Ceftazidime/avibactam in the era of carbapenemase-producing Klebsiella pneumoniae: experience from a national registry study.

BACKGROUND: Infections caused by KPC-producing Klebsiella pneumoniae (Kp) are associated with high mortality. Therefore, new treatment options are urgently required. OBJECTIVES: To assess the outcomes and predictors of mortality in patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam with an emphasis on KPC-Kp bloodstream infections (BSIs). METHODS: A multicentre prospective observational study was conducted between January 2018 and March 2019. Patients with KPC- or OXA-48-Kp infections treated with ceftazidime/avibactam were included in the analysis. The subgroup of patients with KPC-Kp BSIs treated with ceftazidime/avibactam was matched by propensity score with a cohort of patients whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam with in vitro activity. RESULTS: One hundred and forty-seven patients were identified; 140 were infected with KPC producers and 7 with OXA-48 producers. For targeted therapy, 68 (46.3%) patients received monotherapy with ceftazidime/avibactam and 79 (53.7%) patients received ceftazidime/avibactam in combination with at least another active agent. The 14 and 28 day mortality rates were 9% and 20%, respectively. The 28 day mortality among the 71 patients with KPC-Kp BSIs treated with ceftazidime/avibactam was significantly lower than that observed in the 71 matched patients, whose KPC-Kp BSIs had been treated with agents other than ceftazidime/avibactam (18.3% versus 40.8%; P = 0.005). In the Cox proportional hazards model, ultimately fatal disease, rapidly fatal disease and Charlson comorbidity index ≥2 were independent predictors of death, whereas treatment with ceftazidime/avibactam-containing regimens was the only independent predictor of survival. CONCLUSIONS: Ceftazidime/avibactam appears to be an effective treatment against serious infections caused by KPC-Kp.

Population pharmacokinetics of colistin and the relation to survival in critically ill patients infected with colistin susceptible and carbapenem-resistant bacteria.

OBJECTIVES: The aim was to analyse the population pharmacokinetics of colistin and to explore the relationship between colistin exposure and time to death. METHODS: Patients included in the AIDA randomized controlled trial were treated with colistin for severe infections caused by carbapenem-resistant Gram-negative bacteria. All subjects received a 9 million units (MU) loading dose, followed by a 4.5 MU twice daily maintenance dose, with dose reduction if creatinine clearance (CrCL) < 50 mL/min. Individual colistin exposures were estimated from the developed population pharmacokinetic model and an optimized two-sample per patient sampling design. Time to death was evaluated in a parametric survival analysis. RESULTS: Out of 406 randomized patients, 349 contributed pharmacokinetic data. The median (90% range) colistin plasma concentration was 0.44 (0.14-1.59) mg/L at 15 minutes after the end of first infusion. In samples drawn 10 hr after a maintenance dose, concentrations were >2 mg/L in 94% (195/208) and 44% (38/87) of patients with CrCL ≤120 mL/min, and >120 mL/min, respectively. Colistin methanesulfonate sodium (CMS) and colistin clearances were strongly dependent on CrCL. High colistin exposure to MIC ratio was associated with increased hazard of death in the multivariate analysis (adjusted hazard ratio (95% CI): 1.07 (1.03-1.12)). Other significant predictors included SOFA score at baseline (HR 1.24 (1.19-1.30) per score increase), age and Acinetobacter or Pseudomonas as index pathogen. DISCUSSION: The population pharmacokinetic model predicted that >90% of the patients had colistin concentrations >2 mg/L at steady state, but only 66% at 4 hr after start of treatment. High colistin exposure was associated with poor kidney function, and was not related to a prolonged survival.

Carbapenem-resistant Acinetobacter baumannii: in pursuit of an effective treatment.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) has gained global notoriety as a critically important nosocomial pathogen. It mostly affects debilitated patients, causing pneumonia and bloodstream infections with high mortality rates. Difficulties in treating CRAB infections stem from a formidable resistance profile that leaves available only a few antibiotics of uncertain efficacy such as colistin and tigecycline. Despite the relentless attempts to improve therapeutic approaches (as depicted in colistin-oriented randomized clinical trials and the numerous observational studies), progress is still limited. AIMS: We aim (a) to assist physicians to adapt therapeutic approaches in CRAB infections by considering all potentially available antimicrobials, and (b) to present directions for future investigations that emerge through treatment efforts in endemic settings. SOURCES: Articles and reviews from PubMed and Scopus databases; studies from ClinicalTrials.gov; presentations from ECCMID congresses and IDWeek meetings. CONTENT: The review provides a succinct overview of the important pharmacokinetic/pharmocodynamic parameters of relevant antimicrobial agents, a critical appraisal of randomized control trials and observational studies, suggestions for increasing the strength of observational studies and directions facilitating the choice of therapeutic regimens by severity of infection and status of the host. IMPLICATIONS: The lack of an optimal therapeutic regimen for CRAB thus far, as shown in this review, suggests the need to thoroughly investigate alternative approaches through carefully designed trials that should include all relevant drugs. Some of these alternative directions are indicated in the present review.

