The impact of socioeconomic factors on the efficiency of voluntary toxoplasmosis screening during pregnancy: a population-based study.

BACKGROUND: Congenital toxoplasmosis is associated with severe complications. German state health insurance covers rubella, but not toxoplasmosis, immunity screening. We analysed the effect of socioeconomic factors on the efficiency of private toxoplasmosis screening during pregnancy. METHODS: Toxoplasmosis and rubella screening data (n = 5402 mothers) were collected within the population-based Survey of Neonates in Pomerania (SNiP). RESULTS: At the first-trimester screening, 34.4 % (88.1 %) of expecting mothers were immune to toxoplasmosis (rubella). Susceptibility for toxoplasmosis (rubella) was observed in 39.6 % (8.9 %) and 25.8 % (2.95 %) were not tested. Data on a 2(nd) screening were available in a subgroup of women with negative immunity showing less than 45 % participation rate. Active toxoplasmosis (no rubella) infection was observed in 0.3 % (n = 17) of pregnant women. A multiple logistic regression model (AIC = 719.67; AUC = 0.725) revealed that the likelihood of participating in a second toxoplasmosis screening increased among women with a good level of education and a steady partnership and decreased with paternal unemployment and the absence of breastfeeding. The highest probability of non-participation in toxoplasmosis screening was found among women with temporal burden and family responsibilities. A cost-benefit analysis showed that covering general screening for toxoplasmosis with health insurance saved costs. CONCLUSION: Toxoplasmosis carried a substantial risk of infection during pregnancy. Although increased socioeconomic status was positively associated with the participation in toxoplasmosis screening, this was not the case when pregnant women had strong temporal burden and family responsibilities. This data supports the need for toxoplasmosis screening among pregnant women as a general healthcare benefit covered by insurance.

Febrile ulceronecrotic Mucha-Habermann disease following suspected hemorrhagic chickenpox infection in a 20-month-old boy.

We present the youngest pediatric patient so far with febrile ulcerative Mucha-Haberman disease (FUMHD) after an admitting clinical picture of hemorrhagic varicella infection. With a time to diagnosis of 25 days, the 20-month-old boy responded to low dose cyclosporine and prednisolone given for 3 months and is free of disease after 4 years of follow up. We describe a polyclonal CD8+ T cell response with elevated pro-inflammatory cytokines and a fivefold upregulation of the high-affinity Fc receptor type I (CD64) on granulocytes. Early consideration of FUMHD in the differential diagnosis of a systemic inflammatory disease combined with a generalized necrotizing rash is important for early and adequate management of children with this rare and challenging disease.

[Vaccinations in respiratory medicine]. / Impfungen in der Pneumologie.

Vaccinations are the most successful and cost-effective measures for prevention of infections. Important pathogens of respiratory tract infections (e.g. influenza viruses and pneumococci) can be effectively treated by vaccinations. The seasonal trivalent and recently now quadrivalent influenza vaccines include antigens from influenza A and B type viruses, which have to be modified annually oriented to the circulating strains. The effective protection by influenza vaccination varies considerably (too short protection time, mismatch); therefore, administration late in the year is the best approach (November/December). Two pneumococcal vaccines are recommended for adults: the over 30-year-old 23-valent polysaccharide vaccine (PPV23) and the 4-year-old 13-valent conjugate vaccine (PCV13). The immunological and clinical efficacy of PPV23 is controversially discussed; however, a moderate reduction of invasive pneumococcal infections is widely accepted. The PCV13 stimulates a T-cell response and has currently demonstrated its clinical efficacy in an impressive study (CAPiTA). The problem of PCV13 is the relatively limited coverage of only 47% of the currently circulating invasive pneumococcal serotypes.

[Incidence and duration of therapy of pathological hip findings in U2 and U3 examinations (SNiP study)]. / Inzidenz und Therapiedauer pathologischer Hüftbefunde im Rahmen der U2- und U3-Untersuchung (SNiP Studie).

