Defervescence Rate Research Articles

New-generation tetracyclines for severe macrolide-resistant Mycoplasma pneumoniae pneumonia in children: a retrospective analysis

BackgroundMacrolide-resistant Mycoplasma pneumoniae (MRMP) strains are increasingly prevalent, leading to a rise in severe Mycoplasma pneumoniae pneumonia incidence annually, which poses a significant threat to children’s health. This study aimed to compare the effectiveness and safety of oral minocycline and doxycycline for the treatment of severe MRMP pneumonia in children.MethodsThis retrospective analysis included children treated for severe MRMP pneumonia at the Pediatric Department of Tongji Hospital, Shanghai, China, between September 2023 and January 2024 using minocycline and doxycycline. The patients were divided into four groups according to treatment: oral doxycycline alone (DOX group), oral minocycline alone (MIN group), oral doxycycline with intravenous glucocorticoids (DOXG group), and oral minocycline with intravenous glucocorticoids (MING group). Student’s t-test, Mann–Whitney U test, and χ2 or Fisher’s exact tests were used for group comparisons.ResultsA total of 165 patients were included in this study: 84 received minocycline, and 81 received doxycycline. The DOX group had higher fever resolution rates within 24, 48, and 72 h compared to the MIN group (63.2% vs. 31.8%, 79.0% vs. 63.6%, and 100% vs. 90.9%, respectively; all p < 0.05). The DOXG group showed higher fever resolution rates within 24 and 48 h than the MING group (92.3% vs. 83.4%, 100% vs. 92.7%, all p > 0.05). There were no statistically significant differences in time to imaging improvement, cough improvement, and disappearance of wet rales between groups, regardless of glucocorticoid combination. The longer the duration of fever prior to tetracycline therapy, the greater the likelihood of hypoxemia (p = 0.039) and a greater than two-fold elevation in the D-dimer level (p = 0.004).Univariate binary logistic regression model analysis revealed that CRP and erythrocyte sedimentation rate at disease onset were associated with defervescence within 24 h after treatment with tetracyclines alone (p = 0.020, p = 0.027), with erythrocyte sedimentation rate also influencing defervescence within 48 h (p = 0.022).ConclusionDoxycycline treatment resulted in a higher rate of defervescence than minocycline. Prompt treatment reduced the probability of pleural effusion, hypoxemia, pulmonary atelectasis, and D-dimer levels > 2 times the reference value.

Efficacy and safety of infliximab in the treatment of Kawasaki disease: A systematic review and meta-analysis.

Infliximab is a monoclonal antibody specifically binding tumor necrosis factor-alpha and has been approved for the treatment of several inflammatory disorders. However, the efficacy of infliximab in primary treatment of Kawasaki disease (KD) or retreatment of intravenous immunoglobulin (IVIG)-resistant KD in children is controversial. Therefore, we conducted a meta-analysis to compare the efficacy of infliximab alone or in combination with IVIG to IVIG. Eligible randomized and non-randomized trials were retrieved by searching literature databases prior to May 31, 2023. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated for dichotomous variables, and mean difference (MD) with 95% CI was estimated for continuous variables. A total of 14 eligible studies comprising 1257 participants were included. In refractory KD, infliximab alone was associated with a higher effectiveness rate (OR = 4.48, 95% CI 2.67-7.52) and defervescence rate (OR = 5.01, 95% CI 2.99-8.37) and resulted in a 1.08-day-shorter duration of fever (95% CI 0.61-1.55, P < 0.001) and 1.36-day-shorter length of hospital stay (95% CI 0.65-2.08) compared with IVIG. Incidences of coronary artery lesions (CALs), newly developing CALs, and CAL regression did not differ between both groups. For initial treatment of KD, infliximab in addition to IVIG led to a nominally significant higher effectiveness rate (OR = 2.26, 95% CI 1.02-5.01) and a larger reduction of right coronary artery Z score (MD = -0.24, 95% CI -0.27 to -0.21) but did not show additional efficacy in improving other outcomes. The safety profile was similar between both groups. Conclusion: The meta-analysis demonstrates that infliximab alone is a well-tolerated and effective treatment for IVIG-resistant KD. The additional efficacy of infliximab to IVIG for initial treatment of KD is limited. More large and high-quality trials are needed to confirm the efficacy of infliximab, especially for intensification of primary treatment for KD. What is Known: • Infliximab is a novel monoclonal antibody specifically blocking tumor necrosis factor-alpha and is approved for treatment of several immune-mediated inflammatory disorders. • The efficacy of infliximab in treating children with Kawasaki disease is controversial. What is New: • Infliximab is an effective and safe treatment for children with refractory Kawasaki disease but adds limited efficacy to intravenous immunoglobulin for initial treatment of Kawasaki disease.

