In vitro synergy of daptomycin plus rifampin against Enterococcus faecium resistant to both linezolid and vancomycin

In vitro synergy testing of daptomycin plus rifampin was performed against 24 unique isolates of Enterococcus faecium resistant to both linezolid and vancomycin. Synergy testing showed that 21/24 (88%) were synergistic and 3/24 (12%) were indifferent by the Etest method. Time-kill assays revealed synergy for 18/24 (75%) and indifference for 6/24 (25%).     

Treatment of Gram-positive left-sided infective endocarditis with daptomycin

The aim of this study was to evaluate the effectiveness of daptomycin in left-sided infective endocarditis (IE) patients. Fourteen patients with left heart endocarditis, monitored with a diagnosis of IE based on modified Duke criteria between July 2010 and May 2011, and receiving daptomycin as monotherapy, were enrolled. The success of daptomycin in these patients was revealed with improvements in microbiological, biochemical, and radiologic findings, as well as physical examination findings. Patient average age was 63.5 ± 14.2 years (36–80 years); 8 (57 %) were men and 6 (43 %) women. The pathogens methicillin-resistant Staphylococcus aureus (71.5 %), Streptococcus mutans (21.5 %), and methicillin-sensitive Staphylococcus aureus (7 %) were isolated from our patients. Daptomycin was used in initial treatment in 5 (36 %) patients; treatment was subsequently modified to daptomycin in 9 (64 %) patients as a consequence of drug serum level insufficiency, agent sensitivity to the drug administered, or drug side effects. Thirteen patients were discharged in a healthy condition, with successful surgical treatment in 5 (36 %). Only 1, an 80-year-old IE patient, was lost from advanced cardiac failure. No significant side effects were seen in any patient receiving daptomycin. The most frequent side effects were minimal rises in serum CPK levels during treatment; these values returned to normal after treatment. Daptomycin can be used successfully in left heart endocarditis with no significant side effects. Studies involving a wider patient series are now needed to support the use of daptomycin in left heart endocarditis.     

Efficacy of linezolid plus rifampin in an experimental model of methicillin-susceptible Staphylococcus aureus endocarditis

The efficacy of linezolid, alone or in combination with rifampin, against methicillin-susceptible Staphylococcus aureus in rabbits with experimental endocarditis was investigated. Linezolid (50 or 75 mg/kg of body weight), rifampin, and linezolid (25, 50, or 75 mg/kg) plus rifampin produced statistically significant reductions in bacterial counts compared with those in untreated controls. Plasma or valvular vegetation levels of linezolid in the groups treated with the linezolid-rifampin combination were similar to those in the respective linezolid-only treatment groups. At therapeutic levels of linezolid, rifampin resistance was not observed. The results from this experimental model of endocarditis suggest that while rifampin did not provide synergy to the linezolid dosing, it did not antagonize the efficacy of linezolid.     

Clinical experience with daptomycin: bacteraemia and endocarditis

Serious infections due to Staphylococcus aureus, especially those due to methicillin-resistant S. aureus, have become a major challenge. Vancomycin has long been the drug of choice for treatment of such infections, but failures due to its slow bactericidal activity coupled with increasing MICs have necessitated a search for new, more effective agents. Daptomycin has been studied by a number of investigators and has proved to be effective for bacteraemic infections due to staphylococci as well as vancomycin-resistant enterococci and other Gram-positive organisms. In addition, in a randomized controlled trial comparing daptomycin monotherapy with potentially synergistic therapy with either vancomycin or beta-lactam, both used in combination with an aminoglycoside, daptomycin achieved comparable outcomes but with significantly less nephrotoxicity.     

Successful treatment of polymicrobial multivalve infective endocarditis

A 57-year-old man presented with triple valve infective endocarditis. There were vegetations on the tricuspid, mitral, and aortic valve. He had multiple complications such as pulmonary abscess, severe anaemia, and congestive heart failure. His general condition was extremely poor. Intensive medical therapy, such as blood transfusion, mechanical ventilation, and inotropic support, allowed him to tolerate surgery. Triple valve replacement was successfully performed without major complication. Vegetation cultures grew Streptococcus bovis and Enterecoccus faecalis. At 1 year follow-up, the patient is alive in NYHA functional class I.     

