Manuel E. Jiménez-Mejías

Pyogenic, tuberculous, and brucellar vertebral osteomyelitis: a descriptive and comparative study of 219 cases

OBJECTIVES To describe a large series of patients with vertebral osteomyelitis (VO), and to compare the clinical, biological, radiological, and prognostic features of pyogenic (PVO), tuberculous (TVO), and brucellar vertebral osteomyelitis (BVO). METHODS A retrospective multicentre study, which included 219 adult patients with VO with confirmed aetiology, who were diagnosed between 1983 and 1995 in two tertiary care centres. Of these patients, 105 (48%) had BVO, 72 (33%) PVO, and 42 (19%) TVO. RESULTS One hundred and forty eight (67.6%) patients were male and 71 (32.4%) female. The mean (SD) age was 50.4 (16.4) years (range 14–84) and the mean (SD) duration of symptoms before the diagnosis was 14 (16.8) weeks. In 127 patients (57.9%) the vertebral level involved was lumbar, in 70 (31.9%) thoracic, and in 16 (7.3%) cervical. One hundred and nineteen patients (54.4%) received only medical treatment and 100 (45.6%) required both medical and surgical treatment. The presence of diabetes mellitus, intravenous drug abuse, underlying chronic debilitating diseases or immunosuppression, previous infections, preceeding bacteraemia, recent vertebral surgery, leucocytosis, neutrophilia, and increased erythrocyte sedimentation rate (ESR) were significantly associated to PVO. A prolonged clinical course, thoracic segment involvement, absence of fever, presence of spinal deformity, neurological deficit, and paravertebral or epidural masses, were significantly more frequent in the group of TVO. The need for surgical treatment and the presence of severe functional sequelae were more frequent in the groups of PVO and TVO. CONCLUSION There are significant clinical, biological, radiological, and prognostic differences between BVO, PVO, and TVO. These differences can point to the causal agent and orient the initial empirical medical treatment while awaiting a final microbiological diagnosis.

Activity of Tigecycline (GAR-936) against Acinetobacter baumannii Strains, Including Those Resistant to Imipenem

ABSTRACT We determined the in vitro activities of tigecycline and imipenem against 49 isolates of Acinetobacter baumannii, including those resistant to imipenem. The MIC at which 50% of the isolates were inhibited (MIC50) and the MIC90 for tigecycline and imipenem were 2 and 2 mg/liter and 32 and 128 mg/liter, respectively, with 92 and 20%, respectively, of the strains being susceptible. Tigecycline did not show bactericidal activity in the time-kill studies (n = 9 strains). Imipenem showed bactericidal activity against seven out of nine strains. These in vitro results show that tigecycline has good in vitro bacteriostatic activity against A. baumannii, including strains resistant to imipenem.

Postoperative spondylodiskitis: etiology, clinical findings, prognosis, and comparison with nonoperative pyogenic spondylodiskitis.

We studied 31 cases of postoperative pyogenic spondylodiskitis (POS), comparing them with 72 cases of nonpostoperative pyogenic spondylodiskitis (NPOS). POS represents 30.1% of cases of pyogenic spondylodiskitis. The onset of symptoms occurred an average (+/-SD) of 27.7 (+/- 25.3) days following surgery. Predisposing factors were less frequent in POS than NPOS cases (P = .002). Neurological complications and inflammatory signs in the spine were more frequent with POS than with NPOS (P = .002 and P < .00001). Coagulase-negative Staphylococcus and anaerobic bacteria were more frequent in POS than in NPOS (P = .0001 and P = .05). Percutaneous bone biopsies yielded the etiology in 66.7% of cases, open bone biopsies in 100%, blood cultures in 55.6%, and cultures of adjacent foci in 94.4%. Eleven patients (35.5%) were cured with antimicrobial treatment, but surgical treatment was necessary in 64.5%. No relapses or deaths were recorded. Seventeen patients (54.8%) had severe functional sequelae, which were associated with inflammatory signs in the spine (P = .033), higher levels of leukocytosis (P = .05), higher erythrocyte sedimentation rates (P = .05), and paravertebral abscesses (P = .04).

Cerebrospinal fluid penetration and pharmacokinetic/pharmacodynamic parameters of intravenously administered colistin in a case of multidrug-resistant Acinetobacter baumannii meningitis

Described here is a case of meningitis caused by multidrug-resistant Acinetobacter baumannii susceptible only to colistin, which was treated successfully with intravenous colistin sulfomethate sodium (5 mg/kg/day). The levels of colistin in serum and cerebrospinal fluid and the pharmacokinetic/pharmacodynamic parameters of colistin were determined. In this case, intravenously administered colistin penetrated cerebrospinal fluid (25% of serum levels) at levels sustaining bactericidal concentrations.