INTRODUCTION AND OBJECTIVES: Determination of the efficacy of an early ultrasound examination followed by immediate treatment of hip joint dysplasia as well as measuring the therapeutic success in a population-based cohort study of neonates. MATERIAL AND METHODS: The Survey of Neonates in Pomerania (SNiP) study included 4,093 neonates which represents 95.1 % of the total neonatal population. Of these children 2,534 (61.9 %) underwent ultrasound examination of the hip joint during the U2 stage (3-10 days after birth). The mean gestational age was 38.9 weeks. The sonographic classification was performed according to Graf. RESULTS: Initially (U2 stage) 42 (1.66 %) children were reported to be in need of therapy (stage IIc or higher according to Graf). The analysis showed a significantly higher incidence in girls (32 girls vs. 10 boys, p < 0.023, χ(2) test) and in children who had a breech birth (116, 4.6 %). A genetic predisposition was ascertained in 180 (7.1 %) children. The children could be subdivided into two groups: 1) children who underwent hip joint ultrasound during both U2 and U3 and 2) children who were first screened at the U3 stage. Of the 49 out of 54 neonates where the ultrasound findings were positive at the U2 examination the hip joint was matured in 32 children at U3 (4-8 weeks), 11 children had to be treated for 8-12 weeks 5 children were treated for over 3 months and1 child needed surgical correction. CONCLUSION: The early diagnosis of hip maturation disorders and joint dysplasia facilitates early implementation of effective treatment. At our clinic over 60 % of the infants underwent the U2 check up and, given a pathological finding, could undergo early treatment. It was possible to successfully treat 78 % of these children with a Tübingen hip flexion splint in just 4-8 weeks. In contrast, infants who were first examined at the U3 stage needed treatment for 4-12 months. In our opinion, early diagnosis at the age of 3-10 days should be carried out for all newborns.

[Multiresistant pathogens--a challenge for clinicians]. / Multiresistente Erreger--eine infektiologische Herausforderung.

Gram-negative pathogens are currently isolated frequently in invasive nosocomial infections and give rise to major therapeutic problems due to their resistance pattern. Metaanalyses of randomised controlled studies have demonstrated that an antibiotic combination treatment is not indicated in many cases. However, in critically ill patients (septic shock) and also in immunocompromised patients with previous intensive care as well as broad spectrum antibiotic treatment, a combination of antibiotics is recommended. This therapy should be based on the source of the infection, on local resistance data, on antibiotic pretreatment, on basic diseases of the patient and on current liver and renal functions. The start of therapy should be as fast as possible after collection of optimal materials for microbiological analysis. Dosage of selected antibiotics should be based on rational pharmacokinetic and pharmacodynamic parameters. A de-escalation of antibiotics is strongly recommended in all international guidelines based on the microbiological results and the clinical response of the patient. New antibiotics or therapeutic strategies against multiresistant Gram-negative pathogens will not be available in the next 5 to 10 years; therefore, it is absolute mandatory to use the currently still effective antibiotics, like carbapenems and polymyxins, very rationally and restrictively.

[Progress with management of hereditary angioedema]. / Fortschritte im Management des hereditären Angioödems.

Hereditary angioedema (HAE) is a rare type of angioedema caused by a quantitative or functional deficit of C1 inhibitor (C1 INH) that leads to excess production of bradykinin, which can result in acute localized swelling attacks in the skin or mucous membranes of the mouth, head and neck, extremities, gastrointestinal (GI) tract, genitals, trunk, and larynx. Angioedema in the respiratorytract maycause airway obstruction; severe abdominal pain, vomiting, or diarrhea may occur in the GI tract. Patients with HAE may be diagnosed and managed by HAE specialists or by primary care physicians depending on individual circumstances. Proper treatment requires differentiation from other forms of angioedema. Patients with HAE who are managed appropriately with medications that treat and prevent atttacks may have a lower risk of death from laryngeal edema and a better quality of life. Less frequent attacks may allow them to attend work, school, and leisure activities more regularlyand be free of the pain and disfigurement of HAE attacks moreoften.

Acupuncture for treatment of acute vomiting in children with gastroenteritis and pneumonia.

OBJECTIVE: Acupuncture is successfully used to alleviate vomiting in children after general anesthesia. However there is no data on treatment of vomiting in children with gastroenteritis (GE) and pneumonia (PM). METHODS: Descriptive analysis of 18 cases, where acupuncture was used as an individual therapy attempt to treat vomiting in children with GE or PM before starting the conventional antiemetic therapy. Feasibility and acceptance by patients and parents as well as the incidence of vomiting and use of antiemetic drugs after acupuncture were recorded. RESULTS: Acupuncture was feasible in all children and application of the indwelling needles was tolerated without fear. Side effects were not observed. 13 patients stopped vomiting immediately after the insertion of acupuncture needles, none of the patients required conventional antiemetic medication. CONCLUSION: Acupuncture for the treatment of vomiting is feasible and acceptable. Suggested antiemetic effect should be examined in a randomized multicenter controlled trial.

