Outpatient parenteral antibiotic therapy in the elderly: an Italian observational multicenter study.

Bacterial infections are the most frequent cause of hospitalization in elderly patients. In the early eighties, the advantages of Outpatient parenteral Antibiotic therapy (OPAT) were identified in the United States, and suitable therapeutic programs were established. In order to understand the different ways of managing OPAT, a National OPAT Registry was set up in 2003 in Italy. This study analyzes data concerning bacterial infections in 176 elderly patients including demographics, therapeutic management, clinical response, and side-effects. Bone and joint infections (48.9%) and skin and soft tissue infections (27.8%) were the most common infections treated with OPAT. Teicoplanin (28.9%) and ceftriaxone (22.1%) were the top two antibiotics chosen. OPAT was mainly performed at a hospital infusion center (52.8%). The clinical success rate was high and side-effects were low (12.6% of cases). Management of bacterial infections in the elderly with an outpatient program is effective and safe.

Clinical features of bacterial meningitis in Italy: a multicenter prospective observational study.

We carried out a prospective observational study on clinical features of bacterial meningitis. Between October 2002 and June 2005, 322 adult bacterial meningitis cases in 49 infectious disease wards in Italy (MENTORE study group) were enrolled in the study. 133 cases were due to Streptococcus pneumoniae, 44 to Neisseria meningitidis and 145 to other microorganisms. A high SAPS score and coma on admission, as well as need for mechanical ventilation, were more frequent in the pneumococcal meningitis group. Neurological impairment was present in 151 out of 311 patients, and was more frequent in pneumococcal meningitis. A single antibiotic was employed in only 90 of 315 cases; a combination of ceftriaxone and ampicillin was the most frequently administered treatment. Ceftriaxone was also the single most used drug. Adjunctive treatment with steroids was administered in 210 out of 303 patients for a median duration of 7 days. Median duration of fever was 4 days, and median hospital stay was 16 days; hospitalization was significantly longer in the pneumococcal meningitis group. At discharge, neurological impairment was still present in 59 (21%) of 277 patients. Twenty (6.9%) out of 289 patients died during hospitalization. Distribution of adverse outcome (death and neurological impairment) in patients treated with or without steroids and within different time zones between onset of symptoms and commencement of antibiotics was studied; a trend toward a worse prognosis was seen in patients treated more than 24 hours after onset of the disease.In our study, infectious disease clinicians made extensive use of steroids as adjuvant therapy for bacterial meningitis, even in absence of detailed national and local guidelines. Mortality seemed to be lower in comparison with the literature.

Outpatient parenteral antibiotic therapy for bone and joint infections: an italian multicenter study.

In the early eighties, the advantages of outpatient parenteral antibiotic therapy (OPAT) (reduced costs, no hospitalization trauma in children, no immobilization syndrome in elderly, reduction in nosocomial infections by multiresistant organisms) were identified in the United States, and suitable therapeutic programs were established. Currently, more than 250,000 patients per year are treated according to an OPAT program. In order to understand the different ways of managing OPAT and its results, a National OPAT Registry was set up in 2003 in Italy. Analysis of data concerning osteomyelitis, septic arthritis, prosthetic joint infection and spondylodiskitis, allowed information to be acquired about 239 cases of bone and joint infections, with particular concern to demographics, therapeutic management, clinical response, and possible side effects. Combination therapy was the first-line choice in 66.9% of cases and frequently intravenous antibiotics were combined with oral ones. Teicoplanin (38%) and ceftriaxone (14.7%), whose pharmacokinetic/pharmacodynamic properties permit once-a-day administration, were the two top antibiotics chosen; fluoroquinolones (ciprofloxacin and levofloxacin) were the most frequently utilized oral drugs. Clinical success, as well as patients' and doctors' satisfaction with the OPAT regimen was high. Side-effects were mild and occurred in 11% of cases. These data confirm that the management of bone and joint infections in an outpatient setting is suitable, effective and safe.

Impact of liver steatosis on virological response in [corrected] Italian patients with chronic hepatitis C treated with peg-interferon alpha-2b plus ribavarin.