Efficacy of Rifampin and Its Combinations with Imipenem, Sulbactam, and Colistin in Experimental Models of Infection Caused by Imipenem-Resistant Acinetobacter baumannii

ABSTRACT There are currently no defined optimal therapies available for multidrug-resistant (MDR) Acinetobacter baumannii infections. We evaluated the efficacy of rifampin, imipenem, sulbactam, colistin, and their combinations against MDR A. baumannii in experimental pneumonia and meningitis models. The bactericidal in vitro activities of rifampin, imipenem, sulbactam, colistin, and their combinations were tested using time-kill curves. Murine pneumonia and rabbit meningitis models were evaluated using the A. baummnnii strain Ab1327 (with MICs for rifampin, imipenem, sulbactam, and colistin of 4, 32, 32, and 0.5 mg/liter, respectively). Mice were treated with the four antimicrobials and their combinations. For the meningitis model, the efficacies of colistin, rifampin and its combinations with imipenem, sulbactam, or colistin, and of imipenem plus sulbactam were assayed. In the pneumonia model, compared to the control group, (i) rifampin alone, (ii) rifampin along with imipenem, sulbactam, or colistin, (iii) colistin, or (iv) imipenem plus sulbactam significantly reduced lung bacterial concentrations (10.6 ± 0.27 [controls] versus 3.05 ± 1.91, 2.07 ± 1.82, 2.41 ± 1.37, 3.4 ± 3.07, 6.82 ± 3.4, and 4.22 ± 2.72 log10 CFU/g, respectively [means ± standard deviations]), increased sterile blood cultures (0% versus 78.6%, 100%, 93.3%, 93.8%, 73.3%, and 50%), and improved survival (0% versus 71.4%, 60%, 46.7%, 43.8%, 40%, and 85.7%). In the meningitis model rifampin alone or rifampin plus colistin reduced cerebrospinal fluid bacterial counts (−2.6 and −4.4 log10 CFU/ml). Rifampin in monotherapy or with imipenem, sulbactam, or colistin showed efficacy against MDR A. baumannii in experimental models of pneumonia and meningitis. Imipenem or sulbactam may be appropriate for combined treatment when using rifampin.

Tuberculous vertebral osteomyelitis in the new millennium: still a diagnostic and therapeutic challenge

In order to determine the clinical features and current prognosis of tuberculous vertebral osteomyelitis, the charts of all patients diagnosed with definite or probable tuberculous vertebral osteomyelitis from January 1983 to June 2002 (n=78) were reviewed. The mean delay to diagnosis was 6.1 months. Sixty-five (83.3%) patients had inflammatory spinal pain, 35 (44.9%) had some neurological deficit, and only 27 (34.6%) had fever. Paravertebral, epidural, and psoas abscesses were detected in 73.1, 65.4, and 24.4% of the cases, respectively. Culture was positive in 48% of the percutaneous biospies and in 61.7% of the open biopsies. After histological findings were included, the diagnostic yield of percutaneous biopsies was 68%. Fifty-five (70.5%) patients required surgical treatment at some stage of the disease. Although no deaths were directly attributable to tuberculous vertebral osteomyelitis and only 5.1% of patients relapsed, the mean overall hospital stay was 69.1±36.9 days, and 30 (38.5%) patients had severe functional sequelae. In conclusion, diagnosis of tuberculous vertebral osteomyelitis requires a high degree of suspicion. Percutaneous biopsy should be undertaken as soon as possible in any patient with compatible symptoms or radiological images in order to initiate suitable therapy.

Successful treatment of multidrug-resistant Acinetobacter baumannii meningitis with intravenous colistin sulfomethate sodium.

Acinetobacter baumannii is an important emerging pathogen that causes nosocomial infections such as bacteremia, pneumonia, meningitis, urinary tract infections, and surgical-site infections. Acinetobacter meningitis is a severe nosocomial infection with an associated mortality of 20–27% that occurs predominantly secondary to invasive procedures [1, 2]. Carbapenems are considered the treatment of choice in Acinetobacter meningitis. However, since Acinetobacter baumannii may be resistant to a wide variety of antimicrobial agents [2, 3], the treatment of meningitis caused by multidrug-resistant organisms is a serious problem. The use of imipenem for Acinetobacter infections may promote the selection of imipenem-resistant strains, making the use of ampicillin-sulbactam useful [2]. However, some isolates are resistant to almost all available antimicrobial agents, including carbapenems and sulbactam [4, 5]. Polymyxins B and E are the only therapeutic options in these cases. This report describes a clinical case of meningitis caused by multidrug-resistant Acinetobacter baumannii susceptible only to polymyxins and treated successfully with intravenous colistin sulfomethate sodium.

