Fatal cross infection by carbapenem-resistant Klebsiella in two liver transplant recipients.

Members of the family Enterobacteriaceae including Klebsiella have re-emerged as major pathogens in solid organ transplantation. The recent appearance and dissemination of carbapenemase-producing Enterobacteriaceae in Europe and the northeastern United States represents a major challenge to the treatment of enteric gram-negative bacterial infections in immunocompromised patients; however, few reports have detailed the outcomes of such infections. Here we report 2 cases of Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella infections in orthotopic liver transplant recipients, which were the index case and initial secondary case for an outbreak of KPC-producing Enterobacteriaceae in our institution. In both instances, the pathogens were initially misidentified as being carbapenem sensitive, the infections recurred after cessation of directed therapy, and the patients ultimately succumbed to their infections.

Brain abscess.

The epidemiology of brain abscess has changed with the increasing incidence of this infection in immunocompromised patients, particularly solid organ and bone marrow transplant recipients, and the decreasing incidence of brain abscess related to sinusitis and otitis. A number of new neuroimaging modalities, including single photon emission computed tomography, positron emission tomography, perfusion magnetic resonance imaging, and magnetic resonance spectroscopy, provide an initial noninvasive approach to diagnosis. The recommendations for the management of intracranial mass lesions in human immunodeficiency virus-infected individuals has changed as the incidence of toxoplasmic encephalitis has decreased with the use of trimethoprim-sulfamethoxazole prophylaxis. The epidemiology, pathogenesis, microbiology, clinical presentation, diagnosis, treatment and prognosis of brain abscess in the beginning of the 21 st century are provided in this review.

Brain Abscess, Subdural Empyema, and Intracranial Epidural Abscess.

Brain abscess, subdural empyema, and intracranial epidural abscess are three of the most commonly encountered focal suppurative processes of the central nervous system. A great deal has been known about the epidemiology and pathogenesis of these entities for quite some time, but until recent years the associated morbidity and mortality remained very high. New imaging techniques have allowed for more rapid detection and more precise localization of these lesions for surgical drainage. Empiric antimicrobial regimens that are effective within the abscess environment and that are directed against the most likely pathogens have also contributed to the improved outcomes seen in the current literature. This article will discuss some of the more recent advances in the diagnosis and treatment of these suppurative lesions within the central nervous system.

Urbs in rure redux: changing risk factors for rural HIV infection.

The purpose was to ascertain risk factors for HIV infection in a predominantly rural population using descriptive epidemiologic studies performed at a university health sciences center. Participants included adult patients with HIV infection or AIDS who were cared for between January 1982 and January 1993. The relative frequency of cases in minority and female heterosexual patients increased significantly. The male to female ratio among blacks with HIV infection declined to 1.1:1 during the final 3 years of the study. Patients who believed they had acquired infection in Virginia were more likely to cite a rural area of acquisition and to have had multiple heterosexual partners but were less likely to have had male homosexual contact than patients who believed they had been infected in other states. HIV continued to spread into rural areas of Virginia, and the gender ratio among blacks with HIV declined throughout the study. Having multiple heterosexual partners, the main risk factor for HIV transmission worldwide, may now result in HIV infection in rural Virginia.

Case report: increase in CD4 lymphocyte counts after splenectomy in HIV-infected patients.

The records were reviewed of five human immunodeficiency virus (HIV) type 1-infected patients who underwent splenectomy, four for HIV-associated thrombocytopenia and one for gastric compression secondary to splenomegaly. After splenectomy, the four adult patients all had marked, sustained increases in their absolute CD4 lymphocyte counts; greater increases were observed in CD8 lymphocyte counts, accounting for decreases in the CD4:CD8 ratios. In patients 5 (one of triplets, all of whom were infected with HIV after a blood transfusion), absolute CD4 lymphocyte counts were stabilized after splenectomy; the other siblings manifested a decline in CD4 counts, which was associated with a delay in physical development and recurrent episodes of varicella. Immunohistochemical staining of spleen sections demonstrated significantly higher numbers of CD4 cells in splenic tissue from HIV-infected patients than from patients splenectomized secondary to trauma (2,070 +/- 284 vs. 962 +/- 296; p = 0.025). In addition, the HIV-infected patients had significantly higher percentages of CD4 lymphocytes in splenic tissue than in peripheral blood (49.3 +/- 11.0 vs. 20.3 +/- 7.9; p = 0.005), suggesting that CD4 cells were sequestered in the spleens of these patients. These findings have implications for the management of splenectomized HIV-infected patients with regard to optimal timing of initiation of zidovudine therapy and for prophylaxis of Pneumocystis carinii pneumonia.