Comparison of pneumococcal conjugate polysaccharide and free polysaccharide vaccines in elderly adults: conjugate vaccine elicits improved antibacterial immune responses and immunological memory.

BACKGROUND: High functional antibody responses, establishment of immunologic memory, and unambiguous efficacy in infants suggest that an initial dose of conjugated pneumococcal polysaccharide (PnC) vaccine may be of value in a comprehensive adult immunization strategy. METHODS: We compared the immunogenicity and safety of 7-valent PnC vaccine (7vPnC) with that of 23-valent pneumococcal polysaccharide vaccine (PPV) in adults >/=70 years of age who had not been previously vaccinated with a pneumococcal vaccine. One year later, 7vPnC recipients received a booster dose of either 7vPnC (the 7vPnC/7vPnC group) or PPV (the 7vPnC/PPV group), and PPV recipients received a booster dose of 7vPnC (the PPV/7vPnC group). Immune responses were compared for each of the 7 serotypes common to both vaccines. RESULTS: Antipolysaccharide enzyme-linked immunosorbent assay antibody concentrations and opsonophagocytic assay titers to the initial dose of 7vPnC were significantly greater than those to the initial dose of PPV for 6 and 5 of 7 serotypes, respectively (P < .01 and P < .05, respectively). 7vPnC/7vPnC induced antibody responses that were similar to those after the first 7vPnC inoculation, and 7vPnC/PPV induced antibody responses that were similar to or greater than antibody responses after administration of PPV alone; PPV/7vPnC induced significantly lower antibacterial responses, compared with those induced by 7vPnC alone, for all serotypes (P < .05). CONCLUSION: In adults, an initial dose of 7vPnC is likely to elicit higher and potentially more effective levels of antipneumococcal antibodies than is PPV. In contrast with PPV, for which the induction of hyporesponsiveness was observed when used as a priming dose, 7vPnC elicits an immunological state that permits subsequent administration of 7vPnC or PPV to maintain functional antipolysaccharide antibody levels.

Influence of azithromycin and clarithromycin on macrolide susceptibility of viridans streptococci from the oral cavity of healthy volunteers.

Oral viridans streptococci are a reservoir of resistance genes for pathogens. Through prolonged exposure, long-acting macrolides (e.g., azithromycin) may induce the resistance of the commensals to macrolides more frequently than macrolides with a shorter half-life (e.g., clarithromycin). In a prospective, randomized, evaluator-blinded trial in healthy volunteers receiving standard courses of either azithromycin (n = 20) or clarithromycin (n = 20), we compared the susceptibility of oral viridans streptococci to macrolides over a period of 12 weeks. There was a significant temporal increase in the numbers of resistant isolates in both groups (p < 0.0005 at week 1). The proportion of macrolide-resistant isolates over time was significantly higher following azithromycin treatment (p = 0.0005), but returned to baseline values until week 12 in both groups. Temporal differential effects of azithromycin and clarithromycin on the induction of resistance were observed and need to be investigated regarding their effect on co-colonizing pathogens.

Spinal sonography in infants with cutaneous birth markers in the lumbo-sacral region--an important sign of occult spinal dysrhaphism and tethered cord.

AIM: Cutaneous markers in the lumbo-sacral region are indicators of occult spinal dysrhaphism and tethered cord. By means of spinal sonography, anatomical abnormalities of the spinal cord can be shown in the neonatal period. PATIENTS: We report on 6 infants with lumbo-sacral cutaneous abnormalities who were investigated with a high resolution linear transducer (> 7.5 MHz) and a computer sonographic unit (Sequoia, Acuson). The investigations were performed between the first day of life and the ninth week (m: 26 days). The following cutaneous markers could be found: Asymmetrical gluteal crease (4); dermal sinus (2), hairy tuft (1); pigmented naevus (1); cutaneous appendage (1); haemangioma (1); unilateral peroneal paralysis with hypotrophic correspondic leg (1). RESULTS: Sonographic evaluation showed the following abnormalities: Tethered cord (6); diastematomyelia (2); tight filum terminale (2); spinal lipoma (3); lipomyelomeningocele (2), myelocystocele and hydromyelia (1). In all infants, sonographic diagnosis could be confirmed by MR imaging and intraoperatively. Surgical correction was performed at the age of 2 to 12 months (m: 7.7 months). CONCLUSION: All infants with cutaneous markers in the lumbo-sacral region should be investigated by spinal sonography as long as the vertebral arches are not completely ossified. Sonography of the spinal cord may detect occult spinal dysrhaphism and tethered cord and prevent neurological damage by early surgical correction at the end of the first year of life.