BACKGROUND: Whether liver steatosis affects sustained virological response in patients with chronic hepatitis C is still under discussion. AIM: To evaluate the impact of liver steatosis in patients treated (for chronic hepatitis C) with combination therapy. METHODS: We evaluated 97 (male/female 82/15, mean age 41.1 years) consecutive naive patients treated with pegylated interferon alpha-2b plus ribavirin. RESULTS: Prevalence and severity of liver steatosis were significantly associated with genotype 3a [grade 3-4 in 14 of 32 patients (44%) vs. 8 of 65 patients (12%) with other genotypes; P = 0.001], while steatosis grade 1 (<10% of hepatocytes affected) was more frequently associated with genotype 1a/1b [9/39 (23%) vs. 4/57 (7%); P = 0.02]. Overall, sustained virological response was 62.8%, and was statistically uninfluenced by the presence/absence of liver steatosis. On the contrary, the following variables were independently associated with sustained virological response at logistic regression analysis: genotype other than 1a/1b, positive association, (odds ratio 3.4, P < 0.04), and low-grade liver steatosis, negative association, (odds ratio 9.0, P = 0.009), whereas sustained virological response was unaffected by severe liver steatosis, which was mainly associated with genotypes 2 and 3 [steatosis grade 2, 18/29 (62%); grade 3, 10/12 (83%); grade 4, 7/10 (70%)]. CONCLUSIONS: Only low-grade liver steatosis negatively affects the outcome of combination therapy, with peginterferon alpha-2b plus ribavirin, while severe steatosis (which is virus-related in most cases) has no impact on virological response.

Chlamydia pneumoniae infection in HIV-positive patients: prevalence and relationship with lipid profile.

OBJECTIVES: The aims of this study were to evaluate the prevalence and impact of Chlamydia pneumoniae infection in HIV-positive patients and to establish the relationship between C. pneumoniae infection and lipid profile. METHODS: Detection of C. pneumoniae was by polymerase chain reaction (PCR) on Peripheral Blood Mononuclear Cells (PBMCs) collected from 97 HIV-positive patients. Samples were collected after overnight fast in EDTA-treated tubes. On the same day, patients were also tested for routine chemistry, HIV viral load, CD3, CD8 and CD4 cell counts and lipid profile [cholesterol, high-density lipoproteins (HDLs), low-density lipoproteins (LDLs) and triglycerides]. RESULTS: The overall prevalence of C. pneumoniae was 39%. The prevalence of C. pneumoniae was inversely related to the CD4 lymphocyte count (P=0.03). In the naive group, C. pneumoniae-positive patients had both significantly higher HIV load (71 021+/-15 327 vs. 14 753+/-14 924 HIV-1 RNA copies/mL; P=0.03) and lower CD4 cell count (348.0+/-165.4 vs. 541.7+/-294.8; P=0.04) than C. pneumoniae-negative patients. Moreover, treatment-naive patients with C. pneumoniae infection had significantly higher mean levels of cholesterol (185.3+/-56.2 vs. 124.8+/-45.9 mg/dL; P=0.01), triglycerides (117.2+/-74.7 vs. 68+/-27.6 mg/dL; P=0.04) and LDL (122.4+/-60.1 vs. 55.6+/-58 mg/dL; P=0.05) than C. pneumoniae-negative patients. CONCLUSIONS: These data indicate that, in HIV-positive subjects, C. pneumoniae infection is relatively frequent and is associated with both low CD4 cell count and high HIV load. Furthermore, C. pneumoniae appears to be associated with hyperlipidaemia and might therefore represent a further risk factor for cardiovascolar disease in HIV-positive patients.

Human leptospirosis in the Vicenza area (Italy) from 1990 to 2003: an epidemiological and clinical study.

All cases of human leptospirosis observed at the S. Bortolo Hospital, Vicenza, Italy, in the period from September 1990 to December 2003 were retrospectively reviewed. The aim of the study was to define the epidemiological, clinical, diagnostic, and therapeutic aspects of this infection and to compare these with an earlier local study (1979-1990) in order to assess if any changes have occurred over time. The screening test was made using macroscopic agglutination and the diagnosis was definitively confirmed using the microscopic agglutination test (MAT). The etiological serotype was identified in 13 patients (68%) and Leptospira poi was the most frequent serovar. Hepatic and renal involvements were present in a high percentage of patients (71% and 74%, respectively), cardiac involvement in 39%, and hypertriglyceridemia and hepatic steatosis were observed in 68% and 43% of cases, respectively. One patient died because of acute renal and respiratory failure. Intravenous penicillin was the treatment of choice. A consistent reduction in the prevalence was observed during the time period of this study (n = 38) compared with the previous period (n = 86); males were more affected than females in both time periods. In industrialized countries the prevalence of leptospirosis is decreasing; nevertheless, this infection is no longer limited to specific occupational groups and remains a potential fatal disease that should be included in the differential diagnosis of all the patients with unexplained fever.

