occurred in either of the groups. CONCLUSION: CS and PIP/TAZO monotherapy are both safe and effective in the initial treatment of febrile neutropenia in children with cancer.

[Use of systemic antibacterial agents at a university emergency clinic in Bucharest, in the year 2008]. / Observatii privind utilizarea agentilor antibacterieni sistemici într-o clinica universitara de urgenta din municipiul Bucuresti în anul 2008.

OBJECTIVE: use of ATC/DDD (Anatomic Therapeutic Classification/Daily Defined Dose) methodology promoted by World Health Organization for calculating and analysis of systemic antimicrobial agents' annual rates of usage among the adult patients hospitalized in Bucharest municipality. METHODS: descriptive retrospective study conducted in the main university clinic for medical emergencies from Bucharest municipality. Consumption of systemic antimicrobial agents, taken from the clinic pharmacy's records, regarding the 2008 year, has been transformed in defined daily doses and aggregated by ATC subgroups. The number of patient days from 2008 was obtained from clinic administrative service. Antimicrobial agents' usage was expressed as consumption density rate by dividing the defined daily doses counts to the correspondent number of patient days. Analysis of consumption rates has been performed both by whole clinic and also stratified by departments of medical specialties: surgery, internal medicine and intensive care. RESULTS: In the year 2008, the patients carried in the clinic totalized 255,600 days of hospitalization; during the respective time in clinic there were used 36 of individual antibacterial agents that made up 184,857 defined daily doses. At the level of entire clinic the consumption rate of all systemic antimicrobial agents was 72.6 defined daily doses per 100 de patient days (DDD/PD); by medical specialties the indicator's values were 61.2 DDD/100 PD in the department of internal medicine specialties, 62.8 DDD/100 PD in the departament of surgical specialties and 126 DDD/100 PD in the medical/surgical intensive care unit, respectively. Almost 70% of the defined daily doses' total included five antimicrobial agents: co-amoxiclav, cefuroxim, cefoperazone + sulbactam, ciprofloxacine si metronidazol. By ATC subgroups, the top three consumption rates included penicillin plus beta-lactamase inhibitors, 2nd generation cefalosporines and fluorochinolons, respectively. Comparing the own rate with the distributions of NNIS (National Nosocomial Infection Surveillance) system form USA, demonstrated that the usage was into the expected limits for the majority of antimicrobial agents groups considered, excess usage being detected only in the case of 2nd generation cefalosporins (in non-intensive care sector) and in the case of carbapenems in the intensive care units, respectively. CONCLUSIONS: At the whole clinic level, the study detected a rate of systemic antimicrobial agents' usage similar with the correspondent values recently reported even from the South European states or form USA. Excessive usage (against the NNIS standard) might be mitigated through augmentation of the compliance with guidelines for prudent utilization of antimicrobial agents.

[Efficacy and safety of cefoperazone/sulbactam in the treatment of children with mucoviscidosis during exacerbation of the bronchopulmonary process]. / Effektivnost' i bezopasnost' tsefoperazona/sul'baktama pri lechenii obostrenii bronkholegochnogo protsessa u detei s mukovistsidozom.

The use of cefoperazone/sulbactam in combination with amikacin in the treatment of 20 patients with mucoviscidosis and exacerbation of bronchopulmonary pathological process resulted in marked positive dynamics of the clinical and functional indices of the lungs state. The bacteriological effect with respect to the main pathogens in the cases of mucoviscidosis was strain-dependent: eradication of 10 (83.4%) out of 12 Staphylococcus aureus strains and only 3 (15.8%) out of 19 Pseudomonas aeruginosa strains. The most frequent adverse reaction was diarrhea (5 children) successfully corrigated by loperamide. Discontinuation of the drug use was required in 3 patients because of macrohematuria (1 child) and allergic eruption.

In vivo application of biodegradable controlled antibiotic release systems for the treatment of implant-related osteomyelitis.

In this study the construction and in vivo testing of antibiotic-loaded polyhydroxyalkanoate rods were planned for use in the treatment of implant-related osteomyelitis. The rods were constructed of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) and poly(3-hydroxybutyrate-co-4-hydroxybutyrate), carrying 50% (w/w) Sulperazone or Duocid. They were implanted in rabbit tibia in which implant-related osteomyelitis (IRO) had been induced with Staphylococcus aureus. The effectiveness of the antibiotics in the treatment of IRO was determined. The establishment of IRO with bacterial inoculation was complete after 3 weeks with 100% infection rate in all groups. There was no contamination or super-infection. Both antibiotics were found to be highly effective against the bacteria. Following the application of Sulperazone-P(3-HB-co-4-HB) rods, no infective agents could be isolated from the infection site within the 6-week test period, indicating complete treatment of the infection. Macroscopical evaluation at follow-up revealed no drainage, minimal swelling and increase in local warmth, most probably due to the surgery rather than to a reaction towards the implant. The overall scores for radiological findings by the end of 6 weeks were 0.8/5 for the antibiotic-loaded rod implanted in the right limb, and 1.1/5 for the antibiotic-free rod implanted in the left limb. There was no statistical difference between the antibiotic-loaded and antibiotic-free polymeric rods. In vivo drug release was almost complete within the first week. One interesting observation, however, was that the therapy was still very effective even when the release rate was very high. In the SEM of in vitro tested rods, the polymeric component was unchanged in 2 weeks while the drug leached out, leaving voids behind. In vivo, however, the morphology of the implant was significantly modified within 6 weeks post-implantation. Since a substantial degree of the in vivo drug release was complete within 1 week, we believe that dissolution of the drug must be the predominant mechanism through which the drug release is controlled.