Melanoma immunotherapy by targeted IL-2 depends on CD4(+) T-cell help mediated by CD40/CD40L interaction.

The induction of tumor-protective immunity against malignancies remains a major challenge in cancer immunotherapy. A novel, humanized anti-ganglioside-GD(2)-IL-2 immunocytokine (hu14.18-IL-2) induced CD8(+) T cells to eradicate established pulmonary metastases of B78-D14 murine melanoma, in a process that required help by CD4(+) T cells and was mediated by the CD40/CD40 ligand (CD40L) interaction. The anti-tumor effect was diminished in mice deficient in CD4(+) T-cells. Three lines of evidence show that CD4(+) T-cell help was mediated by CD40/CD40L interaction but not by endogenous IL-2 production. First, the hu14.18-IL-2-induced anti-tumor response is partially abrogated in C57BL/6J CD40L knockout (KO) mice in contrast to C57BL/6J IL-2 KO animals, in which the immunocytokine was completely effective. Second, partial abrogation of the anti-tumor effect is induced with anti-CD40L antibodies to the same extent as with CD4(+) T-cell depletion. Third, a complete anti-tumor response induced by hu14.18-IL-2 can be reconstituted in C57BL/6J CD40L KO mice by simultaneous stimulation with an anti-CD40 mAb. These results suggest that help provided by CD4(+) T cells via CD40/CD40L interactions in our tumor model is crucial for effective immunotherapy with an IL-2 immunocytokine.

Targeted interleukin-2 therapy for spontaneous neuroblastoma metastases to bone marrow.

BACKGROUND: Advanced (stage 4) cases of neuroblastoma, a childhood cancer of the nervous system, are associated with high relapse rates, even after intensive chemotherapy, radiotherapy, and autologous bone marrow transplantation. Therefore, the use of monoclonal antibodies directed against the neuroblastoma tumor marker disialoganglioside GD2 (GD2), in combination with recombinant human interleukin 2 (rhIL-2), is under clinical investigation. We hypothesize that targeted cytokine immunotherapy with a recombinant anti-GD2 antibody-interleukin 2 fusion protein (ch14.18-IL-2) is superior to a combination of ch14.18 and rhIL-2. Our purpose was as follows: 1) to develop a syngeneic model for murine neuroblastoma that expresses GD2 and features both experimental and spontaneous metastases to bone marrow and liver, and 2) to assess anti-GD2-targeted IL-2 therapy in this mode. METHODS: A hybrid neuroblastoma cell line was used to generate the GD2-positive NXS2 cell line. Bone marrow and liver metastases were quantified by reverse transcription-polymerase chain reaction for tyrosine hydroxylase and by organ weight or counts of macroscopic tumor foci, respectively. All P values reported are two-sided. RESULTS: Injection of NXS2 cells resulted in disseminated bone marrow and liver metastases exhibiting stable, but heterogeneous expression of GD2. Treatment with fusion protein (10 microg/day for 6 days) effectively suppressed growth of both experimental and spontaneous metastases to bone marrow and liver (P<.001). In contrast, a mixture of rhIL-2 and ch14.18 at equivalent dose levels was inefficient. Only mice treated with ch14.18-IL-2 showed a twofold prolongation in life span (P<.001). CONCLUSION: Targeted IL-2 therapy with a ch14.18-IL-2 fusion protein elicits an effective antitumor response. Our data suggest that a study of ch14.18-IL-2 as an adjuvant treatment in patients with minimal residual disease may be of value.

Targeted therapy with a novel enediyene antibiotic calicheamicin theta(I)1 effectively suppresses growth and dissemination of liver metastases in a syngeneic model of murine neuroblastoma.

