Evaluation of activity and emergence of resistance of Polymyxin B and ZTI-01 (Fosfomycin for Injection) against KPC-Producing Klebsiella pneumoniae

ZTI-01 (fosfomycin for injection) is a broad-spectrum antibiotic with a novel mechanism of action and is currently under development in the United States for treatment of complicated urinary tract infections. Globally, fosfomycin and polymyxin B are increasingly being used to treat multidrug-resistant Gram-negative infections. The objectives were to evaluate the pharmacodynamic activity of polymyxin B and fosfomycin alone and in combination against KPC-producing Klebsiella pneumoniae and to assess the rate and extent of emergence of resistance to different antibiotic regimens. Two clinical isolates, BRKP26 (MIC of polymyxin B[MICPMB], 0.5 mg/liter; MIC of fosfomycin [MICFOF], 32 mg/liter) and BRKP67 (MICPMB, 8 mg/liter; MICFOF, 32 mg/liter) at an initial inoculum of 107 CFU/ml, were evaluated over 168 h in a hollow-fiber infection model simulating clinically relevant polymyxin B (2.5-mg/kg loading dose as a 2 h-infusion followed by 1.5-mg/kg dose every 12 h [q12h] as a 1-h infusion) and fosfomycin (6 g q6h as a 1-h or 3-h infusion) regimens alone and in combination. Population analysis profiles (PAPs) and MIC testing were performed to assess emergence of resistance...

Carbapenem-resistant Enterobacteriaceae on a cardiac surgery intensive care unit: successful measures for infection control.

BACKGROUND: Carbapenem-resistant Enterobacteriaceae (CRE) cause surgical site infections (SSIs) in intensive care units (ICUs). This study aimed to evaluate the impact of intervention and control measures to reduce CRE colonization and infection rates among patients in the ICU of a cardiac surgery hospital following a CRE outbreak. METHODS: An observational study of the pre- and postintervention status of a cohort of colonized or infected patients in the postoperative adult cardiac surgery ICU was performed between April 2013 and December 2014. As well as the usual measures of screening and cohort nursing, the control measures were enhanced during the intervention period by providing alcohol gel at the bedside, daily bathing with no-rinse 2% chlorhexidine-impregnated wash cloths, and disinfection of surfaces around the patient three times per day. RESULTS: The rates of CRE colonization (P<0.001), primary central-line-associated bloodstream infections (P<0.002) and SSIs (P< 0.003) decreased significantly during the postintervention period. CONCLUSION: The implemented measures were effective in controlling colonization and infection with CRE in the cardiac surgery ICU.

Post-surgical mediastinitis due to carbapenem-resistant Enterobacteriaceae: Clinical, epidemiological and survival characteristics.

Invasive infections due to carbapenem-resistant Enterobacteriaceae (CRE), including polymyxin-resistant (PR-CRE) strains, are being increasingly reported. However, there is a lack of clinical data for several life-threatening infections. Here we describe a cohort of patients with post-surgical mediastinitis due to CRE, including PR-CRE. This study was a retrospective cohort design at a single cardiology centre. Patients with mediastinitis due to CRE were identified and were investigated for clinically relevant variables. Infecting isolates were studied using molecular techniques. Patients infected with polymyxin-susceptible CRE (PS-CRE) strains were compared with those infected with PR-CRE strains. In total, 33 patients with CRE mediastinitis were studied, including 15 patients (45%) with PR-CRE. The majority (61%) were previously colonised. All infecting isolates carried blaKPC genes. Baseline characteristics of patients with PR-CRE mediastinitis were comparable with those with PS-CRE mediastinitis. Of the patients studied, 70% received at least one agent considered active in vitro and most patients received at least three concomitant antibiotics. Carbapenem plus polymyxin B was the most common antibiotic combination (73%). Over 90% of patients underwent surgical debridement. Overall, in-hospital mortality was 33% and tended to be higher in patients infected with PR-CRE (17% vs. 53%; P=0.06). In conclusion, mediastinitis due to CRE, including PR-CRE, can become a significant challenge in centres with CRE and a high cardiac surgery volume. Despite complex antibiotic treatments and aggressive surgical procedures, these patients have a high mortality, particularly those infected with PR-CRE.

A space-time model for carbapenemase-producing Klebsiella pneumoniae (KPC) cluster quantification in a high-complexity hospital.

A retrospective space-time permutation model with non-Euclidean distance criteria was applied within a high-complexity hospital setting to quantitatively explore cluster patterns of 273 patients infected with or colonized by carbapenemase-producing Klebsiella pneumoniae during 4 years. Results were compared to standard nosocomial active-surveillance methods. Two clusters were identified in the period, suggesting that space-time strategies for cluster quantification within confined environments may be useful.

Case report of hepatic mucormycosis after liver transplantation: successful treatment with liposomal amphotericin B followed by posaconazole sequential therapy.

Mucormycosis is a rare but emerging fungal infection complicating solid organ transplantation (SOT), with a cumulative incidence of around 2% during the first year after SOT. The associated mortality rate is high, and surgical debridement is frequently required as part of the treatment along with antifungal therapy based mostly on amphotericin B formulations, We describe here an unusual case of hepatic mucormycosis in a liver transplant recipient that was successfully treated with clinical therapy based on liposomal amphotericin B followed by posaconazole, without surgical resection.

Infection with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae in solid organ transplantation.

Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae is spreading globally and represents a challenge in infection control and treatment. Solid organ transplant (SOT) recipients are especially at risk for infection by multidrug-resistant bacteria, and little is known about infection with KPC-producing organisms in this setting. The aim of this study was to describe the clinical and microbiologic aspects of KPC-producing K. pneumoniae infections in SOT recipients. A KPC-2-producing K. pneumoniae outbreak was identified in a public teaching tertiary care hospital in São Paulo, Brazil, in June 2009. During the outbreak, cases of KPC-2-producing K. pneumoniae infection in SOT recipients occurred between July 2009 and February 2010; these cases were retrospectively reviewed. Overall, 12 episodes of infection with KPC-producing K. pneumoniae occurred in 2 heart, 4 liver, and 6 kidney transplant recipients with incidence rates of 16.7%, 12.9%, and 26.3% in heart, liver, and kidney transplantation, respectively. Infection occurred at a median time of 20 days after transplantation. Primary infection sites were as follows: 4 urinary tract infections, 4 bloodstream infections, 2 pneumonias, and 2 surgical site infections. All patients except one had received antibiotics in the last 30 days, mostly piperacillin-tazobactam or glycopeptides. All strains exhibited susceptibility to amikacin and gentamicin. Patients were treated with tigecycline plus polymyxin B (3 cases), polymyxin B plus carbapenem (3 cases), polymyxin B alone (3 cases), or tigecycline plus imipenem (1 case). In 2 cases, patients received only carbapenem, and death occurred before the final culture result. The overall 30-day mortality rate was 42%. In this series of KPC-producing K. pneumoniae infection in SOT recipients, the infection occurrence was high during an institutional outbreak and was potentially life threatening.

Septicemia caused by Vibrio cholerae O1 biotype El Tor, in São Paulo, Brazil.

We reported a case of septicemia by Vibrio cholerae O1, in São Paulo, Brazil. A 70-year-old male patient, living in an urban area, entered the emergency service having sepsis, dying 12 hours later. Blood culture was positive for Vibrio cholerae O1. This is the first case of bacteremia by Vibrio cholerae O1 reported in South America.

Septicemia caused by Vibrio cholerae O1 biotype El Tor, in São Paulo, Brazil

We reported a case of septicemia by Vibrio cholerae O1, in São Paulo, Brazil. A 70-year-old male patient, living in an urban area, entered the emergency service having sepsis, dying 12 hours later. Blood culture was positive for Vibrio cholerae O1. This is the first case of bacteremia by Vibrio cholerae O1 reported in South America.

Leptospirosis mimicking sepsis after orthopedic surgery: a case report.

We report a case of leptospirosis that occurred after elective surgery involving tendon transfer and shoulder arthroscopy. The disease mimicked hospital infection after orthopedic surgery and was at first misdiagnosed as post-operative sepsis. The patient was 60 year old female that developed sepsis with hypotension, shock, bleeding, jaundice and renal insufficiency 4 hours after surgery. Shock treatment procedures were performed and broad spectrum antibiotic therapy was used with coverage for bacteria acquired in hospitals. A careful investigation was carried out by the Hospital Infection Control Service in search of the possible source of the infection. After clinical evaluation by a specialist in infectious diseases, the hypothesis of leptospirosis was put forward based on clinical and epidemiological data. The hypothesis was later confirmed by the positive result of serological tests with the microagglutination method that yielded 1:800 and then 1:12,600 7 days later. This is the first reported case of leptospirosis manifest directly following surgery, mimicking postoperative sepsis.

[Infectious endocarditis in a drug addict]. / Endocardite infecciosa em toxicômanos.

PURPOSE: To compare two groups of patients with infective endocarditis, the drug addicts and non-drug addicts. We attempted to set particularities among the various aspects that involve the patient with endocarditis, due to the concurrent chronic use of cocaine intravenously. METHODS: Twenty nine patients, group B, whose clinical diagnose was compatible with infective endocarditis, with risk factor of parenteral toxicomania by cocaine were treated at Institute "Dante Pazzanese de Cardiologia" and Hospital "Emilio Ribas" in São Paulo, from 1984 to 1990. The data obtained for etiological agents, previous cardiac pathology, affected heart structures, affected heart side and clinical-surgical evolutions of group B were compared to group A (193 patients), which was also composed of patients with endocarditis, without chronic endovenous use of cocaine antecedent. The data obtained were analysed comparatively according to the chi square with Yates correction. RESULTS: Male gender (89.7%) was predominate in group B towards group A (57.0%); (p < 0.01). Previous cardiopathy, either congenital or acquired, as antecedent proning to endocarditis, was found in 89.1% of patients in group A, significantly higher than 17.2% of patients group B (p < 0.001). Staphylococcus aureus was the most frequent agent, which accounted for endocarditis of group B in 86.4% of the cases, significantly higher when compared to 23.9% of cases of group A (p < 0.01). Streptococcus viridans was the most frequent etiological agent for endocarditis of group A (44.8%), significantly higher than group B (4.5%), (p < 0.01). In concern to the affected structures, the tricuspid valve was most affected in group B (65.5%), significantly higher than group A (4.7%) p < 0.001. The mitral valve was significantly more affected in group A (45.1%) in comparison to group B (6.9%), (p < 0.05). In group A 82 patients (42.5%) required surgical treatment and this occurred in 3 patients of group b (10.3%), (p < 0.05). No significant statistical difference was found as for the general mortality (clinical and surgical) in both groups. CONCLUSION: a) presence of previous cardiac disease was lower suggesting permanent contamination blood flow by pathologic agents, mainly of those found in the skin as S. aureus; b) right side of the heart is most frequently affected, specially the tricuspid valve even without previous damage.