Adverse effect of staphylococci slime on in vitro activity of glycopeptides

Adhesion to biomaterial is assumed to be a crucial step in the development of staphylococcal foreign body infections. Production of extracellular slime has major implications for the development and implementation of therapeutic strategies. The effect of extracted slime was investigated on the activity of vancomycin, teicoplanin, linezolid, quinupristin/dalfopristin, rifampicin and ranbezolid against 10 clinical and 4 ATCC staphylococcal isolates. The slime extract caused a 2- to 16-fold increase in the MICs of vancomycin and teicoplanin, with a shift in the MIC(90) from 2 to 32 (vancomycin) and 2 to 16 (teicoplanin), whereas the MICs of linezolid and quinupristin/dalfopristin were only moderately affected. In time-kill studies, a significant decrease in bacterial killing (>3 log(10) cfu/ml) was observed with vancomycin and teicoplanin (4 x MIC) after addition of slime (5 and 20 mg/ml), whereas the effect of killing by linezolid and quinupristin/dalfopristin was very modest. The rifampicin and ranbezolid MICs and kill curves were not influenced by the addition of slime. The present study thus indicated that slime interferes with the antimicrobial effect of glycopeptide drugs (vancomycin, teicoplanin), and that for effective prevention and treatment of prosthetic device-related infections, appropriate and newer antibiotics such as ranbezolid should be considered.     

Influence of Moxifloxacin,Comparator Drugs and Some Fractions of Pulmonary Surfactant on Adherence of Some Respiratory Pathogens

Background: This study evaluated the effect of moxifloxacin and comparator drugs with or without some fractions of pulmonary surfactant, as surfactant protein-A (SP-A) and phospholipids, on the adherence of the most common respiratory pathogens. Materials and Methods: The adherence of respiratory pathogens to a bronchial epithelial cell line was tested. Antimicrobials were used at 1/2, 1/4 and 1/8 minimum inhibitory concentration (MIC), SP-A at 1 and 5 μg/ml and phospholipids at 50 μg/ml. Results: At 1/2 MIC moxifloxacin, ciprofloxacin, amoxicillin-clavunalate and ceftriaxone reduced the adherence of Staphylococcus aureus and Streptococcus pneumoniae to values of 40-50%. At the same concentration, cotrimoxazole reduced the adherence values of Moraxella catarrhalis and Haemophilus influenzae to about 50%, while β-lactams showed high efficacy only on H. influenzae, with adherence values of about 40%. The addition of SP-A and/or phospholipids to the tested antibiotics had no effect on bacterial adherence. Conclusion: The non-interference of SP-A and/or phospholipids with the suppressive effect that some antibiotics exert on bacterial adherence could represent a favorable event during antibiotic therapy. Received: March 23, 2001·Revision accepted: May 10, 2002     

Lower lipoteichoic and teichoic acid CSF concentrations during treatment of pneumococcal meningitis with non-bacteriolytic antibiotics than with ceftriaxone.

In the rabbit model of Streptococcus pneumoniae meningitis, treatment with rifabutin, quinupristin-dalfopristin, moxifloxacin and trovafloxacin led to smaller increases of the CSF concentrations of the pro-inflammatory cell wall components lipoteichoic and teichoic acids (LTA and TA) than did treatment with ceftriaxone. Low doses of moxifloxacin were associated with higher LTA and TA concentrations in CSF than were high doses.     

High carriage rate of high-level penicillin-resistant <Emphasis Type="Italic">Streptococcus pneumoniae</Emphasis>in a Taiwan kindergarten associated with a case of pneumococcal meningitis

Background  

The Taiwan^19F-14 Streptococcus pneumoniae clone and its variants are being found with increasing frequency in the Asia-Pacific region. A 5-year old child with S. pneumoniae meningitis caused by a high-level penicillin resistant strain (MIC = 4 μg/ml) was admitted to a hospital in southern Taiwan. We carried out a study to determine the potential source of this strain.     