The suppression of metastases in malignant diseases is one of the major goals in targeted chemotherapy. This was achieved with an antibody drug conjugate between a novel, rationally designed enediyene antibiotic calicheamicin theta(I)1 of exceptionally high cytotoxic potency and an antiganglioside GD2 monoclonal antibody 14G2a. Effective suppression of hepatic metastases was demonstrated in a novel syngeneic model of murine neuroblastoma that simulates the situation in patients in terms of antigen heterogeneity and presence of the target antigen on normal tissues. Here, we describe the first successful use of calicheamicin theta(I)1 for targeted chemotherapy in a clinically relevant syngeneic metastasis model.

Induction of persistent tumor-protective immunity in mice cured of established colon carcinoma metastases.

The induction of tumor-specific T-cell responses that are effective in eradicating disseminated tumors and in mounting a persistent tumor-protective immunity is one of the major goals of tumor immunotherapy. Here, we demonstrate that we achieved this goal by directing interleukin 2 (IL-2) to the tumor microenvironment of colon carcinoma metastases in syngeneic mice with a recombinant antibody-IL-2 fusion protein (huKS1/4-IL-2). Eradication of established pulmonary metastases is induced by a CD8+ T cell-mediated immune response, which can be transmitted to naive syngeneic severe combined immunodeficient mice by adoptive transfer of CD8+ T cells from immune animals. This immune response was followed by the induction of a long-lived immunity against challenge up to 5 months later with CT26-KSA or wild-type CT26 murine colon carcinoma cells in BALB/c mice. This memory immune response was confirmed by flow cytometric analyses of CD8+ T cells isolated from secondary lymphoid tissue that revealed a phenotypic profile typical of early memory T cells. This long-lived protective tumor immunity was successfully boosted to become optimally effective in all experimental animals by injections of noncurative doses of IL-2 fusion protein 4 days after challenge with tumor cells. Taken together, our results indicate that the huKS1/4-IL-2 fusion protein elicits a long-lived cellular memory immune response that can be amplified by additional applications of IL-2 fusion proteins. This approach could become useful for the treatment of colorectal carcinoma in an adjuvant setting, particularly in patients with minimal residual disease.

Targeted interleukin 2 therapy enhances protective immunity induced by an autologous oral DNA vaccine against murine melanoma.

We demonstrate that a mouse-human chimeric anti-ganglioside GD2-interleukin (IL)-2 fusion protein (ch14.18-IL2) substantially amplifies tumor-protective immunity against murine melanoma induced by an autologous oral DNA vaccine containing the murine ubiquitin gene fused to murine melanoma peptide epitopes gp100(25-35) and TRP-2(181-188). This combination therapy led to the complete rejection of a lethal challenge with B78D14 murine melanoma cells in six of eight mice and a marked suppression of s.c. tumor growth in the two remaining animals. The tumor-protective immunity was mediated by MHC class I antigen- restricted CD8(+) T cells together with CD4(+) T cell help, which was required only for tumor cell killing in the effector phase of the immune response. A single oral vaccination with the DNA vaccine, which was carried by attenuated Salmonella typhimurium, was equally as effective as three such vaccinations applied at 2-week intervals. The immunological mechanisms involved in this antitumor effect were suggested by a decisively increased secretion of tumor necrosis factor alpha TNFTnTNa and IFN-gamma from CD4(+) and CD8(+) T cells and a markedly up-regulated expression on CD8(+) T cells of high-affinity IL-2 receptor alpha chain (CD25), costimulatory molecule CD28, and adhesion molecule lymphocyte function-associated antigen-2 (LFA-2/CD2). Additionally, the combination therapy induced increased expression of costimulatory molecules B7.1 and CD48 on murine antigen-presenting cells. Taken together, our results suggest that IL-2 targeted to the tumor microenvironment by a specific antibody-IL-2 fusion protein is a potent enhancer of tumor-protective immunity induced by an oral DNA vaccine that may ultimately enhance the chances of success in its clinical application.

Elimination of established murine colon carcinoma metastases by antibody-interleukin 2 fusion protein therapy.