Combining VITEK® 2 with colistin agar dilution screening assist timely reporting of colistin susceptibility.

OBJECTIVES: The rise in carbapenem resistance among Gram-negative bacteria has renewed interest in colistin. Recently, the EUCAST-CLSI Polymyxin Breakpoints Working Group declared that broth microdilution (BMD) is the only valid method for colistin susceptibility testing. BMD is not easily incorporated into the routine work of clinical laboratories, and usually this test is incorporated serially, resulting in delayed susceptibility reporting. We tested a strategy of combining VITEK® 2 with a 2 µg/mL colistin agar dilution (VITEK® 2/AD) screening plate to improve performance and time to reporting of colistin susceptibility. METHODS: Colistin susceptibility for 364 clinical isolates was determined by VITEK® 2/AD and compared with the reference standard BMD according to the ISO 20776-1:2007 and CLSI guidelines. The EUCAST colistin susceptibility breakpoint of ≤2 µg/mL was used. Escherichia coli NCTC 13846 served as quality control strain. Agreement, very major error (VME) and major error rates were determined using ISO 20776-2:2007. RESULTS: The VME rate for VITEK® 2 alone was 30.6% (15/49, 95% CI 18.3-45.4%), and was reduced to 10.2% (5/49, 95% CI 3.4-22.2%) using the VITEK® 2/AD combined testing. The combined testing had categorical agreement with BMD of 97% (354/364, 95% CI 95.0-98.7%), and a major error (ME) rate of 1.6% (5/315, 95% CI 0.5-3.7%). Using the combined testing, even against challenging strains, 349 (95.8%, 95% CI 93.3-97.7%) colistin susceptibility results could be reported, and only 15 isolates required further analysis by BMD. DISCUSSION: Our method is simple to apply and allows rapid reporting of colistin susceptibility.

The 3-day rule for stool cultures: should all patients with haematological malignancies be excluded?

OBJECTIVES: The '3-day rule' for stool culture ordering suggests that only selected inpatients with nosocomial diarrhoea should have stool cultures for enteropathogenic bacteria (EPBs). Patients with haematological malignancies are not included in this group. We have analysed the ordering of stool cultures at Laikon Hospital to investigate whether all patients with haematological malignancies should be excluded from the 3-day rule. METHODS: We have retrospectively analysed all inpatient stool specimens sent to the microbiology laboratory for enteropathogenic bacteria culture at Laikon Hospital, Athens, Greece, between January 1, 2014 and December 31, 2014. We classified stool cultures sent after the third day as 'appropriate', 'excluded' with standard rule, 'excluded' with haematological malignancies, and 'inappropriate'. RESULTS: During the study period, 1101/1593 inpatient stool cultures (69.1%) had been ordered after the third day of hospitalization. The total yield for inpatient EPB stool cultures was 0.7% (11/1593). The yield for 'appropriate' cultures was significantly higher than the yield of all 'excluded' specimens (3.7% (3/81) versus 0.3% (2/585), p 0.018) and to 'inappropriate' orders (3.7% (3/81) versus 0.0% (0/485), p 0.0028). There was no difference in the yield between specimens 'excluded' with the standard rule and 'excluded' with haematological malignancies. CONCLUSIONS: In our hospital, the yield of stool cultures from patients with haematological malignancies is similar to that of patients 'excluded' from the standard 3-day rule. If patients with haematological malignancies were not excluded from the rule, we would reduce the inpatient stool cultures by 13.6% (217/1593) at the cost of missing one positive stool culture.

Antibiotic treatment of infections caused by carbapenem-resistant Gram-negative bacilli: an international ESCMID cross-sectional survey among infectious diseases specialists practicing in large hospitals.