Prospective study of preincisional intraparietal single-dose ceftriaxone in reducing postoperative wound infection in type I and II diabetic patients

The risk of wound contamination in diabetic patients after abdominal operations is well known. Preincisional intraparietal injection of antibiotics is used for the prophylaxis of postoperative surgical infections. Whether topically injected antibiotics remain primarily in the surgical wound or are systematically absorbed is uncertain, however. The pharmacokinetics of a preincisional, intraparietal injection of 2 g ceftriaxone was studied in 50 consecutive diabetic (type I and II) patients undergoing abdominal surgery, with determination of serum, wound tissue, and wound fluid antibiotic concentrations. Preincisional intraparietal injection of ceftriaxone resulted in high antibiotic concentrations in the wound fluid. The highest plasma concentrations were achieved at 1.5 h (98.45 μg/ml, SD = 14.54). Plasma concentrations exceeded the minimal inhibitory concentrations of most aerobic gram positive and gram negative organisms with the exception of Pseudomonas aeruginosa, Acinetobacter species, and Streptococcus faecalis for 24 h (10.35 μg/ml, SD = 4.10). No long-lasting or general complications arose in any of the diabetic patients. Our results suggest that preincisional intraparietal administration of ceftriaxone for prophylaxis of wound sepsis in diabetic patients with high risk of infection is effective. Received: 28 October 1998 / Accepted in revised form: 2 September 1999     

Quinupristin/Dalfopristin therapy for infections due to vancomycin-resistant Enterococcus faecium.

The efficacy and safety of quinupristin/dalfopristin for treatment of infections due to vancomycin-resistant Enterococcus faecium were evaluated in 24 hospitalized patients with documented infections (19 bacteremias, 5 localized infections) caused by vancomycin-resistant E. faecium that was susceptible to quinupristin/dalfopristin in vitro. Patients received iv quinupristin/dalfopristin at a dosage of either 7.5 mg/kg every 8 h or 5 mg/kg every 8 h. A favorable clinical response (cure or improvement) occurred in 19 (83%) of 23 evaluable patients; bacteriologic eradication occurred in 17 (74%) of 23 evaluable patients. A favorable clinical response was observed in 12 (80%) of 15 patients who were treated with 7.5 mg/kg of quinupristin/dalfopristin every 8 h and in 7 (88%) of 8 patients treated with 5 mg/kg of quinupristin/dalfopristin every 8 h. Two of four treatment failures were associated with a decrease in the in vitro susceptibility of vancomycin-resistant E. faecium to quinupristin/dalfopristin. Superinfections developed in 6 patients (26%), but only one was caused by Enterococcus faecalis that was resistant to quinupristin/dalfopristin. Myalgias and arthralgias were the only adverse events related to quinupristin/dalfopristin. These conditions occurred in 8 (33%) of 24 patients and were dose-related (8 cases in 16 patients treated with 7.5 mg/kg of quinupristin/dalfopristin every 8 h, no cases in 8 patients treated with 5 mg/kg every 8 h). Mortality associated with vancomycin-resistant E. faecium infection was 17% (4 of 23 patients), whereas mortality from other causes was 52% (12 of 23 patients). These results suggest that quinupristin/dalfopristin is effective as treatment for vancomycin-resistant E. faecium infections in critically ill patients with serious underlying conditions. Except for myalgias and arthralgias at higher dosages, the drug is well-tolerated.     

