Treatment of Post-Traumatic Hand Staphylococcus aureus Osteomyelitis with Oral Linezolid

Abstract

The Authors report on the use of linezolid for the treatment of three patients with osteomyelitis. All three patients had post-traumatic multisensitive hand bone methicillin-susceptible Staphylococcus aureus osteomyelitis, which did not respond to antimicrobial regimens including drugs in vitro active against the isolated strains. Clinical cure and microbiologic eradication was obtained with oral linezolid in all three patients. Linezolid was well tolerated. Mild thrombocytopenia was observed in one patient at the end of the third week of treatment and it was promptly resolved after the discontinuation of linezolid. Linezolid minimum inhibitory concentrations (MICs) consisted of 2 mg/l for all three S. aureus isolates while the bactericidal activity in vitro was not present up to the linezolid concentration of 32 mg/l. In spite of a lack of in vitro bactericidal activity, linezolid was effective in curing the patients and eradicating the infection. Trough and peak plasma concentrations of linezolid were above the MICs of the isolates. These values ranged from 3.93 to 14.95 mg/l at trough and 5.03 to 25.91 mg/l at peak. The oral bioavailability, pharmacokinetic profile and antibacterial spectrum of linezolid make this oxazolidonone antimicrobial an attractive drug for the treatment of chronic osteomyelitis. Prolonged administration requires careful surveillance for side effects, until these complications are better understood.     

High Rate of Oxacillin-Resistant Staphylococcus aureus Isolates in an Italian University Hospital

Summary

We reviewed our routine clinical laboratory records from January 1990 to March 1993 to evaluate the rate of oxacillin-resistance among nosocomial isolates of Staphylococcus aureus. Of 265 clinically significant isolates, 174 (65%) were oxacillin-resist S. aureus (ORSA). Most of these strains were obtained from surgery patients and/or were isolated from surgical wounds. The isolations of S. aureus increased during the study period: 45 in 1990, 50 in 1991, 130 in 1992 and 40 in the first trimester of 1993. The annual rates of ORSA among S. aureus isolated varied from 62 to 68% through these years.

Most ORSA isolates proved resistant to ciprofloxacin, gentamicin and rifampicin, and susceptible to vancomycin, netilmicin and cotrimoxazole. Based on these results, the need for a stringent application of infection control measures is outlined.     

Efficacy of Teicoplanin,Administered in Two Different Regimens,in the Treatment of Experimental Endocarditis Due to Enterococcus faecalis

Abstract

Using a rabbit model of endocarditis, we studied the efficacy of teicoplanin against a strain of Enterococcus faecalis resistant to ampicillin. Rabbits were randomly assigned to receive no antibiotics, teicoplanin 12 or 18 mg/kg of body weight every 12h, for 9 days. The effect of treatment on bacterial counts of vegetations and survival of the animals was evaluated at the end of treatment and 10 days thereafter. The two treatment regimens of teicoplanin produced peak serum levels 18.51±1.84 and 34.66±4.19 μg/ml, and trough levels above 10×MIC of teicoplanin for the infecting organism. Both regimens resulted in significant bacterial reduction in the vegetations as compared to the control group (p<0.001). The drug prevented relapse of the infection 10 days after discontinuation of treatment. By increasing the teicoplanin dosage no additional therapeutic benefit was observed in terms of bacterial killing, sterilization of the vegetations, and survival of the animals, although the higher doses gave numerically superior results. These findings may have meaning for the optimum use of teicoplanin in the treatment of enterococcal endocarditis.     

Linezolid as Rescue Drug: A Clinical Case of Soft Tissue Infection Caused by a Staphylococcus aureus Strain Resistant In Vivo to Teicoplanin

Abstract

The authors report and discuss a patient admitted to intensive care unit (ICU) for acute respiratory failure due to upper airway obstruction caused by face and neck soft tissue infection. An oxacillin-resistant Staphyloccoccus aureus was isolated from necrotic skin lesions and from skin biopsy. The strain was susceptible in vitro to teicoplanin, but it showed resistance In Vivo, despite appropriate dosage. After 6 days of full dose therapy, since the clinical course worsened, teicoplanin was interrupted and linezolid was started. In 48 hours signs of infection regressed, and the patient was discharged from the ICU after 10 days of linezolid treatment. Linezolid resulted as a rescue drug for a life-threatening infection.     