The role of early defervescence in ruling out infective endocarditis: a cohort study

ObjectivesTo evaluate the role of defervescence within 4 days from antibiotic treatment initiation in ruling out infective endocarditis (IE) among patients suspected of such diagnosis. MethodsThis study was conducted at the Lausanne University Hospital, Switzerland (January 2014 to May 2022). All patients with suspected IE being febrile upon presentation were included. IE was classified according to the modified Duke criteria proposed by the 2015 European Society of Cardiology guidelines, before or after applying the criterion ‘resolution of symptoms suggesting IE within 4 days of the introduction of antibiotic therapy’ based solely on early defervescence. ResultsAmong 1022 episodes with suspected IE, 332 (37%) had IE according to Endocarditis-Team evaluation; 248 were classified by clinical Duke criteria as definite and 84 as possible IE. The rate of defervescence within 4 days from antibiotic treatment initiation was similar (p 0.547) among episodes without (606/690; 88%) and those with IE (287/332; 86%); among episodes classified as definite and possible IE by clinical Duke criteria, 211 of 248 (85%) and 76 of 84 (90%), respectively, defervesced within 4 days from antibiotic treatment initiation. By using early defervescence as a rejection criterion, the 76 episodes with final IE diagnosis classified as possible by clinical criteria could be reclassified as rejected. DiscussionThe majority of IE episodes defervesced within 4 days from antibiotic treatment initiation; thus, early defervescence should not be used to rule out the diagnosis of IE.

Efficacy of tetracyclines and fluoroquinolones for the treatment of macrolide-refractory Mycoplasma pneumoniae pneumonia in children: a systematic review and meta-analysis

BackgroundMycoplasma pneumoniae is a common pathogen that causes community-acquired pneumonia in school-age children. Macrolides are considered a first-line treatment for M. pneumoniae infection in children, but macrolide-refractory M. pneumoniae (MRMP) strains have become more common. In this study, we assessed the efficacy of tetracyclines and fluoroquinolones in MRMP treatment in children through a systematic review and meta-analysis.MethodsTwo reviewers individually searched 10 electronic databases (Medline/Pubmed, Embase, the Cochrane Library, and core Korean, Chinese, and Japanese journals) for papers published from January 1, 1990 to March 8, 2018. The following data for each treatment group were extracted from the selected studies: intervention (tetracyclines and fluoroquinolones/comparator), patient characteristics (age and sex), and outcomes (fever duration, hospital stay length, treatment success rate, and defervescence rates 24, 48, and 72 h after starting treatment).ResultsEight studies involving 537 participants were included. Fever duration and hospital stay length were shorter in the tetracycline group than in the macrolide group (weighted mean difference [WMD] = − 1.45, 95% confidence interval [CI]: − 2.55 to − 0.36, P = 0.009; and WMD = − 3.33, 95% CI: − 4.32 to − 2.35, P < 0.00001, respectively). The therapeutic efficacy was significantly higher in the tetracycline group than in the macrolide group (odds ratio [OR]: 8.80, 95% CI: 3.12–24.82). With regard to defervescence rate, patients in the tetracycline group showed significant improvement compared to those in the macrolide group (defervescence rate after 24 h, OR: 5.34, 95% CI: 1.81–15.75; after 48 h, OR 18.37, 95% CI: 8.87–38.03; and after 72 h, OR: 40.77, 95% CI: 6.15–270.12). There were no differences in fever improvement within 24 h in patients in the fluoroquinolone group compared to those in the macrolide group (OR: 1.11, 95% CI: 0.25–5.00), although the defervescence rate was higher after 48 h in the fluoroquinolone group (OR: 2.78, 95% CI: 1.41–5.51).ConclusionTetracyclines may shorten fever duration and hospital stay length in patients with MRMP infection. Fluoroquinolones may achieve defervescence within 48 h in patients with MRMP infection. However, these results should be carefully interpreted as only a small number of studies were included, and they were heterogeneous.