Therapy of chronic hepatitis C virus infection in HIV co-infected people.

The introduction of highly active anti-retroviral therapy (HAART) for Human Immunodeficiency Virus (HIV) infection has significantly improved the life expectancy of HIV positive patients. Hepatitis C virus (HCV) co-infection is common in HIV infected patients and is now a significant cause of morbidity and mortality. Optimal management and treatment of HCV in HIV infected patients is therefore essential. Interferon-alpha (IFN-alpha) and ribavirin is the mainstay of treatment for HCV infection in HIV infected people. The sustained virological response rate (SVR) with combination therapy is lower than that commonly observed in HCV mono-infected patients. This is, at least in part, due to the very high treatment drop out rates. Ribavirin in combination with HAART is associated with particular side effects such as mitochondrial toxicity. Therefore, vigilant monitoring of patients during therapy, in specialist centers is essential. Pegylated interferon (PEG-IFN) plus ribavirin is particularly promising as it is easier to administer and will probably become the treatment of choice for co-infected patients. A SVR is associated with genotype 2 and 3, in addition to a high CD4+ cell count and a low HCV load prior to therapy. The progression of HCV related liver disease in HIV positive patients is faster than in subjects with HCV infection alone. As a result, there is an increasing incidence of cirrhosis and end-stage liver disease in co-infected patients. Liver transplantation is being evaluated in many centers. To date the experiences are very limited but encouraging in term of survival rate.

Clostridial orthopedic infections: case reports and review of the literature.

Clostridia are anaerobic Gram-positive bacilli that can be isolated from the soil and the intestinal tract of humans. These microorganisms are recognized as the cause of devastating soft tissue infections, such as cellulitis, myositis, and gas gangrene. However, such bacteria may also be involved in various postoperative orthopedic infections, including prosthetic joint infection. We present three clinical cases of clostridial orthopedic infection and review the related medical literature.

Type 1 diabetes mellitus in patients with chronic hepatitis C before and after interferon therapy.

Type 1 diabetes mellitus is the result of an autoimmune process characterized by pancreatic beta cell destruction. It has been reported that chronic hepatitis C infection is associated with type 2 diabetes mellitus, but not with type 1. Although the prevalence of markers of pancreatic autoimmunity in hepatitis C virus-positive patients is not significantly different to that reported in the general population, it increases during alpha-interferon therapy from 3 to 7%, probably due to the immunostimulatory effects of this cytokine. To date, 31 case reports of type 1 diabetes mellitus related to interferon treatment have been published. Type 1 diabetes mellitus occurs more frequently in patients treated for chronic hepatitis C than for other conditions and is irreversible in most cases. In 50% of these patients, markers of pancreatic autoimmunity predated treatment, the majority of cases having a genetic predisposition. Thus, in predisposed individuals, alpha-interferon can either induce or accelerate a diabetogenic process already underway. We suggest that islet cell autoantibodies and glutamic acid decarboxylase autoantibodies should be investigated before and during interferon treatment in order to identify subjects at high risk of developing type 1 diabetes mellitus.

The application of cost effectiveness analysis to derive a formulary for urinary tract infections.

According to economic principles an inappropriate prescription is the choice of an antimicrobial with higher/equivalent cost and lower effectiveness (or higher cost and equivalent/lower efficacy) than an alternative (in this case, the former is specified as a "dominated" drug). To identify cost-effective antibiotics we applied the principles of incremental cost-effectiveness analysis (ICEA) to microbiological data of San Bortolo Hospital. Its 27 wards were grouped in 9 functional areas. The resistance patterns of 8 urinary pathogens in the 1997 microbiology data base were assessed. The measure of antibiotic effectiveness was expressed as the percentage of isolates susceptible to each antibiotic tested. The difference in cost (i.e. the incremental change) between each antibiotic and the next more expensive alternative was calculated, and compared with the incremental change in effectiveness. Calculations were made for each pathogen. The antibiotics remaining after exclusion of all "dominated" antibiotics were pooled on a list defined as "Specific Area Formulary". The implications of the use of economic principles within a general antimicrobial policy are discussed.

