J. Prieto

Enhancement of the Susceptibility of Staphylococcus aureus to Phagocytosis after Treatment with Fosfomycin Compared with Other Antimicrobial Agents

Phagocytosis and intracellular killing of invading pathogens by host cells play the major role in resistance to bacterial infections. In vitro, antibiotics improve the susceptibility of microorganisms to antimicrobial activity of leukocytes, suggesting that this effect may contribute to determine the antimicrobial therapy and safe dosing intervals. The susceptibility of Staphylococcus aureus to phagocytosis and killing by human polymorphonuclear leukocytes (PMNL) in the presence of normal human serum in the postantibiotic phase of fosfomycin were compared with ciprofloxacin, cefotaxime and pristinamycin. Pretreatment of S. aureus for 10 min with 4 x MIC of fosfomycin and ciprofloxacin clearly sensitized the bacteria to leukocytic killing in the presence of normal human serum (10% v/v); cefotaxime and pristnamycin failed to enhance the phagocytic killing.

Preoperative skin and nail preparation of the foot: comparison of the efficacy of 4 different methods in reducing bacterial load.

BACKGROUND Orthopedic surgical procedures involving the foot and ankle are associated with high rates of infection. The optimal method of preparing the skin and nails for foot and ankle surgery remains unknown. OBJECTIVE This study was conducted to compare the efficacy of 4 different methods of skin and nail preparation of the foot using various antiseptic solutions. METHODS In this prospective, randomized study, 4 methods of skin and nail preparation were compared in terms of their efficacy in eliminating bacteria from the hallux nailfold and first web space of the normal foot in 28 healthy adult volunteers. Efficacy was determined by evaluating the difference in the total bacterial load before and after skin preparation. The foot-preparation solutions evaluated were 4% chlorhexidine gluconate, 70% isopropyl alcohol, and 7.5% to 10% povidone-iodine. RESULTS The addition of alcohol to povidone-iodine was found to increase the efficacy of the preparation method. The nailfold remained contaminated after any of the preoperative skin- and nail-preparation methods studied. LIMITATIONS This study did not measure clinically relevant infections, and the results may not correlate with decreased rates of infection after surgery. CONCLUSION Incorporation of alcohol and povidone-iodine into the preoperative skin- and nail-preparation process may help reduce the bacterial load. Every effort should be made to lower the risk of contamination from the nail.

Strong slime production is a marker of clinical significance in Staphylococcus epidermidis isolated from intravascular catheters

Biofilm production was assessed in 52 Staphylococcus epidermidis isolates from the catheters of 52 patients with catheter-related bloodstream infections (CR-BSI) and compared with 14 isolates from the skin of healthy volunteers by spectrophotometry. The isolates were classified as non- (G1), weak- (G2) or strong- (G3) slime producers based on optical density, and as producers and non-producers based on the results of the Congo red agar test. Differences (p = 0.012) in the proportion of G1, G2 and G3 among the isolates were found between catheter and healthy skin strains: there was a higher percentage of G1 types among the healthy skin strains (35.7 vs. 11.5%; p = 0.046) and a higher percentage of G3 types among the catheter isolates (44.2 vs. 0%; p = 0.001). No significant differences were found with the Congo red agar test. G3 is a phenotypic marker for CR-BSI.

Effect of clavulanic acid and/or polymorphonuclear neutrophils on amoxicillin bactericidal activity againstStreptococcus pneumoniae

The effects of polymorphonuclear neutrophils (PMNs) and/or clavulanic acid on the bactericidal activity of amoxicillin (at human serum achievable concentrations) against a serotype 3 penicillin-susceptibleStreptococcus pneumoniae strain [minimal inhibitory concentration /minimal bactericidal concentration (MIC/MBC) values of penicillin, amoxicillin, and amoxicillin/clavulanic acid (2:1)=0.01/0.01 μg/ml] and a serotype 9 penicillin-resistant strain [MIC/MBC of penicillin, amoxicillin, and amoxicillin/clavulanic acid (2:1)=1/2 μg/ml] were studied. Against the penicillin-resistant strain, subinhibitory concentrations of amoxicillin reduced the growth rate; this effect was increased by the addition of clavulanic acid. A reduction of the penicillin-resistant initial inocula (3 × 106 cfu/ml) at subinhibitory concentrations was obtained only with amoxicillin plus clavulanic acid and PMNs. At suprainhibitory concentrations, both clavulanic acid and PMNs increased the bactericidal activity of amoxicillin, as evidenced by an increased reduction in the penicillin-resistant initial inocula. The combined effect of these antibiotics and immune defenses may help explain the maintenance of their clinical efficacy in respiratory tract infections, despite the increase in the incidence of penicillin-resistant pneumococci.