Clinical Effectiveness of Intravenous Peramivir versus Oseltamivir for the Treatment of Influenza in Hospitalized Patients.

PurposeTo compare the clinical efficacy between peramivir and oseltamivir in hospitalized patients with influenza.Patients and MethodsRetrospective cohort study examined data from 542 adult patients with laboratory-confirmed seasonal influenza hospitalized in five teaching hospitals and one secondary hospital between August 2017 and May 2018. The main outcome was the defervescence rate within 3 days from the first administration of peramivir or oseltamivir. The secondary outcomes were mortality and duration of hospitalization/intensive care unit (ICU) stay.ResultsOf the 542 enrolled patients, 251 were administered the standard dose of peramivir (300 mg, single dose), 42 were administered peramivir at doses exceeding 300 mg, and 249 were administered oseltamivir (75 mg, twice daily for 5 days). There were more ICU and pneumonia cases and older patients in the peramivir group, especially the high-dose group. The Charlson comorbidity index (CCI) scores were similar among the three groups. There were no significant differences in defervescence rates within 3 days between the three groups. The mortality and duration of hospital and ICU stays also did not differ significantly. The factors associated with 30-day mortality were ICU admission, high CCI score, and pneumonia.ConclusionTreatment of influenza with either peramivir or oseltamivir in hospitalized adults resulted in generally similar clinical outcomes. Peramivir treatment showed good clinical response in influenza patients with pneumonia or admitted to the ICU.

Infliximab versus intravenous immunoglobulin for refractory Kawasaki disease: a phase 3, randomized, open-label, active-controlled, parallel-group, multicenter trial

We compared the efficacy and safety of infliximab with intravenous immunoglobulin (IVIG), a standard therapy, in a phase 3 trial (NCT01596335) for Japanese patients with Kawasaki disease (KD) showing persistent fever after initial IVIG. Patients with initial IVIG-refractory KD, aged 1–10 years, received a single dose of IV infliximab 5 mg/kg or IV polyethylene glycol-treated human immunoglobulin (VGIH) 2 g/kg on day 0. Primary outcome was defervescence rate within 48 h after the start of treatment. Safety was evaluated through day 56. Overall, 31 patients were randomized (infliximab, n = 16; VGIH, n = 15); 31.3% and 60.0% patients discontinued due to worsening KD. Defervescence rate within 48 h was greater with infliximab (76.7%) than VGIH (37.0%) (p = 0.023), and defervescence was achieved earlier with infliximab (p = 0.0072). Coronary artery lesions occurred in 1 (6.3%) and 3 (20.0%) patients receiving infliximab and VGIH, respectively, up to day 21. Adverse events occurred in 15 (93.8%) and 15 (100.0%) patients in the infliximab and VGIH groups, respectively. No serious adverse events in the infliximab group and one in the VGIH group were observed. Infliximab improved the defervescence rate within 48 h and time to defervescence versus standard therapy, and was well tolerated in patients with IVIG-refractory KD.