Surgical prophylaxis in practice.

The use of antibacterial prophylaxis of postoperative infections is firmly established within clean-contaminated procedures. For clean procedures, prophylaxis has traditionally been reserved for operations involving foreign-body implantation. However, evidence that postoperative infections from non-prosthetic clean procedures are highly under-reported suggests that prophylaxis is also advisable, at least for some non-prosthetic procedures, such as breast surgery and herniorrhaphy. Although cefazolin is recommended by current guidelines, cefuroxime and cefamandole have a broader antimicrobial spectrum and should be preferred in clean prosthetic surgery prophylaxis. In this type of surgery glycopeptides are not recommended for routine use but may have a role for major prosthetic implantation in units with a high incidence of methicillin-resistant staphylococci. In the case of clean-contaminated procedures, cefazolin is recommended for routine use, although colorectal procedures require an agent with improved anti-anaerobic activity. In addition, experience has shown that obstetric/gynaecological, gastroduodenal and biliary tract surgery and appendectomy all require broad-spectrum antibacterial prophylaxis. Suitable agents include cefoxitin, cefotetan, ureidopenicillins and beta-lactam/beta-lactamase inhibitor combinations. The traditional surgical classification scheme needs to be replaced with a classification that additionally accounts for patient-specific risk factors. The limitations of the current scheme may partly explain why current guidelines are so seldom followed in clinical practice.

Serum pepsinogen and gastrin levels in HIV-positive patients: relationship with CD4+ cell count and Helicobacter pylori infection.

BACKGROUND: The relationship between serum parameters of gastric function and Helicobacter pylori infection in human immunodeficiency virus (HIV)-positive patients is almost unknown. AIMS: To investigate in HIV-infected patients: (i) the relationship between serum gastrin and serum pepsinogens over the progressive phases of HIV-related disease; (ii) the impact of H. pylori infection on gastrin and pepsinogen serum levels and its relation to antral histology; (iii) the prevalence of parietal cell autoantibodies. METHODS: Fifty-nine HIV-positive patients were studied by upper endoscopy plus gastric antral biopsy. Serum samples were tested for gastrin, pepsinogen A, pepsinogen C and parietal cell autoantibodies. RESULTS: In patients without overt acquired immunodeficiency syndrome (AIDS), or with a CD4+ count of > 100 x 10(6) cells/L, mean serum levels of gastrin and pepsinogen C were higher than in subjects with AIDS or with a CD4+ count of < 100 x 10(6) cells/L (P < 0.01). Only one patient was found to be positive for parietal cell autoantibodies. H. pylori infection was associated with increased values of gastrin and pepsinogen C only in HIV-positive patients without AIDS or with a CD4+ count of > 100 x 10(6) cells/L. Atrophy was more frequent in patients with overt AIDS than in those without overt AIDS (57% vs. 33%, P=N.S.), and/or in patients with a CD4+ count of < 100 x 10(6) cells/L than in those with a CD4+ count of > 100 x 10(6) cells/L (62% vs. 26%, P < 0.05). CONCLUSIONS: HIV-positive patients without overt AIDS have increased serum levels of gastrin and pepsinogen C compared with HIV-positive patients with overt AIDS.

Three-times weekly teicoplanin in the outpatient treatment of acute methicillin-resistant staphylococcal osteomyelitis: a pilot study.

Treatment of osteomyelitis requires prolonged hospital stay, lengthy antibiotic therapy and adequate surgical debridement. Outpatient parenteral antibiotic therapy (OPAT) is a new approach to reduce patient discomfort and hospital costs. Teicoplanin, a glycopeptide antibiotic with a long half-life (72 hours), is one of the most useful drugs for OPAT. We performed a pilot study to assess the safety and efficacy of three-times weekly teicoplanin in the treatment of methicillin-resistant (MR) acute staphylococcal osteomyelitis. Ten patients with acute post-traumatic osteomyelitis were enrolled. Pathogens were MR Staphylococcus aureus (5 patients) and MR coagulase-negative staphylococci (5 patients). After a loading dose of 400 mg b.i.d. for 3 days, patients were treated with an intravenous dose of 1000 mg on Mondays and Wednesdays and with a 1200 mg dose on Fridays. Teicoplanin trough levels were maintained within a 10 to 20 mg/L range. If hardware removal had been possible at enrollment, treatment was carried out for at least 4 weeks. If, on the contrary, hardware removal had not been possible, teicoplanin was administered as suppressive therapy until hardware removal. Treatment was successfully performed in 9 out of 10 patients, whereas in one patient only improvement was achieved. Side effects were not recorded. Three times weekly teicoplanin seems to be a valuable option in the treatment of acute MR staphylococcal osteomyelitis. Further studies are warranted in order to better define the role of this new administration schedule in this field.