Flora bacterianaen pacientes de la Unidad de Cuidados Intensivos 1996-1997 / The bacterial flora in patients of the Intensive Care Unit 1996-1997

Aproximadamente 20 por ciento de las infecciones nosocomiales se produce en la Unidad de Cuidados Intensivos (UCI). Los microorganismos capaces de producir infecciones en los pacientes de UCI son variables y la colonización es una relación directa entre el paciente, la enfermedad de base, el tiempo de estadía y los procedimientos invasivos. El objetivo de este trabajo fue determinar la flora bacteriana según muestras procesadas (traqueobronquial, sonda de foley y catéter venoso); incidencia de cultivos positivos y sensibilidad in vitro de gérmenes aislados de UCI del Hospital Universitario Munuel Núñez Tovar entre 1996 y 1997. Se revisaron un total de 305 muestras. Se aisló: P.aeruginosa (23,63 por ciento), Enterobacter (19.16 por ciento) K.pneumoniae (15.49 por ciento), Acinetobacter (14.96 por ciento), Serratia sp. (8.96 por ciento), E.coli: (3.67 por ciento). S.coagulasa (-) (7.61 por ciento), S.aureus (4.99 por ciento) y P.mirabilis (1.57 por ciento). En conclusión, los agentes causantes de infecciones en UCI más aislados fueron: P.aeruginosa, Enterobacter y K.pneumoniae. Los antimicrobianos con mayor actividad in vitro contra los gérmenes reportados fueron: cefepime, ofloxacina, cefoperazona/sulbactam y piperacilina/tazobactam

Sulbactam-cefoperazone polyhydroxybutyrate-co-hydroxyvalerate (PHBV) local antibiotic delivery system: in vivo effectiveness and biocompatibility in the treatment of implant-related experimental osteomyelitis.

In this study, a novel antibiotic carrier system for use in the treatment of implant-related and chronic osteomyelitis was developed. Sulbactam-cefoperazone was introduced to rods of polyhydroxybutyrate-co-hydroxyvalerate (22 mol % HV, w/w), a member of a family of microbial-origin polymer that is biodegradable, biocompatible, and osteoconductive due to its piezoelectric property. The antibiotic-loaded carrier was implanted into the infection site that was induced by Staphylococcus aureus inoculation into the rabbit tibia. The effectiveness of this was assessed macroscopically, radiographically, bacteriologically, and histopathologically. Findings of infection subsided on day 15 and almost complete remission was observed on day 30. The control side that contained antibiotic-free rods, however, worsened. These findings prompted us to conclude that the novel biodegradable antibiotic carrier developed in the present study seems to be a promising candidate for use in the treatment of severe bone infection.

[Clinical efficacy of fosfomycin in combination with sulbactam/cefoperazone in the treatment of severe infections complicated to blood dyscrasia. Working Group of Kanto Combination Therapy for FOM + SBT/CPZ].

In the treatment of severe infections complicated to blood dyscrasia, the efficacy and usefulness of fosfomycin (FOM) in combination with sulbactam (SBT)/cefoperazone (CPZ) were compared between patients receiving FOM in the first followed by SBT/CPZ (Group A) and those receiving both drugs simultaneously (Group B). The following results were obtained. 1. The efficacy rate was 56.3% for Group A and 47.9% for Group B, with no significant difference. 2. The efficacy for patients suspected of the presence of septicemia, the efficacy rate was 57.9% for Group A and 54.3% for Group B, with no significant difference. 3. As for underlying disease, patients with acute myelogenous leukemia were most prevailing. In these patients, the efficacy rate was 57.1% for Group A and 27.3% for Group B, with no statistically significant difference. However, the efficacy rate tended to be higher in Group A. 4. The administration of antibiotics was effective to restore the neutrophil count to 501/microliters or higher in 77.8% and 45.5% of the cases for Groups A and B, respectively, with significantly higher efficacy for Group A. 5. In the safety evaluation a total of 115 cases were included. Side effects and laboratory abnormalities were seen in 3 cases each, but none of them were serious in degree. From these results, it was confirmed that the combination therapy consisting of administration of FOM followed by SBT/CPZ with some interval is effective for severe infections complicated to blood dyscrasia.