The Use of Ceftriaxone Compared to Chloramphenicol in Typhoid Fever Treatment: an Evidence Based Case Report

Typhoid fever is a disease caused by the gram-negative bacterium Salmonella typhi. Since its introduction in 1949, chloramphenicol for decades become a first-line treatment of typhoid fever. Until now, chloramphenicol is still the first line treatment of typhoid fever in rural areas in Indonesia, especially due to its low cost. However, in addition to the problem of bacterial resistance, chloramphenicol is known to cause side effect such as bone marrow suppression. Right now many other antibiotics are used as regimens for treatment of typhoid fever, one of which is ceftriaxone. This report is created to answer the clinical question whether ceftriaxone is more effective compared to chloramphenicol as first-line treatment of typhoid fever. Structured search was performed on PubMed, EBSCO, and ScienceDirect and after a screening process and appraisal using criteria from Center of Evidence Based Medicine at Oxford University, three articles were selected. Two of the three articles demonstrate higher effectiveness of chloramphenicol in term of defervescence rate (P = 0.35 and P &gt; 0.05). On the other hand, the third article shows higher effectiveness of ceftriaxone in term of defervescence rate (P = 0.0001). The conclusion drawn is that ceftriaxone showed better effectiveness in the treatment of typhoid fever compared to chloramphenicol.

Impact of Surveillance Stool Culture Guided Selection of Antibiotics in Allogeneic Hematopoietic Stem Cell Transplant Patients

INTRODUCTIONAllogeneic stem cell transplant (allo-SCT) patients are at high risk for severe life threatening bacterial infections. Although the prevalence and pattern of resistance varies among centres and countries, there is a growing global problem of resistance to antibiotics. The consequent increased use of broad spectrum antibiotics and injudicious antibiotic policies have contributed to the selection of multidrug resistant (MDR) pathogens. Translocation of organisms which normally colonize the gut into the bloodstream during the febrile neutropenia (FN) has long been postulated as a pathogenic factor for life threatening gram negative infections. This hypothesis had led to utilization of various methods of peritransplant gut decontamination. Our centre has a policy of performing surveillance stool cultures for all patients prior to transplant. While initially our antibiotic policy was independent of any surveillance culture, over recent years stool surveillance culture sensitivity has guided our choice of first line antibiotics in the post transplant FN. This retrospective analysis is aimed at comparing the outcomes of empirical versus surveillance stool culture guided selection of antibiotics in the immediate post allo-SCT FN.METHODOLOGYThis was a retrospective analysis of 190 allo SCT patients from January 2008 to December 2014 at our centre. During the post transplant FN, patients were categorized into two groups. Group-1 (Empirical: n=48) received first line broad spectrum antibiotics as per our hospital policy i.e. cefoperazone + sulbactum combination with amikacin. Group-2 (Surveillance based: n=119) received first line antibiotics based on sensitivity pattern of stool surveillance culture. In both groups, escalation to second line antibiotics (carbapenems with or without colistin or tigecycline) was done if defervescence did not occur in 24-48 hours or blood cultures grew a resistant organism or if there was any clinical deterioration. The primary endpoint was defervescence rate after first line antibiotics in both groups. Secondary endpoints were need for second line antibiotics, duration of total antibiotic use, concordance between blood and surveillance stool culture, incidence and causes of mortality, prevalence of MDR organisms in stool surveillance culture and change in trend of resistant organisms in stool surveillance cultures over last 7 years.RESULTSOne ninety patients underwent allo-SCT from January 2008 to December 2014.The median age of the cohort was 26 years (range 3-57 years) with 136 males and 54 females. The diagnoses were AML-75, ALL-46, CML-19, aplastic anemia-18, MDS-12 and others-20. Group 1 (Empirical) had 48 patients, while 119 were in Group 2 (Surveillance based). Twenty three patients did not have any growth in stool surveillance.In group 1, defervescence to first line antibiotics occurred in 23 (48 %) patients, whereas in group 2, it occurred in 78 (66 %) patients (P= 0.05). Defervescence within 24 hours was seen in 18 (37.5 %) patients in group 1 and 67 (56.3 %) patients in group 2 (P= 0.0425). In group 2, 34.5 % patients required escalation to second line antibiotics, compared to 54 % patients in group 1 (P = 0.0294). The median duration of total antibiotic use was 17.5 days in group 1 and 18 days in group 2 (P= NS). The concordance between blood culture and surveillance stool culture was seen in 3 (1.76 %) patients. There was no significant difference in infection related mortality between the two groups as shown in the figure 1.The prevalence of resistant organisms in the baseline surveillance stool culture changed between the periods 2008-2011 and 2012-2014. The incidence of extended spectrum beta lactamase (ESBL) organisms decreased from 79.66 % in 2008-2011 to 62.1 % in 2012-2014 (P = 0.0351). The incidence of carbapenem resistant (15.25 % vs. 25.26 %), colistin resistant (1.69 % vs. 2.1 %) and vancomycin resistant enterococcus (VRE: 3.38 % vs. 10.52 %) increased from 2008-2011 to 2012-2014 period. The increase in the combined incidence of carbapenem resistant, colistin resistant and VRE was from 20.32 % to 37.86 % (P = 0.0351).CONCLUSIONStool surveillance guided antibiotic usage leads to earlier defervescence in higher number of patients, while also reducing the need for second line antibiotics in patients undergoing allo-SCT. A randomized study is required to prove the importance of stool surveillance in this setting. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

