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Infections due to multidrug-resistant (MDR) organisms continue to increase, and the antimicrobial pipeline remains unacceptably lean. Given this challenge, it is has become necessary to use older antimicrobials for treatment of MDR pathogens despite concerns regarding toxicity and the lack of clinical efficacy data. In some cases, older antimicrobials offer potential advantages compared with new agents, including lower cost and better in vitro activity. In this review, we focus on the pharmacology, in vitro activity, and clinical experience of older agents, including colistin, minocycline, trimethoprim-sulfamethoxazole, and fosfomycin. We also discuss some new antimicrobial agents that are used to treat MDR pathogens. As MDR pathogens continue to outpace the development of new antimicrobials, it will become imperative to develop strategies regarding the optimal use of older agents in terms of monotherapy versus combination therapy, dosing regimens, and treatment of invasive infections caused by these pathogens.

Background: Carbapenem-resistant Enterobacteriaceae (CRE) are rapidly emerging in hospitals in the United States and are posing a significant threat. To better understand the transmission dynamics and the acquisition of resistant strains, a thorough analysis of epidemiologic and molecular characteristics was performed., Methods: CRE isolated at Detroit Medical Center were analyzed from September 2008 to September 2009. bla(KPC) genes were investigated by polymerase chain reaction (PCR), and repetitive extragenic palindromic PCR (rep-PCR) was used to determine genetic similarity among strains. Epidemiologic and outcomes analyses were performed., Results: Ninety-two unique patient CRE isolates were recovered. Sixty-eight strains (74%) were Klebsiella pneumoniae, 7 were Klebsiella oxytoca, 15 were Enterobacter species, and 2 were Escherichia coli. Fifteen isolates (16%) were resistant to colistin, 14 (16%) were resistant to tigecycline, and 2 were resistant to all antimicrobials tested. The mean ± standard deviation age of patients was 63 ± 2 years. Sixty patients (68%) were admitted to the hospital from long-term care facilities. Only 70% of patients received effective antimicrobial therapy when infection was suspected, with a mean time to appropriate therapy of 120 ± 23 hours following sample culturing. The mean length of hospitalization after sample culturing was 18.6 ± 2.5 days. Of 57 inpatients, 18 (32%) died in the hospital. Independent predictors for mortality were intensive care unit stay (odds ratio [OR], 15.8; P = .003) and co-colonization with CRE and either Acinetobacter baumannii or Pseudomonas aeruginosa (OR, 17.2; P = .006). Among K. pneumoniae CRE, rep-PCR revealed 2 genetically related strains that comprised 70% and 20% of isolates, respectively., Conclusions: In this large U.S. cohort of patients with CRE infection, which reflects the modern continuum of medical care, co-colonization with CRE and A. baumannii or P. aeruginosa was associated with increased mortality. Two predominant clones of K. pneumoniae accounted for the majority of cases of CRE infection.

Pseudomonas aeruginosa is an uncommon cause of bacteremia upon hospital admission (UHA) and the chosen empirical antimicrobial therapy may not cover it appropriately. In a multicenter prospective study conducted in Israel, we evaluated risk factors for in-hospital mortality in patients with P. aeruginosa bacteremia UHA and determined the influence of delay in adequate empirical antimicrobial therapy on patients' outcome. Seventy-six adult patients with P. aeruginosa bacteremia within 72 h of hospital admission were included. Demographic, clinical, and treatment data were collected. Microbiological adequacy of empirical therapy was determined. Severe sepsis or septic shock at admission (OR, 21.9; P < 0.001), respiratory or unknown sources of bacteremia (OR, 11.5; P = 0.003), recent hospitalization (OR, 6.2; P = 0.032), and poor functional status (OR, 5.8; P = 0.029) were identified as independent predictors of mortality. Inadequate empirical antimicrobial therapy was marginally associated with increased mortality only among patients who presented with severe sepsis or septic shock (P = 0.051)., (Copyright © 2011 Elsevier Inc. All rights reserved.)