Combination therapy with daptomycin, linezolid, and rifampin as treatment option for MRSA meningitis and bacteremia

Methicillin-resistant Staphylococcus aureus (MRSA) meningitis is associated with a high mortality rate. Treatment is challenging in patients with allergy to vancomycin. Herein, we describe a case of MRSA bacteremia secondary to medical device infection with MRSA that was complicated by MRSA meningitis. This case provides evidence for a possible role of combination therapy of daptomycin, linezolid, and rifampin in cases of MRSA meningitis and bacteremia.     

High-dose daptomycin plus fosfomycin is safe and effective in treating methicillin-susceptible and methicillin-resistant Staphylococcus aureus endocarditis

We describe 3 patients with left-sided staphylococcal endocarditis (1 with methicillin-susceptible Staphylococcus aureus [MSSA] prosthetic aortic valve endocarditis and 2 with methicillin-resistant S. aureus [MRSA] native-valve endocarditis) who were successfully treated with high-dose intravenous daptomycin (10 mg/kg/day) plus fosfomycin (2 g every 6 h) for 6 weeks. This combination was tested in vitro against 7 MSSA, 5 MRSA, and 2 intermediately glycopeptide-resistant S. aureus isolates and proved to be synergistic against 11 (79%) strains and bactericidal against 8 (57%) strains. This combination deserves further clinical study.     

Oral rifampin plus ofloxacin for treatment of Staphylococcus-infected orthopedic implants.

We examined the effectiveness and safety of the combination of rifampin plus ofloxacin given orally for treating prosthetic orthopedic implants infected with staphylococci. The prospective cohort study was conducted in a referral public hospital with ambulatory care services between 1985 and 1991. Consecutive patients from whom Staphylococcus organisms susceptible to the study drugs were isolated from their orthopedic implants and who had no contraindication to the treatment were eligible for the study. All patients were treated orally with rifampin, 900 mg/day, plus ofloxacin, 600 mg/day. Patients with hip prosthesis infection were treated for 6 months, with removal of any unstable prostheses after 5 months of treatment; patients with knee prosthesis infection were treated for 9 months, with removal of the prosthesis after 6 months of treatment; and patients with infected bone plates were treated for 6 months, with removal of the plate after 3 months of treatment, if necessary. Monthly clinical evaluations were conducted until the completion of the treatment and follow-up or telephone interviews were conducted at 6, 12, 24, 36, 48, and 60 months thereafter. Treatment failures were documented by clinical evaluation, sampling of the infected site for culture and antibiotic activity measurement, and fistulography, if possible. Cure was defined as the absence of clinical, biological, and radiological evidence of infection 6 months after the completion of treatment, treatment failure was defined as the absence of cure, and relapse was defined as the reappearance of infection caused by the same Staphylococcus isolate that caused the original infection, regardless of the timing of this secondary infection. Among 51 patients included in the study and evaluable for safety, 4 patients had side effects and were not evaluable for treatment effectiveness; the overall success rate was 74% among 47 patients, with a success rate of 81% for the hip prosthesis group, 69% for the knee prosthesis group, and 69% for the osteosynthesis device group. Eight treatment failures were relaxed to the isolation of a resistant bacterium. The combination of rifampin administered orally plus ofloxacin is a suitable alternative to the conventional long-term intravenous therapy for treatment of orthopedic implants infected with staphylococci.     

High doses of daptomycin (10 mg/kg/d) plus rifampin for the treatment of staphylococcal prosthetic joint infection managed with implant retention: a comparative study

We aimed to analyze the efficacy and safety of high doses of daptomycin (10 mg/kg/d) plus rifampin (D10 + R) for prosthetic joint infection (PJI). This was an observational retrospective multicenter study (2010–2012) including all patients with acute PJI by fluoroquinolone-resistant staphylococci managed with implant retention and D10 + R. Twenty cases were included: 2 (10%) were withdrawn due to toxicity, leaving 18 cases for efficacy evaluation: 13 (72%) women, age 79 years (range 58–90). Clinical failure was observed in 9 (50%) patients: in 5 cases, staphylococci were recovered (28% of microbiological failures); no modification of daptomycin-MIC was observed. These 18 cases were compared with 44 matched historical cases: failure rate was similar, but whereas in the historical series, failure occurred fundamentally during therapy, in the present series, it was recorded after discontinuation of antibiotics. In summary, D10 + R may be the initial treatment of choice for PJI by fluoroquinolone-resistant staphylococci managed with implant retention.     