Myocardial metabolism studied during warm blood antero-retrograde reperfusion in ischaemic human hearts

We propose modified warm blood antegrade-retrograde reperfusion (WBARR) of arrested hearts as a metabolic model with which to study substrate exchange and energy metabolism during the recovery phase after 90 min of ischaemia in man. Eleven anaesthetized patients undergoing aorto-coronary bypass were studied during WBARR. The protocol was designed as follows: period 1, a warm blood reperfusion with potassium (3 min); period 2, a warm blood reperfusion without potassium (2 min). The perfusion flow rate averaged 250±2 ml/min at the beginning of period 1 and 218±19 ml/min at the beginning and at the end of period 2; the perfusion was performed antegradely and retrogradely in the arrested hearts. Samples were simultaneously taken from the coronary venous sinus (CVS) and from the aortic root needle (AR). At the beginning of WBARR lactate release was 85±44 μmol/min and at the end it had significantly decreased to 21±99 μmol/min (P<0.03). Simultaneously, non-esterified fatty acids (NEFA) and β-hydroxy-butyrate were initially released (71±61 and 22±66 μmol/min, respectively), while at the end of the WBARR there was an uptake of both NEFA (20±22 μmol/min; P<0.01) and β-hydroxy-butyrate (12±35 μmol/min; P=0.290). Alanine, glycerol and branched chain amino acid balance across the heart did not significantly change. In summary after 90 min of ischaemia the heart energy metabolism is mainly anaerobic and based on glucose consumption, with lactate, NEFA and amino acids, which are mainly released. After 5 min of WBARR (recovery from ischaemia), lactate release is significantly reduced and NEFA becomes the energy supply of the heart. In conclusion, (1) WBARR is a valuable method with which to study myocardial metabolism in anaesthetized humans and may be combined with the use of tracers; (2) the study of myocardial metabolism in arrested hearts eliminates the imprecisions arising from the non-continuous coronary blood flow; (3) NEFA become an important source of energy utilized by human hearts in the recovery phase from ischaemia. Received: 11 July 1997 / Accepted in revised form: 30 April 1998     

Effects of doxorubicin, mitomycin C, and ethanol on Hep-G2 cells in vitro

There are conflicting results for experiments aimed at determining whether anticancer drug therapy of human hepatocellular carcinoma prolongs the survival rate effectively. The purpose of this study was to assess the effect of low concentrations of doxorubicin, mitomycin C, and ethanol on cell replication (cell number and proliferation), and cell apoptosis of cultured human hepatocellular carcinoma (Hep-G2) cells. After 1 day of exposure doxorubicin inhibited cell replication initially by 72%, but a partial recovery of the cell number was observed. Mitomycin C inhibited to the same extent but without recovery. Ethanol reduced the cell number even further, the maximum inhibition (12 days after exposure) being 96.4%. After 3 days of exposure all three agents stopped cell replication at a level of 2%–4% of the control (P < 0.001). Cell apoptosis was activated most strikingly by mitomycin C (5 μg/ml) after 1 day of exposure and by ethanol (150 μl/ml) after 3 days of exposure. Two-way repeated-measures analysis of variance showed statistically significant differences, with ethanol being the most significant followed by mitomycin C doxorubicin, and the control (P < 0.01). Thus, a low dose of ethanol combined with an exposure time of up to 3 days appears to be an effective regimen to control growth of human hepatocellular carcinoma cells in vitro. The strong induction of apoptosis by ethanol might be of additional benefit for a local application in vivo. Received: 3 April 1998  / Accepted: 30 September 1998     

Coagulase-negative staphylococci: a 20-year study on the antimicrobial resistance profile of blood culture isolates from a teaching hospital

