Evidence-based guideline: Antiepileptic drug selection for people with HIV/AIDS: report of the Quality Standards Subcommittee of the American Academy of Neurology and the Ad Hoc Task Force of the Commission on Therapeutic Strategies of the International League Against Epilepsy.

OBJECTIVE: To develop guidelines for selection of antiepileptic drugs (AEDs) among people with HIV/AIDS. METHODS: The literature was systematically reviewed to assess the global burden of relevant comorbid entities, to determine the number of patients who potentially utilize AEDs and antiretroviral agents (ARVs), and to address AED-ARV interactions. RESULTS AND RECOMMENDATIONS: AED-ARV administration may be indicated in up to 55% of people taking ARVs. Patients receiving phenytoin may require a lopinavir/ritonavir dosage increase of ~50% to maintain unchanged serum concentrations (Level C). Patients receiving valproic acid may require a zidovudine dosage reduction to maintain unchanged serum zidovudine concentrations (Level C). Coadministration of valproic acid and efavirenz may not require efavirenz dosage adjustment (Level C). Patients receiving ritonavir/atazanavir may require a lamotrigine dosage increase of ∼50% to maintain unchanged lamotrigine serum concentrations (Level C). Coadministration of raltegravir/atazanavir and lamotrigine may not require lamotrigine dosage adjustment (Level C). Coadministration of raltegravir and midazolam may not require midazolam dosage adjustment (Level C). Patients may be counseled that it is unclear whether dosage adjustment is necessary when other AEDs and ARVs are combined (Level U). It may be important to avoid enzyme-inducing AEDs in people on ARV regimens that include protease inhibitors or nonnucleoside reverse transcriptase inhibitors, as pharmacokinetic interactions may result in virologic failure, which has clinical implications for disease progression and development of ARV resistance. If such regimens are required for seizure control, patients may be monitored through pharmacokinetic assessments to ensure efficacy of the ARV regimen (Level C).

Pathogens resistant to antimicrobial agents. Epidemiology, molecular mechanisms, and clinical management.

The emergence of resistance to antimicrobial agents continues to be a major problem in the nosocomial setting and now in nursing homes and the community as well. Bacteria use a variety of strategies to avoid the inhibitory effects of antibiotic agents and have evolved highly efficient means for the dissemination of resistance traits. Control of antibiotic-resistant pathogens provides a major challenge for both the medical community and society in general. To control the emergence of resistant pathogens, CDC and infection control guidelines must be adhered to, and antibiotics must be used more judiciously.

Hydrogel/silver ion-coated urinary catheter reduces nosocomial urinary tract infection rates in intensive care unit patients: a multicenter study.

OBJECTIVES: Indwelling urinary catheters are the leading source of nosocomial urinary tract infections (NUTIs). The Bardex I.C. catheter is a hydrogel latex Foley catheter with a monolayer of silver metal applied to the inner and outer surfaces of the catheter. We investigated the Bardex I.C. catheter for its ability to decrease the NUTI rate in critical care units. METHODS: Five hospitals participated in a blind prospective study, exchanging the standard latex Foley catheter for the Bardex I.C. Foley catheter. The device use rate and NUTI rate were monitored. Data were collected and analyzed using Wilcoxon rank sum test and four-way analysis of variance. A cost analysis was also performed. RESULTS: The baseline period, intervention period, and number of device days was similar for both periods. The unadjusted catheter-associated infection rate during the baseline and intervention periods was 7.1 and 4.5 infections per 1000 catheter days, respectively (P <0.01). The adjusted catheter-associated infection rate during the baseline and intervention periods was 8.1 and 4.9 infections per 1000 catheter days, respectively. This was not statistically significant (P = 0. 13). CONCLUSIONS: A trend toward a reduction in NUTIs with the use of the hydrogel/silver-coated catheter was noted in all intensive care units at each institution as shown by the unadjusted and adjusted catheter-associated infection rates. One hospital demonstrated a statistically significant reduction in NUTIs. However, statistical significance was not met when the results were adjusted. The cost analysis at one institution demonstrated cost savings with the use of the silver-coated catheter. Future analysis may require a double-blind, prospective-controlled study of longer duration to reach statistical significance.

Adverse effects of outpatient parenteral antibiotic therapy.