Generic Imatinib in Chronic Myeloid Leukemia Treatment: Long-Term Follow-up

BackgroundSimilar to the application of other generic drugs, the use of generic imatinib in the treatment of chronic myeloid leukemia (CML) leads to significant cost savings, but it also raises issues related to efficacy, safety, and quality. This study assessed the long-term outcome of CML patients after administration of generic imatinib.Patients and MethodsThe cohort of 83 patients was divided into 2 groups depending on whether generic imatinib was applied in the front-line setting or after switching from original imatinib. The groups were compared regarding rates of optimal treatment response, adverse events, and survival.ResultsIn the first group, at the time of switching, rates of complete cytogenetic response experienced, and major molecular response were 95% and 87.5% of patients in the front-line generic imatinib group and the group that switched from original to generic imatinib, respectively. After 24 months of treatment with generic imatinib, the rates of sustained, lost, and experienced major molecular response were 72.5%, 15%, and 12.5%, respectively. In the group treated with front-line generic imatinib at 6 months, 67.4% experienced complete cytogenetic response, while for major molecular response at 12 and 24 months, it was 58.1% and 69.8%, respectively. Estimated 5-year overall survival in the group treated with front-line generic imatinib was 86.1%, while 10-year overall survival in the group treated with second-line generic imatinib was 93.8%.ConclusionResults of this study with long-term follow-up are further evidence that generic imatinib is at least noninferior to original imatinib regarding efficacy and survival, both when provided initially and as a subsequent replacement for original imatinib.     

Treatment of post-traumatic hand Staphylococcus aureus osteomyelitis with oral linezolid

The Authors report on the use of linezolid for the treatment of three patients with osteomyelitis. All three patients had post-traumatic multisensitive hand bone methicillin-susceptible Staphylococcus aureus osteomyelitis, which did not respond to antimicrobial regimens including drugs in vitro active against the isolated strains. Clinical cure and microbiologic eradication was obtained with oral linezolid in all three patients. Linezolid was well tolerated. Mild thrombocytopenia was observed in one patient at the end of the third week of treatment and it was promptly resolved after the discontinuation of linezolid. Linezolid minimum inhibitory concentrations (MICs) consisted of 2 mg/l for all three S. aureus isolates while the bactericidal activity in vitro was not present up to the linezolid concentration of 32 mg/l. In spite of a lack of in vitro bactericidal activity, linezolid was effective in curing the patients and eradicating the infection. Trough and peak plasma concentrations of linezolid were above the MICs of the isolates. These values ranged from 3.93 to 14.95 mg/l at trough and 5.03 to 25.91 mg/l at peak. The oral bioavailability, pharmacokinetic profile and antibacterial spectrum of linezolid make this oxazolidonone antimicrobial an attractive drug for the treatment of chronic osteomyelitis. Prolonged administration requires careful surveillance for side effects, until these complications are better understood.     

Community-Acquired Pneumonia and Bacteremia Due to Methicillin-Resistant Staphylococcus aureus Carrying Panton-Valentine-Leukocidin Gene in Greece: Two Case Reports and Literature Review

Abstract

We report the first two cases of community-acquired necrotizing pneumonia and bacteremia complicated by acute respiratory distress syndrome (ARDS) due to Panton-Valantine leukocidin-producing methicillin-resistant Staphylococcus aureus (MRSA-PVL) in Greece, together with a short literature review. Diagnosis was made by culture and broad spectrum PCR of respiratory secretions and blood. One patient received appropriate therapy and recovered fully. The other one died rapidly due to septic shock and life-threatening hemoptysis. Clinicians should be suspicious of community-acquired pneumonia due to MRSA-PVL strain, because rigorous microbiological diagnosis, early and appropriate therapy is essential for favorable outcome.     