OBJECTIVES: To explore contemporary antibiotic management of infections caused by carbapenem-resistant Gram-negative bacteria in hospitals. METHODS: Cross-sectional, internet-based questionnaire survey. We contacted representatives of all hospitals with more than 800 acute-care hospital beds in France, Greece, Israel, Italy, Kosovo, Slovenia, Spain and selected hospitals in the USA. We asked respondents to describe the most common actual practice at their hospital regarding management of carbapenem-resistant Enterobacteriaceae, Acinetobacter baumannii and Pseudomonas aeruginosa through close-ended questions. RESULTS: Between January and June 2017, 115 of 141 eligible hospitals participated (overall response rate 81.6%, country-specific rates 66.7%-100%). Most were tertiary-care (99/114, 86.8%), university-affiliated (110/115, 89.1%) hospitals and most representatives were infectious disease specialists (99/115, 86.1%). Combination therapy was prescribed in 114/115 (99.1%) hospitals at least occasionally. Respondents were more likely to consider combination therapy when treating bacteraemia, pneumonia and central nervous system infections and for Enterobacteriaceae, P. aeruginosa and A. baumannii similarly. Combination of a polymyxin with a carbapenem was used in most cases, whereas combinations of a polymyxin with tigecycline, an aminoglycoside, fosfomycin or rifampicin were also common. Monotherapy was used for treatment of complicated urinary tract infections, usually with an aminoglycoside or a polymyxin. The intended goal of combination therapy was to improve the effectiveness of the treatment and to prevent development of resistance. In general, respondents shared the misconception that combination therapy is supported by strong scientific evidence. CONCLUSIONS: Combination therapy was the preferred treatment strategy for infections caused by carbapenem-resistant Gram-negative bacteria among hospital representatives, even though high-quality evidence for carbapenem-based combination therapy is lacking.

Management of KPC-producing Klebsiella pneumoniae infections.

BACKGROUND: Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae (KPC-KP) has become one of the most important contemporary pathogens, especially in endemic areas. AIMS: To provide practical suggestion for physicians dealing with the management of KPC-KP infections in critically ill patients, based on expert opinions. SOURCES: PubMed search for relevant publications related to the management of KPC-KP infections. CONTENTS: A panel of experts developed a list of 12 questions to be addressed. In view of the current lack of high-level evidence, they were asked to provide answers on the bases of their knowledge and experience in the field. The panel identified several key aspects to be addressed when dealing with KPC-KP in critically ill patients (preventing colonization in the patient, preventing infection in the colonized patient and colonization of his or her contacts, reducing mortality in the infected patient by rapidly diagnosing the causative agent and promptly adopting the best therapeutic strategy) and provided related suggestions that were based on the available observational literature and the experience of panel members. IMPLICATIONS: Diagnostic technologies could speed up the diagnosis of KPC-KP infections. Combination treatment should be preferred to monotherapy in cases of severe infections. For non-critically ill patients without severe infections, results from randomized clinical trials are needed for ultimately weighing benefits and costs of using combinations rather than monotherapy. Multifaceted infection control interventions are needed to decrease the rates of colonization and cross-transmission of KPC-KP.

Syndrome of Inappropriate Antidiuretic Hormone Secretion Complicating Systemic Nocardiosis in a Renal Transplant Recipient: A Case Report.

BACKGROUND: Infection by Nocardia species is an uncommon cause of severe clinical syndromes, particularly in immunocompromised patients, and solid-organ transplantation is the most common underlying condition. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been described thus far in lung and stem cell transplants with systemic nocardiosis. CASE REPORT: We report the first case of SIADH in a female elderly renal transplant recipient diagnosed with systemic nocardiosis 2 years after transplantation. The SIADH was managed appropriately, and her immunosuppressive regimen remained unchanged but was adjusted at a lower level. The systemic Nocardia infection was successfully treated with intravenous administration of trimethoprim-sulfamethoxazole and imipenem for 2 weeks followed by oral trimethoprim-sulfamethoxazole for a total of 12 months. CONCLUSIONS: The SIADH syndrome is a recognizable complication of Nocardia infection in renal transplant recipients. Prompt identification along with proper management and prolonged antimicrobial treatment are essential to improve patients' outcome.

Prevalence of drug resistance among HIV-1 treatment-naive patients in Greece during 2003-2015: Transmitted drug resistance is due to onward transmissions.