Epidemiological analysis of vancomycin-resistant enterococci in a large tertiary-care hospital in Northern Italy.

The epidemiology of vancomycin-resistant enterococci (VRE) was studied in a large tertiary-care hospital in northern Italy from February 1993 to December 1999. Sixteen cases of bacteraemic and 17 cases of nonbacteraemic active infections caused by VRE were recorded. Fifteen of the bacteraemic and four of the nonbacteraemic infections occurred in patients in the haematology department, while the remainder were registered in other departments of the same hospital. Active surveillance for the presence of VRE in stools led to identification of 51 noninfected carriers over the 1994-1999 period; of these, 32 were haematology patients and the remainder were patients admitted to other departments. All VRE isolates carried the vanA gene. Forty-one Enterococcus faecium isolates and eight Enterococcus faecalis isolates collected in the 1993-1996 period were typed by pulsed-field gel electrophoresis. Twenty-nine isolates of Enterococcus faecium shared either indistinguishable or strictly or possibly related patterns. Of these, 26 were isolated from patients in the haematology department. This is believed to be the first study on the epidemiology of VRE carried out in a large hospital in Italy over a period of several consecutive years. It reports an increase in VRE due to the epidemic spread of genetically related strains and sporadic infections or colonisation by unrelated VRE. It also documents the success of surveillance and of the measures adopted for preventing the spread of VRE in patients at risk.

Deep tissue biopsy vs. superficial swab culture monitoring in the microbiological assessment of limb-threatening diabetic foot infection.

AIMS: The results of ulcer swabbing vs. deep tissue biopsy have been compared prospectively in 29 diabetic patients with limb-threatening foot infection, to investigate the effectiveness and reliability of each method, and to evaluate whether any of the two could be more suitable for the microbiological follow-up of severe lesions. METHODS: Microbiological samples were collected by using both methods at fixed intervals after therapy commencement (i.e. at day 0, 7, 14, and 30). Statistical comparison was performed between the results of each sampling procedure after the end of follow-up. RESULTS: At enrolment, the mean number of isolates per patient was 2.34 by swabbing and 2.07 by tissue biopsy sampling; the rate of isolation for anaerobes with the two methods was 35% and 25%, respectively; no statistical differences could be observed between the two procedures in terms of either species or frequency of isolation. Anaerobic species were never detected after the first 2 weeks of appropriate treatment, and those ulcers which were still active at day 30 yielded almost exclusively Gram-positive bacteria. At the end of follow-up, deep tissue cultures appeared to exhibit a higher diagnostic sensitivity with respect to swabs. CONCLUSIONS: Swabbing and deep tissue cultures appear to be equally reliable for the initial monitoring of antimicrobial treatment in severe diabetic foot infection. However, our experience seems to suggest that deep tissue might be more sensitive than swabbing for monitoring those isolates that have been selected for antibiotic resistance, i.e. those from ulcers that are still active after 30 days of treatment.

Pancreatic hyperamylasemia during acute gastroenteritis: incidence and clinical relevance.

BACKGROUND: Many case reports of acute pancreatitis have been reported but, up to now, pancreatic abnormalities during acute gastroenteritis have not been studied prospectively. OBJECTIVES: To evaluate the incidence and the clinical significance of hyperamylasemia in 507 consecutive adult patients with acute gastroenteritis. METHODS: The clinical significance of hyperamylasemia, related predisposing factors and severity of gastroenteritis were assessed. RESULTS: Hyperamylasemia was detected in 10.2 % of patients studied. Although amylasemia was found over four times the normal values in three cases, the clinical features of acute pancreatitis were recorded in only one case (0.1%). Hyperamylasemia was more likely (17%) where a microorganism could be identified in the stools (p < 0.01). Among patients with positive stool samples, Salmonella spp. and in particular S. enteritidis, was the microorganism most frequently associated with hyperamylasemia [17/84 (20.2 %) and 10/45 (22.2%), respectively], followed by Rotavirus, Clostridium difficile and Campylobacter spp. Patients with hyperamylasemia had more severe gastroenteritis with an increased incidence of fever (80 % vs 50.6 %, O.R. 3.0; P < 0.01), dehydration (18% vs 8.5%; O.R. 2.5; P < 0.05), and a higher mean number of evacuations per day (9.2 vs 7.5; P < 0.05) than those with amylasemia in the normal range. Hyperamylasemia was significantly associated with cholelithiasis, (30.0 % vs 10.7%, O.R. 3.5; P < 0.01) and chronic gastritis or duodenal ulceration (22.0 % vs 10.2%, O.R. 2.4, P < 0.05). CONCLUSIONS: Hyperamylasemia is relatively frequent, and is associated with severe gastroenteritis. However, acute pancreatitis in the setting of acute gastroenteritis, is a rare event.