Long-Term Outcomes with Sequential Tyrosine Kinase Inhibitors Treatment in Chronic Myeloid Leukemia Patients

Objective: Tyrosine kinase inhibitor (TKI) is the standard treatment for chronic myeloid leukemia (CML). In the national list of essential medicines in Thailand, the first, second, and third-line treatments are imatinib, nilotinib, and dasatinib, sequentially, different from the European Leukemia Net guidelines. This study aimed to evaluate the outcomes of CML patients who received sequential treatment with TKI. Methods: This study enrolled CML patients diagnosed between 2008 and 2020 at Chiang Mai University Hospital who received TKI. Medical records were reviewed for demographic data, risk score, treatment response, event-free survival (EFS), and overall survival (OS). Result: One hundred and fifty patients were included in the study, 68 patients (45.3%) were female. The mean age is 45.9 ± 15.8 years. Most patients (88.6%) had good ECOG status (0-1). The CML diagnosis was in the chronic phase in 136 patients (90.6%). The EUTOS long-term survival (ELTS) score revealed a high of 36.7%. At the median follow-up of 8.3 years, 88.6% of patients were in complete cytogenetic response (CCyR), whereas 58.0% were in major molecular response (MMR). The 10-year OS and EFS were 81.33% and 79.33%, respectively. The factors associated with poor OS were high ELTS score (P = 0.01), poor ECOG performance status (P < 0.001), not achieved MMR within 15 months (P = 0.014), and not achieved CCyR within 12 months (P < 0.001). Conclusion: The sequential treatment for CML patients had a good response. Factors predicting survival were ELTS score, ECOG performance status, and early achieving MMR and CCyR.     

An Open Study of Teicoplanin in the Treatment of Gram-Positive Infections

Summary

Teicoplanin, a new glycopeptide antibiotic similar to vancomycin, was evaluated in treating 36 hospitalized patients suffering from various Gram-positive infections. The 36 patients received teicoplanin once daily as a mean intravenous injection of 550 mg/day (range 200-800 mg/day). Previous antimicrobial therapy was used in 28% of patients. The mean duration of therapy was 7.5 days (range 3-38 days). The overall clinical success rate was 94%. 24/36 patients (66%) had positive microbiology. Elimination of the pathogens was seen in 75% of all evaluable cases. Four patients with early prosthetic valve endocarditis due to coagulase negative Staphylococcus (3 patients) and Proptontbacterium acnes (1 patient) had a favorable clinical and microbiological outcome. No adverse drug reactions were observed. Teicoplanin is safe and effective in the therapy of many different infections caused by Gram-positive bacteria.     

国产G-CSF治疗门诊化疗患者的白细胞减少

目的:评价rhG-CSF(国产瑞白)治疗门诊患者化疗后白细胞减少的作用和不良反应。方法:52例患者,均为病理或细胞学证实的恶性肿瘤。在化疗后白细胞计数<2.9×109/L时给予rhG-CSF(国产瑞白)100μg,每日1次,皮下注射,连续5天。结果:rhG-CSF(国产瑞白)100μg,每日1次,连续5天。治疗后可明显增加门诊患者化疗后的白细胞计数,使化疗按期完成,不同原发肿瘤、转移部位、既往是否化疗以及不同化疗方案之间均无显著差别。结论:rhG-CSF(国产瑞白)100μg,每日1次,皮下注射连用5天是门诊化疗患者有价值的辅助治疗手段。     

Long-term intramuscular teicoplanin treatment of chronic osteomyelitis due to oxacillin-resistant Staphylococcus aureus in outpatients