A safety and feasibility study comparing an intermittent high dose with a daily standard dose of liposomal amphotericin B for persistent neutropenic fever

A high intermittent dose regimen (group A: 10 mg kg(-1) on day 1, 5 mg kg(-1) on days 3 and 6) was compared with standard dosing (group B: 3 mg kg(-1) per day for 14 days) of liposomal amphotericin B (LAB) for empirical treatment of persistent febrile neutropenia. A total cumulative dose of 1275 mg (group A) and 2800 mg (group B) was administered. Infusion-related adverse drug events, mainly rigors/chills, occurred more frequently with group A (11/45, 24 % infusions) than with group B (12/201, 6 % infusions) (P=0.002), which extended the mean infusion time by 20 min (P=0.001). Creatinine levels were similar in the two regimens: the A : B ratio of the area under the curve for creatinine (AUC(CREATININE)) for days 2-7 was 1.09 (P=0.27) and for days 2-14 was 1.05 (P=0.51). Rises in creatinine were mild (clinical toxicity criteria 1) in all patients with elevations. Hypokalaemia tended to be less severe in group A with a lower proportion of hypokalaemic days [57/143 (39 %) vs 80/137 (58 %), P=0.21], a higher AUC(POTASSIUM) (A : B ratio of 1.06, P=0.12), a lower proportion of patients with hypokalaemia at the end of study (10 vs 61 %, P=0.01) and fewer potassium-supplemented days [12/210 (6 %) vs 41/210 (19.5 %), P<0.1]. There were mildly elevated median levels of serum bilirubin, alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, which were similar for the two regimens and were usually associated with other co-existing co-morbid conditions. The AUC for these enzymes was also similar in the two groups. No patient had discontinuation of the study drug due to toxicity. Composite success was identical for each regimen (11/15 patients, 73 %). Three of the fifteen patients in group B and none in group A developed invasive fungal infections (IFIs). Beta-D-Glucan levels were similar in both groups for patients without an IFI [AUC(GLUCAN) of 362 and 683 (P=0.36) for groups A and B, respectively]. The rate of defervescence was similar for each regimen (P=0.75). This feasibility study suggests that a short intermittent high-dose course of 10/5/5 mg LAB kg(-1) on days 1, 3 and 6 may be as safe and effective as a standard 14 day course of 3 mg kg(-1) per day, with drug-acquisition cost savings and reduced drug exposure. A larger study is indicated for confirmation of this.