Postoperative infections following total knee replacement: an epidemiological study.

From January 1991 to June 1997 217 patients undergoing monolateral or bilateral total knee replacement (TKR) were consecutively enrolled in a prospective study on the incidence of postoperative infections and related risk factors. Regional antimicrobial prophylaxis (teicoplanin 400 mg) was used in 263 (95%) prostheses implanted; in the remaining 14 implants (5%) perioperative antibiotic prophylaxis (teicoplanin 800 mg) was administered as usual by systemic route. None of the patients experienced local or systemic adverse effects. Over the 2-year follow-up period, 8 (2.9%) primary site infectious complications were recorded, i.e. 4 superficial infections, which were cured without involvement of the prostheses, and 4 deep infections, which required prosthesis removal. Six infections occurred in patients who had undergone previous surgery of the same knee joint, and 2 in patients undergoing primary TKR (p= 0.0005); diabetic patients had infections (13%) more frequently than non-diabetic patients (1.9%, p=0.01). Staphylococci were the leading organisms isolated from infections; however 3 strains of Escherichia coli were isolated from patients who had undergone a previous prosthesis implantation at the same knee joint. Regional administration of teicoplanin appears to be a safe and valuable prophylactic technique; however, in patients at risk of infection a prophylactic regimen which is also active against gram-negative bacteria should probably be considered.

Randomized prospective controlled trial of recombinant granulocyte colony-stimulating factor as adjunctive therapy for limb-threatening diabetic foot infection.

Adult diabetic patients admitted to our Diabetes Center from September 1996 to January 1998 for severe, limb-threatening foot infection were consecutively enrolled in a prospective, randomized, controlled clinical study aimed at assessing the safety and efficacy of recombinant human granulocyte colony-stimulating factor (G-CSF) (lenograstim) as an adjunctive therapy for the standard treatment of diabetic foot infection. Forty patients, all of whom displayed evidence of osteomyelitis and long-standing ulcer infection, were randomized 1:1 to receive either conventional treatment (i.e., antimicrobial therapy plus local treatment) or conventional therapy plus 263 microg of G-CSF subcutaneously daily for 21 days. The empiric antibiotic treatment (a combination of ciprofloxacin plus clindamycin) was further adjusted, when necessary, according to the results of cultures and sensitivity testing. Microbiologic assessment of foot ulcers was performed by both deep-tissue biopsy and swab cultures, performed at enrollment and on days 7 and 21 thereafter. Patients were monitored for 6 months; the major endpoints (i.e., cure, improvement, failure, and amputation) were blindly assessed at weeks 3 and 9. At enrollment, both patient groups were comparable in terms of both demographic and clinical data. None of the G-CSF-treated patients experienced either local or systemic adverse effects. At the 3- and 9-week assessments, no significant differences between the two groups could be observed concerning the number of patients either cured or improved, the number of patients displaying therapeutic failure, or the species and number of microorganisms previously yielded from cultures at day 7 and day 21. Conversely, among this small series of patients the cumulative number of amputations observed after 9 weeks of treatment appeared to be lower in the G-CSF arm; in fact, only three patients (15%) in this group had required amputation, whereas nine patients (45%) in the other group had required amputation (P = 0.038). In conclusion, the administration of G-CSF for 3 weeks as an adjunctive therapy for limb-threatening diabetic foot infection was associated with a lower rate of amputation within 9 weeks after the commencement of standard treatment. Further clinical studies aimed at precisely defining the role of this approach to this serious complication of diabetes mellitus appear to be justified.