We report a surveillance method for influenza that is based on automated hospital laboratory and pharmacy data. During the 2009 H1N1 influenza pandemic, this method was objective, easy to perform, and utilized readily available automated hospital data. This surveillance method produced results that correlated strongly with influenza-like illness surveillance data.

Objectives: To identify predictors and construct a prediction model for nosocomial bloodstream infection (BSI) in older adults., Design: Retrospective case-control study., Setting: Hospitals belonging to the Duke Infection Control Outreach Network., Participants: Patients age 65 and older with a nosocomial BSI and matched uninfected controls., Measurement: Multiple variables were captured and compared between groups. Independent predictors were identified using conditional logistic regression. A prediction model and score was constructed., Results: Eight hundred thirty cases were compared with 830 controls. Eighty-one percent of nosocomial BSIs were catheter related (CRBSI). Methicillin-resistant Staphylococcus aureus (MRSA) was the most common pathogen isolated (23%). Independent predictors of nosocomial BSI in older adults were male sex, obesity, low McCabe score on admission, presence of a central line at admission, gastrostomy at admission, recent surgery, and urinary incontinence. A prediction model score greater than 11 (total possible score 23) was predictive of infection., Conclusion: MRSA is a common cause of CRBSI in older adults. Male sex, obesity, the presence of a central line, a gastrostomy tube, and urinary incontinence at the time of admission were independent predictors of BSI in hospitalized older adults. The prediction model constructed in this study should be validated prospectively in a different cohort., (© 2011, Copyright the Authors. Journal compilation © 2011, The American Geriatrics Society.)

Infection control is the discipline responsible for preventing nosocomial infections. There has been an increasing focus on prevention rather than control of hospital-acquired infections. Individuals working in infection control have seen their titles change from infection control practitioner to infection control professional and most recently to infection preventionist (IP), emphasizing their critical role in protecting patients. The responsibilities of IPs span multiple disciplines including medicine, surgery, nursing, occupational health, microbiology, pharmacy, sterilization and disinfection, emergency medicine, and information technology. This article discusses the structure and responsibilities of an infection control program and the regulatory pressures and opportunities the program faces., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Carbapenem-resistant Klebsiella pneumoniae has spread worldwide and throughout the United States. Colistin is used extensively to treat infections with this organism. We describe a cluster of colistin-resistant, carbapenem-resistant K. pneumoniae infection cases involving three institutions in Detroit, MI. A cluster of five cases of colistin-resistant, carbapenem-resistant K. pneumoniae was identified at Detroit Medical Center (DMC) from 27 July to 22 August 2009. Epidemiologic data were collected, and transmission opportunities were analyzed. Isolates were genotyped by using pulsed-field gel electrophoresis and repetitive extragenic palindromic PCR. Data regarding the use of colistin were obtained from pharmacy records. The index case of colistin-resistant, carbapenem-resistant K. pneumoniae was followed 20 days later by four additional cases occurring in a 6-day interval. All of the patients, at some point, had stayed at one particular institution. The mean number of opportunities for transmission between patients was 2.3 ± 0.5, and each patient had at least one opportunity for transmission with one of the other patients. Compared to 60 colistin-susceptible, carbapenem-resistant K. pneumoniae controls isolated in the previous year at DMC, case patients were significantly older (P = 0.05) and the carbapenem-resistant K. pneumoniae organisms isolated from them displayed much higher MICs to imipenem (P < 0.001). Colistin use was not enhanced in the months preceding the outbreak. Genotyping revealed two closely related clones. This report of a colistin-resistant, carbapenem-resistant K. pneumoniae outbreak is strongly linked to patient-to-patient transmission. Controlling the spread and novel emergence of bacteria with this phenotype is of paramount importance.

Extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae are pathogens that may lead to a spectrum of clinical syndromes. We aimed to identify predictors and outcomes of ESBL bacteremia upon hospital admission (UHA) in a nationwide prospective study. Thus, a multicenter prospective study was conducted in 10 Israeli hospitals. Adult patients with bacteremia due to Enterobacteriaceae diagnosed within 72 h of hospitalization were included. Patients with ESBL producers (cases) were compared to those with non-ESBL producers (controls), and a 1:1 ratio was attempted in each center. A case-control study to identify predictors and a cohort study to identify outcomes were conducted. Bivariate and multivariate logistic regressions were used for analyses. Overall, 447 patients with bacteremia due to Enterobacteriaceae were recruited: 205 cases and 242 controls. Independent predictors of ESBL were increased age, multiple comorbid conditions, poor functional status, recent contact with health care settings, invasive procedures, and prior receipt of antimicrobial therapy. In addition, patients presenting with septic shock and/or multiorgan failure were more likely to have ESBL infections. Patients with ESBL producers suffered more frequently from a delay in appropriate antimicrobial therapy (odds ratio [OR], 4.7; P, <0.001) and had a higher mortality rate (OR, 3.5; P, <0.001). After controlling for confounding variables, both ESBL production (OR, 2.3; P, 9.1) and a delay in adequate therapy (OR, 0.05; P, 0.001) were significant predictors for mortality and other adverse outcomes. We conclude that among patients with bacteremia due to Enterobacteriaceae UHA, those with ESBL producers tend to be older and chronically ill and to have a delay in effective therapy and severe adverse outcomes. Efforts should be directed to improving the detection of patients with ESBL bacteremia UHA and to providing immediate appropriate therapy.

Differences in reported hand hygiene compliance rates were assessed on the basis of the unit affiliation of observers. In 2 hospitals, unit-based observers more often reported higher compliance rates than did non-unit-based observers (79% vs 58.6%; difference, 20.4%; P<.001). Nonstandardized data collection methods contribute to the variability in hand hygiene compliance rates.

The role of suction regulators in nosocomial infections has, to our knowledge, not been studied. A sampling of devices used in hospitals was conducted. Many regulators (173 [37%] of 470) were found to be colonized. A suction circuit model revealed that pathogens can disseminate throughout the circuit (retrograde and antegrade), colonizing an experimental patient stomach.

A phenotypic and genotypic analysis of Acinetobacter baumannii was conducted from 2003 to 2008 in Detroit, MI. The incidence of A. baumannii increased from 1.7 to 3.7/1,000 patient days during the study period. Susceptibility to ampicillin-sulbactam and imipenem decreased from approximately 90% to approximately 40%. Genotyping revealed polyclonality, suggesting either emergence of multiple resistant strains or spread of a common genetic element. The sharp rise mandates major multidisciplinary interventions to optimize management of this multidrug-resistant pathogen.

The prevalence of isolation of imipenem-resistant Enterobacter (IRE) strains is rising, with potential serious consequences in terms of patients' outcomes and general care. The study objective was to define the various epidemiological aspects of the isolation of these strains in comparison to cases of isolation of imipenem-susceptible Enterobacter (ISE) strains. Molecular analysis of IRE strains included genotyping and defining the presence of carbapenemases. We conducted a matched retrospective case-control study of patients hospitalized from April 2003 to December 2006. Each IRE case was matched with an ISE case by age and source of isolation. A multivariate analysis using conditional logistic regression was performed to compare the two patient groups. There were 33 cases of IRE isolations during the study period. Twenty isolates were analyzed and found to belong to three distinct pulsotypes. Cell extracts of all of these isolates hydrolyzed imipenem. PCR and sequencing revealed that these isolates harbored a KPC-2 gene. In multivariate analysis, a high invasive-device score (P = 0.02) remained a predictor of IRE isolation. The mortality in the IRE group was 33%, compared to 9% among controls. Being an IRE case was significantly associated with increased mortality after controlling for confounders in a multivariate model (odds ratio, 8.3 +/- 8.6; 95% confidence interval, 1.07 to 64; P = 0.043). Resistance to imipenem due to bla(KPC-2) among Enterobacter isolates has occurred in several clones in Tel Aviv, affecting particularly patients with multiple invasive devices compared to ISE controls. IRE infections are associated with increased mortality. Enhanced measures to control the hospital spread of IRE are warranted.