The increasing rates of nosocomial infection associated with coagulase–negative staphylococci (CoNS) were the rationale for this study, aiming to categorize oxacillin–resistant CoNS species recovered from blood culture specimens of inpatients at the UNESP Hospital das Clínicas in Botucatu, Brazil, over a 20–year period, and determine their sensitivity to other antimicrobial agents. The mecA gene was detected in 222 (74%) CoNS samples, and the four types of staphylococcal chromosomal cassette mec (SCCmec) were characterized in 19.4%, 3.6%, 54.5%, and 14.4% of specimens, respectively, for types I, II, III, and IV. Minimal inhibitory concentration (MIC) values to inhibit 50% (MIC50) and 90% (MIC90) of specimens were, respectively, 2 and >256 μL/mL for oxacillin, 1.5 and 2 μL/mL for vancomycin, 0.25 and 0.5 μL/mL for linezolid, 0.094 and 0.19 μL/mL for daptomycin, 0.19 and 0.5 μL/mL for quinupristin/dalfopristin, and 0.125 and 0.38 μL/mL for tigecycline. Resistance to oxacillin and tigecycline and intermediate resistance to quinupristin/dalfopristin were observed. Eight (2.7%) of all 300 CoNS specimens studied showed reduced susceptibility to vancomycin. Results from this study show high resistance rates of CoNS to antimicrobial agents, reflecting the necessity of using these drugs judiciously and controlling nosocomial dissemination of these pathogens.     

Antimicrobial resistance in Burkholderia pseudomallei

Four strains of Burkholderia pseudomallei were used to determine the minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill curves with 13 single antimicrobial agents: ceftazidime, piperacillin, imipenem, amoxicillin/clavulanic acid, doxycycline, cotrimoxazole, kanamycin, rifampicin, ciprofloxacin, trovafloxacin, clarithromycin, azithromycin and meropenem. The time-kill studies were also performed with 33 pairs of combinations of the above antimicrobial agents: 15 combinations which would be expected to be used for acute therapy and 18 combinations for maintenance therapy. The results show that the single and combination antimicrobial agents with bactericidal effects against the four strains of B. pseudomallei which should be used for clinical trials in acute melioidosis are: imipenem, meropenem, and imipenem + azithromycin. The combination antimicrobial agents which should be further studied for the ability to eliminate biofilm and intracellular killing effect are ciprofloxacin + clarithromycin, ciprofloxacin + azithromycin, and imipenem + azithromycin.     

Complementary cardioprotective effects of flavonoid metabolites and terpenoid constituents of Ginkgo biloba extract (EGb 761) during ischemia and reperfusion

Hemodynamic and electron spin resonance (ESR) analyses were performed on isolated ischemic and reperfused rat hearts to assess the cardioprotective and antioxidant effects of therapeutically relevant concentrations of Gingko biloba extract (EGb 761; 5, 50 or 200 μg/ml), its terpenoid constituents (ginkgolide A; 0.05 μg/ml and ginkgolide B; 0.05, 0.25 or 0.50 μg/ml), and a terpene-free fraction of EGb 761 (CP 205; 5 or 50 μg/ml). Hearts underwent 10 min of low-flow ischemia, 30 min of no-flow global ischemia, and 60 min of reperfusion. Test substances were added to the perfusion fluid during the last 10 min of control perfusion, low-flow ischemia and the first 10 min of reperfusion. A separate group of rats were treated with CP 205 (60 mg/kg/day; p.o.) for 15 days, after which the hearts were perfused with plain buffer. In ESR experiments, the spin-trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) was added to the perfusate to determine the effects of treatment on post-ischemic myocardial free radical generation. Results showed that in vitro exposure of hearts to EGb 761 (5 or 50 μg/ml) or to ginkgolides A and B (both at 0.05 μg/ml), or in vivo pretreatment of the rats with CP 205 delayed the onset of contracture during ischemia. The strong reperfusion-induced elevation of left ventricular end-diastolic pressure observed in untreated hearts was significantly reduced by in vitro exposure to the lowest concentrations of EGb 761, by ginkgolide A, and to a lesser extent by ginkgolide B, or by prior oral treatment with CP 205. Post-ischemic functional recovery was significantly improved by in vivo administration of CP 205, by perfusion with 5 μg/ml of EGb 761 or with both terpenoids as compared to untreated group but in vitro CP 205 was not effective. ESR analyses revealed that DMPO-OH (the DMPO / hydroxyl radical spin-adduct) concentrations in coronary effluents were markedly decreased by all treatments, except for the lowest concentration of gingkolide B. Perfusing 5 μg/ml EGb 761 resulted in a better inhibition of baseline DMPO-OH concentration than 5 μg/ml CP 205 (−70% and −48% vs. control, respectively), indicating that both terpenoid and flavonoid constituents of EGb 761 are required to produce this effect. CP 205 was significantly more efficient in reducing DMPO-OH concentration when administered in vivo than when applied in vitro, indicating that the antioxidant effect of flavonoid metabolites (formed in vivo) is superior to that of intact flavonol glycosides (present in vitro). Collectively, these findings provide the first evidence that part of the cardioprotection afforded by EGb 761 is due to a specific action of its terpenoid constituents and that this effect involves a mechanism independent of direct free radical-scavenging. Thus, the terpenoid constituents of EGb 761 and the flavonoid metabolites that are formed after in vivo administration of the extract act in a complementary manner to protect against myocardial ischemia-reperfusion injury. Received: 30 September 1999 Returned for revision: 1 December 1999 Revision received: 14 January 2000 Accepted: 8 February 2000     