Colistin Resistance in a Clinical Acinetobacter baumannii Strain Appearing after Colistin Treatment: Effect on Virulence and Bacterial Fitness

ABSTRACT The fitness and virulence costs associated with the clinical acquisition of colistin resistance by Acinetobacter baumannii were evaluated. The growth of strain CR17 (colistin resistant) was less than that of strain CS01 (colistin susceptible) when the strains were grown in competition (72-h competition index, 0.008). In a murine sepsis model, CS01 and CR17 reached spleen concentrations when coinfecting of 9.31 and 6.97 log10 CFU/g, respectively, with an in vivo competition index of 0.016. Moreover, CS01 was more virulent than CR17 with respect to mortality and time to death.

Reduction in external ventricular drain infection rate. Impact of a minimal handling protocol and antibiotic-impregnated catheters.

IntroductionMany strategies have been developed with the aim of reducing external ventricular drain-related infections. Antibiotic-impregnated catheters are one of them.Material and methodsWe report 648 cases of external ventricular drain from a total of 534 patients treated at the Virgen del Rocío Hospital between 1995 and 2006. Three subgroups were considered: group 1 included patients treated between 1995 and 2000, as well as a total of 190 external ventricular drains and 59 cases of infection (31.05%); group 2, with patients treated between 2000 and 2004 and managed with a minimal handling protocol, included 210 external ventricular drains and nine cases of infection (4.29%); and group 3, treated between 2004 and 2006, with 248 external ventricular drains and six cases of infection (2.41%). This latter subgroup included patients managed with a minimal handling protocol and antibiotic-impregnated catheters.ResultsInfection rate was 17% when non-antibiotic-impregnated catheters were employed and 2.41% when antibiotic-impregnated catheters were inserted (p < 0.001). This difference was statistically significant before and after the introduction of a minimal handling protocol, with percentages of 5.31% and 3.27%, respectively (p < 0.001; odds ratio 0.08; absolute risk reduction 27.26%). However, no statistically significant difference was observed in infection rate when the impact of a minimal handling protocol was considered: 4.29% when only the protocol was introduced and 2.41% when both the protocol and antibiotic-impregnated catheters were used (p > 0.05).ConclusionMinimal handling protocols constitute an essential strategy in the reduction of external ventricular drain-related infections. Besides that, the use of antibiotic-impregnated catheters may reduce infection-related hospital costs.

Efficacy of linezolid versus a pharmacodynamically optimized vancomycin therapy in an experimental pneumonia model caused by methicillin-resistant Staphylococcus aureus

OBJECTIVES The British Thoracic Society, American Thoracic Society and Infectious Diseases Society of America guidelines recommend vancomycin for methicillin-resistant Staphylococcus aureus (MRSA) pneumonia, based on evidence suggesting that a vancomycin AUC₀₋₂₄/MIC ratio of 400 predicts clinical success against MRSA pneumonia. The aim of this study was the evaluation of an optimized dose of vancomycin in the treatment of MRSA experimental pneumonia versus linezolid. METHODS In vitro activities of vancomycin and linezolid were tested using time-kill curves. Experimental pneumonia in neutropenic C57BL/6 mice was achieved using two clinical MRSA strains, MR30 and MR33 (vancomycin and linezolid MICs of 1 and 4 mg/L, respectively). In vivo dosages were 30 and 110 mg/kg vancomycin (obtaining an AUC₀₋₂₄/MIC ratio lower and higher than 400, respectively), and 30 mg/kg linezolid. RESULTS Survival rates in controls, and in the groups treated with 120 mg/kg/day vancomycin, 440 mg/kg/day vancomycin and 120 mg/kg/day linezolid were 85.7%, 92.9%, 76.9% and 100%, and 66.7%, 100%, 75% and 100% for MR30 and MR33, respectively. Sterile blood cultures occurred at rates of 21.4%, 64.3%, 100% and 93.8%, and 40%, 66.7%, 100% and 93.3% for MR30 and MR33 strains, respectively. Finally, the respective bacterial lung concentrations (log₁₀ cfu/g) were 8.93 ± 0.78, 6.67 ± 3.01, 3.25 ± 1.59 and 2.87 ± 1.86 for MR30, and 8.62 ± 0.72, 5.76 ± 2.43, 3.97 ± 1.52 and 1.59 ± 1.40 for MR33. CONCLUSIONS These results support that a vancomycin AUC₀₋₂₄/MIC ratio >400 is necessary to obtain a high bacterial lung reduction in MRSA pneumonia, comparable to that achieved with linezolid and better than that with the low dose of vancomycin tested. Linezolid was more efficacious than the pharmacodynamically optimized vancomycin dose in the pneumonia caused by the most virulent strain (MR33).