BACKGROUND: The prevalence of HIV-1 drug resistance among treatment-naïve patients ranges between 8.3% and 15% in Europe and North America. Previous studies showed that subtypes A and B were the most prevalent in the Greek HIV-1 epidemic. Our aim was to estimate the prevalence of resistance among drug naïve patients in Greece and to investigate the levels of transmission networking among those carrying resistant strains. METHODS: HIV-1 sequences were determined from 3428 drug naïve HIV-1 patients, in Greece sampled during 01/01/2003-30/6/2015. Transmission clusters were estimated by means of phylogenetic analysis including as references sequences from patients failing antiretroviral treatment in Greece and sequences sampled globally. RESULTS: The proportion of sequences with SDRMs was 5.98% (n=205). The most prevalent SDRMs were found for NNRTIs (3.76%), followed by N(t)RTIs (2.28%) and PIs (1.02%). The resistance prevalence was 22.2% based on all mutations associated with resistance estimated using the HIVdb resistance interpretation algorithm. Resistance to NNRTIs was the most common (16.9%) followed by PIs (4.9%) and N(t)RTIs (2.8%). The most frequently observed NNRTI resistant mutations were E138A (7.7%), E138Q (4.0%), K103N (2.3%) and V179D (1.3%). The majority of subtype A sequences (89.7%; 245 out of 273) with the dominant NNRTI resistance mutations (E138A, K103N, E138Q, V179D) were found to belong to monophyletic clusters suggesting regional dispersal. For subtype B, 68.1% (139 out of 204) of resistant strains (E138A, K103N, E138Q V179D) belonged to clusters. For N(t)RTI-resistance, evidence for regional dispersal was found for 27.3% and 21.6% of subtype A and B sequences, respectively. CONCLUSIONS: The TDR rate based on the prevalence of SDRM is lower than the average rate in Europe. However, the prevalence of NNRTI resistance estimated using the HIVdb approach, is high in Greece and it is mostly due to onward transmissions among drug-naïve patients.

Malaria in Europe: emerging threat or minor nuisance?

Malaria was eradicated from Europe in the 1970s through a combination of insecticide spraying, drug therapy and environmental engineering. Since then, it has been mostly imported into the continent by international travellers and immigrants from endemic regions. Despite the substantial number of imported malaria cases and the documented presence of suitable anopheline vectors, autochthonous transmission has not been widely observed in Europe, probably as a result of early diagnosis and treatment, afforded by efficient healthcare systems. Current climatic conditions are conducive to malaria transmission in several areas of Southern Europe, and climate change might favour mosquito proliferation and parasite development, further facilitating malaria transmission. Moreover, the continuing massive influx of refugee and migrant populations from endemic areas could contribute to building up of an infectious parasite reservoir. Although the malariogenic potential of Europe is currently low, particularly in the northern and western parts of the continent, strengthening of disease awareness and maintaining robust public health infrastructures for surveillance and vector control are of the utmost importance and should be technically and financially supported to avert the possibility of malaria transmission in Europe's most vulnerable areas.

Streptococcus pyogenes emm Types and Clusters during a 7-Year Period (2007 to 2013) in Pharyngeal and Nonpharyngeal Pediatric Isolates.

Group A streptococcus (GAS) is an important cause of morbidity and mortality worldwide. Surveillance of emm types has important implications, as it can provide baseline information for possible implementation of vaccination. A total of 1,349 GAS pediatric isolates were collected during a 7-year period (2007 to 2013); emm typing was completed for 1,282 pharyngeal (84%) or nonpharyngeal (16%) isolates, and emm clusters and temporal changes were analyzed. Thirty-five different emm types, including 14 subtypes, were identified. The most prevalent emm types identified were 1 (16.7%), 12 (13.6%), 77 (10.9%), 4 (10.8%), 28 (10.4%), 6 (6.8%), 3 (6.6%), and 89 (6.6%), accounting for 82.3% of total isolates. Rheumatogenic emm types comprised 16.3% of total isolates. The emm types 12, 4, and 77 were more prevalent among pharyngeal isolates, and the emm types 1, 89, 6, 75, and 11 were more prevalent among nonpharyngeal isolates. The emm types identified belonged to 13 emm clusters, and the 8 most prevalent clusters comprised 97% of all isolates. There were statistically significant decreases in the prevalence of emm types 12, 4, 5, and 61 and increases in the prevalence of emm types 89, 75, and 11, compared with the period 2001 to 2006. The proposed 30-valent GAS vaccine, which is currently in preclinical studies, encompasses 97.2% of the emm types detected in our study and 97.4% of the erythromycin-resistant strains. In addition, it includes 93.3% of the emm types involved in bacteremia. A much greater diversity of GAS emm types was identified in our area than described previously. Seasonal fluctuations and the introduction of new emm types were observed. Continuous surveillance of emm types is needed in order to evaluate the possible benefits of an M protein-based GAS vaccine.