Candida prosthetic arthritis: report of a case treated with fluconazole and review of the literature.

Prosthetic arthritis due to Candida species is uncommon, with only 15 cases reported in the literature. We recently cared for a human immunodeficiency virus-infected patient who developed Candida parapsilosis prosthetic arthritis unresponsive to resection arthroplasty, intravenous amphotericin B, and suppressive ketoconazole therapy. Treatment with fluconazole led to mycologic cure and symptom improvement, although he subsequently underwent above-the-knee amputation due to continued joint instability. Fluconazole may be useful follow-up therapy after a course of amphotericin B combined with resection arthroplasty or when removal of the prosthesis cannot be accomplished.

Case report: venous thromboembolism in AIDS.

Recently, the authors managed three patients with AIDS and venous thromboembolism. All three were active, ambulatory, and without known risk factors for pulmonary embolism or deep venous thrombosis. One patient had a low titer for IgG anticardiolipin antibody (1:13). Two had low normal values for free protein S, and the third patient had a very low value (5%). Clinicians caring for AIDS patients should be alert to the possibility that venous thromboembolism may complicate HIV infection.

Pharmacologic interventions aimed at preventing the biologic effects of endotoxin.

In summary, an increased understanding of the pathogenesis and pathophysiology of septic shock has led to the development and evaluation of potential adjunctive therapies. Although several agents show promise in certain experimental settings, definitive recommendations regarding the use of these agents are not yet possible. Although several therapies have shown benefit when the subject receives treatment prior to the onset of sepsis, most have had varying degrees of success following the development of septicemia.

Recombinant human interleukin-1 induces meningitis and blood-brain barrier injury in the rat. Characterization and comparison with tumor necrosis factor.

The diversity of infectious agents capable of inducing meningitis and blood-brain barrier (BBB) injury suggests the potential for a common host mediator. The inflammatory polypeptides, IL-1 and TNF, were tested in an experimental rat model as candidate mediators for induction of meningitis and BBB injury. Intracisternal challenge of rIL-1 beta into rats induced neutrophil emigration into cerebrospinal fluid (CSF) and significantly increased BBB permeability to systemically administered 125I-BSA as early as 3 h later (P less than 0.05). This injury was reversible, dose dependent and significantly inhibited by prior induction of systemic neutropenia (via intraperitoneal cyclophosphamide) or preincubation of the rIL-1 beta inoculum (50 U) with an IgG monoclonal antibody to rIL-1 beta. Similar kinetics and reversibility of CSF inflammation and BSA permeability were observed using equivalent dose inocula of rIL-1 alpha. rTNF-alpha was less effective as an independent inducer of meningitis or BBB injury over an inoculum range of 10(1) U (0.0016 micrograms/kg)-10(6) U (160 micrograms/kg) when injected intracisternally, but inoculum combinations of low concentrations of rTNF alpha (10(3) U) and rIL-1 beta (0.0005-5.0 U) were synergistic in inducing both meningitis and BBB permeability to systemic 125I-BSA. These data suggest that in situ generation of interleukin-1 within CSF (with or without TNF) is capable of mediating both meningeal inflammation and BBB injury seen in various central nervous system infections.

Pathogenesis and pathophysiology of meningitis.