Statistical Correlations Between Quantifiable Disease Variables and Prognosis in Hematological Malignancy Patients Treated with Itraconazole as An Empirical Antifungal Therapy: A Prospective Multicenter Observational Study in Korea

We identified the clinical characteristics including disease status for expecting success outcome of empirical antifungal therapy for invasive fungal infection (IFI) using itraconazole in immunocompromised patients with hematological malignancies. The prospective multicenter observational study was performed at 26 medical centers for 9 months. Three hundred seventy six patients with hematological malignancies (median age 48) had been enrolled and analyzed. The patients with possible and probable categories for IFI according to the EORTC/MSG criteria were included. We excluded the patients with proven IFI. IV itraconazole was administered as routine schedule. Oral itraconazole solution was used after the IV itraconazole. Underlying disease consisted of 61% of AML and 15% of ALL. Overall success rate of empirical antifungal therapy with itraconazole was 196/376 (51%). Acute leukemia in non-CR status and advanced stage of MDS patients showed a lower trend of success rate. Combined co-morbidities, underlying lung disease, poor ECOG performance status (≥2), abnormal chest X-ray at the time of initiation of empirical antifungal therapy, no early initiation of empirical antifungal therapy (the duration of baseline neutropenic fever ≥3 days) and antifungal prophylaxis other than itraconazole were associated with decreased overall success rate. Multivariate analysis revealed that poor ECOG performance status (≥2) (P=0.01, HR = 1.90, 95% CI 1.17–3.06) and abnormal chest X-ray (P=0.02, HR = 2.00, 95% CI 1.12–3.58) were significantly associated with poor outcome of empirical antifungal therapy with itraconazole. Overall success rate of empirical antifungal therapy was not affected by antifungal prophylaxis. Defervescence in setting of neutropenia was 70% (264/276). Higher rate of defervescence was observed in the patients with early stage of MDS (92% vs. 40%, P = 0.02). Median time to defervescence after empirical itraconazole therapy was 3 days. Short mean time to defervescence was observed in the patients with acute leukemia in CR status (P = 0.002) or early stage of lymphoid malignancies (P = 0.03). Baseline fungal infections were diagnosed in 13 patients (3%). Of the patients with baseline fungal infections, 7 patients (54%) had a successful outcome. All 7 patients with successful outcome had baseline fungal infection with candidemia. The rate of breakthrough fungal infection was 4% (16/376). Breakthrough aspergillus infection was documented in the half of theses patients (8/16). The rate of breakthrough fungal infection also was not different according to the different disease status. Premature discontinuation of itraconazole therapy because of toxicity or lack of efficacy occurred in 35% (131/376). The proportion of patients who survived for at least 7 days after completion of itraconazole therapy was 90% (338/376). IV itraconazole followed by oral itraconazole solution is an effective regimen for empirical antifungal therapy in the haematological malignancy patients with persistent neutropenic fever. Poor performance status and abnormal chest X-ray were predictive factors for failure of empirical antifungal therapy with itraconazole in the patients with hematological malignancies.Table 1. Outcomes (overall success rate) according to the clinical characteristicsYesNoPCo-morbidities37/90 (41%)156/286 (55%)0.03Diabetes mellitus6/20 (30%)187/356 (53%)0.07Lung disease3/14 (21%)190/362 (53%)0.03ECOG performance status -≥2 (vs. 0 or 1)45/123 (37%)148/253 (59%)< 0.001Galactomannan test – positive3/9 (33%)33/74 (45%)0.73Abnormal chest X-ray23/70 (33%)156/278 (56%)0.001Abnormal chest CT14/51 (28%)5/8 (63%)0.10Duration of baseline neutropenia≥7 days (vs. <7 days)101/206 (49%)92/170 (54%)0.35>10 days (vs. ≤10 days)60/122 (49%)133/254 (52%)0.58Duration of baseline neutropenic fever≥3 days (vs. <3 days)89/193 (46%)104/183 (57%)0.04≥5 days (vs. <5 days)55/124 (44%)138/252 (55%)0.06Antifungal prophylaxis95/183 (52%)98/193 (51%)0.84Other drugs (vs. itraconazole)51/114 (45%)44/69 (64%)0.02

Clinafloxacin monotherapy (CI-960) versus ceftazidime plus amikacin for empirical treatment of febrile neutropenic cancer patients