In vivo and in vitro study of several pharmacodynamic effects of meropenem

Several pharmacodynamic parameters are being studied and applied to the design of dosage regimens. The thigh infection model in neutropenic mice has been used in this study to investigate the in vivo postantibiotic effect (PAE) of meropenem against S. aureus, E. coli and P. aeruginosa. The sub-minimum inhibitory concentration (sub-MIC) postantibiotic effect (PA SME) of 1/2, 1/4 and 1/8 x MIC was also determined in vitro on S. aureus and E. coli after pre-exposure of these microorganisms to 10 x MIC of meropenem. The in vitro PAE was also determined. In vivo killing curves using 2 different short dosage regimens were also studied to relate the lethal effect to the time that serum levels were above the MIC. No significant in vivo and in vitro PAEs were observed. The PA SMEs were higher for S. aureus than for E. coli. The 2 short dosage regimens, in vivo, were equally effective in killing S. aureus, but not E. coli. These results suggest that the pharmacodynamics of meropenem on Gram-negative strains may need further study to elucidate the mechanisms and characteristics of these parameters. On the other hand, we need to standardize a reliable in vitro method to monitor regrowth with a good correlation with the in vivo conditions.

In Vitro Susceptibility to Gemifloxacin and Trovafloxacin of Streptococcus pneumoniae Strains Exhibiting Decreased Susceptibility to Ciprofloxacin

Abstract The in vitro susceptibility to trovafloxacin and gemifloxacin of Streptococcus pneumoniae strains exhibiting decreased susceptibility to ciprofloxacin (MIC ≥2 μg/ml; 30 strains with intermediate resistance [MIC 2 μg/ml] and 43 strains with complete resistance [MIC ≥4 μg/ml]) was determined. Seventy-three strains collected in a surveillance study carried out from May 1996 to April 1997 in Spain (prior to commercialisation of trovafloxacin and gemifloxacin) from patients with respiratory tract infections were tested. The antibacterial activity of gemifloxacin was affected to a lesser extent than that of trovafloxacin by the increase in the MIC of ciprofloxacin, with gemifloxacin showing significantly (P≤0.001) better antibacterial activity than trovafloxacin in all ciprofloxacin MIC categories (MIC50/MIC90 values of 0.015/0.03, 0.015/0.06, 0.03/0.06 and 0.12/0.25 μg/ml for gemifloxacin vs 0.12/0.12, 0.12/1, 0.25/0.5 and 2/4 μg/ml for trovafloxacin in the 2, 4, 8 and ≥16 μg/ml ciprofloxacin MIC categories, respectively). Nine (12.3%) of these 73 strains exhibited decreased susceptibility to trovafloxacin (≥2 μg/ml), whereas all strains were inhibited by 0.25 μg/ml of gemifloxacin.

Efficacy of intraoperative surgical irrigation with polihexanide and nitrofurazone in reducing bacterial load after nail removal surgery