Treating infections caused by carbapenemase-producing Enterobacteriaceae.

Carbapenemase-producing Enterobacteriaceae (CPE) have spread worldwide, causing serious infections with increasing frequency. CPE are resistant to almost all available antibiotics, complicating therapy and limiting treatment options. Mortality rates associated with CPE infections are unacceptably high, indicating that the current therapeutic approaches are inadequate and must be revised. Here, we review 20 clinical studies (including those describing the largest cohorts of CPE-infected patients) that provided the necessary information regarding isolate and patient characteristics and treatment schemes, as well as a clear assessment of outcome. The data summarized here indicate that treatment with a single in vitro active agent resulted in mortality rates not significantly different from that observed in patients treated with no active therapy, whereas combination therapy with two or more in vitro active agents was superior to monotherapy, providing a clear survival benefit (mortality rate, 27.4% vs. 38.7%; p <0.001). The lowest mortality rate (18.8%) was observed in patients treated with carbapenem-containing combinations.

KPC-producing, multidrug-resistant Klebsiella pneumoniae sequence type 258 as a typical opportunistic pathogen.

The virulence of a KPC-producing Klebsiella pneumoniae sequence type 258 (ST258) strain representing those circulating in Greece was assessed in a mouse septicemia model. The strain was virtually avirulent (50% lethal dose, >10(8) and 5 × 10(7) CFU for immunocompetent and neutropenic animals, respectively). Also, it was highly susceptible to serum killing, rapidly phagocytosed in vitro, and classified as K41, which is not among the virulent capsular types. The findings indirectly support the notion that high ST258-associated mortality is largely due to inefficient antimicrobial treatment.

Infectious complications in the first year post renal transplantation.

BACKGROUND: The aim of this study was a prospective assessment and determination of risk factors for infections among renal transplant recipients (Rtr) during the 1st year after renal transplantation (Rtx). METHODS: From June 2004 to October 2005, we performed 133 Rtx in 88 men and 45 women of overall mean age of 46 ± 14 years (range; 13-75). RESULTS: During the first year post-Rtx, 88 (58 men and 30 women) infectious episodes were observed in 60 patients (45%). Thirty-nine (65%) required ≥1 hospitalization. Most common was urinary tract infections (UTI; 54 episodes; 61%). The causative organism was identified in 61 of the 88 (69%) episodes: In 51 it was bacterial, in 8 cytomegalovirus (CMV), and in 2 fungi. Forty-three episodes (49%) were observed during the first 3 months; 22 (25%) between 3 and 6 months and 23 (26%) between 6 and 12 months post-Rtx. There were no significant differences between patients with versus without hospitalization owing to infections with regard to recipient gender and age, duration of dialysis pre-Rtx, donor kidney source, acute rejection episodes, donor age, or arterial hypertension. Diabetes was a significant risk factor for infections (odds ratio [OR], 1.154; 95% confidence interval [CI], 1.045-1.274; P = .001], as well as an immunosuppressive regimen that included tacrolimus, mammalian target of rapamycin inhibitor, corticosteroids, and anti-interleukin-2 monoclonal antibody as initial treatment (OR, 3.053; 95% CI, 1.007-9.349; P = .043). There was an increased prevalence of CMV infections after the chemoprophylaxis period (OR, 0.456; 95% CI, 0.358-0.580; P = .002). Mean duration of hospitalization was 11.5 days (range, 2-109). In 3 of 133 (5%) Rtr, the outcome was fatal. CONCLUSION: The frequency of infections during the 1 st year post-Rtx is influenced by the primary disease of the Rtr as well by the choice of immunosuppressive regimen. UTI remains the commonest infection, accounting for half of all infections in the first 3 months post-Rtx. There was an increased risk for CMV infection after the chemoprophylaxis period.

Combined disc methods for the detection of KPC- and/or VIM-positive Klebsiella pneumoniae: improving reliability for the double carbapenemase producers.