Advances in the understanding of the pathogenesis and pathophysiology of meningitis have occurred primarily through the use of experimental animal models. These models have proven to be particularly valuable in experimental bacterial meningitis, focusing on the bacterial virulence factors responsible for the initiation of infections, CNS invasion, and induction of SAS inflammation. Recent studies have examined the formation of host inflammatory cytokines in response to these virulence factors. These cytokines may be responsible for many of the pathophysiologic consequences of bacterial meningitis (eg. increased BBB permeability, cerebral edema, and increased intracranial pressure). Meningitis due to C. neoformans occurs most commonly in patients with defects in cell-mediated immunity (eg, AIDS), and the depletion of T helper cells in AIDS patients may allow unrestricted cryptococcal growth. Viral meningitis is an illness of low prevalence when compared with the overall occurrence of viral infections at other sites. CNS infection usually occurs by means of traversal across barriers that normally exclude viral invasion of the CNS, primarily through hematogenous dissemination from initial sites of infection. These advances in the pathogenesis and pathophysiology of bacterial, fungal, and viral meningitis may lead to the development of innovative treatment strategies for these disorders.

Bacterial meningitis in adults.

Bacterial meningitis continues to be an important cause of morbidity and mortality despite the availability of effective bactericidal antibiotics. Penicillin or ampicillin remains the drug of choice for meningitis caused by Streptococcus pneumoniae and Neisseria meningitidis. The third generation cephalosporins have revolutionized the treatment of gram-negative meningitis. Future therapy for bacterial meningitis will use recent developments in the understanding of pathogenic and pathophysiologic mechanisms underlying this disease.

Pentamidine. A risk-benefit analysis.

With the advent of the acquired immunodeficiency syndrome (AIDS), the therapeutic importance of pentamidine isethionate has greatly increased. This review summarises its pharmacology, its toxicity and clinical experience in the treatment of Pneumocystis carinii pneumonia (PCP). Data are conflicting as to whether pentamidine is more or less effective than cotrimoxazole (trimethoprim-sulfamethoxazole) for the treatment of PCP in individuals with AIDS, but due to its toxicity and expense, it is considered as second-line therapy by many authorities. Hypoglycaemia has been encountered in up to 27% of treatment courses with pentamidine, and nephrotoxicity in 25%. In an attempt to circumvent the toxicities associated with parenteral administration, aerosolised delivery has been evaluated for both therapy and prevention of PCP. Aerosolised pentamidine, on the basis of early clinical results, convenience and low toxicity, may become the drug of choice for prevention of PCP in individuals at high risk. However, its role in the treatment of PCP remains to be defined. Preliminary studies suggest that it is effective, but the data are insufficient to support its use outside of clinical trials.

Bacterial meningitis: recent advances in pathophysiology and treatment.

PURPOSE: To review recent advances in the understanding of pathogenic and pathophysiologic mechanisms underlying bacterial meningitis that may lead to the development of adjunctive strategies for treating this disorder. DATA IDENTIFICATION: Studies published from 1975 to 1989 were identified using Index Medicus and by reviewing the bibliographies of identified articles. STUDY SELECTION: We reviewed the experimental and human studies evaluating pathogenesis, pathophysiology, and antimicrobial treatment of bacterial meningitis, as well as those reviews that have contributed to our understanding of meningitis. DATA EXTRACTION: We evaluated the data on the pathogenesis, pathophysiology, and treatment of bacterial meningitis and considered in depth the information from animal models that may have potentially important applications in the treatment of human disease. RESULTS OF DATA SYNTHESIS: Penicillin and ampicillin remain the drugs of choice for meningitis caused by Streptococcus pneumoniae and Neisseria meningitidis. The third-generation cephalosporins have revolutionized the treatment of gram-negative bacillary meningitis; one such agent, ceftazidime, is also useful for treating Pseudomonas aeruginosa meningitis. Modification of subarachnoid space inflammation by anti-inflammatory agents may lessen many of the pathophysiologic consequences of bacterial meningitis. A recent study of adjunctive dexamethasone therapy in infants and children with bacterial meningitis showed that the incidence of long-term neurologic sequelae was lower in the corticosteroid group. CONCLUSION: Future therapy for bacterial meningitis will use recent developments in the understanding of pathogenic and pathophysiologic mechanisms underlying this disease. Additional studies using monoclonal antibodies against specific virulence factors and investigations into the production of inflammatory cytokines in response to bacterial cell products may lead to additional treatments that decrease the high morbidity and mortality in patients with bacterial meningitis.