A recombinant humanized antibody-interleukin 2 fusion protein (huKS1/4-IL-2) was used to direct IL-2 to the tumor microenvironment and elicit a T cell-mediated eradication of established pulmonary and hepatic CT26-KSA colon carcinoma metastases in syngeneic BALB/c mice. This antitumor effect was specific because a fusion protein, which was nonreactive with these tumor cells, failed to exert any such effect. The efficacy of the huKS1/4-IL-2 fusion protein in eliminating metastases was documented because mixtures of monoclonal antibody huKS1/4 with recombinant human IL-2 were ineffective and, at best, only partially reduced tumor load. Two lines of evidence indicated the eradication of metastases and the absence of minimal residual disease in animals treated with the fusion protein: first, the lack of detection of CT26-KSA cells by reverse transcription-PCR, which can detect one tumor cell in 10(6) liver cells; and second, the tripling of life span. The effector mechanism involved in this tumor eradication is dependent on T cells because the IL-2-directed therapy is ineffective in T cell-deficient SCID mice. The essential effector cells were further characterized as CD8+ T cells by in vivo depletion studies. Such T cells, isolated from tumor-bearing mice after fusion protein therapy, elicited MHC class I-restricted cytotoxicity in vitro against colon carcinoma target cells. Taken together, these data indicate that fusion protein-directed IL-2 therapy induces a T cell-dependent host immune response capable of eradicating established colon cancer metastases in an animal tumor model.

[Management of community-acquired pneumonia in the physician's office]. / Fieber-Husten-Auswurf-Pleuraschmerz-Lungeninfiltrat. Nicht immer ist Verlass auf die Leitsymptome der Pneumonie.

The classical form of a community-acquired pneumonia is that caused by infection with pneumococcus, and differs clinically from atypical pneumonia in particular by fever-related differences. The diagnosis is based on the five cardinal symptoms: fever, cough, sputum production, pleuritic chest pain and a pulmonary infiltrate. Depending on whether there are further risk factors involved, a more or less comprehensive clinical and laboratory diagnostic work-up is needed. As a rule, oral antibiotic treatment with aminopenicillin, macrolides, fluorchinolones, ketolides or cephalosporins is applied, but decision-taking is also codetermined, for example, by whether an atypical pneumonia is suspected, or whether additional risk factors need to be taken into account.

HIV infection does not influence clinical outcomes in hospitalized patients with bacterial community-acquired pneumonia: results from the CAPO international cohort study.

In a case-control study, outcomes for 58 human immunodeficiency virus (HIV)-positive patients with community-acquired pneumonia (CAP) were compared with outcomes for 174 HIV-negative patients with CAP. No differences were found in the time to clinical stability, the length of hospitalization, and mortality. Clinical outcomes for hospitalized patients with CAP may not be influenced by HIV infection.

Immunocytokines: a promising approach to cancer immunotherapy.

Recombinant antibody-cytokine fusion proteins are immunocytokines that achieve high cytokine concentrations in the tumor microenvironment and thereby effectively stimulate cellular immune responses against malignancies. The activation and expansion of immune effector cells, such as CD8+ T lymphocytes, by interleukin-2 immunocytokines resulted in the eradication of established pulmonary and hepatic metastases of murine melanoma and colorectal carcinoma in syngeneic mouse models. These immunocytokines were equally effective in eliminating established bone marrow and liver metastases of murine neuroblastoma by activating natural killer cells. The effective eradication of metastases by immunocytokines resulted in significant prolongation in life span of mice over that of controls receiving equivalent mixtures of antibody and interleukin-2, which failed to reduce the growth of disseminated metastases. Proof of concept was established, indicating that immunocytokine-induced activation and expansion of immune effector cells in the tumor microenvironment can effectively eradicate established tumor metastases. This promising new approach to cancer immunotherapy may lead to clinical applications that improve treatment of cancer patients with minimal residual disease in an adjuvant setting.

Management of serious nosocomial bacterial infections: do current therapeutic options meet the need?

Hospital-acquired bacterial infections pose a formidable challenge for healthcare providers, as patients often need to be treated empirically, at least initially, although delay of appropriate initial antimicrobial therapy is known to increase morbidity significantly and to increase mortality among affected patients. This elevated risk is compounded by the presence of antibiotic-resistant bacteria, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase-producing Enterobacteriaceae, Escherichia coli and Klebsiella pneumoniae. Prompt initiation of treatment with an appropriate antimicrobial agent that is active against both Gram-positive and Gram-negative organisms is prudent for patients with nosocomial infections. As the continued usefulness of vancomycin comes into question, the number of alternative agents that provide efficacy equal to that of vancomycin remains limited. The development of novel and effective alternative agents, such as tigecycline, is therefore important.