Objectives: To perform a molecular and epidemiologic investigation of multidrug-resistant (MDR) Acinetobacter baumannii in an institution were polyclonal outbreaks have been observed and determine whether these polyclonal outbreaks had an endogenous origin or were caused by in-hospital patient-to-patient transmission., Design: Retrospective analysis of prospectively collected data., Setting: An epidemiologic and genotypic investigation of incident cases of MDR A. baumannii infection in an Israeli university tertiary care center., Patients: Hospitalized patients with MDR A. baumannii isolated from clinical samples during a 13-week period, from April 15, 2003, through July 15, 2003., Intervention: All patients with new MDR A. baumannii infections were recruited, and isolates were typed using pulsed-field gel electrophoresis. Data on in-hospital movements and consultations were extracted from computerized databases. Quantification of transmission opportunities (TOPs), defined as encounters between an established carrier and a future carrier of MDR A. baumannii, and analysis of ward clusters were performed., Results: We studied 96 MDR A. baumannii isolates, which belonged to 18 different pulsed-field gel electrophoresis clones. In 65% of cases, TOPs involving patients with the same clone were demonstrated, which is significantly greater than the number of TOPs involving patients with different clones (P=.01)., Conclusion: Although outbreaks of MDR A. baumannii infection may be polyclonal, we believe that patient-to-patient transmission explains most cases of transmission. Polyclonal local outbreaks reflect several clonal outbreaks occurring simultaneously. The cause of polyclonal outbreaks of A. baumannii infections clustered by ward and time remains to be explained.

Isolating carriers of multidrug-resistant (MDR) Acinetobacter baumannii is the main measure to prevent its spread. Identification of carriers accompanied by contact precautions is essential. We aimed to determine the appropriate surveillance sampling sites and the duration of carriage of MDR A. baumannii. We studied prospectively two groups of patients from whom MDR A. baumannii was previously isolated: (i) those with recent clinical isolation (or=6 months). Screening for carriage was conducted from six sites: nostrils, pharynx, skin, rectum, wounds, and endotracheal aspirates. Strains recovered concurrently from different sites were genotyped using pulsed-field gel electrophoresis. Twelve of 22 with recent clinical isolation of MDR A. baumannii had >or=1 positive screening culture, resulting in a sensitivity of 55% when six body sites were sampled. Sensitivities of single sites ranged from 13.5% to 29%. Among 30 patients with remote clinical isolation, screening cultures were positive in 5 (17%), with a mean duration of 17.5 months from the last clinical culture. Remote carriers had positive screening cultures from the skin and pharynx but not from nose, rectum, wounds, or endotracheal aspirates. Eleven strains from five patients were genotyped. In all but one case, isolates from different sites in a given patient were clonal. Current methodology is suboptimal to detect MDR A. baumannii carriage. The sensitivity of surveillance cultures is low, even when six different body sites are sampled. The proportion of individuals with previous MDR A. baumannii isolation who remain carriers for prolonged periods is substantial. These data should be considered when designing measures to limit the spread of MDR A. baumannii.

The population structure of group B streptococcus (GBS) from a low-incidence region for invasive neonatal disease (Israel) was investigated using multilocus genotype data. The strain collection consisted of isolates from maternal carriage (n=104) and invasive neonatal disease (n=50), resolving into 46 sequence types. The most prevalent sequence types were ST-1 (17.5 %), ST-19 (10.4 %), ST-17 (9.7 %), ST-22 (8.4 %) and ST-23 (6.5 %). Serotype III was the most common, accounting for 29.2 % of the isolates. None of the serotypes was significantly associated with invasive neonatal disease. burst analysis resolved the 46 sequence types into seven lineages (clonal complexes), from which only lineage ST-17, expressing serotype III only, was significantly associated with invasive neonatal disease. Lineage ST-22 expressed mainly serotype II, and was significantly associated with carriage. The distribution of the various sequence types and lineages, and the association of lineage ST-17 with invasive disease, are consistent with the results of analyses from a global GBS isolate collection. These findings could imply that the global variation in disease incidence is independent of the circulating GBS populations, and may be more affected by other risk factors for invasive GBS disease, or by different prevention strategies.