PURPOSE: Although home parenteral antimicrobial therapy has become common, few studies have carefully examined its adverse effects. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of 269 patients who received 291 courses of home parenteral antimicrobial therapy through a hospital-based home infusion program during a 2-year period. Patients with human immunodeficiency virus (HIV) infection were not included. RESULTS: The majority (59%) of patients were treated for bone and joint infections. Patients had a mean age of 47 years. The mean duration of antibiotic therapy was 40 days. Of monitored courses, leukopenia occurred in 16%, neutropenia in 7%, thrombocytopenia in 4%, and eosinophilia in 12%, usually after a month of therapy; these adverse effects were most frequently associated with the use of beta-lactam antibiotics. Nephrotoxicity occurred in 8% of monitored courses at a mean of 27 days and was most commonly associated with amphotericin B. Diarrhea occurred in 7% and rash in 4% of patients, and both were most commonly seen with beta-lactam antibiotics. Of those patients with permanent indwelling catheters, 11% of those with central catheters and 9% of those with peripherally inserted central catheters (PICCs) developed line complications. Overall, 8% of patients required rehospitalization. CONCLUSION: Home infusion antibiotic therapy exposes patients to the complications associated with inpatient antibiotic therapy and needs to be monitored closely to prevent serious complications and rehospitalizations.

Vancomycin-dependent Enterococcus faecalis clinical isolates and revertant mutants.

Three vancomycin-dependent clinical isolates of Enterococcus faecalis of the VanB type were studied by determining (i) the sequence of the ddl gene encoding the host D-Ala:D-Ala ligase and the vanSB-vanRB genes specifying the two-component regulatory system that activates transcription of the vanB operon, (ii) the level of expression of resistance genes by using DD-dipeptidase activity as a reporter, and (iii) the proportions of the peptidoglycan precursors synthesized. Each strain had a mutation in ddl leading to an amino acid substitution (D295 to V; T316 to I) or deletion (DAK251-253 to E) at invariant positions in D-Ala:D-Ala, D-Ala:D-Lac, and D-Ala:D-Ser ligases. These mutations resulted in impaired host D-Ala:D-Ala ligases since only precursors terminating in D-Ala-D-Lac were synthesized under vancomycin-inducing conditions. Two types of vancomycin-independent revertants of one isolate were obtained in vitro after growth in the absence of vancomycin: (i) vancomycin-resistant, teicoplanin-susceptible mutants had a 6-bp insertion in the host ddl gene, causing the E251-to-EYK change that restored D-Ala:D-Ala ligase activity, (ii) constitutive vancomycin-resistant, teicoplanin-resistant mutants had substitutions (S232 to F or E247 to K) in the vicinity of the autophosphorylation site of the VanSB sensor and produced exclusively precursors ending in D-Ala-D-Lac. Vancomycin- and teicoplanin-dependent mutants obtained by growth in the presence of teicoplanin had an 18-bp deletion in VanSB, affecting residues 402 to 407 and overlapping the G2 ATP binding domain. The rapid emergence of vancomycin-independent revertants in vitro suggests that interruption of vancomycin therapy may not be sufficient to cure patients infected with vancomycin-dependent enterococci.

Increased oxacillin activity associated with glycopeptides in coagulase-negative staphylococci.

Vancomycin resistance in methicillin-resistant staphylococci presents a potential therapeutic problem. In order to understand the impact of low-level vancomycin resistance in coagulase-negative staphylococci, stepwise selection of vancomycin resistance was accomplished by growing Staphylococcus haemolyticus in culture media with increasing concentrations of vancomycin. A >40-fold increase in susceptibility to beta-lactam antibiotics was observed. No obvious alterations in the growth curve, the presence of the mecA gene, total DNA restriction fragment length polymorphism (RFLP), beta-lactamase production, or the crude protein fraction were detected in the Staphylococcus haemolyticus-derived clones when compared to the original isolate. The proportion of the oxacillin-heteroresistant population also remained similar. A comparable phenomenon occurred with the selection of Staphylococcus epidermidis exhibiting low-level resistance to vancomycin. Additionally, it was observed that clinical isolates of coagulase-negative staphylococci grown in the presence of sub-minimum inhibitory concentrations of either vancomycin or teicoplanin lost their high-level resistance to oxacillin. Checkerboard tests showed that the combination of vancomycin and oxacillin was synergistic for two isolates of Staphylococcus haemolyticus, two of four isolates of Staphylococcus epidermidis, and one isolate of Staphylococcus hominis.

Pathogens resistant to antimicrobial agents. Epidemiology, molecular mechanisms, and clinical management.

The emergence of resistance to antimicrobial agents continues to be a major problem among both nosocomial and community-acquired pathogens. Bacteria employ a variety of strategies to avoid the inhibitory effects of antibiotic agents, and have evolved highly efficient means for the dissemination of resistance traits. The result has been the emergence of multidrug-resistant pathogens such as penicillin-resistant pneumococci, vancomycin-resistant enterococci, methicillin-resistant staphylococci, as well as a variety of multiresistant gram-negative organisms. Control of antibiotic-resistant pathogens will provide a major challenge for both the medical community and society in general. The implication of a failure to meet this challenge is the eventual arrival of the "post antibiotic era."