Antimicrobial susceptibility pattern of Corynebacterium striatum.

The in vitro activities of 16 antimicrobial agents against 86 strains of Corynebacterium striatum were evaluated by microdilution using cation-adjusted Mueller-Hinton broth. MICs at which 90% of strains were inhibited were 0.06 microgram/ml for teicoplanin, 1 microgram/ml for vancomycin, 0.03 to 8 micrograms/ml for beta-lactams, 8 micrograms/ml for sparfloxacin, 16 micrograms/ml for ciprofloxacin, 16/304 micrograms/ml for co-trimoxazole (trimethoprim-sulfamethoxazole), 64 micrograms/ml for tetracycline, 128 micrograms/ml for gentamicin, and > 128 micrograms/ml for amikacin, erythromycin, and rifampin.     

Characterization of antibiotic-resistant Corynebacterium striatum strains.

Antibiotic-resistant Corynebacterium strains were isolated from 14 Harborview and one Veterans Administration Hospital patients in Seattle during the period 1987-90. These clindamycin-erythromycin resistant strains were shown to hybridize with the ermCd gene, which was cloned from a Corynebacterium diphtheriae plasmid and encodes for a rRNA methylase. Thirteen of these strains also hybridized with the tetM gene probes, and were tetracycline resistant. The ermCd gene could be transferred, by conjugation, while the tetM gene was not transferable.     

Successful treatment of HIV-associated pneumocystis carinii pneumonia with dapsone plus trimethoprim]

Standard treatments of HIV-associated Pneumocystis carinii pneumonia (PCP) consist of high dose intravenous or oral cotrimoxazole or intravenous pentamidine. Both treatment modalities are associated with a high incidence of side effects which strengthen the need for alternative therapies. Since April 1987 we have used the combination of dapsone plus trimethoprim (DP+TMP) as primary treatment for PCP in patients who could be managed on an outpatient basis. We report the results of an analysis of the efficacy and toxicity of this treatment in 20 episodes of PCP in 18 patients. PCP was diagnosed by identification of the pathogens in bronchoalveolar lavage specimens. Chest X-ray revealed bilateral involvement in 11 and unilateral in 7 cases and no infiltration in one patient. Treatment over three to four weeks was successful in 14 of 20 PCPs (70%). In six cases (30%) treatment was changed to another regimen after a mean of seven days due to a maculopapular rash (n = 2), haematotoxic side effects (n = 2), persistent fever (n = 1) and for unexplained reasons (n = 1). Less severe side effects not causing a change in treatment were a slight to moderate neutropenia (n = 10), a moderate elevation of liver enzymes (n = 2) and a well tolerated rash (n = 2). The success rate of DP+TMP was in the same range as it is known for the standard regimens, whereas the rate of severe side effects appears to be lower. The results suggest that in AIDS patients DP+TMP may be used as first line treatment of PCP which is not severe enough for hospitalisation.     

Role of tolerance in treatment and prophylaxis of experimental Staphylococcus aureus endocarditis with vancomycin, teicoplanin, and daptomycin.

The role of Staphylococcus aureus tolerance in the treatment and prophylaxis of endocarditis in rats was investigated. The efficacies of vancomycin, teicoplanin, and daptomycin, alone and in combination with rifampin, were compared in rats with endocarditis infected with a tolerant strain of S. aureus and in rats with endocarditis infected with its nontolerant variant. In vitro the cloxacillin-tolerant strain was also tolerant to vancomycin and teicoplanin, but not to daptomycin. However, tolerance to these antibiotics did not influence the results of treatment of experimental S. aureus endocarditis. There was no difference in the bacterial densities in the vegetations of rats infected with either the tolerant or the nontolerant strain after 5 days of treatment with any of the antibiotic regimens. Of all antibiotics, daptomycin was the most effective in reducing bacterial numbers in vegetations. Combination of rifampin with vancomycin or teicoplanin improved the results of treatment for the tolerant as well as the nontolerant strains. Daptomycin was as effective alone as in combination with rifampin. In contrast, tolerance influenced the prophylactic effects of vancomycin and teicoplanin. The proportion of rats with sterile vegetations after prophylaxis with vancomycin or teicoplanin at a low dose was lower for those infected with the tolerant strain than for those infected with the nontolerant strain. A low dose of daptomycin was equally effective against the tolerant and the nontolerant strains. However, higher doses of all three antibiotics afforded almost full protection against both strains.