Background: The dramatic spread of vancomycin-resistant enterococci (VRE) among hemodialysis (HD) patients led to the replacement of vancomycin with cephalosporins as part of the primary empiric therapy for bacterial infections in HD units. The aim of the study was to examine the effects of this new regimen on the colonization rate of resistant bacteria among HD patients., Methods: Rectal swabs were taken from 105 HD patients and 91 control hospitalized patients. Groups were matched for age, sex, nursing home residency and background diseases. Enterococci were tested for vancomycin resistance, Staphylococcus aureus isolates were tested for methicillin resistance (MRSA), and Enterobacteriaceae were tested for extended-spectrum beta-lactamase (ESBL) activity., Results: In the HD group 1 VRE, 1 MRSA and 9 ESBL-producing organisms were isolated compared to 1 MRSA and 1 ESBL organism in the control group (p = 0.018 for ESBL). In the year prior to the study, the use of cephalosporins had been enhanced in the HD group compared to the control group (p < 0.001), and in the HD ESBL-positive patients compared to the HD ESBL-negative ones (p = 0.007). The overall use of antibiotics in the control group was the same as in the HD group. In a subanalysis of the HD group alone, the ESBL carriers were older, sicker, used more antibiotics, were hospitalized frequently and had a higher mortality rate, compared to noncarriers., Conclusions: The use of cephalosporins as first-line therapy in HD patients in central Israel reduced the prevalence of VRE colonization but may have contributed to the emergence of ESBL-producing organisms through induction of selection pressure. This may lead to serious complications in the management of these patients., (Copyright 2005 S. Karger AG, Basel.)

Objective: To determine the maternal group B Streptococcus (GBS) prevalence of carriage and serotype distribution and the neonatal disease incidence to formulate a policy for treatment and prevention regarding GBS diseases in southern Israel., Study Design: A prospective study was conducted between January and October 2000. Cultures were obtained from 681 healthy, pregnant women and processed as recommended. Samples were cultured on blood-agar plates with and without added gentamicin. GBS was identified by beta-hemolysis and a positive CAMP test and confirmed by agglutination with specific antiserum. Serotyping was done by the Lancefield precipitin method using monospecific antisera to polysaccharides Ia, Ib and II-VIII and surface proteins C, R and X., Results: Carriage prevalence of 12.3% and neonatal disease incidence of 0.095/1,000 live births were documented. Surface proteins C and R were found in 85.7% of positive cases. Serotypes Ia (17.8%), Ib (10.7%), II (27.4%), III (20.2%) and V (14.3%) were distributed as previously reported from developed countries., Conclusion: Developing a pentavalent vaccine based on serotypes Ia, Ib, II, III and V in conjugation to a GBS cell wall protein transporter, such as C or R, has theoretical advantages in the southern Israeli population over vaccines that use foreign proteins.

Background: In southern Israel, a discrepancy between a relatively high prevalence of Group B streptococcus maternal carriage (12.3%) and a very low incidence of neonatal disease (0.1/1,000 live births) has been found despite the fact that no preventive strategy has been implemented., Objectives: To determine the risk factors for maternal carriage in order to clarify this discrepancy and further examine the different aspects of GBS in southern Israel., Methods: Cultures for GBS were obtained from 681 healthy pregnant women, and relevant demographic and obstetric data were collected. The medical records of 86 neonates born to carrier women were retrospectively examined. Statistical analysis was performed using the Pearson chi-square test., Results: Women who were not born in Israel, particularly immigrants from the former USSR, were significantly prone to carry the pathogen compared to native Israeli women (Bedouins and Jews) (P = 0.03)., Conclusions: A high GBS transmission rate is expected among immigrants who came from areas with a high prevalence of maternal carriage to one with a low incidence of neonatal disease environment and were not subject to any preventive strategy. Clinical attention should be directed to this issue throughout Israel.