Fatal Vibrio parahemolyticus septicemia in a patient with cirrhosis. A case report and review of the literature.

Vibrio parahemolyticus has been well documented to cause outbreaks of infectious diarrhea, usually related to poor food handling; only rarely has it been reported to cause fetal septicemia. In contrast, Vibrio vulnificus is a well-known cause of septicemia, especially in patients with cirrhosis. A 31-year-old woman with cirrhosis who developed fatal V. parahemolyticus sepsis after ingesting raw seafood is described. We review the clinical syndromes associated with sepsis caused by these two organisms. Leg pain and bullous skin lesions may be a clue to the diagnosis. Febrile patients with cirrhosis should be questioned regarding recent seafood ingestion, and appropriate antibiotics chosen if this history is obtained. Physicians should inform patients at risk to avoid raw seafood in an attempt to prevent this potentially lethal syndrome.

Tobramycin uptake in Escherichia coli membrane vesicles.

The uptake of tobramycin was measured in Escherichia coli membrane vesicles prepared in KMES [K(+)-2-(N-morpholino)ethanesulfonic acid] buffer at pH 6.6. Uptake occurred in vesicles energized with ascorbic acid and phenazine methosulfate, in which the electrical potential (delta psi) was -120 mV, but not in vesicles energized with D-lactate (delta psi = -95 mV). The addition of nigericin to vesicles energized with D-lactate did not induce tobramycin uptake despite an increase in delta psi to -110 mV. However, when delta psi was increased or decreased by the addition of nigericin or valinomycin, respectively, uptake in vesicles energized with ascorbic acid and phenazine methosulfate was stimulated or inhibited, respectively, confirming studies with whole cells showing that uptake of aminoglycosides is gated by delta psi rather than by proton motive force (delta microH+) or delta pH. N-ethylmaleimide prevented uptake, suggesting that the aminoglycoside transporter is a cytoplasmic membrane protein with accessible sulfhydryl groups. The observation that uptake is gated in vesicles as well as in whole cells suggested that diffusion occurs through a voltage-gated channel. In vesicles preloaded with tobramycin, no efflux occurred after the addition of the protonophore carbonyl cyanide m-chlorophenylhydrazone. In susceptible cells, aminoglycosides themselves decreased the magnitude of delta psi. We propose a mechanism of aminoglycoside-induced killing in which aminoglycosides themselves close the voltage-gated channel by decreasing the magnitude of delta psi. Channel closure causes aminoglycosides accumulated prior to the fall in delta psi to be trapped, which in turn causes irreversible uptake and subsequent bactericidal effects.

IS6770, an enterococcal insertion-like sequence useful for determining the clonal relationship of clinical enterococcal isolates.

Enterococci expressing resistance to antimicrobial agents are increasingly important nosocomial pathogens. Effective strategies to prevent or abort outbreaks of resistant enterococcal infection will rely on an accurate understanding of the mechanisms by which these organisms spread. A 1065-bp insertion-like sequence (IS6770) is present in varying copy numbers in > 90% of enterococcal strains thus far examined. Hybridization patterns resulting from hybridization of enterococcal genomic DNA with an internal IS6770 probe vary considerably between unrelated strains and correlate well with results of pulsed-field gel electrophoresis and field-inversion gel electrophoresis in identifying clonal relationships among enterococcal isolates. IS6770 analysis of several outbreaks of resistant enterococci has confirmed the spread of single resistant clones rather than the emergence of resistance within the resident flora. These results suggest that IS6770 hybridization will be a useful tool for tracing the epidemiology of nosocomial enterococcal infections.

Urinary tract infection with an Enterococcus faecalis isolate that requires vancomycin for growth.

OBJECTIVE: To characterize the nutritional requirements and potential origin of a fastidious urinary tract Enterococcus faecalis isolate that apparently requires the antimicrobial agent vancomycin to grow. DESIGN: Case report and detailed microbiologic and molecular epidemiologic analysis. SETTING: University teaching hospital. MEASUREMENTS: Growth of the vancomycin-dependent strain was monitored using various standard laboratory media with and without supplementation with vancomycin and other substrates. This strain was compared with other vancomycin-resistant but nondependent E. faecalis strains by examining plasmid profiles and pulsed-field gel electrophoresis patterns of genomic DNA and by analyzing vancomycin-resistance genes identified by the polymerase chain reaction. RESULTS: An E. faecalis isolate, strain TJ310, was isolated repeatedly from the urine of a patient receiving long-term vancomycin therapy. This strain grew in primary culture but not on subculture, suggesting an unusual growth requirement, and ultimately was found to require the glycopeptide antibiotic vancomycin to grow. Strain TJ310 appeared to be closely related to other vancomycin-resistant but nondependent E. faecalis isolates with the vanB genotype previously isolated from the same patient, suggesting that vancomycin dependence may have evolved in vivo in a vancomycin-resistant enterococcal strain during continuous exposure to high concentrations of vancomycin in the urine. CONCLUSIONS: This is the first reported example of a clinical bacterial isolate that requires an antimicrobial agent to grow.