BACKGROUND A common challenge of nail avulsion surgery is the associated bacterial contamination and infection that can manifest. The toe has a difficult anatomy to antiseptically prepare and properly maintain throughout the surgical procedure, lending to this widespread problem. OBJECTIVE We conducted a controlled, prospective randomized study to examine the antiseptic efficacy of 3 intraoperative irrigation methods during nail avulsion surgery. METHODS We compared intraoperative antiseptic irrigation using 0.9% saline solution (24 patients), 0.2% nitrofurazone (22 patients), and 0.1% polihexanide (25 patients). Swab samples were taken from each patient at 5 distinct stages throughout the surgical procedure, and bacterial culture analysis was performed (positive culture rate, total inocula count, reduction of bacterial load, and identification of specific micro-organisms). RESULTS All 3 intraoperative irrigation methods reduced the total bacterial load, but polihexanide was significantly more effective. Furthermore, no patient from the polihexanide group developed postoperative infection. The reduction in bacterial load was lost for all 3 methods after partial nail avulsion surgery, returning to similar values as the initial presurgical bacterial load. An intraoperative irrigation step after partial nail avulsion with saline, nitrofurazone, and polihexanide was effective in reducing the bacterial load by 95.2%, 96.6%, and 99.5%, respectively. LIMITATIONS Our patients underwent phenol-based nail avulsion, resulting in no bacterial load after complete nail removal because of the intrinsic antiseptic nature of the phenol. CONCLUSIONS Intraoperative irrigation with 0.1% polihexanide substantially reduced the bacterial load and subsequent infections, highlighting the importance of an irrigation step in nail avulsion surgery.

Effect of polymorphonuclear neutrophils on serum bactericidal activity againstStreptococcus pneumoniae after amoxicillin administration

The effect of phagocytic killing on serum bactericidal activity againstStreptococcus pneumoniae was investigated 0, 1.5, 8 and 12 h after a single 875 mg oral dose of amoxicillin in healthy adults. Killing curves were determined with polymorphonuclear neutrophils (PMN), serum or PMN plus serum. Global killing (i. e. intracellular and extracellular killing) over 3 h of incubation was expressed as the area under the killing curve (AUKC; log cfu × h/ml). Amoxicillin did not affect the activity of PMN alone. For serum alone, the AUKC of post-administration samples (with supra-inhibitory amoxicillin concentrations) was significantly lower than in baseline samples. For serum plus PMN, significant bactericidal activity of serum was still found in samples after antibiotic concentrations had reached sub-inhibitory levels.

Influence of Human Serum on the Postantifungal Effect of Four Antifungal Agents on Candida albicans

This study evaluates the influence of both fresh and heated human serum on the postantifungal effect (PAFE) induced by different concentrations of amphotericin B (AmB), 5-fluorocytosine (5-Fc), Ketoconazole (Kz) and fluconazole (Flu) on two strains of Candida albicans. The concentrations were selected in harmony with the pharmacokinetic properties and toxicity of the drugs. Without serum there was no delay in the growth of yeast cultures pretreated with Kz or Flu, leading to negative PAFEs, however with AmB and 5-Fc the PAFEs were positive. When assays were made in the presence of 10% fresh human serum, the duration of the PAFEs increased with all drugs tested, and those induced by azolic agents became positive. In the presence of 10% human serum heated at 56 degrees C for 30 min, the PAFEs of the antifungal agents were similar to those obtained in the absence of serum. Our results suggest that fresh serum positively influenced PAFE which may be an important factor in determining the dosing regimen for infection by yeasts.

Postantibiotic Effect of Ciprofloxacin Compared with that of Five Other Quinolones

The antimicrobial activity (minimal inhibitory concentration, MIC, and killing kinetics) and postantibiotic effect (PAE) of different concentrations (MIC and 6 mg/1) of ciprofloxacin, norfloxacin, ofloxacin, pefloxacin, fleroxacin and lomefloxacin on pure cultures of Staphylococcus aureus and Escherichia coli were compared in vitro. The MIC, killing kinetics and PAE were determined by standard methods. Ciprofloxacin displayed the lowest MICs, while the highest were those of norfloxacin against S. aureus and lomefloxacin against E. coli. The killing curves showed ciprofloxacin to be the most and norfloxacin the least active. The bactericidal power was dependent on the concentration. At MIC, the fluoroquinolones, with the exception of norfloxacin, induced PAEs of 1-2 h. The effect was, in all cases, greater against E. coli. When assayed at 6 mg/l the PAEs were increased to 2-5 h, the best results being obtained by ciprofloxacin followed by ofloxacin. Norfloxacin produced no PAE on S. aureus and scarcely reached 1.3 h against E. coli. There was a close relationship between bactericidal power and PAE.