Objective To assess the efficacy and safety of clinafloxacin as a single agent for the empirical treatment of febrile episodes and bacterial infections in neutropenic cancer patients.Methods An open label, active-controlled, randomized, parallel treatment, multicenter study was conducted where clinafloxacin monotherapy was compared to the combination of ceftazidime plus amikacin (plus optional vancomycin or teicoplanin). Four hundred and nineteen patients were randomized to receive either intravenous clinafloxacin 200 mg every 12 h or intravenous ceftazidime (2 g) iv every 8 h plus intravenous amikacin (15 mg/kg) per day in divided doses. All randomized patients were to receive a minimum of 48 h of primary study drug treatment, after which the primary treatment could be modified. Clinical and microbiological responses were evaluated at 7-21 days post-treatment after study treatment and long term (maximum 28 days), in intent-to-treat and modified intent-to-treat populations.Results Clinafloxacin and ceftazidime-amikacin were statistically equivalent for the 72-h defervescence rate, overall defervescence rate, time to defervescence, clinical success rate, by-pathogen microbiological eradication rate, and survival rate. Clinical cure was achieved in 84% (59/70) of patients who received clinafloxacin monotherapy. There were no significant differences between treatments in rates of adverse events or treatment discontinuation rates due to adverse events.Conclusions Clinafloxacin appears to be an appropriate agent for empirical treatment in febrile neutropenic cancer patients.

Acyclovir in immunocompromised patients with cytomegalovirus disease: A controlled trial at one institution

Nine of 16 immunocompromised patients with laboratory-documented cytomegalovirus (CMV) disease were given intravenous acyclovir in a randomized, placebo-controlled, double-blind treatment study. Fifteen of the 16 patients were organ transplant recipients, 11 of whom had a renal allograft. Patients given acyclovir (500 mg/m 2 three times daily for seven days) experienced no major side effects. Acyclovir recipients had a significantly faster rate of improvement (p = 0.0437, Breslow test; p = 0.0595, Mantel-Cox), and a more rapid rate of defervescence (p = 0.0338, Breslow test; p = 0.0208, Mantel-Cox). The median day of improvement was 7 for the acyclovir recipients, and at least 31 for the placebo recipients. The median day afebrile was 13 for the acyclovir group and at least 31 for the placebo group. Three of the nine acyclovir recipients died, two of whom were semicomatose and septic with Bacteroides fragilis before the first dose of acyclovir was given. Four of the seven placebo recipients died. Although CMV could be recovered from throat and urine of acyclovir recipients throughout the study, viremia ceased after the first day of drug infusion. We conclude that acyclovir may be useful for treatment of CMV disease in certain immunosuppressed patients especially renal allograft recipients. Because the clinical response to acyclovir was not uniform and the number of patients studied was small, we are conducting another larger controlled trial of acyclovir for febrile renal transplant patients with CMV infections to extend and clarify the results of the first study. Patients randomized to acyclovir will receive 500 mg/m 2 three times daily for two weeks. The protocol includes in vitro testing of patients' CMV isolates for susceptibility to acyclovir and monitoring plasma concentrations of the drug.

Acute Nonspecific Lung Abscess: A Controlled Study Comparing Orally and Parenterally Administered Penicillin G

A controlled study was undertaken to compare oral and parenteral administration of penicillin G in the treatment of acute nonspecific lung abscess. Eighteen patients received 1.2 million units four times a day by mouth and 18 were given either 500,000 units intramuscularly every eight hours (five cases) or 20 million units per day intravenously for two weeks followed by orally administered penicillin (13 cases). Medication was continued until the process resolved or stabilized on serial roentgenograms. Those treated parenterally and orally were comparable with respect to various background factors. Two patients receiving penicillin orally failed to show a clinical response in six days but then responded to orally administered tetracycline. One patient on intravenously administered penicillin did not respond in six days but was treated successfully with clindamycin by mouth. The rate of defervescence and the rate of cavity disappearance was similar in the two groups.