Combination of Quinupristin/Dalfopristin and Glycopeptide in Severe Methicillin-Resistant Staphylococcal Infections Failing Previous Glycopeptide Regimens

Background: We report our experience with quinupristin/dalfopristin in combination with a glycopeptide in the treatment of severe staphylococcal infections failing previous glycopeptide regimens. Patients and Methods: Five patients, affected by persistent bacteremia (n = 2), post-cardiothoracic surgery infection (n = 2), and post-traumatic bone infection (n = 1) due to methicillin-resistant Staphylococcus aureus (MRSA, n = 4) methicillin-resistant coagulase-negative Staphylococcus (MRCNS, n = 1) and unsuccessfully treated with antibiotics including a glycopeptide, were treated with a quinupristin/dalfopristin and glycopeptide combination. Results: Three patients were clinically cured; one patient with MRSA thoracic aorta prosthetic infection relapsed after 3 months; one patient was lost to follow-up. Conclusion: Quinupristin/dalfopristin, in combination with a glycopeptide, is an effective treatment option for severe methicillin-resistant staphylococcal infections failing previous glycopeptide regimens. Received: July 28, 2001 · Revision accepted: March 13, 2002     

Role of endogenous and exogenous cholecystokinin in experimental acute pancreatitis induced in rats by the duodenal loop technique

The role of endogenous cholecstokinin (CCK) release and exogenous CCK-8 administration in the development and progression of acute pancreatitis and in the early recovery phase of acute pancreatitis were investigated in rats with closed duodenal loop (CDL)-induced pancreatitis. The subcutaneous injection of CCK-8 (2 μg/kg) stimulated a physiological level of pancreatic enzyme secretion in normal control rats, but did not lead to any biochemical or histological evidence of acute pancreatitis. A higher dose of CCK-8 (8 μg/kg), however, did produce both biochemical and histological evidence of acute pancreatitis in the normal control rats. When 2 μg/kg of CCK-8 was injected subcutaneously in rats 6 and 12h after the creation of the CDL, either the biochemical nor the histological findings of acute pancreatitis showed any progression compared with the changes in controls given to CCK-8. Serum CCK levels, measured by radio-immunoassay, increased significantly from mean levels of 5.39 pg/ml (±0.95 SD) before creation of the CDL to 42.06 pg/ml (±2.27 SD) 6h after, and 41.95 pg/ml (±1.88 SD) 12h after its creation (P<0.01). The difference between serum CCK levels at 6 and 12h was not statistically significant. Following the release of the loop, serum CCK levels decreased gradually, especially in rats in which the loop was released 6h after being created. Although no marked biochemical and histological changes of acute pancreatitis were observed following the admistration of 2 μg/kg of CCK-8 to rats upon release of the loop 6h and 12h after its creation, a higher dose of CCK-8 (8 μg/kg) in these rats adversely affected both the biochemical and histological findings of acute pancreatitis. Based on these findings, it was concluded that neither endogenous CCK release, as a result of the CDL, nor physiological stimulation of the pancreas by exogenous CCK-8 administration, caused progression from edematous to hemorrhagic acute pancreatitis, and neither CCK treatment had any adverse effect on the early recovery phase of CDL-induced acute pancreatitis. A pharmacological dose of CCK, however, exacerbated the acute pancreatitis, even in the early recovery stage.     