Oxacillin-resistant staphylococci are the most serious pathogens in chronic osteomyelitis and only glycopeptides have been shown to be efficacious against them. We assessed the safety and efficacy of a regimen of teicoplanin 400 mg/day i.m. as long-term treatment in outpatients with osteomyelitis. A total of 76 patients received teicoplanin. Twenty-five patients had chronic prosthetic osteomyelitis (20 hip) and 51 patients had osteomyelitis caused by osteo-synthesis devices. Oxacillin-resistant Staphylococcus aureus was isolated in pure culture in 55 patients (72%). A total of 21 patients had polymicrobial infection with a total of 48 isolated strains. All patients were treated with teicoplanin 400 mg i.m. once-a-day alone or with other drugs for a minimum of 4 months. Only one patient had side effects requiring discontinuation of treatment. The teicoplanin dose was reduced to 200 mg/day i.m. in 2 patients to decrease creatinine clearance values. Seventy out of 76 patients were cured.     

Long-Term Results of CAP Therapy in Chronic Lymphocytic Leukemia

This study was designed to study the efficacy and toxicity of an adriamycin-containing regimen (CAP: cyclophosphamide, adriamycin, and prednisone) in patients with previously untreated chronic lymphocytic leukemia (CLL). CAP was given to clinical complete remission followed by 18 months of cyclophosphamide-prednisone (CP) maintenance. Forty-seven patients with previously untreated CLL were treated. These patients initially presented with advanced stage (Rai III or IV) or had less advanced stage (Rai 0-II) patients and demonstrated evidence of disease progression. Patients received 750 mg/m² of cyclophosphamide intravenously on day 1, 50 mg/m² of adriamycin intravenously on day 1 and 100 mg/day of prednisone on days 1-5. Courses were repeated at 3-week intervals until clinical CR, at which time maintenance with cyclophosphamide and prednisone (CP) was commenced. A maximum cumulative dose of 450 mg/m² of adriamycin (9 courses of CAP) was given. Twenty (43%) of 47 patients obtained a CR and 11 (23%) obtained a partial remission. Bone marrow biopsy criteria were used to define response in addition to clinical and peripheral blood responses. All patients have been followed for 10 years. The median survival was 259 weeks. No patient remains in remission. No impact of response on survival was found. Surprisingly, the response rate and survival were higher and longer for patients with more advanced stages and higher tumor burdens. The median survival times for patients with Rai stage IV and Binet stage C disease were 93 months and 81 months, respectively. Although the regimen was well tolerated, three patients, each with an antecedent cardiac risk factor, developed congestive heart failure. Adriamycin containing regimens can be safely given to elderly patients with CLL and show promise in the treatment of advanced stage disease.     

Frequency and Transferability of Trimethoprim and Sulfonamide Resistance in Methicillin-Resistant Staphylococcus aureus and Staphylococcus epidermidis

A total of 374 Staphylococcus aureus and 126 Staphylococcus epidermidis strains from 14 countries were studied for their resistance to methicillin, trimethoprim (Tp) and sulfonamides (Su), alone and combined (TpSu). The frequency of resistance to Tp, Su and TpSu was much higher in methicillin-resistant S. epidermidis (MRSE) than in methicillin-resistant S. aureus (MRSA). Considerable differences, however, existed in isolates from different countries. Resistance to Tp, Su or TpSu in MRSA was low or absent in isolates from Switzerland, Spain, Japan, Mexico, Argentina and Chile, but high in isolates from Germany and Brazil. High level Tp resistance mostly resided on large plasmids. It could be transferred in 17 out of 97 strains. Su resistance was never cotransferred. Strains cured of their large Tp resistance plasmids remained Su-resistant, which suggests a chromosomal location of Su resistance.     