In vitro activity of novobiocin against multiresistant strains of Enterococcus faecium.

Sixty strains of vancomycin- and ampicillin-resistant Enterococcus faecium were evaluated for their susceptibilities to novobiocin in vitro. In Mueller-Hinton broth, novobiocin inhibited all strains when it was used at a concentration of < or = 2 microgram/ml and 40 of 60 strains when it was used at a concentration of < or = 0.5 micrograms/ml. MICs were 8- to 16-fold higher in 50% serum. Novobiocin alone resulted in 2-log-unit killing at 24 h. Combinations of novobiocin and a fluoroquinolone (either ciprofloxacin or ofloxacin) were additive and bactericidal for quinolone-susceptible strains in either broth or 50% serum. Gentamicin did not affect novobiocin activity, and rifampin and doxycycline were antagonistic.

Listeria monocytogenes peritonitis: case report and literature review.

Listeria monocytogenes is a Gram-positive bacillus that is pathogenic in both the normal and compromised host. We describe Listeria peritonitis and cerebritis in a patient with cirrhosis due to non-A, non-B hepatitis, and review the 11 other cases of Listeria peritonitis reported in the English-language literature. Listeria is a rare cause of peritonitis in debilitated, older patients, with two-thirds of the cases occurring in patients with chronic liver disease. Listeria peritonitis may also occur in patients undergoing peritoneal dialysis, or in those with malignancy. Peritonitis due to Listeria is clinically similar to spontaneous bacterial peritonitis, and is associated with fever, variable abdominal pain, and neutrocytic ascites; bacteremia commonly accompanies Listeria peritonitis. This syndrome can be successfully treated with antimicrobial drugs, although the third-generation cephalosporins commonly used in the therapy of spontaneous bacterial peritonitis are not recommended. Ampicillin may be the drug of choice, with combination therapy with an aminoglycoside reserved for cases that do not respond to ampicillin alone.

Inconsistent bactericidal activity of triple-combination therapy with vancomycin, ampicillin, and gentamicin against vancomycin-resistant, highly ampicillin-resistant Enterococcus faecium.

Combination therapy with ampicillin, vancomycin, and gentamicin in vitro against several clinical isolates of vancomycin-resistant, highly ampicillin-resistant Enterococcus faecium, including VanA and VanB strains, was evaluated. The MICs of ampicillin were not significantly decreased by induction with vancomycin, and the combination of ampicillin and vancomycin was not inhibitory for any strain. Triple-combination therapy was least active against highly resistant VanA isolates, achieving a reduction of less than 1 log CFU at 24 h, but demonstrated slightly more activity against VanB strains.

Tobramycin uptake in Escherichia coli is driven by either electrical potential or ATP.

Aminoglycoside antibiotics such as streptomycin and tobramycin must traverse the bacterial cytoplasmic membrane prior to initiating lethal effects. Previous data on Escherichia coli, Staphylococcus aureus, and Bacillus subtilis have demonstrated that transport of aminoglycosides is regulated by delta psi, the electrical component of the proton motive force. However, several laboratories have observed that growth of bacterial cells can occur in the apparent absence of delta psi, and we wished to confirm these studies with E. coli and further investigate whether transport of aminoglycosides could occur in the absence of a membrane potential. Treatment of acrA strain CL2 with the protonophore carbonyl cyanide m-chlorophenylhydrazone (CCCP) dissipated delta psi, decreased intracellular ATP levels, and resulted in cessation of growth; after a variable period of time (3 to 7 h), growth resumed, ultimately achieving growth rates comparable to those of untreated cells. Absence of delta psi in these cells was confirmed by absence of [3H]tetraphenyl phosphonium+ uptake as measured by membrane filtration, lack of flagellar motion, and inability of these cells to transport proline (but not methionine). Regrowth was associated with restoration of normal intracellular ATP as measured by luciferin-luciferase bioluminescence assay. Unlike unacclimatized CL2 cells treated with CCCP, these cells transported [3H]tobramycin similarly to untreated cells; aminoglycoside-induced killing was seen in association with transport. These studies suggest that under certain circumstances aminoglycoside transport can be driven by ATP (or other high-energy activated phosphate donors) alone, in the absence of a measurable delta psi. delta uncBC mutants of CL2 incapable of interconverting delta psi and ATP were treated with CCCP, resulting in dissipation of delta psi but no alteration in ATP content. Despite maintenance of normal ATP, there was no transport of [3H] bramycin, confirming that under normal growth conditions ATP has no role in the transport of aminoglycosides.