Pneumonia Due to Drug-Resistant <Emphasis Type="Italic">Streptococcus pneumoniae</Emphasis>

Pneumonia is a major infectious disease associated with significant morbidity and mortality, with Streptococcus pneumoniae the predominant pathogen in community-acquired cases, accounting for 20% to 50% of bacterial cases. Although pneumococcal resistance to β-lactams is now common worldwide, high-dose parental penicillin G, many other parental β-lactams and some oral β-lactams continue to be efficacious. The new Clinical and Laboratory Standards Institute susceptibility breakpoints for parental penicillin G for nonmeningeal infections (≤2 μg/mL, susceptible; 4 μg/mL, intermediate; ≥8 μg/mL, resistant) introduced in 2008 facilitate appropriate reporting and use of penicillin G. Pneumococcal vaccine usage in children from 2000 has led to significant decreases in morbidity and mortality due to S. pneumoniae in all age groups, and the increase in resistant serotypes, such as 19A, appears to be decreasing following the introduction of an expanded valence vaccine in 2010. Judicious use of antimicrobial agents is the best long-term approach in order to reduce S. pneumoniae resistance.     

Influence of protamine on adhesion, chemotaxis and proliferation of human vascular smooth muscle cells

Summary It has been shown that, in streptozotocin diabetic rats, protamine-retarded insulin administered in vivo stimulates intimal hyperplasia in balloon-injured carotid artery. The aim of this study was to evaluate the influence of protamine on cultured human vascular smooth muscle cells (hVSMC), by observing its effects on adhesion, chemotaxis and proliferation. hVSMC were isolated during abdominal surgery, cultured and utilized at passages 6–10. We observed that protamine stimulates: 1) cell adhesion in the concentration range 0.04–20 μg/ml (analysis of variance, ANOVA, p < 0.0001); 2) cell chemotaxis in the absence of fetal calf serum (FCS) in the concentration range 1–200 μg/ml (ANOVA, p < 0.0001) and in the presence of 1 % FCS in the concentration range 5–200 μg/ml (ANOVA, p < 0.0001), further enhancing the chemotaxis induced by 10 % FCS in the concentration range 20–200 μg/ml (ANOVA, p < 0.0001); 3) cell proliferation and ³H-thymidine incorporation from 1 to 5 μg/ml (ANOVA, p < 0.0001); 4) cell c-fos oncoprotein nuclear expression. We also observed that protamine effects on chemotaxis, proliferation and c-fos expression are inhibited by heparin that human insulin stimulates cell proliferation and ³H-thymidine incorporation (ANOVA, p < 0.0001) at concentrations equal to or greater than 480 pmol/l and that these effects of insulin persist in the presence of protamine. In conclusion, protamine influences hVSMC behaviour by interfering with biological functions involved in atherogenesis. The concentrations used in this short-term in vitro study were higher than those probably occurring in vivo in patients chronically treated by protamine-retarded insulin preparations: further studies, therefore, are needed to evaluate the safety of protamine as a retardant of insulin action in vivo. [Diabetologia (1997) 40: 67–75] Received: 23 May 1996 and in revised form: 19 September 1996     

Serum adiponectin concentrations correlate with severity of rheumatoid arthritis evaluated by extent of joint destruction