Klebsiella pneumoniae strains co-producing klebsiella pneumoniae carbapenemase (KPC) and verona integron-encoded metallo-beta-lactamase (VIM) are frequently isolated in Greece and have also occurred in other European countries. Conventional combined disc tests exhibit low sensitivity against these emerging pathogens. We have evaluated modifications of the KPC/Metallo-ß-Lactamase Confirmation kit (ROSCO) exhibiting high diagnostic value against KPC, VIM and KPC + VIM producers. The key changes were the inclusion of additional combined tablets containing meropenem plus two inhibitors (dipicolinic acid (1000 µg per tablet) for metallo-ß-lactamases and a boronic acid derivative for KPCs) and the replacement of aminophenylboronic acid by phenylboronic acid (400 µg per tablet).

Risk factors for previously unknown meticillin-resistant Staphylococcus aureus carriage on admission to 13 surgical wards in Europe.

BACKGROUND: Early identification of meticillin-resistant Staphylococcus aureus (MRSA) carriers may be helpful for clinical and epidemiological reasons. AIM: To identify and compare risk factors of previously unknown MRSA carriage on admission to 13 surgical wards in France, Greece, Italy, and Spain. METHODS: The study was a prospective observational cohort study which enrolled consecutive patients screened for MRSA on admission to surgical wards. Sociodemographic data, comorbidities and possible risk factors for MRSA were recorded. A multivariate logistic regression model was used to predict probabilities of previously unknown MRSA colonization on admission based on patient characteristics. Prediction rules for MRSA carriage were developed and evaluated using the c-statistic. FINDINGS: Of 2901 patients enrolled, admission screening identified 111 (3.8%) new MRSA carriers. Independent risk factors for MRSA carriage were urinary catheterization (odds ratio: 4.4; 95% confidence interval: 2.0-9.9), nursing home residency (3.8; 1.9-7.7), chronic skin disease (2.9; 1.5-5.8), wounds/ulcers (2.4; 1.5-4.0), recent hospitalization (2.2; 1.5-3.3), diabetes (1.6, 1.02-2.5), and age >70 years (1.5; 1.03-2.3). However, risk factors varied between centres. The c-statistic for the common prediction rule for all centres was 0.64, indicating limited predictive power. CONCLUSIONS: Risk profiles for MRSA carriers vary between surgical wards in European countries. Identifying local risk factors is important, as a common European prediction rule was found to be of limited clinical value.

Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions.

SUMMARY: The spread of Enterobacteriaceae, primarily Klebsiella pneumoniae, producing KPC, VIM, IMP, and NDM carbapenemases, is causing an unprecedented public health crisis. Carbapenemase-producing enterobacteria (CPE) infect mainly hospitalized patients but also have been spreading in long-term care facilities. Given their multidrug resistance, therapeutic options are limited and, as discussed here, should be reevaluated and optimized. Based on susceptibility data, colistin and tigecycline are commonly used to treat CPE infections. Nevertheless, a review of the literature revealed high failure rates in cases of monotherapy with these drugs, whilst monotherapy with either a carbapenem or an aminoglycoside appeared to be more effective. Combination therapies not including carbapenems were comparable to aminoglycoside and carbapenem monotherapies. Higher success rates have been achieved with carbapenem-containing combinations. Pharmacodynamic simulations and experimental infections indicate that modification of the current patterns of carbapenem use against CPE warrants further attention. Epidemiological data, though fragmentary in many countries, indicate CPE foci and transmission routes, to some extent, whilst also underlining the lack of international collaborative systems that could react promptly and effectively. Fortunately, there are sound studies showing successful containment of CPE by bundles of measures, among which the most important are active surveillance cultures, separation of carriers, and assignment of dedicated nursing staff.

Interventional strategies and current clinical experience with carbapenemase-producing Gram-negative bacteria.

The wide dissemination of carbapenemase-producing Gram-negatives (CPGNs), including enterobacterial species and non-fermenters, has caused a public health crisis of global dimensions. These organisms cause serious infections in hospitalized patients, and are associated with increased mortality. Cross-transmission is common, and outbreaks may occur in healthcare facilities where the infection control practices are inadequate. CPGNs exhibit extensive drug-resistant phenotypes, complicate therapy, and limit treatment options. Systematic data on therapy are limited. However, regimens combining two or more active agents seem to be more efficacious than monotherapy in carbapenemase-producing Klebsiella pneumoniae infections. Strict infection control measures, including active surveillance for timely detection of colonized patients, separation of carriers from non-carriers, and contact precautions, are of utmost importance, and may be the only effective way of preventing the introduction and transmission of these bacteria in healthcare settings.