Lincomycin resistance in methicillin-resistant Staphylococcus aureus strains of hospital origin

A total of 170 Staphylococcus aureus strains isolated during a one-year period at the University Hospital of Patras Medical School were examined for resistance to a battery of antimicrobial agents by disk diffusion and minimum inhibitory concentration (MIC) determination. Fifty-five isolates were lincomycin- and methicillin-resistant (LMRSA). In the group of 55 LMRSA isolates 13 were also resistant to vancomycin. All the LMRSA isolates were not typed by the international set and the experimental phages 88A and 25 at routine typing dilution (RTD), while 18 isolates were lysed by phages at 100XRTD and 1000XRTD. Reverse phage-typing and heat shock treatment of the LMRSA isolates had no effect on their typability. Plasmid profiles coupled with restriction endonuclease analysis of plasmid DNA established that the LMRSA isolates represent different strains. Membrane-protein profiles by polyacrylamide gel electrophoresis (PAGE) showed that LMRSA strains could belong to one group. This method proved useful and sensitive for characterization of LMRSA.     

The role of methicillin-resistant Staphylococcus aureus in orthopaedic implant surgery

The problems presented by methicillin-resistant Staphylococcus aureus (MRSA) must be accommodated in both prophylactic and treatment regimens for orthopaedic implant surgery. The rationale of pre-admission nasal swabbing in directing prophylaxis for orthopaedic patients is discussed. The potential advantage of nasal mupirocin for Staphylococcus aureus and MRSA carriers is described. Methicillin-resistant Staphylococcus epidermidis is commented upon as another hazard in orthopaedics. Criteria for choosing glycopeptides in the treatment of implant infections are discussed, and need to be defined in orthopaedic units. Treatment regimens are briefly described.     

Lincomycin Resistance in Methicillin-Resistant Staphylococcus aureus Strains of Hospital Origin

Summary

A total of 170 Staphylococcus aureus strains isolated during a one-year period at the University Hospital of Patras Medical School were examined for resistance to a battery of antimicrobial agents by disk diffusion and minimum inhibitory concentration (MIC) determination. Fifty-five isolates were lincomycin- and methicillin-resistant (LMRSA). In the group of 55 LMRSA isolates 13 were also resistant to vancomycin. All the LMRSA isolates were not typed by the international set and the experimental phages 88A and 25 at routine typing dilution (RTD), while 18 isolates were lysed by phages at 100XRTD and 1000XRTD. Reverse phage-typing and heat shock treatment of the LMRSA isolates had no effect on their typability. Plasmid profiles coupled with restriction endonuclease analysis of plasmid DNA established that the LMRSA isolates represent different strains. Membrane-protein profiles by polyacrylamide gel electrophoresis (PAGE) showed that LMRSA strains could belong to one group. This method proved useful and sensitive for characterization of LMRSA.     

宫颈癌相关的上尿路梗阻的处理

目的:探讨宫颈癌相关的上尿路梗阻的处理.方法:选取2002年5月～2003年9月就诊的35例因宫颈癌导致的输尿管梗阻患者,17例为初诊病例,18例为复诊病例,其中13例肿瘤复发,5例无肿瘤复发依据.35例中27例双侧肾盂积水,8例单侧积水.18例复诊和5例初诊患者在膀胱镜下试行放置双J管,分别有6例和4例成功置入,另12例复诊患者中3例接受双侧输尿管皮肤造口术,4例接受单侧经皮肾盂穿刺造瘘术,余5例未处理积水:另13例初诊患者术中放置双J管.结果:5例未处理积水的患者均于2个月内死亡.23例留置双J管的患者,积水均在置管后不同程度地改善,其中4例分别于4、5、7、9个月后死于肿瘤广泛转移;10例成功换管,2例无法逆行换管,余7例术后未满6个月,尚未更换双J管.所有行膀胱镜操作的23例患者中,3例发生尿路感染.7例外引流患者随访已达l～9个月,积水均有改善.4例肾盂穿刺的患者均在术后发生引流管堵塞,1例发生引流管脱落,无操作相关性死亡.结论:对于因宫颈癌导致的上尿路梗阻患者,首选膀胱镜下逆行置管,恶性狭窄须双侧置管,若失败,再根据不同原因和不同病情,制定合适的治疗方案.