Adiponectin is a hormone released by adipose tissue with antidiabetic, antiatherogenic, and anti-inflammatory properties. The present observational study focused on the relation between serum adiponectin level and the disease severity of established rheumatoid arthritis (RA). Ninety patients with more than 5-year diagnosis of RA and 42 age- and BMI-matched control were enrolled. The severity of RA was evaluated according to the number of destructed joints of overall 68 joints on plain radiographs (37 patients had mild RA and 53 had severe RA). Serum adiponectin level was significantly higher in the severe RA group (17.7 ± 6.7 μg/ml) than in the control (9.1 ± 3.8 μg/ml) and mild RA groups (13.9 ± 6.5 μg/ml) (control vs. mild RA group, P < 0.001; mild RA vs. severe RA group, P < 0.01). These results suggest that increased number of joint destruction is associated with hyperadiponectinemia in established RA patients.     

Meropenem monotherapy versus combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients

 Infections remain the major cause of morbidity and mortality among neutropenic cancer patients. The current study addresses the question whether monotherapy with the new broad-spectrum carbapenem meropenem exhibits efficacy comparable to that of the standard combination therapy with ceftazidime and amikacin for empirical treatment of febrile neutropenic patients. Seventy-one patients with hematological malignancies (55%) or solid tumors (45%), neutropenia <500/μl, and fever <38.5  °C were randomly assigned to either meropenem (1 g every 8 h) or ceftazidime (2 g every 8 h) and amikacin (15 mg/kg/day) intravenously. Meropenem (n=34) and ceftazidime/amikacin (n=37) were equivalent with respect to the clinical response at 72 h (62% versus 68%) (p<0.05) and at the end of unmodified therapy (59% versus 62%). Gram-positive bacteremia responded poorly in the meropenem and ceftazidime/amikacin group (29% versus 25%), whereas all gram-negative bacteremias responded except for one in the meropenem group caused by Pseudomonas aeruginosa. All patients survived to 72 h. One patient in each group died of gram-positive sepsis resistant to study medication. No significant side effects occurred in any regimen. This study suggests that meropenem monotherapy might be as effective as combination therapy with ceftazidime and amikacin for the empirical treatment of febrile neutropenic patients. Received: 13 June 1997 / Accepted in revised form: 5 December 1997     

New Gram-positive agents in nosocomial infection

Multidrug-resistant Gram-positive pathogens such as vancomycin-resistant enterococci, methicillin-resistant Staphylococcus aureus, and methicillin-resistant coagulase-negative staphylococci account for a significant number of nosocomial infections, and new options for therapy have been lacking. During the past year, two agents have been released that have activity against these organisms: quinupristin/dalfopristin and linezolid. Although neither agent is a panacea, these recently released agents offer new options for therapy.     

In Vitro Activity of LY333328, a New Glycopeptide, against Extracellular and Intracellular Vancomycin-Resistant Enterococci

Summary The objectives of the study were to observe the activity of LY333328, a new semisynthetic glycopeptide, compared to that of vancomycin against six strains of Enterococcus faecium and Enterococcus faecalis, including four vancomycin-resistant strains. Bacteria ingested by polymorphonuclear leukocytes (PMN) as well as extracellular bacteria were studied using a colony count method. The activity against intracellular bacteria was tested with the drugs present in the extracellular medium, as well as after preincubating the PMN and removal of the drugs. LY333328 is active against the tested enterococci, regardless of their susceptibility to vancomycin, with MICs of 1–2mg/l. It is bacteriostatic against extracellular enterococci at concentrations of 2 μg/ml and above regardless of their resistance to vancomycin. After 4 h incubation at 10 MIC, vancomycin-resistant strains of E. faecium and E. faecalis located intracellularly were reduced by 55% and 90%, respectively. Even after preincubation and removal of the drug, LY333328 had an effect at 10 MIC with a 20–30% reduction in the inoculum. The results suggest that in contrast to vancomycin, LY333328 is active against intracellular vancomycin-resistant enterococci, particularly E. faecalis, even after removal of the extracellular drug. Received: December 15, 1999 · Revision accepted: May 5, 2000